LipidBank - Vitamin A

No	Structure	COMMON NAME	NAME	DATA No	INFORMANT	SYMBOL	FORMULA	MOL.WT(ave)	Download	BIOOGICAL ACTIVITY	PHYSICAL AND CHEMICAL PROPERTIES						SPECTRAL DATA					CHROMATOGRAM DATA	SOURCE	CHEMICAL SYNTHESIS	METABOLISM	GENETIC INFORMATION	NOTE	REFERENCES
No	Structure	COMMON NAME	NAME	DATA No	INFORMANT	SYMBOL	FORMULA	MOL.WT(ave)	Download	BIOOGICAL ACTIVITY	MELTING POINT	BOILING POINT	DENSITY	REFRACTIVE INDEX	OPTICAL ROTATION	SOLUBILITY	UV SPECTRA	IR SPECTRA	NMR SPECTRA	MASS SPECTRA	OTHER SPECTRA	CHROMATOGRAM DATA	SOURCE	CHEMICAL SYNTHESIS	METABOLISM	GENETIC INFORMATION	NOTE	REFERENCES
1		all-trans-retinol	((2E,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraen-1-ol	VVA0001	Hiroyuki Kagechika	ROH	C₂₀H₃₀O	286.452		Relative physiological activity for All trans-retinyl acetate is 100%.(Ref. 0046) New physiological functions of vitamin A have been identified in addition to its role in vision (Ref. 0005), namely its role in immune defence reducing morbidity of measles, (Ref. 0006) of respiratory and possibly HIV infections (Ref. 0007), in gene regulation (Ref. 0008), in cell differentiation (Ref. 0009) and morphogenesis.(Ref. 0010/0011)	62-64C(Ref. 0013)	120-125 at 5x10^-³mm		n22,D:1.6410		insol in lcohol, methanol, chloroform, ether, fats and oils	l_m_a_x=324-325 nm(E¹^%₁_c_m 1832 in Ethanol, 1830 in Petro. ether, 1835 in Isopropanol ),326.5 nm(E¹^%₁_c_m 1745 in Cyclohexane)(Ref. 0013)		¹H-NMR(d,CDCl₃,220MHz):1.03(6H,1-Me),~1.47(2H,J= n.o,2-CH₂), ~1.61( 2H,J= n.o,3-CH₂),1.72(3H,5-Me),1.85(3H,13-Me),1.97(3H,9-Me),2.02(2H, J= n.o,4-Me),4.29 ( 2H,J=6.8Hz,15-CH₂),5.67 (1H,J=6.8 Hz,14-H),6.08(1H,J=11.0Hz, 10-H),6.09(1H,J=~16Hz,8-H ), 6.14(1H,J=~16Hz,7-H),6.27(1H,J=14.8Hz,12-H),6.60(1H, J=11.0,14.8Hz,11-H)(Ref. 0003) ¹³C-NMR(d,CDCl₃,22.63MHz):12.5,12.6,19.4,21.7,29.0,29.0,33.1,34.2,39.8,59.1,124.8,126.5,128.9, 130.2,130.6,135.6,136.2,136.5,137.7,137.9,(Ref. 0004)	m/e : M+286,268,255,241,225,213,199,185,173,159,145,133,119,105,91,81,69,55,41(70ev,270C)	Fluorescence (in ethanol at 25C):Ex.347nm, Em. 490nm(Ref. 0023)		Fish liver oils Animals8Liver,Lung.Kidney)	by b-ionone and propargyl halide(Ref. 0012) by conversion of retinal(Ref. 0015/0016/0017)	The dietary preformed retinoids are mainly converted to all-trans-retinol by retinyl-ester hyrdolase, and uptaken from intesitine.The absorbed all-trans-retinol is packaged as retinyl esters(palmitate,stearate,linolate) in chylomicrons. Chylomicrons are secreted into the lymphatic system, and the bulk of the chylomicron retinoids are taken up by the liver,where the majority of the body's retinoids are stored mainly in the parenchymal cells and the stellate cells in the form of complex with protein. During hepatic storage and metabolism,Retinyl esters are hydrolyzed to retinol by bile-salt-independent or bile-salt-dependent retinyl ester hydrolase, which in turn is esterified by ARAT or LRAT.Hydrolyzed retinol is released to the bloodstream binding to RBP,controlling the supply of retinol to target tissues.Other tissues except liver can store retinols,part of which is oxidized to retinal or retinoic acid. (Ref. 0001)(Ref. 0002)			[0001] / [0002] / [0003] / [0004] / [0005] / [0006] / [0007] / [0008] / [0009] / [0010] / [0011] / [0012] / [0013] / [0015] / [0016] / [0017] / [0023] / [0046]
2		All-Trans-3,4-Didehydro Retinol	(2E,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1,3-dienyl)-nona-2,4,6,8-tetraen-1-ol	VVA0002	Hiroyuki Kagechika		C₂₀H₂₈O	284.436		40-51% of relative biological activity of all-trans-retinyl acetate as a acetate form. (Ref. 0046)	63-65,17-19C(Ref. 0013)					nsol in water or glycerol. Sol in abs alcohol, methanol, chloroform, ether, fats and oils	l_m_a_x=350,286,276 nm(E¹^%₁_c_m 1,455, 715, 555 in ethanol)(Ref. 0013)		¹³C-NMR(d,CDCl₃,22.63MHz):12.6,12.6,20.2,26.7,26.7,33.9,39.9,59.2,124.7,124.9,125.4,126.5,129.9,130.6,130.8,135.7,136.4,136.7,137.1,138.5(Ref. 0004)				freshwater fish liver oils					[0004] / [0013] / [0046]
3		9-cis-retinol	(2E,4E,6Z,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraen-1-ol	VVA0003	Hiroyuki Kagechika		C₂₀H₃₀O	286.452		Relative physiological activity for All trans-retinyl acetate is 22%.(Ref. 0046)	81-82C(Ref. 0013)						l_m_a_x=323,258nm (E:1477,382 respecticely in ethanol)(Ref. 0013)		¹³C-NMR(d,CDCl₃,22.63MHz):12.7,19.4,20.7,21.8,29.0,29.0,33.2,34.3,39.8,124.0,128.6,128.7,129.4,130.0,130.0,134.8,135.7,136.7,137.1,138.2(Ref. 0004)									[0004] / [0013] / [0046]
4		11-cis-retinol	(2E,4Z,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraen-1-ol	VVA0004	Hiroyuki Kagechika		C₂₀H₂₈O	284.436		Relative physiological activity for All trans-retinyl acetate is 23%.(Ref. 0046)							l_m_a_x=319,233nm (E:1220,370 respecticely in ethanol)(Ref. 0013)		¹³C-NMR(d,CDCl₃,22.63MHz):12.2,17.1,19.4,21.7,29.0,29.0,33.1,34.3,39.7,59.4(OCH₂),125.2,126.4,127.1,129.1,130.5,132.6,136.1,137.1,138.0,138.1(Ref. 0004>									[0004] / [0013] / [0046]
5		11-cis-3,4-didehydroretinol	(2E,4Z,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1,3-dienyl)-nona-2,4,6,8-tetraen-1-ol	VVA0005	Hiroyuki Kagechika		C₂₀H₂₈O	284.436		Relative physiological activity for All trans-retinyl acetate is 15%.(Ref. 0046)							l_m_a_x=344,286,278nm (E:990,566,493 respecticely in ethanol)(Ref. 0013)											[0013] / [0046]
6		13-cis-retinol	(2Z,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraen-1-ol	VVA0006	Hiroyuki Kagechika		C₂₀H₂₈O	284.436		Relative physiological activity for All trans-retinyl acetate is 70-85%.(Ref. 0046)	58-60C(Ref. 0013)						l_m_a_x=328nm (E:1686 respecticely in ethanol)(Ref. 0013)		¹H-NMR(d,CDCl₃,220MHz):1.03(6H,1-Mex2),~1.47(2H,J= n.o,2-CH₂),~1.61( 2H,J= n.o,3-CH₂),1.71(3H,5-Me),~1.95(3H,13-Me),1.96(3H,9-Me),2.03(2H,J= n.o,4-Me),4.30(2H,J=7.0Hz,15-CH₂),5.55(1H,J=7.0Hz,14-H),6.10(1H,J=~16Hz,8-H),6.13(1H,10-H),6.17 (1H,J=~16Hz,7-H),~6.60(1H,J=~15.0Hz,12-H),~6.65(1H,J=~15.0Hz,11-H)(Ref. 0003) ¹³C-NMR(d,CDCl₃,22.63MHz CW offset ¹H-decoupling):12.7,19.4,20.4,21.6,29.0,29.0,33.1,34.3,39.8,58.4,127.1,127.1,128.6,128.7,129.3,130.2,135.6,136.8,137.6,137.9,(Ref. 0004)									[0003] / [0004] / [0013] / [0046]
7		Retinol Acetate/All-trans-retinyl Acetate	(2E,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-en-1-yl)-2,4,6,8-nonatetraen-1-yl-acetate	VVA0007	Hiroyuki Kagechika		C₂₂H₃₂O₂	328.488		Same as all-trans retinol	57-58C(Ref. 0046)						l_m_a_x=325nm (E¹^%₁_c_m1560 in ethanol, 1590 in hexane)(Ref. 0014)		¹H-NMR(d,CDCl₃,220MHz):1.03(6H,1-Me),~1.46(2H,J= n.o,2-CH₂),~1.61( 2H,J= n.o,3-CH₂),1.71(3H,5-Me),1.89(3H,13-Me),1.96(3H,9-Me),2.02(2H,J= n.o,4-Me),2.05 ( 3H,J=7.0Hz,Acetyl),4.72 (2H,J=6.8Hz,15-CH₂),5.61 (1H,J=6.8Hz,14-H),6.10 (1H,J=11.0Hz, 10 -H),6.10 (1H,J=~16Hz,8-H),6.19(1H,J=~16Hz,7-H),6.29(1H,J=14.8Hz,12-H),6.60 (1H,J=11.0,14.8 Hz,11-H),(Ref. 0003) ¹³C-NMR(d,CDCl₃,22.63MHz):19.35,21.67,12.73,12.73,20.88(CH₃),29.00,29.00,33.10,34.30,39.78,61.27(OCH₂)124.60,125.82,127.00,129.26,130.22,135.89,136.46,137.66,137.95,139.02,170.66(CO)(Ref. 0004)	M+:m/e328(100%), Fragment ion: m/e 313(4%),285(2%),268(40%),255(32%),253(5!%),145(83%),132(54%),119(63%),105(69%),95(40%),91(46%),81(51%),43(61%)(Ref. 0024)	Fluorescence(in cyclohexane,25C):Ex. 345 nm, Em. 495nm (Ref. 0023) X-Ray Analysis(Ref. 0022)		Animals( mainly Liver, Lung, Kidney) Fish liver oils		same as all trans retinol:A part of all-trans-retinol is involved in diet, and stored in liver as retinyl acetate.(Ref. 0001)			[0001] / [0003] / [0004] / [0014] / [0022] / [0023] / [0024] / [0046]
8		all-trans-retinyl Palmitate	(2E,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-en-1-yl)-2,4,6,8-nonateetraen-1-yl-palmitate / (2E,4E,6E,8E)-Hexadecanoic acid 3,7-dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2, 4,6,8,tetraenyl ester	VVA0008	Hiroyuki Kagechika		C₃₆H₆₀O₂	524.860		Same as all-trans-retinol							l_m_a_x=325nm (E¹^%₁_c_m 940 in ethanol)(Ref. 0014)				Fluorescence (in ethanol 25C):Ex.325 nm Em.470 nm		Animals(mainly Liver, Lung and Kidney) Fish liver oils		All-trans-retinyl palmitate is hydrolyzed and converted to all-trans-retinol by retinyl-ester hydrolase in intestine and pancreas.(Ref. 0001)			[0001] / [0014]
9		all-trans-retinyl stearate	(2E,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-en-1-yl)-2,4,6,8-nonateetraen-1-yl-stearate/(2E,4E,6E,8E)-Octadecanoic acid3,7-dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2, 4,6,8,tetraenyl ester	VVA0009	Hiroyuki Kagechika		C₃₈H₆₄O₂	552.914																	All-trans-retinyl stearate is hydrolyzed and converted to all-trans-retinol by retinyl-ester hydrolase in intestine and pancreas, and a part of retinol is stored as all-trans-retinyl acetate.(Ref. 0001)			[0001]
10		all-trans-retinyl oleate	(2E,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-en-1-yl)-2,4,6,8-nonateetraen-1-yl-oleate/(2E,4E,6E,8E)-Octadec-9-enoic acid 3,7-dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2, 4,6,8,tetraenyl ester	VVA0010	Hiroyuki Kagechika		C₃₈H₆₂O₂	550.898																	All-trans-retinyl oleate is hydrolyzed and converted to all-trans-retinol by retinyl-ester hydrolase in intestine and pancreas, and a part of retinol is stored as all-trans-retinyl oleate.(Ref. 0001)			[0001]
11		all-trans-retinyl linolate	(2E,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-en-1-yl)-2,4,6,8-nonateetraen-1-yl-linolate/(2E,4E,6E,8E)-Octadeca-9,12,15-enoic acid 3,7-dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)- nona-2, 4,6,8,tetraenyl ester	VVA0011	Hiroyuki Kagechika		C₃₈H₅₈O₂	546.866																	All-trans-retinyl linolate is hydrolyzed and converted to all-trans-retinol by retinyl-ester hydrolase in intestine and pancreas, and a part of retinol is stored as all-trans-retinyl linolate.(Ref. 0001)			[0001]
12		All-trans-Retinal	(2E,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetranal	VVA0012	Hiroyuki Kagechika		C₂₀H₂₈O	284.436		Relative physiological activity for All trans-retinyl acetate is 91%.(Ref. 0046)all-trans-retinal directly and markedly inhibits cloned rod CNG channels in excised patches. 11-cis-retinal and all-trans-retinol also inhibited the channels, but at somewhat higher concentrations. Single-channel analysis suggests that all-trans-retinal reduces average open probability of rod CNG channels by inactivating channels for seconds at a time. At physiological cGMP levels, all-trans-retinal inhibited in the nanomolar range. Our results suggest that all-trans-retinal may be a potent regulator of the channel in rods during the response to bright light, when there is a large surge in the concentration of all-trans-retinal.(Ref. 0025/0026/0027/0028/0029/0030/0031)	61-62C(Ref. 0013)					Sol in ethanol,chloroform,cyclohexane,petr ether,oils .Insol in water	l_m_a_x=381 nm (E¹^%₁_c_m 1,510 in ethanol), 368 nm(E¹^%₁_c_m 1,690 in n-heptane)(Ref. 0014)		¹H-NMR(d,CDCl₃,220MHz):1.03(6H,1-Me),~1.46(2H,J= n.o,2-CH₂),~1.62( 2H,J= n.o,3-CH₂),1.72(3H,5-Me),~2.0(2H,J= n.o,4-Me),2.03(3H,9-Me),2.32(3H,13-Me),5.97( 1H,J=8.3Hz,14-H),6.17(1H,J=16.0Hz,8-H),6.19(1H,J=11.3Hz,10-H),6.35(1H,J=16.0Hz,7-H),7.15(1H,J=11.3,15.0Hz,11-H),6.37 (1 H,J=15.0Hz,12-H),10.09(1H,J=8.3Hz,CHO)(Ref. 0003) ¹³C-NMR(d,CDCl₃,22.63MHz):13.0,13.0,19.3,21.7,29.0,29.0,33.2,34.1,39.6,128.9,129.4,129.6,130.3,132.4,134.5,137.1,137.6,141.1,154.5,190.7(CO)(Ref. 0004)		Fluorescence (in ether:isopentane:ethanol =5:5:2, -196C):Ex.420nm,Em.500nm X-Ray Analysis(Ref. 0022)		Retina	by Vitamin A1 (Ref. 0032)				[0003] / [0004] / [0013] / [0014] / [0022] / [0025] / [0026] / [0027] / [0028] / [0029] / [0030] / [0031] / [0032] / [0046]
13		All-Trans-3,4-Didehydro Retinal	(2E,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1,3-dienyl)-nona-2,4,6,8-tetraenal	VVA0013	Hiroyuki Kagechika		C₂₀H₂₆O	282.420		57% of relative biological activity of all-trans-retinyl acetate.(Ref. 0046)	78-79,66-68C(Ref. 0013)						l_m_a_x=401,314nm (E:1470, 395 respectively in ethanol)(Ref. 0013)		¹³C-NMR(d,CDCl₃,22.63MHz):12.9,13.1,20.3,26.8,26.8,34.0,40.0,125.0,127.7,128.3,129.0,130.0,130.0,132.3,134.8,136.4,138.2,140.9,154.3,190.5(Ref. 0004)				Freshwater fish retina					[0004] / [0013] / [0046]
14		9-cis-retinal	(2E,4E,6Z,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraenal	VVA0014	Hiroyuki Kagechika		C₂₀H₂₈O	284.436		Relative physiological activity for All trans-retinyl acetate is 19%.(Ref. 0046)	64C(Ref. 0013)						l_m_a_x=373nm (E:1270 respecticely in ethanol)(Ref. 0013)		¹H-NMR(d,CDCl₃,220MHz):1.05(6H,1-Me),1.75(3H,5-Me),2.00(3H,9-Me),2.30 (3H,13-Me),5.94(1H,J=8.2Hz,14-H),6.06(1H,J=11.8Hz,10-H),6.27(1H,J=15.4Hz,12-H),6.31(1H,J=15.9Hz,7-H),6.64(1H,J=15.9Hz,8-H),7.20(1H,J=11.8,15.4Hz,11-H),10.07(1H,J=8.2Hz,CHO)(Ref. 0003) ¹³C-NMR(d,CDCl₃,22.63MHz):13.2,19.3,20.9,21.8,29.0,29.0,33.2,34.1,39.7,127.9,128.9,129.4,130.4,131.1,131.2,133.8,138.1,140.0,154.3,167.8(CO)(Ref. 0004)									[0003] / [0004] / [0013] / [0046]
15		11-cis-retinal	(2E,4Z,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraenal	VVA0015	Hiroyuki Kagechika		C₂₀H₂₈O	284.436		Relative physiological activity for All trans-retinyl acetate is 48%.(Ref. 0046)Application(intraperitoneal injection)of 11-cis-retinal to Rpe65 ^-^/^- mice increased the rod ERG signal, increased levels of rhodopsin, and decreased opsin phosphorylation. Therefore, exogenous 11-cis-retinal improves photoreceptor function by regenerating rhodopsin and removes constitutive opsin phosphorylation. Our results indicate that opsin, which has not been exposed to 11-cis-retinal, does not generate the activity generally associated with the bleached apoprotein.(Ref. 0033/0034/0035/0036)	63-65C(Ref. 0013)						l_m_a_x=376.5 290 and254 nm (E¹^%₁_c_m 878,412 and 614 respectively in ethanol)(Ref. 0013)		¹H-NMR(d,CDCl₃,220MHz):1.02(6H,1-Me),1.71(3H,5-Me),1.99(3H,9-Me),2.36 (3H,13-Me),5.92 (1H,J=13.0Hz,12-H),6.07(1H,J=8.0Hz,14-H),6.14(1H,J=16.0Hz,8-H),6.32(1H,J=16.0Hz,7-H)6.54(1H,J=11.5Hz,10-H),6.69(1H,J=11.5,13.0Hz,11-H),10.10(1H,J=8.0Hz,CHO)(Ref. 0003)		X-Ray Analysis(Ref. 0022)		Retina	(Ref. 0037)				[0003] / [0013] / [0022] / [0033] / [0034] / [0035] / [0036] / [0037] / [0046]
16		11-cis-3,4-didehydroretinal	(2E,4Z,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1,3-dienyl)-nona-2,4,6,8-tetraenal	VVA0016	Hiroyuki Kagechika		C₂₀H₂₆O	282.420									l_m_a_x=393,321,252nm (E:882,512,452 respecticely in ethanol)(Ref. 0013)											[0013]
17		13-cis-retinal	(2Z,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1,3-dienyl)-nona-2,4,6,8-tetraenal	VVA0017	Hiroyuki Kagechika		C₂₀H₂₈O	284.436		Relative physiological activity for All trans-retinyl acetate is 93%.(Ref. 0046)	77C(Ref. 0013)						l_m_a_x=375,257nm (E:1250,336 respecticely in ethanol)(Ref. 0013)		¹H-NMR(d,CDCl₃,220MHz):1.04(6H,1-Me),~1.47(2H,J= n.o,2-CH₂),~1.63(2H,J=n.o,3-CH₂),1.73(3H,5-Me),~2.0(2H,J=n.o,4-Me),2.03(3H,9-Me),2.15(3H,13-Me),5.85(1H,J=8.0Hz,14-H),6.18(1H,J=~16.0Hz,8-H),6.24(1H,J=11.0Hz,10-H),6.36(1H,J=~16.0Hz,7-H),7.04(1H,J=11.0,15.0Hz,11-H),7.30 (1H,J=15.0Hz,12-H),10.21(1H,J=8.0Hz,CHO)(Ref. 0003) ¹³C-NMR(d,CDCl₃,22.63MHz):13.0,19.3,21.1,21.7,29.0,29.0,33.2,34.3,39.7,126.5,127.7,129.4,129.6,130.3,133.4,137.0,137.6,141.3,154.2,174.0(CO)(Ref. 0004)									[0003] / [0004] / [0013] / [0046]
18		Tretinoin/All-Trans Retinoic Acid	((2E,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraenoic acid	VVA0018	Hiroyuki Kagechika	ATRA	C₂₀H₂₈O₂	300.435		A pleiotropic biological activities of vitamin A except visual function result from the binding and activating of retinoid nuclear receptors by all-trans-retinoic acid. (Ref. 0067) All-trans-retinoic acid is effective to acute promyelocytic leukemia (APL).(Ref. 0068)Relative physiological activity for All trans-retinyl acetate is 100%.(Ref. 0046)Differentiation-inducing activity,proliferation-inhibitory activity(Ref. 0018)	179-180C(Ref. 0013)					ether 1.56 acetone 1.09 ethanol 0.33 water 0.01 (W/V%)	l_m_a_x=350nm (E¹^%₁_c_m 1,510 in Ethanol)(Ref. 0013)	1685,1601,1570,1251,1184,962cm^-¹(Ref. 0018)	¹H-NMR(d,CDCl₃,220MHz):1.02(6H,1-Me),~1.47(2H,2-CH₂),~1.62(2H,3-CH₂),1.72(3H,5-Me),2.01(3H,9-Me),~2.02(2H,CH₂),2.37(3H,13-Me),5.79(1H,14-H),6.14(1H,J=16.0Hz,8-H),6.15(1H,J=11.5Hz,10-H),6.29(1H,J=16.0Hz,7-H),6.31(1H,J=15.0Hz,12-H), 7.03 (1H,J=11.5,15.0Hz,11-H)(Ref. 0003) ¹³C-NMR(d,CDCl₃,22.63MHz):12.9,13.9,19.5,21.6,29.0,29.0,33.3,34.5,40.0,118.5,128.7,129.8,129.8,131.1,135.5,137.6,138.0,139.3,153.2,168.6(CO)(Ref. 0004)	Fragment(m/e):M +300,285,255,105,91,77,55,41(Ref. 0018)	Fluorescence (in Ethanol 25C):Ex.334 nm, Em.484 nm X-ray analysis(Ref. 0018/0022)			by oxidation of retinal (Ref. 0019) Single-step process for all-trans nad 13-cis isomers (Ref. 0020/0021)	All-trans-retinoic acid is metabolized to 13-cis-RA, 9-cis-RA, retunoyl b-glucuronide, 5,6-epoxyretinoic acid, 4-hydroxyretinoic acid, 4-oxoretinoic acid, and 3,4-didehydroretinoic acid. The 4-oxidization or 4-hydroxylation occurs in liver.(Ref. 0001)	Teratogenecity		[0001] / [0003] / [0004] / [0013] / [0018] / [0019] / [0020] / [0021] / [0022] / [0046] / [0067] / [0068]
19		All-Trans-3,4-Didehydro-Retinoic acid	(2E,4E,6Z,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1,3-dienyl)-nona-2,4,6,8-tetraenoic acid	VVA0019	Hiroyuki Kagechika		C₂₀H₂₆O₂	298.419		6.7% of relative biological activity of all-trans-retinyl acetate.(Ref. 0046)All-Trans-3,4-Didehydro-Retinoic acid possesses morphogenetic properties in the chick limb.(Ref. 0001)	183-184C(Ref. 0013)						l_m_a_x=370,305nm (E¹^%₁_c_m 1395,443 respectively in Ethanol)(Ref. 0013)								All-Trans-3,4-Didehydro-Retinoic acid is one of the metabolites from all-trans- retinoic acid.(Ref. 0001)			[0001] / [0013] / [0046]
20		13-cis-retinoic acid,Isotretinoin	(2Z,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraenoic acid	VVA0020	Hiroyuki Kagechika		C₂₀H₂₈O₂	300.435		Relative physiological Activity for all-trans-retinyl acetate is 24%.(Ref. 0046)Keratolytic 13-cis-retinoic acid so dramatically reduces sebaceous gland size and sebum excretion (Ref. 0044), presumably due to the inhibition on lipogenesis in human sebaceous gland (Ref. 0045).	174-175C(Ref. 0013)						l_m_a_x=354 nm(E¹^%₁_c_m 1,325 in ethanol)(Ref. 0013)		¹H-NMR(d,CDCl₃,220MHz):1.03(6H,1-Me),~1.46(2H,2-CH₂),~1.63(2H,3-CH₂),1.72(3H,5-Me),2.00(3H,9-Me),~2.0(2H,4-Me),2.10(3H,13-Me),5.69(1H,14-H),6.17(1H,J=16.0Hz,8-H),6.29(1H,J=11.5Hz,10-H),6.29(1H,J=16.0Hz,7-H),7.03 (1H,J=11.5,15.0Hz,11-H),7. 77(1H,J=15.0Hz,12-H),~9.9(1H,COOH)(Ref. 0003) ¹³C-NMR(d,CDCl₃,22.63MHz):12.9,19.4,21.1,21.6,29.0,29.0,33.3,34.4,40.0,115.9,128.9,129.4,130.1,130.3,132.9,137.4,137.9,140.3,153.3,171.4(CO)(Ref. 0004)					Single step process(Ref. 0020/0021)	13-cis retinoic acid is one of metabolites from all-trans-retinoic acid.(Ref. 0001)			[0001] / [0003] / [0004] / [0013] / [0020] / [0021] / [0044] / [0045] / [0046]
21		9-cis-retinoic acid	(2E,4E,6Z,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraenoic acid	VVA0021	Hiroyuki Kagechika		C₂₀H₂₈O₂	300.435		Relative physiological activity for All trans-retinyl acetate is about 10%.(Ref. 0046) Thyroid-stimulating hormone(TSH) of the anterior pituitary gland is regulated by the binding ofthe thyroid hormone-activated thyroid receptor to the TSH gene at the same time as the binding of the 9-cis-retinoic acid-activated retinoid X receptor to the same gene. Both interactions, separately or simultaneously, can suppress and thus regulate the expression fo the TSH gene. 9-cis-retinoic acid suppresses the expression of the TSH gene of the anterior pituitary gland (Ref. 0038/0039/0040/0041). 9-cis-retinoic avid induces and activates acyl-coenzyme A:cholesterol acyltransferase (ACAT) by increase in ACAT-1 messenger ribonucleic acid (mRNA) in undifferentiated human monocytotic THP-1 cells (Ref. 0042). 9-cis-retinoic avid stimulates leptin messenger ribonucleic acid (mRNA) expression and secretion in human syncytiotrophoblast (Ref. 0043).	189-191C(Ref. 0013)						l_m_a_x=345 nm (E¹^%₁_c_m 1,230 in ethanol)(Ref. 0013)		¹H-NMR(d,CDCl₃,220MHz):1.04(6H,1-Me),~1.48(2H,2-CH₂),~1.64(2H,3- CH₂),1.75(3H,5-Me),2.01(3H,9-Me),~2.04(2H,4-CH₂),2.37(3H,13-Me),5.82(1H,14-H),6.09(1H,J=11.3Hz,10-H),6.27(1H,J=14.7Hz,12-H),6.31(1H,J=15.7Hz,7-H),6.67(1H,J=15.7Hz,8-H),7.15( 1H,J=11.3,14.7Hz,11-H)(Ref. 0003) ¹³C-NMR(d,CDCl₃+DMSO-d₆ 1:1,22.63MHz):13.4,18.9,20.5,21.6,28.8,28.8,32.7,33.9,39.3,119.6,128.1,129.0,129.4, 129.6,129.6,134.7,137.3,137.6,151.2,167.8(CO)(Ref. 0004)						9-cis-retinoic acid is one of the metabolites from all-trans-retinoic acid.(Ref. 0001)			[0001] / [0003] / [0004] / [0013] / [0038] / [0039] / [0040] / [0041] / [0042] / [0043] / [0046]
22		9,13-di-cis-retinoic acid	(2Z,4E,6Z,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraenoic acid	VVA0022	Hiroyuki Kagechika		C₂₀H₂₈O₂	300.435		Relative physiological activity for All trans-retinyl acetate is 7%.(Ref. 0046)	135-136C(Ref. 0013)						l_m_a_x=346nm (E:1150 respecticely in ethanol)(Ref. 0013)		¹H-NMR(d,CDCl₃,220MHz):1.04(6H,1-Me),~1.48(2H,2-CH₂),~1.65(2H,3-CH₂),1.75(3H,5-Me),2.02(3H,9-Me),~2.05(2H,4-CH₂),2.10(3H,13-Me),5.66(1H,14-H),7.68(1H,J=15.0Hz,12-H),6.64(1H,J=15.7Hz,8-H),6.27(1H,J=15.7Hz,7-H),6.18(1H,J=11.5Hz,10-H),7.11(1H,J=11.5,15.0Hz,11-H)(Ref. 0003)									[0003] / [0013] / [0046]
23		11-cis-Retinoic acid	(2E,4Z,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraenoic acid	VVA0023	Hiroyuki Kagechika		C₂₀H₂₈O₂	300.435			94-96C(Ref. 0013)						l_m_a_x=342,243nm (E:926,426 respecticely in ethanol)(Ref. 0013)		¹H-NMR(d,CDCl₃,220MHz):1.03(6H,1-Me),~1.45(2H,2-CH₂),~1.62(2H,3-CH₂),1.72(3H,5-Me),1.98(3H,9-Me),~2.02(2H,CH₂),2.36(3H,13-Me),5.90(1H,14-H),5.91(1H,J=~11.5Hz,12-H),6.14(1H,J=16.0Hz,8-H),6.28(1H,J=16.0Hz,7-H),6.52(1H,J=~11.5Hz,10-H),6.60( 1H,J=~11.5,~11.5Hz,11-H)(Ref. 0003)									[0003] / [0013]
24		all-trans-4-hydroxyretinoic acid	(2E,4E,6E,8E)-9-(3-Hydroxy-2,6,6-trimethyl-cyclohex-1-enyl)-3,7-dimethyl-nona-2,4,6,8-tetraenoic acid	VVA0024	Hiroyuki Kagechika		C₂₀H₂₈O₃	316.435																	all-trans-retinoic acid is converted to all-trans-4-hydroxyretinoic acid by the cytochrome P-450 system, for example, P-450 isozyme P4502C8 of human liver microsomes.When all-trans-retinoic acid binds to CRABP, microsomal enzymes of rats testes catalyze the conversion to all-trans-4-hydroxyretinoic acid.(Ref. 0001)			[0001]
25		all-trans-4-oxoretinoic acid	(2E,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-3-oxo-cyclohex-1-enyl)-nona-2,4,6,8-tetraenoic acid	VVA0025	Hiroyuki Kagechika		C₂₀H₂₆O₃	314.419																	All-trans-retinoic acid is converted to all-trans-4-oxoretinoic acid by thecytochrome P-450 system, for example, P-450 isozyme P4502C8 of human liver microsomes.When all-trans-retinoic acid binds to CRABP, microsomal enzymes of rats testes catalyze the conversion to all-trans-4-hydroxyretinoic acid.(Ref. 0001)			[0001]
26		DACP analog of retinoic acid	(2E,4E,6E,8E)-9-(2-Acetyl-5,5-dimethyl-cyclopent-1-enyl)-3,7-dimethyl-nona-2,4,6,8-tetraenoic acid	VVA0026	Hiroyuki Kagechika		C₂₀H₂₆O₃	314.419		This compound binds to cellular retinoic acid-binding protein and inhibit growth of mouse epidermis and organ cultures of hamster trachea.(Ref. 0069/0070)														Oxidative cleavage of ethyl all-trans retinoate by CrO₃-H₂SO₄ at low temperature, then cyclization under acidic condition byHClO₄, and hydrolysis furnishes the product.				[0069] / [0070]
27		19-Hydroky-all-trans-retinoic acid	(2E,4E,6E,8E)-7-Hydroxymethyl-3-methyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8- tetraenoic acid	VVA0027	Hiroyuki Kagechika	19-Hydroxy-ATRA	C₂₀H₂₈O₃	316.435		Differentiation-Inducing activity on human promyelocytic leukemia HL-60 cells, which is in accordance with its binding activity to nuclear reinoic acid receptors (RARs).(Ref. 0047)	151-152C(Ref. 0047)								¹H-NMR(d,CD₃OD):1.09(6H,s),1.52-1.55(2H,m),1.66-1.72(2H,m),1.77(3H,s),2.08(2H,t,J=6Hz),2.37(3H,d,J=1.10Hz),4.54(2H,s),5.86(s),6.11(d,J=16.5Hz),6.31(d,J=11.5Hz),6.47(d,J=15Hz),6.57(d,J=16.5Hz),7.24(dd,J=11.5,15Hz)(Ref. 0047)					b-Ionone was oxidized withPb(OAC)₄. The resultant acetate was hydrolyzed, and the 10-hydroxy group was protected by tert-butyldimethylsilylation. The obtained silylether ws allowed to react with triethylphosphoacetate, followed by successive reduction with DIBAL and oxidation with active MnO₂. The obtained aldehyde was allowed to react with methyl-g-dimethylphosphonosenecioate to give methyl esters of 19-hydroxy-ATRA and of 19-hydroxy-13CRA in the ratio of 1.3 : 1. Separation using silica gel column chromatography, and alkaline hydrolysis followed by recrystallization gave 19-hydroxy-ATRA.(Ref. 0047)				[0047]
28		19-Hydroxy-13-cis-retinoic acid	(2Z,4E,6E,8E)-7-Hydroxymethyl-3-methyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8- tetraenoic acid	VVA0028	Hiroyuki Kagechika	19-Hydroxy-13CRA	C₂₀H₂₈O₃	316.435		Differentiation-Inducing activity on human promyelocytic leukemia HL-60 cells, which is in accordance with its binding activity to nuclear reinoic acid receptors (RARs).(Ref. 0047)	137C(dec)(Ref. 0047)								¹H-NMR(d,CD₃OD):1.09(6H,s),1.52-1.55(2H,m),1.66-1.72(2H,m),1.78(3H,s),2.08(2H,t,J=6Hz),2.13(3H,d,J=1.10Hz),4.54(2H,s),5.73(s),6.12(d,J=16Hz),6.33(d,J=11.5Hz),6.57(d,J=16.5Hz),7.22(dd,J=11.5,15Hz),7.83(d,J=15Hz)(Ref. 0047)					b-Ionone was oxidized withPb(OAC)₄. The resultant acetate was hydrolyzed, and the 10-hydroxy group was protected by tert-butyldimethylsilylation. The obtained silylether ws allowed to react with triethylphosphoacetate, followed by successive reduction with DIBAL and oxidation with active MnO₂. The obtained aldehyde was allowed to react with methyl-g-dimethylphosphonosenecioate to give methyl esters of 19-hydroxy-ATRA and of 19-hydroxy-13CRA in the ratio of 1.3 : 1. Separation using silica gel column chromatography, and alkaline hydrolysis followed by recrystallization gave 19-hydroxy-13CRA.(Ref. 0047)				[0047]
29		19-Oxo-all-trans-retinoic acid	(2E,4E,6E,8E)-7-Formyl-3-methyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraenoic acid	VVA0029	Hiroyuki Kagechika	19-Oxo-ATRA	C₂₀H₂₆O₃	314.419		Differentiation-Inducing activity on human promyelocytic leukemia HL-60 cells, which is in accordance with its binding activity to nuclear reinoic acid receptors (RARs).(Ref. 0047)	132C(dec)(Ref. 0047)								¹H-NMR(d,CD₃OD):1.09(6H,s),1.53-1.56(2H,m),1.66-1.73(2H,m),1.78(3H,d,J=0.73Hz),2.10(2H,t,J=6Hz),2.39(3H,d,J=1.10Hz),6.03(s),6.25(d,J=16.5Hz),6.78(d,J=15Hz),6.93(d,J=16.5Hz),7.25(d,J=12Hz),7.73(dd,J=12,15Hz),10.44(s)(Ref. 0047)					Swern oxidation of[(COCl₂)/DMSO in CH₂Cl₂,-60C] of 19-hydroxy-ATRA gave 19-oxo-ATRA after recrystallization from ether.(Ref. 0047)				[0047]
30		19-Oxo-9-cis-retinoic acid	(2E,4E,6Z,8E)-7-Formyl-3-methyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraenoic acid	VVA0030	Hiroyuki Kagechika	19-Oxo-9-CRA	C₂₀H₂₆O₃	314.419		Differentiation-Inducing activity on human promyelocytic leukemia HL-60 cells, which is in accordance with its binding activity to nuclear reinoic acid receptors (RARs).(Ref. 0047)	154.5-156C(Ref. 0047)								¹H-NMR(d,CD₃OD):1.11(6H,s),1.54-1.57(2H,m),1.68-1.74(2H,m),1.83(3H,d,J=0.73Hz),2.12(2H,t,J=6Hz),2.37(3H,d,J=1.10Hz),6.07(s),6.36(d,J=1.516.5Hz),6.95(d,J=15Hz),7.05(d,J=16.5Hz),7.06(d,J=11.5Hz),7.29(dd,J=12,15Hz),9.61(s)(Ref. 0047)					Swern oxidation of[(COCl₂)/DMSO in CH₂Cl₂,-60C] of the methyl ester of 19-hydroxy-ATRA followed by alkaline hydrolysis and recrystallization from AcOEt/n-hexane gave 19-oxo-9CRA.Isomerization of the 9-double bond occured under the alkaline hydrolysis reaction conditions.(Ref. 0047)				[0047]
31		20,14-retro-retinoic acid	(4E,6E,8E)-7-Methyl-3-methylene-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-4,6,8-trienoic acid	VVA0031	Hiroyuki Kagechika		C₂₀H₂₈O₂	300.435		1.8% of relative biological activity of all-trans-retinoic acid on differentiation inducing activity on human promyelocytic leukemia cell line HL-60.(Ref. 0048)	60-62C(Ref. 0048)								¹H-NMR(d,CDCl₃,220MHz):3.35(1H,14-H),5.15(1H,20-H),5.25(1H,20-H),6.08(1H,10-H),6.09(1H,8-H),6.19(1H,7-H),6.32(1H,12-H),6.65(1H,11-H).(Ref. 0048)	HRMS(C₂₀H₂₈O₂)=300.2104(+1.5mmu).(Ref. 0048)				By treatment of all-trans-retinoic acid with mixed solution of n-BuLi and diisopropylaminein n-hexane and THF.(Ref. 0048)				[0048]
32		14-methyl-20,14-retro-retinoic acid	(4E,6E,8E)-2,7-Dimethyl-3-methylene-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-4,6,8-trienoic acid	VVA0032	Hiroyuki Kagechika		C₂₁H₃₀O₂	314.462		1.8% of relative biological activity of all-trans-retinoic acid on differentiation inducing activity on human promyelocytic leukemia cell line HL-60.(Ref. 0048)									¹H-NMR(d,CDCl₃,220MHz):3.56(1H,14-H),5.17(1H,20-H),5.24(1H,20-H),6.07(1H,10-H),6.09(1H,8-H),6.19(1H,7-H),6.27(1H,12-H),6.76(1H,11-H).(Ref. 0048)	HRMS(C₂₁H₃₀O₂)=314.2247(+0.1mmu).(Ref. 0048)				By treatment of all-trans-retinoic acid with mixed solution of n-BuLi and diisopropylamine and HMPA in n-hexane and THF,then with methyl iodide.(Ref. 0048)				[0048]
33		14-methyl-all-trans-retinoic acid	(2E,4E,6E,8E)-2,3,7-Trimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraenoic acid	VVA0033	Hiroyuki Kagechika		C₂₁H₃₀O₂	314.462		1.8% of relative biological activity of all-trans-retinoic acid on differentiation inducing activity on human promyelocytic leukemia cell line HL-60.(Ref. 0048)	130-131C(Ref. 0048)								¹H-NMR(d,CDCl₃,220MHz):5.24(1H,20-H),5.30(1H,20-H),6.15(1H,8-H),6.23(1H,10-H),6.27(1H,7-H),6.70(1H,12-H),6.98(1H,11-H).(Ref. 0048)	HRMS(C₂₁H₃₀O₂)=314.2241(-0.5mmu).(Ref. 0048)				By the treatment of 14-methyl-20,14-retro-retinoic acid with t-BuOK/t-BuOH.(Ref. 0048)				[0048]
34		11-cis retro-g-retinal	(2E,4Z,6E,9Z)-9-(2,2-Dimethyl-6-methylene-cyclohexylidene)-3,7-dimethyl-nona-2,4,6-trienal	VVA0034	Hiroyuki Kagechika		C₂₀H₂₈O	284.436									l_m_a_x=343nm(in Ethanol),(Ref. 0049)		¹H-NMR(d,CDCl₃,90MHz):1.04(6H,s,gem.CH₃),1.84(3H,s,C-9-CH₃),2.38(3H,s,C-13-CH₃),2.99(2H,d,J=8Hz,C-8-CH₃),4.62(1H,d,J=3Hz,exoCH₂),5.01(1H,m,exoCH₂),5.26(1H,t,J=8Hz,C-8-H₂),5.89(1H,d,J=10Hz,C-10-H),6.09(1H,d,J=8Hz),6.41(1H,d,J=12Hz,C-12-H),6.63(1H,dd,J=10,12Hz,C-11-H),10.12(1H,d,J=8Hz,C-15-H)(Ref. 0049)	m/e=284.214(M⁺,C20H28O requires284.214)(Ref. 0049)				by treatment of retro-g-retinoate with sodium bis-(2-methoxyethoxy)-aluminum hydride in abs. ether, then with active manganese dioxide.(Ref. 0049)				[0049]
35		9-cis retro-g-retinal	(2E,4E,6Z,9Z)-9-(2,2-Dimethyl-6-methylene-cyclohexylidene)-3,7-dimethyl-nona-2,4,6-trienal	VVA0035	Hiroyuki Kagechika		C₂₀H₂₈O	284.436									l_m_a_x=343nm(in Ethanol)(Ref. 0049)		¹H-NMR(d,CDCl₃,90MHz):1.02(6H,s,gem.CH₃),1.84(3H,s,C-9-CH₃),2.20(2H,t,J=6Hz,C-4-H₂),2.30(3H,s,J=6Hz,C-13-CH₃),3.14(2H,d,J=7Hz,C-8-H₂),4.64(1H,d,J=3Hz,exoCH₂),5.09(1H,m,exoCH₂),5.17(1H,t,J=7Hz,C-7-H),5.97(1H,d,J=8Hz,C-14-H),5.99(1H,d,J=11Hz,C-10-H),6.25(1H,d,J=15Hz,C-12-H),6.94(1H,dd,J-11,15Hz,C-11-H),10.13(1H,d,J=8Hz,C-15-H)(Ref. 0049)	m/e=284.215(M⁺,C20H28O requires284.214)(Ref. 0049)				by treatment of 9-cis retro-g-retinoate with sodium bis-(2-methoxyethoxy)-aluminum hydride in abs. ether, then with active manganese dioxide.(Ref. 0049)				[0049]
36		8-18 bonded retinal	(2E,4E,6Z)-7-(4,4-Dimethyl-4,5,6,7-tetrahydro-1H-inden-2-yl)-3-methyl-octa-2,4,6-trienal	VVA0036	Hiroyuki Kagechika		C₂₀H₂₆O₂	298.419											¹H-NMR(d,CDCl₃,200MHz):2.07(3H,s,9-Me),2.30(3H,s,13-Me),3.17(2H,sharp s,18-H₂),6.32(1H,d,J=16Hz,12-H),6.06(1H,d,J=12Hz,10-H),6.63(1H,s,7-H),7.36(1H,dd,,J=16,12Hz,11-H),10.10(1H,d,J=8.5Hz,CHO)(Ref. 0050)					By irradiation of (2E,4E,6E)-7-(4,4-Dimethyl-4,5,6,7-tetrahydro-1H-inden-2-yl)-3-methyl-octa-2,4,6-trienal using high pressure(30W) Hg lamp with a Pyrex filter in MeOH.(Ref. 0050)				[0050]
37			(2E,4E,6Z)-7-(7,7-Dimethyl-4,5,6,7-tetrahydro-1H-inden-2-yl)-3-methyl-octa-2,4,6-trienal	VVA0037	Hiroyuki Kagechika		C₂₀H₂₆O₂	298.419		binding capacity with cattle opsin(2% digitonin,10mmol HEPES buffer(pH 7.0), 25C, in the dark, 48h)(Ref. 0050)									¹H-NMR(d,CDCl₃,200MHz):2.06(3H,s,9-Me),2.32(3H,s,13-Me),3.20(2H,brs,18-H₂),6.32(1H,d,J=16Hz,12-H),6.07(1H,d,J=12Hz,10-H),6.45(1H,s,7-H),7.37(1H,dd,J=16,12Hz 11-H),10.10(1H,d,J=8Hz,CHO)(Ref. 0050)					By irradiation of (2E,4E,6E)-7-(7,7-Dimethyl-4,5,6,7-tetrahydro-1H-inden-2-yl)-3-methyl-octa-2,4,6-trienal using high pressure(30W) Hg lamp with a Pyrex filter in MeOH.(Ref. 0050)				[0050]
38		6-s-cis-locked retinal	(2E,4Z,6E)-7-(1,1-Dimethyl-4,5,6,7-tetrahydro-1H-inden-2-yl)-3-methyl-octa-2,4,6-trienal	VVA0038	Hiroyuki Kagechika		C₂₀H₂₆O	282.420		binding capacity with cattle opsin(2% digitonin,10mmol HEPES buffer(pH 6.86))(Ref. 0051)							l_m_a_x(Ethanol)=370nm(e 13100),335nm(e 14800)(Ref. 0051)		¹H-NMR(d,CDCl₃):1.07(6H,s,gem-Me₂),2.07(3H,s,9-Me),2.20(3H,s,13-Me),5.99(1H,s,7-H),6.20(1H,d,J=11Hz,10-H),6.26(1H,d,J=15.5Hz,12-H),6.92(1H,dd,J=15.5Hz,11HZ,11-H),10.05(1H,d,J=8Hz,15-H)(Ref. 0051) ¹³C-NMR(CDCl₃):22.4(19-C),13.4(20-C)(Ref. 0051)					By irradiation of By irradiation of (2E,4E,6E)-7-(4,4-Dimethyl-4,5,6,7-tetrahydro-1H-inden-2-yl)-3-methyl-octa-2,4,6-trienal using high pressure(300W) Hg lamp with a Pyrex filter in MeOH.(Ref. 0051)				[0051]
39		11-cis- and 12s-trans-fixed retinal	(7Z,9Z,14Z)-{4-[1-Methyl-3-(2,6,6-trimethyl-cyclohex-1-enyl)-allylidene]-cyclopent-2-enylidene}-acetaldehyde	VVA0039	Hiroyuki Kagechika		C₂₀H₂₆O	282.420									l_m_a_x(Ethanol)=263nm(e 13300),405nm(e 18500)(Ref. 0052)		¹H-NMR(d,CDCl₃,200MHz):1.05(6H,s,1-Me₂),1.76(3H,s,5-Me),2.05(3H,s,9-Me),3.73(1H,d,J=1.5Hz,20-H),5.97(td,J=1.5HZ,7HZ,14-H),6.32(1H,d,J=16Hz,7-H),6.42(1H,d,J=16Hz,8-H),6.61(1H,d,J=5Hz,12-H),7.27((1H,d,J=5Hz,11-H),9.88(1H,d,J=7Hz,CHO)(Ref. 0052)	M⁺=282.197 (C₂₀H₂₆O requires M⁺=282.198)(Ref. 0052)				by treatment of trans-b-ionylidenecyclopent-2-2-en-1-one with mixture of butyl-lithium and cyanomethylphosphonate, then purified. Subsequently treatment with DIBAH.(Ref. 0052)				[0052]
40		11Z-6s-cis-fixed bicyclic retinal	(2E,4Z,6E)-7-(4,4-Dimethyl-4,5,6,7-tetrahydro-1H-inden-2-yl)-3-methyl-octa-2,4,6-trienal	VVA0040	Hiroyuki Kagechika		C₂₀H₂₆O	282.420		binding capacity with bovine opsin(Ref. 0054)							l_m_a_x(Ethanol)=422nm,299nm,229nm l_m_a_x(hexane)=407nm(e 14000),295nm(e 8000),229nm(e 9000)(Ref. 0053)	n_m_a_x(KBr) /cm^-¹ 1660(C=O), 1581(C=C) (Ref. 0053)	¹H-NMR(d,C₆D₆,200MHz):1.11(6H,s,gem-Me),1.85(6H,s,9- and 13-Me),2.84(2H,s,18H₂),5.61(1H,d,J=12Hz,12-H),6.22(1H,d,J=8Hz,14-H),6.47(1H,t-like,J=12Hz,11-H),6.60(1H,s,7-H),6.77(1H,d,J=12Hz,10-H),10.07(1H,d,J=8Hz,CHO)(Ref. 0053)	M⁺ 282.199(C₂₀H₂₆O requires M 282.198)(Ref. 0053)				by photoisomerization(irradiation with a daylight fluorescent lamp) of corresponding All-trans-bicyclic retinal(Ref. 0040)				[0040] / [0053] / [0054]
41		11Z-6s-trans-fixed bicyclic retinal	(2E,4Z,6E)-7-(4,7a-Dimethyl-5,6,7,7a-tetrahydro-1H-inden-2-yl)-3-methyl-octa-2,4,6-trienal	VVA0041	Hiroyuki Kagechika		C₂₀H₂₆O	282.420		binding capacity with bovine opsin(Ref. 0054)							l_m_a_x(Ethanol)=405nm,310nm,258nm,227nm(sh) l_m_a_x(Methanol)=405nm(Ref. 0053)	n_m_a_x(KBr) /cm^-¹ 1664,1660(C=O), 1593(C=C) (Ref. 0053)	¹H-NMR(d,CDCl₃,200MHz):1.05(3H,s,1-Me),1.74(3H,s,5-Me),2.06(3H,s,9-Me),2.39(3H,s,13-Me),5.95(1H,d,J=10Hz,12-H),6.08(1H,d,J=8Hz,14-H),6.55(1H,s,7-H),6.61(1H,d,J=10Hz,10-H),6.70(1H,t-like,J=10Hz,11-H),10.10(1H,d,J=8Hz,CHO)(Ref. 0053)	M⁺ 282.197(C₂₀H₂₆O requires M 282.198)(Ref. 0053)				by photoisomerization(irradiation with a daylight fluorescent lamp) of corresponding All-trans-bicyclic retinal(Ref. 0041>				[0041] / [0053] / [0054]
42		(11Z)-8,18-ethanoretinal	(2E,4Z,6E)-7-(4,4-Dimethyl-2,3,4,7,8,9-hexahydro-1H-benzocyclohepten-6-yl)-3-methyl-octa-2,4,6-trienal	VVA0042	Hiroyuki Kagechika		C₂₂H₃₀O	310.473		binding capacity with bovine opsin(Ref. 0055)							l_m_a_x/nm(e/dm³mol^-¹cm^-¹) 386(17935),296(10368),266(10942),230(9860)(Ref. 0055)	n_m_a_x(KBr) /cm^-¹ 1660, 1575(Ref. 0055)	¹H-NMR(d,C₆D₆,500MHz):1.07(6H,s,1,1-gem-Me),1.42-1.47(2H,m,2-H₂),1.55-1.62(2H,m,3-H₂),1.80(3H,d,J=1Hz,13-Me),1.86(3H,br,s,9-Me),1.88(2H,t,J=7.5,18-H₂),2.05(2H,quintet-like,J=7Hz,18a-H₂),2.09(2H,t,J=6.5Hz,4-H₂),2.29(2H,t,J=7Hz,18b-H₂),5.63(1H,br d,J==12Hz,12-H),6.16(1H,br d,J=8Hz,14-H),6.45(1H,br s,7-H), 6.47 (1H, t-like,J=12Hz,11-H),6.90(1H,br d,J=12,10-H),9.95(1H,d,J=8Hz,CHO)(Ref. 0055) ¹³C-NMR(d,C₆D₆,500MHz):14.17(Me),17.51(Me),19.99(CH₂),28.15(CH₂),29.02(1,1-gem-Me),32.39(CH₂),33.04(CH₂),34.24(C),36.24(C),39.28(CH₂),122.34(CH),128.23(CH),130.65(CH),130.88(CH),131.78(CH),137.28(C),139.77(C),142.42(C),145.19(C),154.08(C),189.76(C)(Ref. 0055)	HRMS:m/z 310.2297(Calc.for C₂₂H₃₀O:M⁺,310.2296)(Ref. 0055)				synthethizedby 6-step reactions from3-(4,4-Dimethyl-2,3,4,7,8,9-hexahydro-1H-benzocyclohepten-6-yl)-but-2-enoic acid ethyl ester.(Ref. 0042)				[0042] / [0055]
43		(11Z)-8,18-methano-retinal	(2E,4Z,6E)-7-(8,8-Dimethyl-3,4,5,6,7,8-hexahydro-naphthalen-2-yl)-3-methyl-octa-2,4,6-trienal	VVA0043	Hiroyuki Kagechika		C₂₁H₂₈O	296.446		binding capacity with bovine rhodopsin.(Ref. 0056)							l_m_a_x/nm(MeOH,e/dm³mol^-¹cm^-¹) 258.5(13100),374(17600)(Ref. 0056)	n_m_a_x(KBr) /cm^-¹ 1660, 1575(Ref. 0056)	¹H-NMR(d,CD₃OD):0.86(3H,s,Me),1.14(3H,s,Me),1.06-1.20(2H,m,[CH₂x1/2]x2),1.48-1.54(2H,m,CH₂),1.57-1.63(1H,m,CH₂x1/2),1.63-1.72(2H,m,CH₂), 1.72-1. 80(1H,m,CH₂x1/2),1.86-1.90(2H,m,CH₂),1.96-2.01(1H,m,CH₂x1/2) ,2.01-2.06 (1H ,m,CH₂x1/2),2.05(3H,s,Me),2.39(3H,d,J=1Hz,Me),2.51(1H,dd,J=12.5,8.5Hz,CH₂x1/2), 6 .02(1H,br d,J=10Hz,=CH),6.06(1H,br d,J=10Hz,=CH),6.44(1H,br s,=CH),6.83(1H,d,J=11.5Hz ,=CH ),6.86 (1H,dd, J=11.5,10Hz ,=CH),10.05(1H,d,J=8.5Hz,CHO)(Ref. 0056) ¹³C-NMR(d,CD₃OD):14.37(Me),18.30(Me),20.76(CH₂),25.28(CH₂),26.17(CH₂),28.64(Me),29.20(Me),30.76(CH₂),31.92(CH₂),33.07(C),35.05(CH₂),40.23(CH₂),123.63(CH),128.24(CH),130.86(CH),131.74(CH),133.08(C),133.47(CH),135.70(C),137.96(C),142.98(C),144.20(C),193.36(CHO)(Ref. 0056)	HRMS:M⁺ 324.2422 Calc. forC₂₃H₃₂O:M,324.2451(Ref. 0056)				synthethizedby 5-step reactions from8,8-Dimethyl-3,4,5,6,7,8-hexahydro-1H-naphthalen-2-one(Ref. 0056)				[0056]
44		(11Z)-8,18-propano-retinal	(2E,4Z,6E)-7-(4,4-Dimethyl-1,2,3,4,7,8,9,10-octahydro-benzocycloocten-6-yl)-3-methyl-octa-2,4,6-trienal	VVA0044	Hiroyuki Kagechika		C₂₃H₃₂O	324.500		binding capacity with bovine rhodopsin.(Ref. 0056)							l_m_a_x/nm(MeOH,e/dm³mol^-¹m^-¹) 408(14700),308(10200), 233(8700)(Ref. 0056)	n_m_a_x(KBr) /cm^-¹ 1660, 1580,1550(Ref. 0056)	¹H-NMR(d,CD₃OD):1.05(6H,s,Mex2),1.50-1.54(2H,m,CH₂),1.63-1.68(2H,m,CH₂),2.05(3H,s,Me),2.06-2.12(4H,m,CH₂x2),2.33(2H,t,J=5.5Hz,CH₂),2.40(3H,d,J=1 Hz,Me),6.01(1H,dq,J=8.5,1Hz,=CH),6.02(1H,br d,J=10.5Hz,=CH),6.39(1H,br s,=CH),6.81(1H,br d ,J=11Hz,=CH),6.83(1H,br t,J=11Hz,=CH),10.03(1H,d,J=8.5Hz, CHO)(Ref. 0056) ¹³C-NMR(d,CD₃OD):13.71(Me),18.30(Me),20.42(CH₂),25.06(CH₂),29.00(Mex2),30.60(CH ₂),32.01(CH₂),33.61(C),40.41(CH₂),121.76(CH),125.30(CH),130.57(CH),131.06(CH),133.41(C),133.76(CH),136.64(C),136.72(C),143.34(C),159.18(C),193.50(CHO)(Ref. 0056)	HRMS:M⁺,296.2138 Calc. for C₂₁H₂₈O:M 296.2139)(Ref. 0056)				synthethizedby 14-step reactions from 3,3-Dimethyl-2-oxo-cyclohexanecarbocylic acid methyl ester.(Ref. 0056)				[0056]
45		Etretinate	ethyl (2E,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nona-tetraenoate/(2E,4E,6E,8E)-9-(4-Methoxy-2,3,6-trimethyl-phenyl)-3,7-dimethyl-nona-2,4,6,8-tetraenoic acid ethyl ester	VVA0045	Hiroyuki Kagechika		C₂₃H₃₀O₃	354.483		Etretinate has been effectively used in the treatment of psoriasis and a variety of ichthyosiform disorders(Ref. 0064),but is highly toxic, at least partially due to its prolonged residence in the body(Ref. 0065). (Ref. 0063/0066)	104-108C(dec)					Solvent volume (mi) for 1g of etretinate:Chloroform;1.91,Dichloromethane;1.94,Dioxane;4.47,Ethyl acetate;7.56,Aceton;10.2, Ether;15.8,Hexane;85.9,Ethanol;199,Methanol;381,Water;1.64x107	l_m_a_x=363 nm (e 1% 1cm;1313 in Dioxane)	1712,1612,1588,1448,1242,1148,1129,966,836cm^-¹(8)		m/z : M⁺354, 339,281,203,163,150,131(9)					Serum concentrations of etretinate and the active metabolite, the carboxylic acid derivative, are maximum after 3-5 h and 4-8 h, respectively. More than 99% of etretinate and the carboxylic acid bind to the proteins in the serum. Etretinate is mainly absorbed at intestines, and metabolized at intestines and liver to form the active carboxylic acid.	Teratogenecity		[0063] / [0064] / [0065] / [0066]
46		Am80	4-[(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid	VVA5001	Hiroyuki Kagechika	Am80	C₂₂H₂₅O₃N	351.439		As a potent RAR (retinoic acid receptor) agonist, Am80 induces the differentiation of human promyelocyte leukemia cells HL-60.(Ref. 5002) In all three subtypes of RAR (a, b, g), Am80 can activate both RARa and RARb. Therapeutic applications of Am80 are wide both in the field of darmatology and chemoprevention/therapy of cancer, and Am80 is also well known as potent therapeutic agent for acute promyelocytic leukemia (APL). (Ref. 5003)	231-232C (Ref. 5001)					Soluble in many organic solvents such as ethanol, methanol, ethyl acetate, dichloromethane, dimethylsulfoxide (DMSO), dimethylformamide (DMF) and acetone.	UV l_m_a_x 207 (4.55), 232 (4.25), 281 (4.16).	(KBr) 1645, 1690 cm^-¹ (Ref. 5001)	¹H-NMR (d, CD₃OD, 100 MHz) 1.28 (s, 6 H), 1.30 (s, 6 H), 1.71 (s, 4 H), 7.29 (d, 1 H, J = 8 Hz), 7.46 (dd, 1 H, J = 2.8 Hz), 7.63 (d, 1 H, J = 2 Hz), 8.00 (d, 2 H, J = 8 Hz), 8.12 (d, 2 H, J = 8 Hz). (Ref. 5001); ¹³C-NMR (d, CD₃OD, 100 MHz) 32.3 (q), 34.9 (s), 35.3 (s), 36.2 (t), 120.0 (d), 127.7 (d), 128.5 (d), 130.6 (d), 134.4 (s), 136.8 (s), 140.1 (s), 142.4 (s), 146.3 (s), 167.5 (s), 168.6 (s). (Ref. 5001)	M⁺ 351				Condensation of 5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthylamine and terephthalic acid monomethyl ester chloride gave methyl 4-[(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoate, which was hydrolized to Am80. (Ref. 5001)				[5001] / [5002] / [5003]
47		Am580/CD336/Ro40-6055	4-[(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]benzoic acid	VVA5002	Hiroyuki Kagechika	Am580	C₂₂H₂₅O₃N	351.439		As a potent RAR (retinoic acid receptor) agonist, Am580 induces the differentiation of human promyelocyte leukemia cells HL-60.(Ref. 5001) In all three subtypes of RAR (a, b, g), Am580 can activate both RARa and RARb. Therapeutic potential of Am580 is similar to that of Am80. (Ref. 5003)	265-267C(Ref. 5001)					Soluble in many organic solvents such as ethanol, methanol, ethyl acetate, dichloromethane, dimethylsulfoxide (DMSO), dimethylformamide (DMF) and acetone.		(KBr) 1655, 1678 cm^-¹	¹H-NMR (d, CD₃OD, 100 MHz) 1.33 (s, 6 H), 1.36 (s, 6 H), 1.76 (s, 4 H), 7.47 (d, 1 H, J = 8 Hz), 7.70 (dd, 1 H, J = 2, 8 Hz), 7.84 (d, 2 H, J = 8.5 Hz), 7.94 (d, 1 H, J = 2 Hz), 8.02 (d, 2 H, J = 8.5 Hz). (Ref. 5001)					Condensation of 5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthoic acid and methyl p-aminobenzoate gave methyl 4-[5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamide]benzoate, which was hydrolyzed to Am580. (Ref. 5001)				[5001] / [5003]
48		TTNPB/Arotinoid/AGN191183/Ro13-7410	4-[(E)-2-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-propenyl]benzoic acid	VVA5003	Hiroyuki Kagechika	TTNPB	C₂₄H₂₈O₂	348.478		As a pan-RAR agonist, TTNPB exerted in low doses a marked therapeutic effect in the antipapalloma test in mice.(Ref. 5004) And TTNPB and other arotinoids have very potent anticancer activity in experimental animals.(Ref. 5005)	247-248 C (Ref. 5004)						UV_m_a_x(ethanol), 304 (22600). (Ref. 5004)		¹H-NMR (d, CDCl₃/DMSO, 60 MHz) 1.38 (s, 6 H), 1.42 (s, 6 H), 1.79 (s, 4 H), 2.37 (d, 3 H, J = 1Hz), 6.88 (s broad, 1 H), 7.28-7.60 (m, total of 5 H), 8.08 (2 H). (Ref. 5004)					Wittig reaction of ethyl 4-formylbenzoate with [1-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-ethyl]triphenylphosphonium bromide gave ethyl 4-[(E)-2-5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphtyl)propenyl]banzoate, which was hydrolyzed to TTNPB. (Ref. 5004)				[5004] / [5005]
49		Am555S/TAC-101	4-[[3,5-Bis(trimethylsilyl)benzoyl]amino]benzoic acid	VVA5004	Hiroyuki Kagechika	Am555S	C₂₀H₂₇O₃Si₂	371.598		As a potent RAR agonist, Am555S induces the differentiation of human promyelocyte leukemia cells HL-60.(Ref. 5006) And this compound strongly activate RARa, weakly activate RARb, and does not or only slightly activate RARg in all three subtypes of RAR.(Ref. 5007) Because of the subtype selectivity, Am555S could be beneficial in clinical use mostly at the view point of adverse effects.(Ref. 5003)	280 C (Ref. 5006)					Soluble in many organic solvents such as Ethyl acetate, dichloromethane, dimethylformamide, and ethanol.			¹H-NMR (d, CDCl₃, 400 MHz) 0.33 (s, 18 H), 7.80 (d, 2 H, J = 8.5 Hz), 7.85 (br s, 1 H), 7.92 (br s, 1 H), 7.95 (br s, 2 H), 8.13 (d, 2 H, J = 8.5 Hz). (Ref. 5006)					A mixture of 3,5-bis(trimethylsilyl)benzoic acid, CaCO₃, SOCl₂, and a drop of DMF in dry benzene ws stirred at room temperature. After filteration and removal of the solvent, the residue was dissolved in dry benzene. To this solution were added methyl 4-aminobenzoate and trimethylamine, and the mixture was stirred. The crude mixture was chromatographed on silica gel to give methyl 4-[[3,5-bis(trimethylsilyl)phenyl]carboxamide]benzoate, which was hydrolized to give Am555S. (Ref. 5006)				[5003] / [5007]
50		Ch55	(E)-4-[3-[3,5-Bis(1,1-dimethylethyl)]phenyl-3-oxo-1-propenyl]benzoic acid	VVA5005	Hiroyuki Kagechika	Ch55	C₂₄H₂₈O₃	364.477		As a potent RAR agonist, Ch55 induces the differentiation of human promyelocyte leukemia cells HL-60.(Ref. 5008) Different from retinoic acids, this retinoid does not bind to cellular retinoic acid binding protein (CREBP).(Ref. 5009)	202-203.5 C (Ref. 5008)					Soluble in many organic solvents such as Ethyl acetate, dichloromethane, dimethylformamide, and ethanol.			¹H-NMR (d, CDCl₃, 100 MHz) 1.41 (s, 18 H), 7.64 (d, 1 H, J = 16 Hz), 7.69 (d,1 H, J = 2 Hz), 7.70 (d, 2 H, J = 8 Hz), 7.74 (d, 1 H, J = 16 Hz), 7.83 ( d, 2 H, J = 2 Hz), 8.10 (d, 2 H, J = 8 Hz). (Ref. 5007)					3,5-di-tert-butylacetophenone and terephatalaldehydic acid methyl ester were dissolved in methanol and 1 N NaOH was added. The mixuture was stirred overnight and extracted with ethyl acetate. The crude product was purified by recrystallization to give Ch55. (Ref. 5008)				[5007] / [5008] / [5009]
51		Fv80	4-(6,7,8,9-Tetrahydro-6,6,9,9-tetramethyl-4H-4-oxo-naphto[2,3-b]pyran-2-yl)benzoic acid	VVA5006	Hiroyuki Kagechika	Fv80	C₂₄H₂₄O₄	376.445		As a potent RAR agonist, Fv80 induces the differentiation of human promyelocyte leukemia cells HL-60.(Ref. 5008)	>300 C (Ref. 5008)					Soluble in many organic solvents such as Ethyl acetate, dichloromethane, dimethylformamide, and ethanol.			¹H-NMR (d, CDCl₃-DMSO-d₆, 100 MHz) 1.37 (s, 12 H), 1.77 (s, 4 H), 2.8-3.7 (br s, OH), 6.86 (s, 1 H), 7.57 (s, 1 H), 8.05 (d, 2 H, J = 8Hz), 8.06 (s,1 H), 8.16 (d, 2 H, J = 8 Hz). (Ref. 5008)					Concentrated H₂SO₄ was added to a solution of methyl 4-[1-hyroxy-3-oxo-3-(5,6,7,8-tetrahydro-3-hydroxy-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoate in AcOH and refluxed for 30 min. The solution was poured into water and extracted with AcOEt. After removal of the solvent, the crude product was purified by silica gel chlumn chromatography to give methyl 4-(6,7,8,9-tetrahydro-6,6,9,9-tetramethyl-4H-4-oxonaphtho[2,3-b]pyran-2-yl)benzoate, which was hydrolyzed to give Fv80. (Ref. 5008)				[5008]
52		Re80	4-[1-Hydroxy-3-oxo-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl2-naphthalenyl)-1-propenyl]benzoic acid	VVA5007	Hiroyuki Kagechika	Re80	C₂₄H₂₆O₅	394.460		As a potent RAR agonist, Fv80 induces the differentiation of human promyelocyte leukemia cells HL-60.(Ref. 5008)	232-233 C (Ref. 5008)					Soluble in many organic solvents such as Ethyl acetate, dichloromethane, dimethylformamide, and ethanol.			¹H-NMR (d, CDCl₃, 100 MHz) 1.31 (s, 6 H), 1.35 (s, 6 H), 1.72 (s, 4 H), 3.97 (s, 3 H), 6.83 (s, 1 H), 6.96 (s, 1 H), 7.68 (s, 1 H), 8.00 (d, 2 H, J = 8 Hz), 8.10 (d, 2 H, J = 8 Hz), 11.62 (s, 1 H), 15.51 (s, 1 H). (Ref. 5008)					To a solution of terephathalic acid 3-acetyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl methyl ester in pyridine was added KOH, and the mixture was stirred overnight. The solution was poured into 20 % of AcOH and extracted with AcOEt. After evapolation, the crude mixture was purified on siliga gel column chromatography to give methyl 4-[1-hydroxy-3-oxo-3-(5,6,7,8-tetrahydro-3-hydroxyl-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoate, which was hydrolyzed to Re80.(Ref. 5008)				[5008]
53		AGN 193836	2,6-Difluoro-4-[(3'-hydroxy-4'-bromo-5',6',7',8'-tetrahydro-5',5',8',8'-tetramethylnaphtahlen-2'-yl)carbamoyl]benzoic acid	VVA5008	Hiroyuki Kagechika	AGN 193836	C₂₂H₂₂O₄NBrF₂	482.315		AGN 193836 is the RARa specific agonist, which binds only to and transactivates exclusively through RARa. Such a subtype selective agonsit is very likely to associate with fewer toxic effects and hence would be a useful drug of improved therapeutic index in the treatment of a subset of retinoid responsive diseases.(Ref. 5010)									¹H-NMR (d, acetone-d₆, 300 MHz) 10.23 (b, 1H), 8.01 (s, 1 H), 7.52 (d, 2 H, J = 10.2 Hz), 4.8 (b, 1 H), 1.75 (m, 2 H), 1.65 (m, 2 H), 1.60 (s, H), 1.31 (s, 6 H).(Ref. 5010)	Ms (m/z) 483, 481, 439, 401 (base peak) (Ref. 5010)				1-bromo-2-methoxymethoxy5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-3-yl acid and ehyl 4-amino-2,6-difluorobenzoate were coupled by using EDC and DMAP in dichloromethane to afford ethyl 2,6-difluoro-4-[(3'-methoxymethoxy-4'-bromo-5',6',7',8'-tetrahydro-5',5',8',8'-tetramethylnaphthalene-2'-yl)carbamoyl]benzoate, which was hydrolyzed and the methoxymethyl group was removed to yield AGN 193836.(Ref. 5010)				[5010]
54		CD666	(E)-4-[3-Hydroxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl2-naphthyl)-2-propenyl]benzoic acid	VVA5009	Hiroyuki Kagechika	CD666	C₂₄H₂₈O₃	364.477		CD666 selectively binds to and activates RARg. The affinity of CD666 for RARg is at least 35 time greater than for RARa or RARb. Since RARg is predominantly expressed in adult skin, the specific ligand for this subtype could provide therapeutic entities with a higher therapeutic index at lower teratogenic risk. (Ref. 5011)	137-138 C (Ref. 5011)								¹H-NMR (d, DMSO-d₆) 1.03 (s, 6 H), 1.05 (s, 6 H), 1.43 (s, 4 H), 5.02 (t, 1 H), 6.31-6.56 (2 H), 6.91-7.69 (7 H). (Ref. 5011)	EI-MS: m/z 364 (M⁺), 347 (M-OH)⁺. (Ref. 5011)				Aldol type coupling between 1-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethylnaphthalene-2-yl)ethanone and Methl 4-formylbenzoate gave 4-[3-Oxo-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-naphthalene-2-yl)propenyl]benzoic acid, which was reduced to afford CD666. (Ref. 5011)				[5011]
55		AGN 193639	4-[[(5,5-Dimethyl-5,6-dihydro-8-(2-thienyl)-2-naphthlenyl)carbonyl]amino]benzoic acid	VVA5010	Hiroyuki Kagechika	AGN 193639	C₂₄H₂₁O₃NS	403.494		AGN 193639 can bind to all three subtypes (a, b, g) of RAR, but acts as an RARb selective agonist and exhibits RARa/g antagonistic activities in terms of transactivation activity. (Ref. 5012)									¹H-NMR (d, acetone-d₆, 300 MHz) 1.34 (s, 6 H), 2.38 (d, 2 H, J = 4.9 Hz), 6.27 (t, 1 H, J = 4.9 Hz), 7.12 (m, 2 H), 7.44 (dd, 1 H, J = 1.3, 5.0 Hz), 7.55 (d, 1 H, J = 8.0 Hz), 7.88 (m, 3 H), 8.02-7.91 (m, 3 H), 9.75 (s, 1 H); ¹³C-NMR (d, acetone-d₆, 75 MHz) 167.2, 167.7, 150.0, 144.6, 142.7, 134.2, 133.9, 133.1, 131.5, 129.6, 128.3, 127.9, 126.8, 126.3, 125.5, 125.1, 120.2, 39.1, 34.5, 28.2. (Ref. 5012)	EI-MS: m/z 403 (M⁺) (Ref. 5012)				Amidation between 5,5-dimethyl-5,6-dihydro-8-(2-thienyl)-2-naphthalenecarboxylic acid and ethyl 4-aminobenzoate gave ethyl 4-[[(5,5-dimethyl-5,6-dihydro-8-(2-thienyl)-2-naphthalenyl)carbonyl]amino]benzoate, which was hydrolyzed to afford AGN 193639. (Ref. 5012)				[5012]
56		Adapalene/CD271/Differin	6-[3-(1-Adamantyl)-4-methoxyphenyl]-2-naphthoic Acid	VVA5011	Hiroyuki Kagechika	Adapalene	C₂₈H₂₈O₃	412.520		Adapalene can bind selectively to RARb and RARg and induce the F9 teratocarcinoma cell-differentiation as an RAR agonist. (Ref. 5013) In vitro and in vivo studies have shown that adapalene affects the cellular differentiation, keratinization, and inflammatory processes that are abnormall present in acne vulgaris. With its chemical stability, adapalene is clinically effective as an anti-acne agent. (Ref. 5014)	mp 319-322 C (Ref. 5013)							IR (KBr) 1690, 1300, 1235 cm^-¹ (Ref. 5013)	¹H-NMR (d, DMSO-d₆, 250 MHz) 1.75 (s, 6 H), 2.06 (s, 3 H), 2.13 (s, 6 H), 3.86 (s, 3 H), 7.11 (d, 1 H, J = 8.5 Hz), 7.57 (d, 1 H, J = 2 Hz), 7.65 (dd, 1 H, J = 8.5, 2 Hz), 7.88 (dd, 1 H, J = 8.5, 2 Hz), 7.97 (dd, 1 H, J = 8.5, 2 Hz), 8.07 (d, 1 H, J = 8.5 Hz), 8.15 (d, 1 H, J = 8.5 Hz), 8.22 (br s, 1 H), 8.60 )br s, 1 H). (Ref. 5013)	MS (EI) m/z 421 (M⁺) (Ref. 5013)				2-(1-Adamantyl)-4-bromoanisole was converted into zincate derivative and then condensated with methyl 6-bromo-2-naphthoate to afford methyl 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoate, which was saponified to give adapalene. (Ref. 5013)				[5013] / [5014]
57		Tazatotene/AGN190168/Tazorac/Zorac	Ethyl 6-[(3,4-dihydro-4,4-dimethyl-2H-1-benzothiopyran-6-yl)ethynyl]-3-pyridinecarboxylate	VVA5012	Hiroyuki Kagechika	Tazarotene	C₂₁H₂₁O₂NS	351.463		As an RARb/g selective agonist, tazarotene is being developed as a potent therapeutic agent foracne and psoriasis. (Ref. 5015/5016/5017)																		[5015] / [5016] / [5017]
58		CD437/AHPN	6-[3-(1-Adamantyl)-4-hydroxyphenyl]-2-naphthoic acid	VVA5013	Hiroyuki Kagechika	CD437	C₂₇H₂₆O₃	398.494		CD437 can selectively bind to RARg subtype and induce the differentiation of F9 teratocarcinoma cell in vitro. (Ref. 5013) The RARg selectivity is conserved in a functional transactivation assay. (Ref. 5011) Since RARg is predominantly expressed in adult skin, such a specific ligand could provide therapeutic entities with a higher therapeutic index at lower teratogenic risk.	mp 274-275 C (Ref. 5013)							IR (KBr) 1690, 1230 cm^-¹ (Ref. 5013)	¹H-NMR (d, DMSO-d₆, 250 MHz) 1.76 (s, 6 H), 2.07 (s, 3 H), 2.17 (s, 6 H), 6.92 (d, 1 H, J = 8.2 Hz), 7.50 (d, 1 H, J = 8.2 Hz), 7.52 (s, 1 H), 7.86 (dd, 1 H, J = 8.5, 2 Hz), 7.97 (dd, 1 H, J = 8.5, 2 Hz), 8.06 (d, 1 H, J = 8.5 Hz), 8.09 (d, 1 H, J = 8.5 Hz), 8.17 (s, 1 H), 8.59 (s, 1 H). (Ref. 5013)	MS m/z 398 (M⁺) (Ref. 5013)				Methyl 6-[3-(1[Adamantyl)-4-[tert-butyldimethylsilyl)-oxy]phenyl]-2-naphthoate was deprotected with TBAF and saponificated to yield CD437. (Ref. 5013)				[5011] / [5013]
59		BMS961	4-[[hydroxy(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)acetyl]amino]benzoic acid	VVA5014	Hiroyuki Kagechika	BMS961	C₂₃H₂₇NO₄	381.465		BMS961 can be a potent therapeutic agent for various skin disorders because of its RARg selective agonistic activity. The RARg selectivity over RARa or RARb was elucidaded in terms of the docking simulation between RARs and the ligand. (Ref. 5018)																		[5018]
60		CD394/TD-550	4-[(4-methoxy-3-tricyclo[3.3.1.13,7]dec-1-ylbenzoyl)amino]benzoic acid	VVA5015	Hiroyuki Kagechika	CD394	C₂₅H₂₇NO₄	405.486		Like other retinoids, CD394 was proved to be a promising agent for cancer chemoprevention and therapy. (Ref. 5019) As an RAR antagonist, CD394 inhibits the activity of an RAR agonist. (Ref. 5020) And CD394 does not have the ability to bind to cellular retinoic acid-binding protein (CRABP). (Ref. 5021)																		[5019] / [5020] / [5021]
61		AGN193109/CD3106	4-[[5,6-dihydro-5,5-dimethyl-8-(4-methylphenyl)-2-naphthalenyl]ethynyl]benzoic acid	VVA5016	Hiroyuki Kagechika	AGN193109	C₂₈H₂₄O₂	392.489		AGN193109 can bind strongly to RARs but not activate them. (Ref. 5022) Furthermore, AGN193109 was found to be an inverse agonist for RARs, which can inhibit the basal transactivation activities in the absence of an RAR agonist. (Ref. 5023) Because of the distinct function from classical agonists and antagonsits, the inverse agonist may posesse unique therapeutic potentials.														7-bromo-4,4-dimethyl-3,4-dihydro-2H-naphthalene-1-one was subjected to Pd catalyzed coupling reaction with TMS-acetylene. After removal of the TMS group, the terminal acetylene was subjected to a second Pd catalyzed coupling reaction with Ethyl 4-iodobenzoate. Convertion of the resulting Ethyl 4-(5,5-dimethyl-8-oxo-5,6,7,8-tetrahydronaphthalene-2-ylethynyl)benzoate to vinyl triflate followed by Pd catalyzed coupling with organozinc reagent prepared from 4-bromotoluene provide the ethyl ester of AGN193109, which was saponified to AGN193109. (Ref. 5022)				[5022] / [5023]
62		AGN194574	2,6-difluoro-4-[[8-bromo-2,2-dimethyl-4-(4-methylphenyl)-6-chromanyl)carbonyl]amino]benzoic acid	VVA5017	Hiroyuki Kagechika	AGN194574	C₂₆H₂₀O₄NBrF₂	528.342		As an RARa selective antagonist, AGN194574 can bind to RARa with 1000-fold and 10000-fold higher affinity than to RARb and RARg respectively, without causing the activation of the receptor. (Ref. 5024) Because RAR subtypes have distinct roles and tissue distribution patterns, RAR subtype selective retinoids will have more restricted pharmacological effects and better therapeutic indices in specific disease applications.									¹H-NMR (d, acetone-d₆) 9.33 (bs, 1 H), 8.07 (d, 1 H, J = 2.1 Hz), 7.66 (d, 1 H, J = 2.1 Hz), 7.54 (d, 2 H, J = 9.9 Hz), 7.27 (s, 4 H), 5.88 (s, 1 H), 2.38 (s, 3 H), 1.56 (s, 6 H). (Ref. 5024)	MS (EI) m/e 514, 512, 485, 483, 47, 468. (Ref. 5024)				8-Bromo-2,2-dimethyl-4-(4-methylphenyl)-4(2H)-chroman-6-carboxylic acid and ethyl 4-amino-2,6-difluorobenzoate ware coupled using EDC and DMAP to afford Ethyl 2,6-difluoro-4-[[[8-bromo-2,2-dimethyl-4-(4-methylphenyl)-6-chromanyl]carbonyl]amino]benzoate, which was hydrolyzed to AGN194574. (Ref. 5024)				[5024]
63		Ro41-5253	4-[(1E)-2-[7-(heptyloxy)-3,4-dihydro-4,4-dimethyl-1,1-dioxo-2H-1-benzothiopyran-6-yl]-1-propenyl]benzoic acid	VVA5018	Hiroyuki Kagechika	Ro41-5253	C₂₈H₃₆O₅S	484.648		Ro41-5253 can bind selectively bind to RARa without causing activation of the receptor. Thus, Ro41-5253 inhibit the activity of both natural and synthetic RARa agonists. As an RARa selective atonist, Ro41-5253 can inhibit retinoid-induced differentiation of the promyelocytic cell line HL-60 and revert retinoid-induced inhibition of mouse B-cell proliferation. (Ref. 5025)																		[5025]
64		BIPh	4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-1-phenyl-1H-naphth[2,3-d]imidazol-2-yl)benzoic acid	VVA5019	Hiroyuki Kagechika	BIPh	C₂₈H₂₈O₂N₂	424.534		As an RAR pan-antagonist, BIPh can inhibit the binding of an RAR agonist to RARs and the differentiation of promyeocytic leukemia cel l line HL-60 caused by an RAR agonist. (Ref. 5026)	mp 297 C (Ref. 5026)							IR (KBr) 1690, 1610 cm^-¹ (Ref. 5026)	¹H-NMR (d, DMSO-d₆, 400 MHz) 7.88 (d, 2 H, J = 8.4 Hz), 7.77 (s, 1 H), 7.56 (m, 3 H), 7.40 (d, 2 H, J = 7 Hz), 7.09 (s, 1 H), 1.70 (s, 4 H), 1.36 (s, 6 H), 1.23 (s, 6 H). (Ref. 5026)					A mixture of N-phenyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene-2,3-diamine and methyl terephthalaldehydrate were heated to give methl ester of BIPh, which was hydrolyzed to afford BIPh. (Ref. 5026)				[5026]
65		SR11335	4-[5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-4-(2,2,2-trifluoro-1-methoxyethyl)-2-antracenyl]benzoic acid	VVA5020	Hiroyuki Kagechika	SR11335	C₂₈H₂₉O₃F₃	470.523		As an RAR pan-agonist, SR11335 represses the retinoid-induced events such as the transcriptional activation of the HIV-1-RARE (Ref. 5027), various subtypes of RXR-RAR heterodimer activaon and the differentiation of promyocytic cell line HL60. (Ref. 5028) Since retinoids have been shoen to enhance replication of several viruses such as the human immunodeficiency virus type 1 (HIV-1) and human cytomegalovirus, an RAR antagonist can be a potent therapeutic agent for viral infections.																		[5027] / [5028]
66		ER27191	4-[4,5,7,8,9,10-hexahydro-7,7,10,10-tetramethyl-1-(3-prtidylmethyl)anthra[1,2-b]pyrrol-3-yl]benzoic acid	VVA5021	Hiroyuki Kagechika	ER27191	C₃₃H₃₄O₂N₂	490.635		As an potent RAR antagonist, ER27191 blocks the binding of all-trans retinoic acid to RARs and the differentiation of HL-60 cells caused by all-trans retinoic acid. Because of this chracter, ER28191 can be used for the treatment of hypervitaminosis A. (Ref. 5029)	mp 282 C (Ref. 5029)								¹H-NMR (d, DMSO-d₆, 400 MHz) 0.91 (s, 6 H), 1.17 (s, 6 H), 1.50 (s, 4 H), 2.68-2.85 (m, 4 H), 5.58 (s, 2 H), 6.90 (s, 1 H), 7.15 (s, 1 H), 7.34-7.43 (m, 3 H), 7.53 (d, 2 H, J = 8.4 Hz), 7.92 (d, 2 H, J = 8.4 Hz), 8.37 (brs, 1 H), 8.46 (brs, 1 H). (Ref. 5029)	MS 490 (M⁺) (Ref. 5029)				The coupling reaction between 3-(aminomethyl)pyridine and methyl 4-[1-(3,4,5,6,7,8-hexahydro-5,5,8,8-tetramethyl-1(2H)-oxoanthracen-2-yl)-2,2-dimethoxyethyl]benzoate was proceeded in AcOH to yield methyl 4-[4,5,7,8,9,10-hexahydro-7,7,10,10-tetramethyl-1-(3-pyridilmethyl)anthra[1,2-b]pyrrol-3-yl]benzoate, which was hydrolyzed to ER27191. (Ref. 5029)				[5029]
67		LE135	4-(5H-7,8,9,10-tetrahydro-5,7,7,10,10-pentamethylbenzo[e]naphtho[2,3-b][1,4]diazepin-13-yl)benzoic acid	VVA5022	Hiroyuki Kagechika	LE135	C₂₉H₃₀O₂N₂	438.561		LE135 is an RARb selective antagonist (Ref. 5026/5030), which bolcks the binding and differentiation-inducing activity of all-trans retinoic acid only on RARb. Because of the activity, LE135 exhibits AP-1 activity and retinoic acid-induced apoptosis in human breast cancer cells. (Ref. 5031)	mp 281-285 C (Ref. 5026)							IR (KBr) 1705, 1605 cm^-¹. (Ref. 5026)	¹H-NMR (d, CDCl₃, 400 MHz) 8.13 (d, 2 H, J = 8.4 Hz), 7.87 (d, 2 H, J = 8.4 Hz), 7.40 (m, 1 H), 7.24 (s, 1 H), 7.07 (d, 1 H, J = 8.1 Hz), 6.96 (m, 2 H), 6.84 (s, 1 H), 3.27 (s, 3 H), 1.66 (s, 4 H), 1.32 (s, 3 H), 1.28 (s, 3 H), 1.26 (s, 3 H), 1.25 (s, 3 H). (Ref. 5026)	MS M⁺ 438. (Ref. 5026)				Methyl 4-[[5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-3-(N-methyl-N-phenylamino)-2-naphthalenyl]carbamoyl]benzoate was heated with polyphosphoric acid to give methyl 4-(5H-7,8,9,10-tetrahydro-5,7,7,10,10-pentamethylbenzo[e]naphtho[2,3-b][1,4]diazepin-13-yl)benzoate, which was hydrolyzed to afford LE135. (Ref. 5026)				[5026] / [5030] / [5031]
68		LE540	4-(13H-10,11,12,13-Tetrahydro-10,10,13,13,15-pentamethyldinaphtho[2,3-b] [1,2-e][1,4]diazepin-7-yl)benzoic acid	VVA5023	Hiroyuki Kagechika	LE540	C₃₃H₃₂O₂N₂	488.619		In spite of the low binding afinity to RARs, LE540 inhibits the HL-60 cells differentiation induced by an RAR agonist in a dose-dependent manner. (Ref. 5030) Although LE540 works as an antagonist in all three subtype of RARs at high concentration, there is slight selectivity toward RARb.	mp >300 C (Ref. 5030)								¹H-NMR (d, CDCl₃, 400 MHz) 8.87 (d, 1 H, J = 8.4 Hz), 8.20 (d, 2 H, J = 8.4 Hz), 7.95 (d, 2 H, J = 8.8 Hz), 7.85 (d, 1 H, J = 7.7 Hz), 7.65 (m, 3 H), 7.42 (s, 1 H), 7.30 (s, 1 H), 7.17 (d, 1 H, J = 8.4 Hz), 3.08 (s, 3 H), 1.68 (s, 4 H), 1.38 (s, 3 H), 1.36 (s, 3 H), 1.22 (s, 3 H), 1.21 (s, 3 H). (Ref. 5030)					Methyl 4-[[5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-3-[N-methyl-N-(1-naphthyl)amino]-2-naphthyl]carbamoyl]benzoate was cyclized in dichloromethane and polyphosphoric acid and the product was hydrolized under basic condition to give LE540. (Ref. 5030)				[5030]
69		BR403	4-[4-(2-proryl-1,2-dicarba-closo-dodecaboran-1-yl)phenylamino]benzoic acid	VVA5024	Hiroyuki Kagechika	BR403	C₁₅H₂₇O₂NB₁₀	361.490		As a RAR pan-agonist, BR403 induces the differentiation of HL-60 cells and activates the expression of the target genes of RARs. (Ref. 5032) Although the agonistic activitis of BR403 is not as strong as Am80, one of the majorest RAR agonist, BR403 possesses significant therapeutic potentials in the field of boron neutron capture therapy (BNCT) because of its high density of boron atoms. (Ref. 5032/5033)														4-(2-propyl-1,2-dicarba-closo-dodecaboran-1-yl)aniline and ethyl 4-iodobenzoate were coupled in the presense of tris(dibenzylidenacetone)dipalladium(0) and (R)-BINAP to give ethyl 4-(2-propyl-dicarba-closo-dodecabaran-1-yl)phenylamino benzoate, which was methylated on the nitrogen atom and hedrolyzed to yield BR403. (Ref. 5032)				[5032] / [5033]
70		BMS753/BMS194753	4-[[(2,3-dihydro-1,1,3,3-tetramethyl-2-oxo-1H-inden-5-yl)carbonyl]amino]benzoic acid	VVA5025	Hiroyuki Kagechika	BMS753	C₂₁H₂₁O₄N	351.396		BMS753 is an RARa selective agonist. (Ref. 5034)																		[5034]
71		BMS411/BMS185411	4-[[5,6-dihydro-5,5,-dimethyl-8-phenyl-2-naphthalenyl)carbonyl]amino]benzoic acid	VVA5026	Hiroyuki Kagechika	BMS411	C₂₆H₂₃O₃N	397.466		BMS411 is an RARb selective agonist. (Ref. 5034)																		[5034]
72		BMS228987	4-[2-[8-(3,3-dimethyl-but-1-enyl)-5,5-dimethyl-5,6-dihydro-naphhalen-2-yl]vinyl]benzoic acid	VVA5027	Hiroyuki Kagechika	BMS228987	C₂₇H₃₀O₂	386.526		BMS228987 is characterized as a selective RARb and RARa agonist of high affinity. (Ref. 5034)																		[5034]
73		BMS394/BMS270394	3-Fluoro-4-[2-(R)-hydroxy-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene-2-yl)acetylamino]benzoic acid	VVA5028	Hiroyuki Kagechika	BMS270394	C₂₃H₂₆O₄NF	399.455		BMS270394 is an RARg specific agonist. (Ref. 5034)																		[5034]
74		BMS204493/BMS493	4-[2-5,5-dimethyl-8-(4-tolyl)-5,6-dihydronaphthalen-2-yl)vinyl]benzoic acid	VVA5029	Hiroyuki Kagechika	BMS493	C₂₈H₂₆O₂	394.505		BMS493 is an RAR pan-antagonist. (Ref. 5034)																		[5034]
75		BMS614/BMS195614	4-[[[5,6-dihydro-5,5-dimethyl-8-(3-quinolinyl)-2-naphthalenyl]carbonyl]amino]benzoic acid	VVA5030	Hiroyuki Kagechika	BMS614	C₂₉H₂₄O₃N₂	448.513		BMS195614 is an RARa selective antagonist (Ref. 5034) and the mechanism of the activity has been eagarly explored. (Ref. 5035/5036)																		[5034] / [5035] / [5036]
76		CD367/AGN191312/SR3961	4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthracenyl)-benzoic acid	VVA5031	Hiroyuki Kagechika	CD367	C₂₅H₂₆O₂	358.473		As an RAR agonist, CD367 makes the mucociliary epithelium of the trachea lose its normal pattern of differentiaion and CD367 makes F9 embryonal carcinoma cells differentiate into parietal endoderm. (Ref. 5037) But several biological activities of CD367, such as apoptosis induction, are not mediated through the retinoidal pathway.	mp 270-272 C (Ref. 5037)						UV l_m_a_x (ethanol) 224 (36000), 267 (51000), 303 (18000). (Ref. 5037)	IR (mull) 1680, 1610, 1425 cm^-¹. (Ref. 5037)	¹H-NMR (d, CDCl₃/5% DMSO-d₆, 400 MHz) 1.28 (s, 12 H), 1.66 (s, 4 H), 7.52 (dd, 2 H, J = 2, 8 Hz), 7.65 (d, 2 H, J = 8 Hz), 7.68 (s, 1 H), 7.69 (d, 1 H, J = 8 Hz), 7.73 (s, 1 H), 7.88 (br s, 1 H), 8.02 (d, 2 H, J = 8 Hz). ¹³C-NMR (d, CDCl₃/5% DMSO-d₆, 400 MHz) 32.5, 34.6, 35.0, 124.3, 124.7, 125.4, 125.5, 126.9, 127.8, 129.4, 130.3, 131.3, 131.9, 136.4, 145.0, 145.5, 168.4. (Ref. 5037)					Friedel-Crafts alkylation of ethyl 4-(2-naphthalenyl)benzoate with 2,5-dichloro-2,5-dimethylhexane using AlCl₃ gave 4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthracenyl)benzoate, which was hydrolyzed to afford CD367. (Ref. 5037)				[5037]
77		CD564	6-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbonyl]-2-naphthalenecarboxylic acid	VVA5032	Hiroyuki Kagechika	CD564	C₂₆H₂₆O₃	386.483		The transactivation assay using all three subtypes of RAR showed that CD564 is an RAR b/g selective agonist. (Ref. 5038/5039)																		[5038] / [5039]
78		SR11228	5-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naththalenyl)carbonyl]-2-naphthlenecarboxylic acid	VVA5033	Hiroyuki Kagechika	SR11228	C₂₆H₂₆O₃	386.483		Although SR11228 induces transactivation of RARs only weakly, it shows potent anti-AP-1 activity. And SR11228 cannnot induce differentiation in F-9 cells, while the have the ability to inhibit efficiently proliferation of cancer cells. Since adverse effects are the main problem of retinoid therapy, such a new type of retinoid can be a useful therapeutic agent. (Ref. 5040)																		[5040]
79		SR11254	(E)-6-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)(hydroxyimino)methyl]-2-naphthalenecarboxylic acid	VVA5034	Hiroyuki Kagechika	SR11254	C₃₆H₂₇O₃N	521.605		SR11254 showed RARg selectivity in transactivation assay. (Ref. 5039) RAR subtype selective retinoids can be reasonable therapeutic agents with reduced adverse effects.								IR(KBr) 2960, 2926, 1692, 1416. (Ref. 5039)	¹H-NMR (d, DMSO-d₆) 1.15 (s, 6 H), 1.21 (s, 6 H), 1.62 (s, 4 H), 7.03 (dd, 1 H, J = 8.2, 1.8 Hz), 7.29 (d, 1 H, J = 8.3 Hz), 7.47 (d, 1 H, J = 1.8 Hz), 7.50 (d, 1 H, J = 1.5 Hz), 7.92 (s, 1 H), 7.98 (dd, 1 H, J = 8.6, 1.6 Hz), 8.05 (d, 1 H, J = 8.8 Hz), 8.17 (d, 1 H, J = 8.6 Hz), 8.64 (s, 1 H), 11.38 (s, 1 H). (Ref. 5039)	MS (DCI) m/e 402 (MH⁺). (Ref. 5039)				The E-isomer of methyl 6-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-yl)[(pivaloyloxy)imino]methyl]naphthalene-2-carboxylete was saponified at room temperature to give SR11254.(Ref. 5039)				[5039]
80		4-HPR/Fenretinide/Ro22-4667	N-(4-hydroxyphenyl)-retinamide	VVA5035	Hiroyuki Kagechika	4-HPR	C₂₆H₃₃O₂	377.539		4-HPR is a synthetic analog of retinoic acid, which has a potential as chemopreventative agent for cancer. A key distinction between 4-HPR and retinoic acid lies in the ability of 4-HPR to induce apoptosis. And it has revealed that apoptosis in response to 4-HPR primarily occurs by a receptor-independent mechanism. (Ref. 5041)																		[5041]
81		MX781	4-[3-[4-[(2-methoxyethoxy]-3-tricyclo[3..3.1.13,7]dec-1-ylphenyl]-3-oxo-1-propenyl]benzoic acid	VVA5036	Hiroyuki Kagechika	MX781	C₃₀H₃₄O₆	490.587		MX781 is an RAR-pan antagonist and is an effective therapeutic agent against estrogen receptor-positive and -negative breast cancer cells through the induction of apoptosis. (Ref. 5042)																		[5042]
82		AGN194301	4-[[[8-bromo-2,2-dimethyl-4-(4-methylphenyl)2H-1-benzopyran-6-yl]carbonyl]amino]2-fluorobenzoic acid	VVA5037	Hiroyuki Kagechika	AGN194301	C₂₆H₂₁O₄BrFN	510.352		AGN194301 is an RARa selective antagonist both in a binding assay and in a transactivation assay. (Ref. 5043)									¹H-NMR (d, acetone-d₆) 8.09 (d, 1 H, J = 2.1 Hz), 7.91 (t, 1 H, J = 7.5 Hz), 7.68 (d,1 H, J = 2.1 Hz), 7.83 (dd, 1 H, J = 2.1, 12.8 Hz), 7.50 (dd, 1 H, J = 2.1, 7.5 Hz), 7.27 (s, 4 H), 5.87 (s, 1 H), 2.37 (s, 3 H), 1.56 (s, 6 H). (Ref. 5043)	MS (EI) m/e 511, 503, 496, 494, 452, 450, 357, 355, 312. (Ref. 5043)				Ethyl 2-Fluoro-4-[[[8-bromo-2,2-dimethyl-4-(4-methylphenyl)-6-chromanyl]carbonyl]amino]benzoate was saponified to give AGN194301. (Ref. 5043)				[5043]
83		SR11237/BMS188649	4-[2-(5,6,7,8-tetrahydro-5,5,8,8	VVA5038	Hiroyuki Kagechika	SR11237	C₂₄H₂₈O₄	380.477		SR11237 is the first reported RXR specific agonist, which binds to and activates RXR as potent as 9-cis retinoic acid. (Ref. 5044) Since RXR ligands can control retinoidal action and other nuclear receptors' function by regulating RXR- heterodimers, an adeuate RXR ligand can be a therapeutically useful agent.																		[5044]
84		LG1069	4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)ethenyl]benzoic acid	VVA5039	Hiroyuki Kagechika	LG1069	C₂₄H₂₈O₂	348.478		LG1069 binds to and activates all three subtypes of RXR dose dependently (Ref. 5045). In RXR-RAR heterodimer action, LG1069 cannot activate the heterodimer alone but it can enhance the potency of RAR agonist. Thus RXR agonists such as LG1069 are called retinoid synergists.	mp 234 C. (Ref. 5045)						UV l (MeOH) 264 nm (16400). (Ref. 5045)		¹H-NMR (d, CDCl₃) 1.28 (s, 6 H), 1.31 (s, 6 H), 1.70 (s, 4 H), 1.95 (s, 3 H), 5.35 and 5.83 (s, 2 H), 7.08 (s, 1 H), 7.13 (s, 1 H), 7.38 (d, 2 H, J = 8.1 Hz), 8.03 (d, 2 H, J = 8.1 Hz). (Ref. 5045)	HRFAB-MS (M + H) 349.2178. (Ref. 5045)				Condensation of methyl 4-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)carbonyl]benzoate with methyltriphenylphosphonium bromide-sodium amide in tetrahydrofuran afforded the corresponding olefin, which was hydrolyzed to give LG1069. (Ref. 5045)				[5045]
85		LG100268	6-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl]nicotinic acid	VVA5040	Hiroyuki Kagechika	LG100268	C₂₄H₂₉O₂N	363.493		LG100268 binds strongly to and strongly activates all three subtypes of RXR. In RXR-RAR heterodimer action, LG100268 cannot activate the heterodimer alone but it can enhance the potency of RAR agonist. Thus RXR agonists such as LG100268 are called retinoid synergists. (Ref. 5046)	mp 277-279 C. (Ref. 5046)								¹H-NMR (d, CDCl₃) 1.28 (s, 6 H), 1.32 (s, 6 H), 1.38 (d, 2 H, J = 4.0 Hz), 1.72 (s, 4 H), 1.87 (d, 2 H, J = 4.0 Hz), 2.12 (s, 3 H), 6.78 (d, 1 H, J = 10 Hz), 7.11 (s, 1 H), 7.26 (s, 1 H), 8.00 (d, 1 H, J = 10 Hz), 9.14 (s, 1 H). (Ref. 5046)									[5046]
86		PA024	2-[(cyclopropylmethyl)(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)amino]-5-pyrimidinecarboxylic acid	VVA5041	Hiroyuki Kagechika	PA024	C₂₃H₂₉O₂N₃	379.495		As a potent RXR agonist, PA024 activate RXR homodimer in transactivation assay. And PA024 work as a retinoid synergist in RXR-RAR heterodimer action, thus, PA024 enhance the HL-60 cells differentiation inducing activity of RAR agonist. (Ref. 5047)	mp 232 C. (Ref. 5047)								¹H-NMR (d, DMSO-d₆) 8.73 (s, 2 H), 7.36 (d, 1 H, J = 8.4 Hz), 7.22 (d, 1 H, J = 1.2 Hz), 7.02 (dd, 1 H, J = 8.4, 1.2 Hz), 3.84 (d, 2 H, J = 6.8 Hz), 1.67 (s, 4 H), 1.28 (s, 6 H), 1.24 (s, 6 H), 1.18 (br m, 1 H), 0.42 (dd, 2 H, J = 5.1, 13 Hz), 0.14 (dd, 2 H, J = 5.1, 10 Hz). (Ref. 5047)					Ethyl 2-[N-(5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene-2-yl)amino]pyrimidine-5-carboxylate was alkylated using NaH and cyclopropylmethyl bromide to give ethyl ester of PA024, which was hydrolyzed to afford PA024. (Ref. 5047)				[5047]
87		TZ335	5-[[4-[methyl(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)amino]phenyl]methylene]-2,4-thiazolidinedione	VVA5042	Hiroyuki Kagechika	TZ335	C₂₆H₃₀O₂N₂S	434.595		TZ335 enhanced the potency of RAR agonist in HL-60 cells differntiation assay as an RXR agonist. Because TZ335 has a thiazolidinedione moiety that is unique for PPARg agonist, TZ335 may elicit the PPARg-RXR heterodimer activity by affecting the both part of the heterodimer. (Ref. 5048)																		[5048]
88		LG100754	(2E,4E,6Z)-7-3-n-propyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-yl)-3-methylocta-2,4,6-trienoic acid	VVA5043	Hiroyuki Kagechika	LG100754	C₂₆H₃₆O₃	396.562		Because LG100754 binds to RXR but it cannot activate RXR, it is an RXR antagonist. (Ref. 5049) However, this antagonistic activity is restricted to RXR-homodimer, that is, LG100754 acts as RXR agonist in RXR-RAR heterodimer action. (Ref. 5050)																		[5049] / [5050]
89		HX600	4-(7,8,9,10-tetrahydro-5,7,7,10,10-pentamethyl-5H-benzo[b]naphtho[2,3-e][1,4]diazepin-12-yl)benzoic acid	VVA5044	Hiroyuki Kagechika	HX600	C₂₉H₃₀O₂N₂	438.561		HX600 is a potent RXR agonist and work as retinoid synergist in RXR-RAR heterodimer. (Ref. 5051) However, binding affinity of HX600 to RXR is far lower than other RXR agonists. (Ref. 5052)																		[5051] / [5052]
90		HX630	4-[2,3-(2,5-dimethyl-2,5-hexano)dibenzo[b,f][1,4]thiazepin-11-yl]benzoic acid	VVA5045	Hiroyuki Kagechika	HX630	C₂₉H₂₉O₂NS	455.612		HX630 is a potent RXR agonist and work as retinoid synergist in RXR-RAR heterodimer. However, binding affinity of HX630 to RXR is far lower than other RXR agonists. (Ref. 5052)	mp 299 C. (Ref. 5052)								¹H-NMR (d, CDCl₃) 8.17 (d, 2 H, J = 8.4 Hz), 7.94 (d, 2 H, J = 8.4 Hz), 7.48 (dd, 1 H, J = 7.7, 1.1 Hz), 7.45 (s, 1 H), 7.37 (m, 2 H), 7.13 (m, 1 H), 7.04 (s, 1 H), 1.64 (m, 4 H), 1.31 (s, 3 H), 1.28 (s, 3 H), 1.15 (s, 3 H), 1.07 (s, 3 H). (Ref. 5052)					Methyl 4-[[2-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)thio]-phenyl]carbamoyl]benzoate was cyclized using phosphoric acid gave methyl ester of HX600, which was hydrolyzed to afford HX600. (Ref. 5052)				[5052]
91		HX531	4-(5H-2,3-(2,5-dimethyl-2,5-hexano)-5-methyl-8-nitrobenzo[b,e][1,4]diazepin-11-yl)benzoic acid	VVA5046	Hiroyuki Kagechika	HX531	C₂₉H₂₉O₄N₃	483.558		HX531 works as antagonist for both homodimeric and heterodimeric RXR. In some cases, HX531 not only represses the activity of RXR agonist but also represses the activity of an agonist on the other side of heterodimer. And HX531 also has an RAR antagonistic activity. (Ref. 5053)	mp >300 C. (Ref. 5053)								¹H-NMR (d, CDCl₃) 8.15 (m, 3 H), 8.01 (dd, 1 H, J = 8.8, 2.6 Hz), 7.90 (d, 2 H, J = 7.3 Hz), 7.00 (d, 1 H, J = 9.2 Hz), 6.93 (s, 1 H), 6.92 (s, 1 H), 3.31 (s, 3 H), 1.65 (m, 4 H), 1.32 (s, 3 H), 1.27 (s, 3 H), 1.14 (s, 3 H), 1.07 (s, 3 H).					Methyl ester of HX600 (RXR agonist) was nitrated using KNO₃ and sulfuric acid, and the product was hydrolyzed under basic condition to give HX531. (Ref. 5053)				[5053]
92		HX603	4-(5H-2,3-(2,5-dimethyl-2,5-hexano)-5-n-propyldibenzo[b,e][1,4]diazepin-11-yl)benzoic acid	VVA5047	Hiroyuki Kagechika	HX603	C₃₁H₃₄O₂N₂	466.614		HX603 works as antagonist for both homodimeric and heterodimeric RXR. In some cases, HX603 not only represses the activity of RXR agonist but also represses the activity of an agonist on the other side of heterodimer. And HX603 also has an RAR antagonistic activity. (Ref. 5053)	mp 248.5 C. (Ref. 5053)								¹H-NMR (d, CDCl₃) 8.16 (d, 2 H, J = 8.4 Hz), 7.92 (d, 2 H, J = 8.4 Hz), 7.33 (d, 1 H, J = 7.7 Hz), 7.16 (t, 1 H, J = 6.4 Hz), 7.09 (t, 1 H, J = 6.4 Hz), 6.98 (d, 1 H, J = 7.7 Hz), 6.92 (s, 1 H), 6.87 (s, 1 H), 3.69 (m, 1 H), 3.56 (m, 1 H), 1.65 (m, 6 H), 1.32 (s, 3 H), 1.26 (s, 3 H), 1.14 (s, 3 H), 1.05 (s, 3 H), 0.93 (t, 3 H, J = 7.3 Hz). (Ref. 5053)									[5053]
93		PA452	2-[N-(3-n-hexyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-yl)-N-methylamino]pyrimidine-5-carboxylic acid	VVA5048	Hiroyuki Kagechika	PA452	C₂₆H₃₇O₃N₃	439.590		PA452 is an RXR specific antagonist, which does not affect the activity of an RAR agonist in RXR-RAR heterodimer action. And PA452 binds to all three subtypes of RXR and repress the activity of RXR agonist in both homodimeric and heterodimeric RXR. (Ref. 5054)	mp 238 C. (Ref. 5054)								¹H-NMR (d, CDCl₃) 8.99 (s, 1 H), 8.82 (s, 1 H), 7.12 (s,1 H), 6.85 (s, 1 H), 3.89 (t, 2 H , J = 6.8 Hz), 3.48 (s, 3 H), 1.68 (s, 4 H), 1.57 (quint, 2 H, J = 6.8 Hz), 1.30 (s, 3 H), 1.25 (s, 6 H), 1.25 (m, 4 H), 1.20 (s, 3 H), 0.83 (t, 3 H, J = 6.8 Hz). (Ref. 5054)					Ethyl 2-[N-(3-n-hexyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-yl)-N-methylamino]pyrimidine-5-carboxylate was hydrogenated under basic condition to afford PA452. (Ref. 5054)				[5054]
94		Tp140	2-hydroxy-5-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)cthynyl]2,4,6-cycloheptatrien-1-one	VVA5049	Hiroyuki Kagechika	Tp140	C₂₃H₂₄O₂	332.435		Tp140 is a potent RAR agonist, which causes HL-60 cells differentiation. That activity was strongly increased by an RXR agonist in RXR-RAR heterodimer. (Ref. 5055)																		[5055]
95		Tp80	5,6,7,8-tetrahydro-N-(4-hydroxy-5-oxo-1,3,6-cycloheptatrien-1-yl)-5,5,8,8-tetramethyl-2-naphthalenecarboxyamide.	VVA5050	Hiroyuki Kagechika	Tp80	C₂₂H₂₅O₃N	351.439		Tp80 is a potent RAR agonist, which causes HL-60 cells differentiation. That activity was strongly increased by an RXR agonist in RXR-RAR heterodimer. (Ref. 5055)																		[5055]
96			(2E,4E,6E)-7-[3,5-Di-tert-butyl-2-(2,2-difluoro-ethoxy)-phenyl]-octa-2,4,6-trienoic acid	VVA5051	Hiroyuki Kagechika	LG101506	C₂₀H₃₈F₂O₃	364.511		RXR-selective modulator:hypoglycemic efficacy(db/db mouse model) (Ref. 0057)	165 and 178C(CH₃CN)								¹H-NMR(d,CDCl₃,400MHz):7.31(d, J=2.4Hz, 1H), 6.95(d, J=2.4Hz, 1H), 6.59 (dd, J=15.3, 11.0Hz, 1H), 6.29(d, J=11.0Hz, 1H), 6.28(d, J=15.3Hz, 1H), 5.96(dt, J=55.3HZ, 4.3Hz, 1H), 5.78(s, 1H), 3.95(m, 2H), 2.22(s, 3H), 2.15(s, 3H), 1.41(s, 9H), 1.30(s, 9H).	HRMS for C₂₅H₃₅F₂O₃(MH⁺): calcd, 421.2554; found 421.2696				By hydrolysis of Ethyl (2E,4E,6Z)-7-[3,5-Di-tert-butyl-2-(2,2-difluoroethoxy) -benzene]-3-methylocta-2,4,6-truenoate. (Ref. 0058)				[0057] / [0058]
97			(2E,4E)-3-Methyl-5-[2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-cyclopent-1-enyl]-penta-2,4,-dienoic acid	VVA5052	Hiroyuki Kagechika	ALRT1550	C₂₅H₃₂O	348.521		RXR-selective modulator:hypoglycemic efficacy(db/db mouse model) (Ref. 0057)														By 6steps from (3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-boronic acid and 1,2-Dibromo-cyclopentene.(Ref. 0059)				[0057] / [0059]
98			4-(3,5,5,8,8,-Pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-ylsulfanyl)-benzoic acid	VVA5053	Hiroyuki Kagechika		C₂₂H₂₆O₂S	354.507		RXR-selective ligand.This compound has activity in nontransfected cells as demonstrateted by their ability to induce TGase activity in Hl-60 cells.(Ref. 0057/0060)	249-250C(Ref. 0060)							3300-2400(COOH), 1672(C=O) cm^-¹(Ref. 0060)	¹H-NMR(d,CDCl₃,300MHz): 1.25(s, 6H), 1.31(s, 6H), 1.69(s, 4H), 2.29(2, 3H),7.05(d, 2H, J=8.5Hz), 7.25(s, 1H), 7.26(s, 1H), 7.92(d, 2H, J=8.5Hz).(Ref. 0060) ¹³C-NMR(d, CDCl₃, 75MHz):20.3, 31.7, 31.8, 34.1, 34.2, 34.9, 35.0, 125.4, 125.5, 126.3, 129.1, 130.6, 134.6, 139.0, 144.2, 146.9, 147.1, 171.0(Ref. 0060)	MS(EI,70eV) m/z 354(M⁺, 41), 335(67), 173(100).(Ref. 0060)				By hydrolysis of Ethyl 4-[(5,6,7,8-Tetrahydro-3,5,5,8,8-pentamethyl-2-naphthyl) sulfoxy]benzoate.(Ref. 0060)				[0057] / [0060]
99			(2E,4E,6E)-6-Fluoro-7-(1-isopropyl-7-methyl-1,2,3,4-tetrahydro-quinolin-6-yl)-3-methyl-octa-2,4,6-trienoic acid	VVA5054	Hiroyuki Kagechika		C₂₀H₂₄FNO₂	329.409		RXR-selective modulator.high binding affinity to RXRs.(Ref. 0057/0061)	138-139C(EtOH)(Ref. 0061)								¹H-NMR(d,CDCl₃,400MHz): 1.21(d, J=6.8Hz,6H), 1.92(tt, J=6.0, 6.0Hz, 2H), 2.12(d, J=3.6Hz, 3H), 2.21(d, J=0.8Hz, 3H), 2.74(t, J=6.0Hz, 2H), 3.20(t, J=6.0Hz, 2H), 3.70(s, 3H), 4.13(hept, J=6.8Hz, 1H), 5.86(s, 1H), 6.52(d, J=15.6Hz, 1H), 6.66(d, J=8.4Hz, 1H), 6.71(dd, J=15.6, 26.4Hz, 1H), 6.87(d, J=2.0Hz, 1H), 6.95(dd, J=2.4Hz, 8.8Hz, 1H)(Ref. 0061)	HRMS Calcd for C₂₁H₂₆FNO₂: 343.1947. Found: 343.1955(Ref. 0061)				By 13steps from 1-(1-methylethyl)-1,2,3,4-tetrahydroquinoline.(Ref. 0060/0061)				[0057] / [0060] / [0061]
100			(6S,7S)-(2E,4E)-5-[2-(5,5,8,8)-Tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-cyclopropyl]-penta-2,4-dienoic acid	VVA5055	Hiroyuki Kagechika		C₂₃H₃₀O₂	338.483		hypoglycemic agent(Ref. 0057/0062)	137-138C(Ref. 0062)				[a]²¹_D:+86.30(c, 0.0015, CH₂Cl₂)(Ref. 0062)				¹H-NMR(d,CDCl₃,300MHz):1.14-1.20(m, 2H), 1.20(s, 3H), 1.27(s, 9H), 1.42(s, 3H), 1.66(s, 4H), 1.68-1.80(m, 1H), 1.98(s, 3H), 5.27(dd, J=9.9, 15.4Hz, 1H), 5.64(s, 1H),6.21(d, J=15.4Hz, 1H), 7.03(dd, J=1.9, 8.1Hz, 1H), 7.12(d, J=1.9Hz, 1H), 7.24(d, J=8.1Hz,H)(Ref. 0062) ¹³C-NMR(d, CDCl₃, 300MHz): 13.75, 22.19, 28.67, 29.82, 30.67, 31.80, 31.84, 31.97, 33.99,34.19, 35.18, 115.40, 126.31, 126.48, 127.53, 131.33, 139.63, 141.47, 142.85, 144.57, 155.17, 172.54(Ref. 0062)					By 10steps from 6-Bromo-1,1,4,4-tetramethyl-1,2,3,4-tetrahedronaphthalene.(Ref. 0062)				[0057] / [0062]

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AUTHOR	:	Canan Koch, S. S., Dardashti, L. J., Hebert, J. J., White, S. K., Croston, G. E., Flatten, K. S., Heyman, R. A., and Nadzan, A. M.
TITLE	:	Identification of the first retinoid X, receptor homodimer antagonist PubMed ID:8765503
JOURNAL	:	J Med Chem.
VOL	:	39 PAGE : 3229-3234 (1996)

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[5050]

AUTHOR	:	Lala, D. S., Mukherjee, R., Schulman, I. G., Koch, S. S., Dardashti, L. J., Nadzan, A. M., Croston, G. E., Evans, R. M., and Heyman, R. A.
TITLE	:	Activation of specific RXR heterodimers by an antagonist of RXR homodimers PubMed ID:8837780
JOURNAL	:	Nature.
VOL	:	383 PAGE : 450-453 (1996)

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[5051]

AUTHOR	:	Umemiya, H., Kawachi, E., Kagechika, H., Fukasawa, H., Hashimoto, Y., and Shudo, K.
TITLE	:	Synergists for retinoid in cellular differentiation of human promyelocytic leukemia cells HL-60 PubMed ID:8536354
JOURNAL	:	Chem Pharm Bull (Tokyo).
VOL	:	43 PAGE : 1827-1829 (1995)

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[5052]

AUTHOR	:	Umemiya, H., Fukasawa, H., Ebisawa, M., Eyrolles, L., Kawachi, E., Eisenmann, G., Gronemeyer, H., Hashimoto, Y., Shudo, K., Kagechika, H.
TITLE	:	Regulation of Retinoidal Actions by Diazepinylbenzoic Acids. Retinoid Synergists Which Activate the RXR-RAR Heterodimers. PubMed ID:9435893
JOURNAL	:	J. Med. Chem.
VOL	:	40 PAGE : 4222-4234 (1997)

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[5053]

AUTHOR	:	Ebisawa, M., Umemiya, H., Ohta, K., Fukasawa, H., Kawachi, E., Christoffel, G., Gronemeyer, H., Tsuji, M., Hashimoto, Y., Shudo, K., et al.
TITLE	:	Retinoid X receptor-antagonistic diazepinylbenzoic acids PubMed ID:10748721
JOURNAL	:	Chem Pharm Bull (Tokyo).
VOL	:	47 PAGE : 1778-1786 (1999)

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[5054]

AUTHOR	:	Takahashi, B., Ohta, K., Kawachi, E., Fukasawa, H., Hashimoto, Y., and Kagechika, H.
TITLE	:	Novel retinoid X receptor antagonists: specific inhibition of retinoid synergism in RXR-RAR heterodimer actions PubMed ID:12139443
JOURNAL	:	J Med Chem.
VOL	:	45 PAGE : 3327-3330 (2002)

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AUTHOR	:	Ebisawa, M., Ohta, K., Kawachi, E., Fukasawa, H., Hashimoto, Y., and Kagechika, H.
TITLE	:	Novel retinoidal tropolone derivatives. Bioisosteric relationship of tropolone ring with benzoic acid moiety in retinoid structure PubMed ID:11310685
JOURNAL	:	Chem Pharm Bull (Tokyo).
VOL	:	49 PAGE : 501-503 (2001)

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