公开(公告)号：US6040449A

公开(公告)日：2000-03-21

申请号：US290607

申请日：1999-04-13

申请人： Yoshimi Tsuchiya ,  Takashi Nomoto ,  Hirokazu Ohsawa ,  Kumiko Kawakami ,  Kenji Ohwaki ,  Masaru Nishikibe

发明人： Yoshimi Tsuchiya ,  Takashi Nomoto ,  Hirokazu Ohsawa ,  Kumiko Kawakami ,  Kenji Ohwaki ,  Masaru Nishikibe

IPC分类号： C07D211/46 ,  C07D211/58 ,  C07D401/06 ,  C07D405/06 ,  C07D409/06

CPC分类号： C07D401/06 ,  C07D211/58 ,  C07D405/06 ,  C07D409/06

摘要： In the production of fluorine-containing 1,4-disubstituted piperidine derivatives by the reaction of a carboxylic acid of formula where Ar represents aryl or heteroaryl and R.sup.10 represents C.sub.3 -C.sub.6 cycloalkyl in which up to 4 hydrogen atoms are substituted with fluorine or C.sub.3 -C.sub.6 cycloalkyl having 1 to 2 protected or unprotected hydroxyl or oxo groups, or a reactive derivative thereof, with a piperidine derivative of formula [IV] as defined in the specification, especially useful results are obtained using 4-amino-1-(6-aminopyridin-2-ylmethyl)piperidine or a salt thereof, e.g., trihydrochloride, as the piperidine derivative.

摘要翻译： 在通过下式的羧酸的反应制备含氟的1,4-二取代的哌啶衍生物时，其中Ar表示芳基或杂芳基，R10表示C3-C6环烷基，其中最多4个氢原子被氟或C3- 具有1至2个受保护或未保护的羟基或氧代基团的C 6环烷基或其活性衍生物与本说明书中定义的式[IV]哌啶衍生物特别有用的结果是使用4-氨基-1-（6- 氨基吡啶-2-基甲基）哌啶或其盐，例如三盐酸盐作为哌啶衍生物。

公开(公告)号：US5948792A

公开(公告)日：1999-09-07

申请号：US903768

申请日：1997-07-31

申请人： Yoshimi Tsuchiya ,  Takashi Nomoto ,  Hirokazu Ohsawa ,  Kumiko Kawakami ,  Kenji Ohwaki ,  Masaru Nishikibe

发明人： Yoshimi Tsuchiya ,  Takashi Nomoto ,  Hirokazu Ohsawa ,  Kumiko Kawakami ,  Kenji Ohwaki ,  Masaru Nishikibe

IPC分类号： C07D211/46 ,  C07D211/58 ,  C07D401/06 ,  C07D405/06 ,  C07D409/06 ,  A61K31/445

CPC分类号： C07D401/06 ,  C07D211/58 ,  C07D405/06 ,  C07D409/06

摘要： Novel fluorine-containing 1,4-disubstituted piperidine derivatives, represented by general formula �I! ##STR1## such as, for example, (2R)-N-�1-(6-aminopyridin-2-ylmethyl)piperidin-4-yl!-2-�(1R)-3,3-difluorocyclopentyl!-2-hydroxy-2-phenylacetamide or pharmaceutically acceptable salt thereof, are potent and selective antagonists for muscarinic M.sub.3 receptors with little side effects. The compounds of formula �I! exhibit excellent oral activity, duration of activity and pharmacolkinetics. They are useful for treatment and prophylaxis of respiratory diseases, such as chronic obstructive pulmonary diseases; urinary diseases, such as urinary incontinence; and digestive diseases, such as irritable bowel syndrome, and motion sickness.

摘要翻译： 由通式[I]表示的新型含氟1,4-二取代哌啶衍生物，例如（2R）-N- [1-（6-氨基吡啶-2-基甲基）哌啶-4-基] - 2 - [（1R）-3,3-二氟环戊基] -2-羟基-2-苯基乙酰胺或其药学上可接受的盐是毒副反应较少的毒蕈碱M3受体的有效和选择性拮抗剂。 式[I]的化合物表现出优异的口服活性，活性持续时间和药物动力学。 它们可用于治疗和预防呼吸系统疾病，如慢性阻塞性肺疾病; 尿病如尿失禁; 和消化系统疾病，如肠易激综合征，晕车等。