公开(公告)号：US5286858A

公开(公告)日：1994-02-15

申请号：US774945

申请日：1991-10-11

申请人： Minoru Moriwaki ,  Syuji Yuasa ,  Hiroyuki Kitani ,  Michio Terasawa

发明人： Minoru Moriwaki ,  Syuji Yuasa ,  Hiroyuki Kitani ,  Michio Terasawa

IPC分类号： A61K31/55 ,  A61K31/00 ,  A61K31/554 ,  A61P7/02 ,  A61P9/00 ,  A61P11/00 ,  A61P29/00 ,  A61P37/00 ,  A61P37/08 ,  A61P43/00 ,  C07D495/14 ,  C07D495/12

CPC分类号： C07D495/14

摘要： Stable crystals of an acid addition salt of an optically active thienotriazolodiazepine compound or its hydrate of the formula ##STR1## wherein R.sup.1 is hydrogen, R.sup.2 is 2-phenylethyl substituted by alkyl having 1 to 5 carbon atoms, 2-morpholinocarbonylethyl or alkyl having 6 to 12 carbon atoms, or R.sup.1 and R.sup.2 may combinedly form a saturated 5-membered ring having one substituent selected from the group consisting of morpholinomethyl, morpholinocarbonyl and N,N-dipropylcarbamoyl, R.sup.3 is halogen, alkyl having 1 to 5 carbon atoms or alkoxy having 1 to 5 carbon atoms, R.sup.4 is trifluoromethyl or alkyl having 1 to 5 carbon atoms, R.sup.5 is hydrogen or methyl, m is 1-2, and n is 0-2. The present invention provides optically active thienotriazolodiazepine compounds having strong PAF-antagonistic activity as markedly stable crystals which are excellent in crystalline property, permit purification by recrystallization, and have high chemical purity and optical purity, thereby rendering industrial large-scale synthesis attainable. In addition, crystallization thereof facilitates medicinal standardization and pharmaceutical formulation.

摘要翻译： 光学活性噻吩并三唑并噻嗪类化合物或其水合物（*化学结构*）（I）的酸加成盐的稳定晶体，其中R 1为氢，R 2为被具有1至5个碳原子的烷基取代的2-苯乙基， 吗啉代羰基乙基或具有6至12个碳原子的烷基，或者R 1和R 2可以组合形成具有一个选自吗啉代甲基，吗啉代羰基和N，N-二丙基氨基甲酰基的一个取代基的饱和五元环，R 3是卤素， 5个碳原子或具有1至5个碳原子的烷氧基，R4是三氟甲基或具有1-5个碳原子的烷基，R5是氢或甲基，m是1-2，n是0-2。 本发明提供具有优异结晶性的显色稳定结晶的具有强PAF拮抗作用的光学活性噻吩并三唑并氮杂化合物，可以通过重结晶进行纯化，化学纯度高，光学纯度高，从而可实现工业化的大规模合成。 此外，其结晶有助于药物标准化和药物制剂。