公开(公告)号：US5401740A

公开(公告)日：1995-03-28

申请号：US273624

申请日：1994-07-12

申请人： Takao Nishi ,  Makoto Komatsu ,  Yasuo Koga ,  Yoshio Shu ,  Katsumi Tamura

发明人： Takao Nishi ,  Makoto Komatsu ,  Yasuo Koga ,  Yoshio Shu ,  Katsumi Tamura

IPC分类号： C07D215/22 ,  C07D215/227 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D411/12 ,  C07D417/12 ,  C07D521/00 ,  A61K31/47 ,  A61K31/505 ,  C07D403/12

CPC分类号： C07D215/227 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D411/12 ,  C07D417/12

摘要： The novel carbostyril derivative represented by the general formula (1) ##STR1## [in the formula, A, R.sup.1, R.sup.2 and the carbon-carbon bond between 3- and 4-positions in the carbostyril skeleton have the same definitions as above] has an excellent platelet aggregation inhibitory activity, a phosphodiesterase inhibitory activity, a venticular contraction activity (a positive contraction activity), an anti-ulcer activity, an anti-inflammatory activity, a cerebral blood flow increasing activity, a thrombus dissociation activity, a thromboxane A.sub.2 antagonism activity, etc. The carbostyril derivative of the present invention is characterized in that it exhibits the above activities for a long time, is low in toxicity (particularly low in toxicity to hearts of cardiovascular hyperplasia, myocardipathy, etc.), and is low in circulation activities such as heart rate increasing activity, blood pressure decreasing activity and the like. Also, the carbostyril derivative of the present invention has advantages in that it is easily absorbed by the intestinal tract and easily migrates into blood. Therefore, the carbostyril derivative of the present invention can be used most suitably as a preventive and remedy for thrombi such as apoplexia, cerebral infarction, myocardial infarction and the like, a cerebral circulation improving agent, an anti-inflammatory agent, an anti-asthmatic agent, a cardiotonic agent and a phosphodiesterase inhibitory agent.

摘要翻译： 由通式（1）表示的新型喹诺酮衍生物（1）[在式中，A，R1，R2和喹诺酮骨架中3-和4-位之间的碳 - 碳键具有相同的定义 上述]具有优异的血小板聚集抑制活性，磷酸二酯酶抑制活性，通气收缩活性（正收缩活性），抗溃疡活性，抗炎活性，脑血流增加活性，血栓解离活性， 血栓素A2拮抗活性等。本发明的喹诺酮衍生物的特征在于其长时间显示上述活性，毒性低（对心脏心脏增生，心肌病等的心脏毒性特别低）， 并且循环活动低，如心率增加活动，降血压活动等。 此外，本发明的喹诺酮衍生物具有容易被肠道吸收并易于迁移到血液中的优点。 因此，本发明的喹诺酮衍生物可以最适合地用作血栓形成的预防和治疗方法，例如复杂不良，脑梗死，心肌梗塞等，脑循环改善剂，抗炎剂，抗哮喘 药剂，强心剂和磷酸二酯酶抑制剂。

公开(公告)号：US5227381A

公开(公告)日：1993-07-13

申请号：US929097

申请日：1992-08-13

申请人： Takao Nishi ,  Makoto Komatsu ,  Yasuo Koga ,  Yoshio Shu ,  Katsumi Tamura

发明人： Takao Nishi ,  Makoto Komatsu ,  Yasuo Koga ,  Yoshio Shu ,  Katsumi Tamura

IPC分类号： C07D215/22 ,  C07D215/227 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D411/12 ,  C07D417/12 ,  C07D521/00

CPC分类号： C07D215/227 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D411/12 ,  C07D417/12

摘要： Carbostyril compounds or salts thereof of the formula ##STR1## wherein A is a C.sub.1 -C.sub.6 alkylene group; R.sup.1 is a C.sub.3 -C.sub.8 cycloalkyl-C.sub.1 -C.sub.6 alkyl group which may have, as a substituent, a group selected from the group consisting of C.sub.1 -C.sub.6 alkoxycarbonyl groups, a carboxy group, C.sub.2 -C.sub.6 alkanoyloxy-C.sub.1 -C.sub.6 alkyl groups, amino-C.sub.1 -C.sub.6 alkyl groups, C.sub.1 -C.sub.6 alkylamino-C.sub.1 -C.sub.6 alkyl groups and hydroxy-C.sub.1 -C.sub.6 alkyl groups, a C.sub.3 -C.sub.8 cycloalkyl group, a tetrahydropyranyl-C.sub.1 -C.sub.6 alkyl group, a C.sub.1 -C.sub.3 alkylenedioxy group-substituted C.sub.1 -C.sub.6 alkyl group, a phenyl-C.sub.1 -C.sub.6 alkyl group having, as a substituent on the phenyl ring, 1 to 3 groups selected from the group consisting of C.sub.1 -C.sub.6 alkyl groups and a hydroxyl group, or a piperidinyl-C.sub.1 -C.sub.6 alkyl group having a C.sub.1 -C.sub.6 alkyl group as a substituent; R.sup.2 is a 5-membered or 6-membered saturated or unsaturated heterocyclic-C.sub.1 -C.sub.6 alkyl group, said heterocyclic being selected from the group consisting of pyrrolidinyl, morpholino, piperidinyl, thiomorpholino, imidazolyl, 1,2,4-triazolyl, furyl, piperazinyl, pyridyl, tetrahydropyranyl and 1,3-oxathiolranyl groups which may have, as a substituent thereon 1 to 3 groups selected from the group consisting of hydroxy-C.sub. 1 -C.sub.6 alkyl groups, C.sub.2 -C.sub.6 alkanoyloxy-C.sub.1 -C.sub.6 alkyl groups, a hydroxyl group, C.sub.1 -C.sub.6 alkyl groups, amino-C.sub.1 -C.sub.6 alkyl groups, C.sub.1 -C.sub.6 alkylamino-C.sub.1 -C.sub.6 alkyl groups, C.sub.1 -C.sub.6 alkoxy groups, C.sub.1 -C.sub.6 alkoxy-C.sub.1 -C.sub.6 alkoxy groups, C.sub.1 -C.sub.6 alkoxy-C.sub.1 -C.sub.6 alkyl groups, a thio group and C.sub.1 -C.sub.6 alkylamido groups; the carbon-carbon bond between the 3- and 4-positions in the carbostyril skeleton being a single bond or a double bond and pharmaceutical compositions containing the compound as the active ingredient.

摘要翻译： 其中A为C1-C6亚烷基的卡波斯特尔化合物或其盐， R1是可以具有选自C1-C6烷氧基羰基，羧基，C2-C6烷酰氧基-C1-C6烷基的基团作为取代基的C3-C8环烷基-C1-C6烷基， 氨基-C 1 -C 6烷基，C 1 -C 6烷基氨基-C 1 -C 6烷基和羟基-C 1 -C 6烷基，C 3 -C 8环烷基，四氢吡喃基-C 1 -C 6烷基，C 1 -C 3亚烷基二氧基 - 取代的C 1 -C 6烷基，作为苯环上的取代基的苯基-C 1 -C 6烷基，选自C 1 -C 6烷基和羟基的1至3个基团或哌啶基-C 1 具有C 1 -C 6烷基的-C 6烷基作为取代基; R2是5元或6元饱和或不饱和杂环-C 1 -C 6烷基，所述杂环选自吡咯烷基，吗啉代，哌啶基，硫代吗啉代，咪唑基，1,2,4-三唑基，呋喃基， 哌嗪基，吡啶基，四氢吡喃基和1,3-氧硫杂环戊酰基，其可以具有1至3个选自羟基-C 1 -C 6烷基，C 2 -C 6烷酰氧基-C 1 -C 6烷基， 羟基，C 1 -C 6烷基，氨基-C 1 -C 6烷基，C 1 -C 6烷基氨基-C 1 -C 6烷基，C 1 -C 6烷氧基，C 1 -C 6烷氧基-C 1 -C 6烷氧基，C 1 -C 6烷氧基 -C 1 -C 6烷基，硫基和C 1 -C 6烷基酰胺基; 喹诺酮骨架中3-和4-位之间的碳 - 碳键是单键或双键，以及含有该化合物作为活性成分的药物组合物。

公开(公告)号：US5541198A

公开(公告)日：1996-07-30

申请号：US367196

申请日：1995-01-18

申请人： Takao Nishi ,  Tetsuyuki Uno ,  Yoshio Shu ,  Katsumi Tamura ,  Minoru Okada

发明人： Takao Nishi ,  Tetsuyuki Uno ,  Yoshio Shu ,  Katsumi Tamura ,  Minoru Okada

IPC分类号： A61K31/47 ,  A61K31/33 ,  A61P7/02 ,  A61P9/10 ,  C07D401/00 ,  C07D401/12

CPC分类号： C07D401/12

摘要： Carbostyril derivatives useful for inhibiting the adhesion of platelets represented by general formula ##STR1## [wherein, R.sup.1 is a hydrogen atom, a fluorine atom or a methyl group; R is a group of the formula ##STR2## (R.sup.2 is a methyl group, a trifluoromethyl group or a nitro group), or a group of the formula ##STR3## (R.sup.3 is a fluorine atom and p is an integer of 2 or 3); and n is an integer of 2 or 3], or salts thereof.Said carbostyril derivatives or salts are useful as an agent for inhibiting the adhesion of platelets.

摘要翻译： PCT No.PCT / JP94 / 00760 Sec。 371 1995年1月18日第 102（e）日期1995年1月18日PCT提交1994年5月11日PCT公布。 第WO94 / 26732号公报 日期：1994年11月24日用于抑制由通式表示的血小板的粘附的卡波斯特尔衍生物[其中，R1是氢原子，氟原子或甲基; R是下式的基团（R 2是甲基，三氟甲基或硝基）或下式的基团（R 3是氟原子，p是2或3的整数） ）; n为2或3的整数]或其盐。 所述喹诺酮衍生物或盐可用作抑制血小板粘附的药剂。