公开(公告)号：US06589963B2

公开(公告)日：2003-07-08

申请号：US10148386

申请日：2002-05-31

Applicant: Hiroshi Matsui ,  Hideo Kobayashi ,  Satoru Azukizawa ,  Masayasu Kasai ,  Akihisa Yoshimi ,  Hiroaki Shirahase

Inventor： Hiroshi Matsui ,  Hideo Kobayashi ,  Satoru Azukizawa ,  Masayasu Kasai ,  Akihisa Yoshimi ,  Hiroaki Shirahase

IPC: C07D40112

CPC classification number: C07D217/22

Abstract: A heterocyclic compound of the formula [I] wherein R1 is hydrogen atom or lower alkyl, R2 is hydrogen atom, alkyl optionally having a substituent and the like, R3 is hydrogen atom, lower alkyl and the like, A is a single bond or >N—R5 wherein R5 is hydrogen atom or lower alkyl, B is lower alkylene, and Y is aryl optionally having a substituent and the like, and a pharmaceutically acceptable salt thereof show a hypoglycemic action, a blood hypolipidemic action, an insulin resistance-improving action and a PPAR activating action, and are useful as a hypoglycemic agent, a hypolipidemic agent, an insulin resistance improver, a therapeutic agent of diabetes, a therapeutic agent of diabetic complication, a glucose tolerance improver, an anti-atherosclerosis agent, an anti-obesity agent, an antiinflammatory agent, an agent for the prophylaxis or treatment of PPAR-mediated disease and an agent for the prophylaxis or treatment of syndrome X.

Abstract translation: 式[I]的杂环化合物，其中R 1为氢原子或低级烷基，R 2为氢原子，任选具有取代基的烷基等，R 3为氢原子，低级烷基等，A为单键或> N-R5其中R5为氢原子或低级烷基，B为低级亚烷基，Y为任选具有取代基的芳基等，其药学上可接受的盐呈低血糖作用，降血脂作用，胰岛素抵抗改善 作用和PPAR活化作用，并且可用作降血糖药，降血脂药，胰岛素抵抗改善剂，糖尿病治疗剂，糖尿病并发症治疗剂，葡萄糖耐量改善剂，抗动脉粥样硬化剂，抗 - - 促肥剂，抗炎剂，预防或治疗PPAR介导的疾病的药剂和用于预防或治疗综合症的药剂。

公开(公告)号：US06872732B2

公开(公告)日：2005-03-29

申请号：US10478863

申请日：2002-05-27

Applicant: Hiroshi Matsui ,  Hideo Kobayashi ,  Satoru Azukizawa ,  Masayasu Kasai ,  Akihisa Yoshimi ,  Hiroaki Shirahase

Inventor： Hiroshi Matsui ,  Hideo Kobayashi ,  Satoru Azukizawa ,  Masayasu Kasai ,  Akihisa Yoshimi ,  Hiroaki Shirahase

IPC: A61P3/04 ,  A61P3/06 ,  A61P3/10 ,  A61P9/10 ,  A61P9/12 ,  A61P29/00 ,  A61P43/00 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  A61K31/47 ,  C07D401/12

CPC classification number: C07D413/12 ,  C07D413/14 ,  C07D417/12

Abstract: The novel heterocyclic derivative of the present invention is a novel heterocyclic derivative having the formula (I′) wherein R1 is a hydrogen atom or C1-6 alkyl, R2 is —CO—C(R4)═C(R4)—R5 wherein R4 is a hydrogen atom or C1-4 alkyl, and R5 is C4-8 alkyl, C2-8 alkenyl, aryl or aromatic heterocycle, —CO—C≡C—R6 wherein R6 is C1-8 alkyl and the like, R3 is a hydrogen atom or C1-4 alkyl, X is an oxygen atom or a sulfur atom, R20 is optionally substituted phenyl, and n is an integer of 1 to 4, or a pharmaceutically acceptable salt thereof. The compound (I′) of the present invention is useful as a hypoglycemic agent, a hypolipidemic agent, an insulin resistance improver, a therapeutic agent of diabetes, a therapeutic agent of diabetic complications, a glucose tolerance improver, an anti-arteriosclerosis agent, an anti-obesity agent, an antiinflammatory agent, an agent for the prophylaxis or treatment of PPAR-mediated diseases and an agent for the prophylaxis or treatment of syndrome X.

Abstract translation: 本发明的新型杂环衍生物是具有式（I'）的新型杂环衍生物，其中R 1是氢原子或C 1-6烷基，R 2是-CO-C（R 4） = C（R 4）-R 5其中R 4是氢原子或C 1-4烷基，R 5是C 4-8烷基，C 2-8烯基，芳基或芳族杂环， CO-C = CR 6其中R 6为C 1-8烷基等，R 3为氢原子或C 1-4烷基，X为氧原子或硫原子，R 20为氢原子， 为任选取代的苯基，n为1〜4的整数，或其药学上可接受的盐。 本发明的化合物（I'）可用作降血糖剂，​​降血脂药，胰岛素抵抗改善剂，糖尿病治疗剂，糖尿病并发症治疗剂，葡萄糖耐量改善剂，抗动脉硬化剂， 抗肥胖剂，抗炎剂，预防或治疗PPAR介导的疾病的药剂和用于预防或治疗症状X的药剂。

公开(公告)号：US07557123B2

公开(公告)日：2009-07-07

申请号：US10478862

申请日：2002-05-27

Applicant: Hiroshi Matsui ,  Hideo Kobayashi ,  Satoru Azukizawa ,  Masayasu Kasai ,  Akihisa Yoshimi ,  Hiroaki Shirahase

Inventor： Hiroshi Matsui ,  Hideo Kobayashi ,  Satoru Azukizawa ,  Masayasu Kasai ,  Akihisa Yoshimi ,  Hiroaki Shirahase

IPC: A61K31/47 ,  C07D217/02 ,  C07D401/02

CPC classification number: C07D413/12 ,  C07D217/26 ,  C07D417/12

Abstract: The novel heterocyclic compound of the present invention is a novel heterocyclic compound having the formula (I) Y: R15—C(R14)═N—O— wherein R1 is H or C1-6 alkyl, R2 is H, —CO—C(R4)═C(R4)—R5 wherein R4 is H or C1-4 alkyl, and R5 is C4-8 alkyl, C2-8 alkenyl and the like, and the like, Y is the following group wherein X is O or S, R7 is the same as R4, R8 is R10—C(R9)═C(R9)— wherein R9 is the same as R4, R10 is C3-6 alkyl and the like, and the like, R14 is the same as R4, and R15 is aryl and the like, Y—(CH2)n-O— is bonded to the 6- or 7-position of the tetrahydroisoquinoline skeleton, and n is an integer of 1 to 4, or a pharmaceutically acceptable salt thereof. The compound (I) of the present invention is useful as a hypoglycemic agent, a hypolipidemic agent, an insulin resistance improver, a therapeutic agent of diabetes, a therapeutic agent of diabetic complications, a glucose tolerance improver, an anti-arteriosclerosis agent, an anti-obesity agent, an antiinflammatory agent, an agent for the prophylaxis or treatment of PPAR-mediated diseases or an agent for the prophylaxis or treatment of syndrome X.

Abstract translation: 本发明的新型杂环化合物是具有式（I）Y：R 15 -C（R 14）-NO-的新型杂环化合物，其中R 1为H或C 1-6烷基，R 2为H，-CO-C（R 4 ）-C（R4）-R5，其中R4是H或C1-4烷基，R5是C4-8烷基，C2-8链烯基等，Y是下列基团，其中X是O或S， R 7与R 4相同，R 8是R 10 -C（R 9）-C（R 9） - ，其中R 9与R 4相同，R 10是C 3-6烷基等，R 14与R 4相同， R 15为芳基等，Y-（CH 2）n O-键合于四氢异喹啉骨架的6-位或7-位，n为1〜4的整数，或其药学上可接受的盐。 本发明的化合物（I）可用作降血糖药，降血脂药，胰岛素抵抗改善剂，糖尿病治疗剂，糖尿病并发症治疗剂，葡萄糖耐量改善剂，抗动脉硬化药， 抗肥胖剂，抗炎剂，预防或治疗PPAR介导的疾病的药物或用于预防或治疗综合征X的药剂。