公开(公告)号：US4465681A

公开(公告)日：1984-08-14

申请号：US403664

申请日：1982-07-28

申请人： Takanori Oe ,  Mineo Tsuruda ,  Kazuhiro Goto ,  Masao Hisadome

发明人： Takanori Oe ,  Mineo Tsuruda ,  Kazuhiro Goto ,  Masao Hisadome

IPC分类号： A61K31/44 ,  A61K31/4418 ,  A61K31/4427 ,  A61P29/00 ,  A61P37/00 ,  A61P37/04 ,  C07D213/61 ,  C07D213/64 ,  C07D213/69 ,  C07D213/70 ,  C07D401/14 ,  C07D521/00

CPC分类号： C07D213/64 ,  C07D213/61 ,  C07D213/70 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08

摘要： Pyridine derivatives of the formula: ##STR1## or pharmaceutically acceptable acid addition salts thereof, wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are the same or different and each represents hydrogen atom or lower alkyl group, or R.sup.1 and R.sup.2, or R.sup.3 and R.sup.4 together with the adjacent nitrogen atom form a heterocycle, A.sup.1 and A.sup.2 are the same or different and each represents alkylene or hydroxy-substituted alkylene group, Y.sup.1 and Y.sup.2 are the same or different and each represents oxygen or sulfur atom, and Z represents ##STR2## These compounds show pharmacological activities such as potentiating activity for leukocyte phagocytosis, potentiating activity for macrophage phagocytosis, potentiating activity for the production of rosette forming cells in the spleen and anti-adjuvant arthritis activity, and are useful as medicines.

摘要翻译： PCT No.PCT / JP81 / 00374 Sec。 371日期1982年7月28日 102（e）日期1982年7月28日PCT 1991年12月9日PCT PCT。 出版物WO82 / 02045 日期：1982年6月24日。下式的吡啶衍生物：其中R 1，R 2，R 3和R 4相同或不同，各自表示氢原子或低级烷基，或者R 1和 R2或R3和R4与相邻氮原子一起形成杂环，A1和A2相同或不同，各自表示亚烷基或羟基取代的亚烷基，Y1和Y2相同或不同，各自表示氧或硫原子 ，Z表示这些化合物显示药理活性，例如白细胞吞噬的增强活性，巨噬细胞吞噬的增强活性，在脾中产生玫瑰花形成细胞的增强活性和抗佐剂关节炎活性，并且可用作药物 。

公开(公告)号：US4386092A

公开(公告)日：1983-05-31

申请号：US297696

申请日：1981-08-28

申请人： Takanori Oe ,  Minoru Moriwaki ,  Kazuhiro Goto ,  Masao Hisadome

发明人： Takanori Oe ,  Minoru Moriwaki ,  Kazuhiro Goto ,  Masao Hisadome

IPC分类号： A61K31/435 ,  A61P25/04 ,  A61P29/00 ,  A61P35/00 ,  A61P37/08 ,  C07D471/04 ,  C07D513/04 ,  A61K31/425

CPC分类号： C07D471/04 ,  C07D513/04

摘要： A heterocyclic-substituted oxoalkanoic acid derivative having immunomodulatory activities of the formula: ##STR1## wherein R.sup.1 is hydrogen, lower alkyl, phenyl which may be substituted by at least one substituent selected from halogen, lower alkyl, lower alkoxy, mono- or di-lower alkyl amino-substituted lower alkoxy, lower alkylthio, lower alkylsulfinyl, amino, nitro and cyano at any position(s) on the nucleus, thienyl or furyl, each of R.sup.2 and R.sup.3 is hydrogen or lower alkyl, A is lower alkylene, X is sulfur or vinylene, Y is nitrogen or methine which may be substituted by lower alkyl, Z is carbonyl or direct bond.

摘要翻译： PCT No.PCT / JP81 / 00007 Sec。 371日期1981年8月28日 102（e）日期1981年8月28日PCT提交1981年1月13日PCT公布。 出版物WO81 / 02013 日本1981年7月23日。具有下式的免疫调节活性的杂环取代的氧代链烷酸衍生物：其中R 1是氢，低级烷基，可以被至少一个选自卤素，低级烷基，低级 烷氧基，单 - 或二 - 低级烷基氨基取代的低级烷氧基，低级烷硫基，低级烷基亚磺酰基，氨基，硝基和氰基在任何位置，噻吩基或呋喃基，R2和R3各自为氢或低级烷基 A为低级亚烷基，X为硫或亚乙烯基，Y为可被低级烷基取代的氮或次甲基，Z为羰基或直接键。

公开(公告)号：US5006520A

公开(公告)日：1991-04-09

申请号：US373296

申请日：1989-06-13

申请人： Takanori Oe ,  Hiroyuki Sueoka ,  Masao Hisadome ,  Keiji Yamagami

发明人： Takanori Oe ,  Hiroyuki Sueoka ,  Masao Hisadome ,  Keiji Yamagami

IPC分类号： C07D231/56 ,  C07D471/04

CPC分类号： C07D471/04 ,  C07D231/56

摘要： Novel fused pyrazole compounds of the general formula ##STR1## wherein all the symbols are as defined in the specification or its pharmaceutically acceptable salt which possesses a stimulating action on phagocytosis of leukocytes, a stimulating action on phagocytosis of macrophages, a restorative action on leukopenia, a stimulating action on non-specific resistance to infection, an antitumour action, an activating action on immune responses and the like, and thereof is of use as a pharmaceutical.

公开(公告)号：US20060167014A1

公开(公告)日：2006-07-27

申请号：US11298980

申请日：2005-12-12

申请人： Kunitomo Adachi ,  Yoshiyuki Aoki ,  Tokushi Hanano ,  Hiroshi Morimoto ,  Masao Hisadome

发明人： Kunitomo Adachi ,  Yoshiyuki Aoki ,  Tokushi Hanano ,  Hiroshi Morimoto ,  Masao Hisadome

IPC分类号： A61K31/495 ,  C07D241/04

CPC分类号： C07D239/42 ,  C07C2601/02 ,  C07D213/74 ,  C07D233/88 ,  C07D239/47 ,  C07D239/48 ,  C07D239/50 ,  C07D239/52 ,  C07D239/545 ,  C07D277/42 ,  C07D295/135

摘要： The present invention relates to a piperazine compound of the formula wherein R1 and R2 are each hydrogen, halogen, lower alkyl, lower alkoxy, amino, substituted amino, nitro, hydroxy or cyano, R3, R4 and R5 are each hydrogen, halogen, lower alkyl, lower alkoxy, nitro, amino, substituted amino or hydroxy, R6 and R7 are each hydrogen, lower alkyl, lower alkyl substituted by halogen, aralkyl, acyl or lower acyl substituted by halogen, R8 and R9 are each hydrogen or lower alkyl, Y is lower alkylene and the like, and ring A is phenyl, pyrimidyl, thiazolyl, pyridyl, pyrazyl or imidazolyl, a pharmaceutically acceptable salt thereof and pharmaceutical agents containing these compounds. The compound of the present invention has superior TNF-α production inhibitory effect and/or IL-10 production promoting effect, and, since it is free of or shows only strikingly reduced expression of an effect on the central nervous system, the compound is useful as a highly safe and superior TNF-α production inhibitor an/or IL-10 production promoter and is useful as an agent for the prophylaxis or treatment of various diseases caused by abnormal TNF-α production, diseases curable with IL-10, such as chronic inflammatory diseases, acute inflammatory diseases, inflammatory diseases due to infection, autoimmune diseases, allergic diseases, and TNF-α mediated diseases.

摘要翻译： 本发明涉及下式的哌嗪化合物其中R 1和R 2各自为氢，卤素，低级烷基，低级烷氧基，氨基，取代的氨基，硝基， 羟基或氰基，R 3，R 4和R 5各自为氢，卤素，低级烷基，低级烷氧基，硝基，氨基，取代的 氨基或羟基，R 6和R 7各自为氢，低级烷基，被卤素取代的低级烷基，芳烷基，酰基或被卤素取代的低级酰基， 8和R 9各自为氢或低级烷基，Y为低级亚烷基等，环A为苯基，嘧啶基，噻唑基，吡啶基，吡唑基或咪唑基，其药学上可接受的盐 和含有这些化合物的药剂。 本发明的化合物具有优异的TNF-α产生抑制作用和/或IL-10产生促进作用，并且由于其没有或显示出仅显着降低对中枢神经系统的作用的表达，所以该化合物是有用的 作为高度安全和优越的TNF-α产生抑制剂和/或IL-10产生促进剂，并且可用作预防或治疗由异常TNF-α产生引起的各种疾病的药剂，可用IL-10固化的疾病，例如 慢性炎性疾病，急性炎性疾病，感染引起的炎性疾病，自身免疫疾病，过敏性疾病和TNF-α介导的疾病。

公开(公告)号：US20070232614A1

公开(公告)日：2007-10-04

申请号：US11587759

申请日：2005-04-27

申请人： Tetsuko Fukuda ,  Akira Mogami ,  Masao Hisadome ,  Kunitomo Adachi ,  Hirotsugu Komatsu

发明人： Tetsuko Fukuda ,  Akira Mogami ,  Masao Hisadome ,  Kunitomo Adachi ,  Hirotsugu Komatsu

IPC分类号： A61K31/497 ,  A61P41/00 ,  C07D241/04

CPC分类号： A61K31/506 ,  C07D213/74 ,  C07D239/42 ,  C07D239/52 ,  C07D277/42

摘要： The present invention provides a therapeutic drug for non-viral hepatitis, which contains a piperazine compound represented by the following formula (I) or pharmaceutically acceptable salt thereof as an active ingredient.

摘要翻译： 本发明提供一种非病毒性肝炎的治疗药物，其含有下述式（I）表示的哌嗪化合物或其药学上可接受的盐作为有效成分。

公开(公告)号：US5045541A

公开(公告)日：1991-09-03

申请号：US391603

申请日：1989-07-02

申请人： Toru Nakao ,  Minoru Kawakami ,  Masao Hisadome ,  Tetsuya Tahara

发明人： Toru Nakao ,  Minoru Kawakami ,  Masao Hisadome ,  Tetsuya Tahara

IPC分类号： A61K31/50 ,  A61K31/502 ,  A61K31/535 ,  A61P7/00 ,  A61P31/04 ,  A61P35/00 ,  A61P37/00 ,  A61P37/04 ,  C07D237/36 ,  C07D401/04 ,  C07D405/12 ,  C07D491/04 ,  C07D491/052 ,  C07D495/04

CPC分类号： C07D401/04 ,  C07D237/36 ,  C07D491/04 ,  C07D495/04

摘要： Fused pyridazine compounds ##STR1## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are the same or different and respectively hydrogen, a halogen, hydroxy, nitro, amino, cyano, trifluoromethyl, and alkyl, an alkoxy or an alkanoylamino; one of R.sub.a and R.sub.b is a group of the formula--O--Y--NR.sup.5 R.sup.6wherein R.sup.5 and R.sup.6 are the same or different and respectively hydrogen, an alkyl, a phenylalkyl or a substituted phenylalkyl or a group forming a heterocycle together with the adjacent nitrogen atom and Y stands for a straight- or branched-chain alkylene which may have hydroxy group as a substituent on the chain, and the other is hydrogen, or both of R.sub.a and R.sub.b are the same or different and respectively a group of the formula--O--Y--NR.sup.5 R.sup.6wherein R.sup.5 and R.sup.6 are of the same meanings as defined above; W is .dbd.CH-- or .dbd.N; X is CH.sub.2, S, SO, SO.sub.2 or O; and the bond designated by a broken line in its part stands for a single bond or a double bond, or their pharmaceutically acceptable salts or hydrates and their pharmaceutical use.Said compounds possess stimulating effects on phagocytosis of leukocytes and macrophages, restorative effects on leukopenia, protective effects against infection, antitumor actions and the like and thus they are useable for the prophylaxis or therapy of human diseases accompanied by immunodeficiency.

公开(公告)号：US06455528B1

公开(公告)日：2002-09-24

申请号：US09529491

申请日：2000-04-14

申请人： Kunitomo Adachi ,  Yoshiyuki Aoki ,  Tokushi Hanano ,  Hiroshi Morimoto ,  Masao Hisadome

发明人： Kunitomo Adachi ,  Yoshiyuki Aoki ,  Tokushi Hanano ,  Hiroshi Morimoto ,  Masao Hisadome

IPC分类号： A61K31506

CPC分类号： C07D239/42 ,  C07C2601/02 ,  C07D213/74 ,  C07D233/88 ,  C07D239/47 ,  C07D239/48 ,  C07D239/50 ,  C07D239/52 ,  C07D239/545 ,  C07D277/42 ,  C07D295/135

摘要： The present invention relates to a piperazine compound of the formula wherein R1 and R2 are each hydrogen, halogen, lower alkyl, lower alkoxy, amino, substituted amino, nitro, hydroxy or cyano, R3, R4 and R5 are each hydrogen, halogen, lower alkyl, lower alkoxy, nitro, amino, substituted amino or hydroxy, R6 and R7 are each hydrogen, lower alkyl, lower alkyl substituted by halogen, aralkyl, acyl or lower acyl substituted by halogen, R8 and R9 are each hydrogen or lower alkyl, Y is lower alkylene and the like, and ring A is phenyl, pyrimidyl, thiazolyl, pyridyl, pyrazyl or imidazolyl, a pharmaceutically acceptable salt thereof and pharmaceutical agents containing these compounds. The compound of the present invention has superior TNF-&agr; production inhibitory effect and/or IL-10 production promoting effect, and, since it is free of or shows only strikingly reduced expression of an effect on the central nervous system, the compound is useful as a highly safe and superior TNF-&agr; production inhibitor an/or IL-10 production promoter and is useful as an agent for the prophylaxis or treatment of various diseases caused by abnormal TNF-&agr; production, diseases curable with IL-10, such as chronic inflammatory diseases, acute inflammatory diseases, inflammatory diseases due to infection, autoimmune diseases, allergic diseases, and TNF-&agr; mediated diseases.

摘要翻译： 本发明涉及式R 1和R 2的哌嗪化合物各自为氢，卤素，低级烷基，低级烷氧基，氨基，取代的氨基，硝基，羟基或氰基，R 3，R 4和R 5各自为氢，卤素，低级烷基 ，低级烷氧基，硝基，氨基，取代的氨基或羟基，R6和R7各自为氢，低级烷基，被卤素取代的低级烷基，芳烷基，酰基或被卤素取代的低级酰基，R8和R9分别为氢或低级烷基，Y 是低级亚烷基等，环A是苯基，嘧啶基，噻唑基，吡啶基，吡唑基或咪唑基，其药学上可接受的盐和含有这些化合物的药物。 本发明的化合物具有优异的TNF-α产生抑制作用和/或IL-10产生促进作用，并且由于其没有或显示出仅显着降低对中枢神经系统的作用的表达，所以该化合物是有用的 作为高度安全和优越的TNF-α产生抑制剂和/或IL-10产生促进剂，并且可用作预防或治疗由异常TNF-α产生引起的各种疾病的药剂，可用IL-10固化的疾病，例如 慢性炎性疾病，急性炎性疾病，感染引起的炎性疾病，自身免疫疾病，过敏性疾病和TNF-α介导的疾病。

公开(公告)号：US4965264A

公开(公告)日：1990-10-23

申请号：US320267

申请日：1988-11-18

申请人： Toru Nakao ,  Kenji Morita ,  Masao Hisadome ,  Shuzo Takehara

发明人： Toru Nakao ,  Kenji Morita ,  Masao Hisadome ,  Shuzo Takehara

IPC分类号： C07D495/04

CPC分类号： C07D495/04

摘要： A thienocinnoline compound of the general formula ##STR1## wherein R stands for hydrogen, a halogen or a lower alkyl, Ar stands for an aryl, a heteroaryl, or an aryl or a heteroaryl having as a substituent at least a halogen, a lower alkyl, a lower alkoxy, nitro, amino, hydroxy, trifluoromethyl and/or a lower alkanoylamino; and the bond between 5a-position and 6-position represents a single bond or a double bond, which is useful as an antianxiety agent, amnesia-treating drug, a brain function-activating drug, an antidementiac drug or a potentiating agent of biological protection.