Toborinone, OPC-18790, Tobonone, -Drug Synthesis Database

【结构式】

【药物名称】Toborinone, OPC-18790, Tobonone

【化学名称】(±)-6-[3-(3,4-Dimethoxybenzylamino)-2-hydroxypropoxy]carbostyril
　　　　　　(±)-6-[3-(3,4-Dimethoxybenzylamino)-2-hydroxypropoxy]-1,2-dihydroquinolin-2-one

【CA登记号】143343-83-3, 128668-62-2 ((R)-isomer), 128668-65-5 ((S)-isomer), 128667-95-8 (undefined isomer)

【分子式】C₂₁H₂₄N₂O₅

【分子量】384.43583

【开发单位】Otsuka (Originator)

【药理作用】CARDIOVASCULAR DRUGS, Heart Failure Therapy, Phosphodiesterase III Inhibitors

合成路线1 合成路线2

合成路线1

6-Hydroxy-2(1H)-quinolinone (I) is alkylated with epichlorohydrin in the presence of K2CO3 in MeOH to afford 6-(2,3-epoxypropoxy)-2(1H)-quinolinone (II). Ring opening of the epoxide (II) with 3,4-dimethoxybenzylamine gives OPC-18790. This compound is also obtained by the reductive alkylation of 6-(3-amino-2-hydroxypropoxy)-2(1H)-quinolinone (III) with 3,4-dimethoxybenzaldehyde.

参考文献中间体

【1】 Sumida, T.; Fujioka, T.; Teramoto, S.; Tominaga, M.; Yabuuchi, Y.; Mori, T.; Hosokawa, T.; Novel positive inotropic agents; synthesis and biological activities of 6-(3-amino-2-hydroxypropoxy)-2(1H)-quinolinone derivatives. J Med Chem 1992, 35, 20, 3607-12.
【2】 Fujioka, T.; OPC-18790. Drugs Fut 1993, 18, 12, 1114.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
	13920	(3,4-Dimethoxyphenyl)methanamine; 3,4-Dimethoxybenzylamine; Veratrylamine	5763-61-1	C₉H₁₃NO₂	详情	详情
	18304	3,4-Dimethoxybenzaldehyde; Veratraldehyde	120-14-9	C₉H₁₀O₃	详情	详情
(I)	13913	6-Hydroxy-2(1H)-quinolinone		C₉H₇NO₂	详情	详情
(II)	13914	6-(2-Oxiranylmethoxy)-2(1H)-quinolinone		C₁₂H₁₁NO₃	详情	详情
(III)	13915	6-(3-Amino-2-hydroxypropoxy)-2(1H)-quinolinone		C₁₂H₁₄N₂O₃	详情	详情

合成路线2

The synthesis of the (+)-(R)-isomer of OPC-18790 has been published: The condensation of 6-hydroxyquinolin-2(1H)-one (I) with (S)-(+)-epichlorohydrin (II) by means of triethylamine in methanol gives (S)-(+)-6-(3-chloro-2-hydroxypropoxy)quinolin-2(1H)-one (III), which by reaction with KOH in isopropanol/water yields the (R)-(-)-epoxide (IV). Finally, this compound is condensed with 3,4-dimethoxybenzylamine (V) by heating its mixture at 80 C. The (+)-(R)-isomer is about 10-fold more potent than the (-)-(S)-isomer.

参考文献中间体

【1】 Fujioka, T.; Teramoto, S.; Tominaga, M.; Mori, T.; Sumida, T.; Yabuuchi, Y.; Tsujimi, S.; Takemoto, K.; Hosokawa, T.; Synthesis and biological activities of optically active 6-[3-(3,4-dimethox ybenzylamino)-2 hydroxypropoxy]-2(1H)-quinolinone (OPC-18790). Chem Pharm Bull 1996, 44, 8, 1596.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	13913	6-Hydroxy-2(1H)-quinolinone		C₉H₇NO₂	详情	详情
(II)	13917	(S)-Epichlorohydrin; (2S)-2-(Chloromethyl)oxirane;(S)-(+)-epichlorohydrin	67843-74-7	C₃H₅ClO	详情	详情
(III)	13918	6-[[(2S)-3-Chloro-2-hydroxypropyl]oxy]-2(1H)-quinolinone		C₁₂H₁₂ClNO₃	详情	详情
(IV)	13919	6-[(2R)Oxiranylmethoxy]-2(1H)-quinolinone		C₁₂H₁₁NO₃	详情	详情
(V)	13920	(3,4-Dimethoxyphenyl)methanamine; 3,4-Dimethoxybenzylamine; Veratrylamine	5763-61-1	C₉H₁₃NO₂	详情	详情

Extended Information