专利号:US-7772278-B2 优先权日:1999-03-01 标 题:Nitrosated and nitrosylated prostaglandins, compositions and methods of use 发明人:GARVEY DAVID S; GASTON RICKY D; LETTS L GORDON; DE TEJADA INIGO SAENZ; TAM SANG WILLIAM; WORCEL MANUEL 权利人:NITROMED INC 摘要:The invention describes novel nitrosated and/or nitrosylated prostaglandins, and novel compositions comprising at least one nitrosated and/or nitrosylated prostaglandin, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and/or at least one vasoactive agent. The invention also provides novel compositions comprising at least one prostaglandin and at least one S-nitrosothiol compound, and, optionally, at least one vasoactive agent. The prostaglandin is preferably a prostaglandin E 1 compound, more preferably alprostadil, and the S-nitrosothiol compound is preferably S-nitrosoglutathione. The invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing cerebrovascular disorders, cardiovascular disorders, benign prostatic hyperplasia (BPH), glaucoma, peptic ulcers or for inducing abortions.
专利号:US-8017776-B2 优先权日:2003-07-15 标题 :Methods for synthesis of acyloxyalkyl compounds 发明人:BHAT LAXMINARAYAN; GALLOP MARK A 权利人:XENOPORT INC 摘要:Disclosed herein are methods for synthesizing 1-(acyloxy)-alkyl prodrug derivatives of drugs through oxidation of 1-acyl-alkyl derivatives of drugs under anhydrous reaction conditions. The methods typically proceed stereospecifically, in high yield, do not require the use of activated intermediates and/or toxic compounds and are readily amenable to scale-up.
专利号:US-8143437-B2 优先权日:2002-02-19 标题:Methods for synthesis of prodrugs from 1-acyl-alkyl derivatives and compositions thereof 发明人:GALLOP MARK A; XIANG JIA-NING; YAO FENMEI; BHAT LAXMINARAYAN; ZHOU CINDY X 权利人:GALLOP MARK A; XIANG JIA-NING; YAO FENMEI; BHAT LAXMINARAYAN; ZHOU CINDY X; XENOPORT INC 摘要:The present invention provides a method for synthesizing 1-(acyloxy)-alkyl derivatives from 1-acyl-alkyl derivatives, which typically proceeds stereospecifically, in high yield, does not require the use of activated intermediates and/or toxic compounds and is readily amendable to scale-up. The current invention also provides 1-acyl-alkyl derivatives of known drug components and methods for synthesizing these 1-acyl-alkyl derivatives.
专利号:US-2005239725-A1 优先权日:2002-02-19 标题:Methods for synthesis of prodrugs from 1-acyl-alkyl derivatives and compositions thereof
专利号:US-2005070715-A1 优先权日:2003-07-15 标 题:Methods for synthesis of acyloxyalkyl compounds
专利号:US-7560483-B2 优先权日:2002-02-19 标题 :Methods for synthesis of prodrugs from 1-acyl-alkyl derivatives and compositions thereof
1: A multicentre randomized comparative clinical trial of 200 mg RU486 (mifepristone) single dose followed by either 5 mg 9-methylene PGE(2) gel (meteneprost) or 600 microg oral PGE(1) (misoprostol) for termination of early pregnancy within 28 days of missed menstrual period. ICMR Task Force Study. Indian Council of Medical Research. Contraception. 2000 Sep;62(3):125-30. French. French.
合成参考文献
参考文献:10.1016/0020-7292(82)90026-1 摘要:Shapiro AG, Lasseter K, Cobiella A, Domenzain M. Intravaginal administration of 9-deoxo-9-methylene-16,16-dimethyl PGE2for cervical dilation prior to suction curettage. International Journal of Gynecology & Obstetrics. 1982 Apr;20(2):137–40. doi: 10.1016/0020-7292(82)90026-1. 参考文献:10.1016/s0090-9556(25)08014-6 摘要:Steffenrud S. Metabolism of 9-deoxo-16,16-dimethyl-9-methylene prostaglandin E2 in humans. Drug Metabolism and Disposition. 1983 May;11(3):255–65. doi: 10.1016/s0090-9556(25)08014-6. 参考文献:10.1016/s0015-0282(16)49089-8 摘要:Wallach EE, Castadot RG. Pregnancy termination: techniques, risks, and complications and their management. Fertility and Sterility. 1986 Jan;45(1):5–17. doi: 10.1016/s0015-0282(16)49089-8. 摘要:Friedli A, De Grandi P. [Preoperative dilatation of the cervix uteri by vaginal application of 9-deoxo-16, 16-dimethyl-9-methylene PGE2 in pregnancy interruption during the 1st trimester. Double-blind clinical study]. J Gynecol Obstet Biol Reprod (Paris). 1986;15(2):215–21. 参考文献:10.1007/bf00583936 摘要:Christensen N, Bygdeman M, Greén K, Jonasson H, Rundgren M, Wallin C, Vesterqvist O, Leksell LG. The prostaglandin-analogue-9-deoxo-16,16-dimethyl-9-methylene-PGE2 inhibits the antidiuretic effect of vasopressin (AVP) in the conscious sheep. Pflügers Archiv - European Journal of Physiology. 1984 Dec;402(4):360–3. doi: 10.1007/bf00583936.