公开(公告)号：US06262272B1

公开(公告)日：2001-07-17

申请号：US09403985

申请日：1999-01-19

申请人： John Anthony Ragan ,  Teresa Woodall Makowski ,  David Jon Am Ende ,  Pamela Jane Clifford ,  Gregory Randall Young ,  Alyson Kay Conrad ,  Shane Allen Eisenbeis ,  George Joseph Quallich ,  Douglas John Meldrum Allen

发明人： John Anthony Ragan ,  Teresa Woodall Makowski ,  David Jon Am Ende ,  Pamela Jane Clifford ,  Gregory Randall Young ,  Alyson Kay Conrad ,  Shane Allen Eisenbeis ,  George Joseph Quallich ,  Douglas John Meldrum Allen

IPC分类号： C07D40100

CPC分类号： C07D405/12 ,  C07D209/42 ,  C07D307/83 ,  C07D307/84

摘要： A method for preparing pyrrole-carboxyamides which selectively bind to GABAa receptors; which comprises reacting 1,3-cycloakane-diones with bromoethylacetate followed by reaction of the resulting product with an acid halide followed by reaction with an aromatic amine and finally with an amonium source at an elevated temperature.

摘要翻译： 制备选择性结合GABAa受体的吡咯 - 羧酰胺的方法; 其包括使1,3-环烷二酮与乙酸乙酯反应，随后将所得产物与酰卤反应，随后与芳族胺反应，最后在升高的温度下与二铵源反应。

公开(公告)号：US07129263B2

公开(公告)日：2006-10-31

申请号：US10966712

申请日：2004-10-15

申请人： Stanton Furst McHardy ,  John Anthony Ragan ,  Derek Lawrence Tickner ,  Brian Clement Vanderplas ,  Jotham Wadsworth Coe

发明人： Stanton Furst McHardy ,  John Anthony Ragan ,  Derek Lawrence Tickner ,  Brian Clement Vanderplas ,  Jotham Wadsworth Coe

IPC分类号： A61K31/403 ,  C07D209/52

CPC分类号： C07D209/52

摘要： This present invention relates to a new and improved reductive amination process for the preparation of 3-azabicyclo[3.1.0]hexane derivatives and pharmaceutical compositions comprising such derivatives. The invention particularly relates to using such derivatives to treat certain disorders and conditions, including, for example, irritable bowel syndrome, drug addiction or dependency, alcohol addiction or dependency, depression, and eating disorders.

摘要翻译： 本发明涉及用于制备3-氮杂双环[3.1.0]己烷衍生物的新的和改进的还原胺化方法和包含这些衍生物的药物组合物。 本发明特别涉及使用这些衍生物来治疗某些疾病和病症，包括例如肠易激综合征，药物成瘾或依赖性，酒精成瘾或依赖性，抑郁症和进食障碍。

公开(公告)号：US06147214A

公开(公告)日：2000-11-14

申请号：US403266

申请日：1999-10-15

申请人： John Anthony Ragan

发明人： John Anthony Ragan

IPC分类号： C07D217/22 ,  A61K31/4725 ,  A61P3/06 ,  A61P9/10 ,  C07C233/66 ,  C07C233/75 ,  C07C233/76 ,  C07C233/80 ,  C07D217/02 ,  C07D217/04

CPC分类号： C07C233/80 ,  C07C233/66 ,  C07C233/75 ,  C07C233/76 ,  C07D217/02

摘要： An improved process, and intermediates, for the preparation of 4'-trifluoromethyl-biphenyl-2-carboxylic acid (1,2,3,4-tetrahydro-isoquinoline-6-yl) amide (I), are disclosed. Compound (I) is useful as an inhibitor of microsomal triglyceride transfer protein and/or apolipoprotein B secretion, and which are accordingly useful for the preparation and treatment of atherosclerosis and its clinical sequelae, for lowering serum lipids, and related diseases.

摘要翻译： PCT No.PCT / IB98 / 00493 Sec。 371 1999年10月15日第 102（e）日期1999年10月15日PCT提交1998年4月6日PCT公布。 第WO98 / 47875号公报 日期1998年10月29日为制备4'-三氟甲基 - 联苯-2-羧酸（1,2,3,4-四氢 - 异喹啉-6-基）酰胺（I）的改进方法和中间体是 披露 化合物（I）可用作微粒体甘油三酯转运蛋白和/或载脂蛋白B分泌的抑制剂，因此可用于制备和治疗动脉粥样硬化及其临床后遗症，降低血清脂质和相关疾病。

公开(公告)号：US06521630B1

公开(公告)日：2003-02-18

申请号：US09650486

申请日：2000-08-29

申请人： Anton Franz Joseph Fliri ,  Todd William Butler ,  Randall James Gallaschun ,  John Anthony Ragan ,  Brian Patrick Jones

发明人： Anton Franz Joseph Fliri ,  Todd William Butler ,  Randall James Gallaschun ,  John Anthony Ragan ,  Brian Patrick Jones

IPC分类号： A61K31517

CPC分类号： C07D401/14 ,  C07D401/04 ,  C07D401/06 ,  C07D401/08 ,  C07D401/12

摘要： The present invention relates to tetrahydroquinazoline-2,4-diones derivatives of the formula (I): pharmaceutically acceptable salts thereof, wherein A is (CH2)n where n is equal to 0, 1 or 2; U is CH2, NH, or NR3, R1 and R2 are selected independently from H, (C1-C6)alkyl, Cl, F, CN, nitro, CF3, —NHC(O)R6 and —OR7, or R1 and R2, together with the atoms to which they are attached, form a carbocyclic or heterocyclic five- or six-membered ring, R3 is selected from the group consisting of H, (C1-C6)malkyl, C(═O)—(C1-C6)alkyl, where m=1 or 2; R4 and R5 are selected from H, (C1-C6)alkyl, Cl, F, —CF3, —CN, —NHC(═O)R6, —OR7, a 5-to 7-membered aryl or heteroaryl ring, where m, R6 and R7 are as defined above; and R6 and R7 are selected independently from H, (C1-C6)alkyl or a 5- to 7-membered aryl or heteroaryl ring; V is CH, CR3, or N; W is CH2, C(O), or S(O)2; X is C or N; and Y is CH, CR1,CR2, or N. The invention also relates to pharmaceutical compositions containing the same and to methods of use thereof, including in the inhibition of serotonin reuptake, the inhibition of the binding of 5-HT2A serotonin receptors and the treatment of diseases, conditions or disorders of the central nervous system. Further, the present invention is also directed to methods for the preparation of 4-(4-phenyl-1,2,3,6-tetrahydropyridin-1-yl)-propyl-1,2,3,4-tetrahydroquinazoline-2,4-dione compounds and intermediates useful thereof.

摘要翻译： 本发明涉及式（I）的四氢喹唑啉-2,4-二酮衍生物：其药学上可接受的盐，其中A是（CH2）n，其中n等于0,1或2; U是CH 2，NH或NR 3，R 1和R 2独立地选自H，（C 1 -C 6）烷基，Cl，F，CN，硝基，CF 3，-NHC（O）R 6和-OR 7或R 1和R 2， 与其连接的原子一起形成碳环或杂环的五元或六元环，R 3选自H，（C 1 -C 6）烷基，C（= O） - （C 1 -C 6） ）烷基，其中m = 1或2; R4和R5选自H，（C1-C6）烷基，C1，F，-CF3，-CN，-NHC（= O）R6，-OR7，5-7元芳基或杂芳基环，其中m ，R6和R7如上所定义; 并且R 6和R 7独立地选自H，（C 1 -C 6）烷基或5至7元芳基或杂芳基环; V是CH，CR 3或N; W是CH 2，C（O）或S（O）2; X为C或N; 并且Y是CH，CR1，CR2或N.本发明还涉及含有该组合物的药物组合物及其使用方法，包括抑制5-羟色胺再摄取，抑制5-HT2A 5-羟色胺受体的结合和 治疗中枢神经系统的疾病，病症或病症。 此外，本发明还涉及制备4-（4-苯基-1,2,3,6-四氢吡啶-1-基） - 丙基-1,2,3,4-四氢喹唑啉-2， 4-二酮化合物及其有用的中间体。