公开(公告)号：US4900752A

公开(公告)日：1990-02-13

申请号：US304641

申请日：1989-02-01

申请人： Kiyotomo Seto ,  Hiroo Matsumoto ,  Yoshimasa Kamikawaji ,  Kazuhiko Ohrai ,  Kyoko Nakayama ,  Ryozo Sakoda ,  Yukinori Masuda

发明人： Kiyotomo Seto ,  Hiroo Matsumoto ,  Yoshimasa Kamikawaji ,  Kazuhiko Ohrai ,  Kyoko Nakayama ,  Ryozo Sakoda ,  Yukinori Masuda

IPC分类号： C07D491/052 ,  A61K31/352 ,  A61K31/41 ,  A61K31/4245 ,  A61P9/02 ,  A61P9/12 ,  A61P11/06 ,  C07D20060101 ,  C07D498/04

CPC分类号： C07D498/04

摘要： A compounds of the formula (I): ##STR1## wherein A represents OH or OC(O)CH.sub.3-n X.sub.n, B represents hydrogen atom, or A and B together represent a bond; R.sup.1 represents hydrogen atom, R.sup.2 represents hydrogen atom, C(Z)CH.sub.3-n X.sub.n or C(Z)NHCH.sub.3-n X.sub.n or R.sup.1 and R.sup.2 together represents (CH.sub.2).sub.m, (CH.sub.2).sub.m-1 C(Z), N(R.sup.3)(CH.sub.2).sub.2 C(Z), (CH.sub.2).sub.m-2 NHC(Z) or (CH.sub.2).sub.m-2 OC(Z) in which X represents fluorine atom, chlorine atom, bromine atom, a methyl group or a methoxy group and n represents 0 or an integer of 1 to 3, Z represents oxygem atom or sulfur atom, m represents an integer of 4 or 5 and R.sup.3 represents hydrogen atom or a methyl group, and pharmacological acceptable salts of the compounds which can form salts, processes therefor and pharmaceutical use of the compounds.

摘要翻译： 本发明包括式（I）的化合物：其中A表示OH或OC（O）CH 3 -n Xn，B表示氢原子，或A和B一起表示键; R 1表示氢原子，R 2表示氢原子，C（Z）CH 3 -n Xn或C（Z）NHCH 3 -n X n或R 1和R 2一起表示（CH 2）m， ）m-1C（Z），N（R 3）（CH 2）2 C（Z），（CH 2）m -NHHC（Z）或（CH 2）m -OOC（Z） 原子，溴原子，甲基或甲氧基，n表示0或1〜3的整数，Z表示氧原子或硫原子，m表示4或5的整数，R 3表示氢原子或 甲基和可以形成盐的化合物的药理学可接受的盐，其制备方法，化合物的药物用途和包含该化合物的组合物。

公开(公告)号：US5272271A

公开(公告)日：1993-12-21

申请号：US726897

申请日：1991-07-08

申请人： Kiyotomo Seto ,  Hiroo Matsumoto ,  Yoshimasa Kamikawaji ,  Kazuhiko Ohrai ,  Keisuke Ohdoi ,  Ryozo Sakoda ,  Yukinori Masuda

发明人： Kiyotomo Seto ,  Hiroo Matsumoto ,  Yoshimasa Kamikawaji ,  Kazuhiko Ohrai ,  Keisuke Ohdoi ,  Ryozo Sakoda ,  Yukinori Masuda

IPC分类号： A61K31/41 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  A61P11/00 ,  A61P11/08 ,  A61P13/02 ,  A61P15/00 ,  C07D498/04 ,  C07F7/18 ,  C07D403/04 ,  C07D271/12

CPC分类号： C07D498/04 ,  C07F7/1856

摘要： A compound of the formula (I): ##STR1## wherein X.sup.1 and X.sup.2 do not exist or represent oxygen atom; A represents OH or acyloxy group having 1 to 4 carbon atoms; B represents hydrogen atom; A and B together represent a bond; R.sup.1 and R.sup.2 represent hydrogen atom or alkyl group having 1 to 4 carbon atoms, or R.sup.1 and R.sup.2 together represent 1,2-ethylene, 1,3-propylene, 1,4-butylene or 1,5-pentylene, and these alkylene groups may be substituted by alkyl group having 1 to 4 carbon atoms; R.sup.3 represents amido group of the formula: ##STR2## wherein n, R.sup.4, R.sup.5, R.sup.6, R.sup.7. R.sup.8. R.sup.9, R.sup.10 and R.sup.11 represent specific groups, and the pharmacological acceptable salts of the compounds which can form salts have strong activity for lowering blood pressure, and process therefor and pharmaceutical use of the compounds.

公开(公告)号：US5919806A

公开(公告)日：1999-07-06

申请号：US530252

申请日：1995-09-29

申请人： Kiyotomo Seto ,  Hiroo Matsumoto ,  Yoshimasa Kamikawaji ,  Kazuhiko Ohrai ,  Toru Yamashita ,  Yukinori Masuda

发明人： Kiyotomo Seto ,  Hiroo Matsumoto ,  Yoshimasa Kamikawaji ,  Kazuhiko Ohrai ,  Toru Yamashita ,  Yukinori Masuda

IPC分类号： A61K31/41 ,  A61K31/4178 ,  A61K31/4192 ,  A61K31/422 ,  A61K31/4245 ,  A61K31/433 ,  A61K31/454 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/506 ,  A61K31/5355 ,  A61K31/5377 ,  A61P9/04 ,  C07D491/04 ,  C07D491/052 ,  C07D498/04 ,  C07D513/04 ,  A61K31/37

CPC分类号： C07D491/04 ,  A61K31/4178 ,  A61K31/4192 ,  A61K31/422 ,  A61K31/4245 ,  A61K31/433 ,  A61K31/454 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/506 ,  A61K31/5355 ,  A61K31/5377 ,  C07D513/04

摘要： Disclosed are cardiotonic medicines containing, as the active ingredient, at least one of compounds of formula (I) and their pharmacologically acceptable salts when they form salts. ##STR1## wherein X.sup.1 and X.sup.2 do not exist or represents an oxygen atom; A represents OH or a C.sub.1 -C.sub.4 acyloxy group; B represents a hydrogen atom or may form a chemical bond along with A; X is an oxygen atom, nitrogen, sulfur, etc.; R.sup.1 and R.sup.2 each represents a hydrogen atom, a C.sub.1 -C.sub.4 alkyl group, etc.; R.sup.3 and R.sup.4 each represents a hydrogen atom, a C.sub.1 -C.sub.4 alkyl group, etc., or they may together form a 1,4-butylene or 1,5-pentylene group. The compounds have a strong activity of reinforcing the contraction of cardiac muscles and a strong activity of reducing the rate of heart beats. As they are not toxic, they are useful as cardiotonic medicines.

摘要翻译： PCT No.PCT / JP94 / 00544 Sec。 371 1995年9月29日第 102（e）1995年9月29日PCT PCT 1994年4月1日PCT公布。 第WO94 / 22442号公报 日期1994年10月13日被公开是强心药，当它们形成盐时，含有作为活性成分的至少一种式（I）化合物及其药理学上可接受的盐。 其中X1和X2不存在或表示氧原子; A表示OH或C1-C4酰氧基; B代表氢原子或与A形成化学键; X是氧原子，氮，硫等; R1和R2各自表示氢原子，C1-C4烷基等; R3和R4各自表示氢原子，C1-C4烷基等，或者它们可以一起形成1,4-亚丁基或1,5-亚戊基。 这些化合物具有强化心肌收缩的强烈活性和降低心脏搏动速率的强烈活性。 因为它们没有毒性，它们可用作强心药物。

公开(公告)号：US5846991A

公开(公告)日：1998-12-08

申请号：US998671

申请日：1997-12-29

申请人： Keizo Tanikawa ,  Yoshimasa Kamikawaji ,  Keisuke Odoi ,  Tsutomu Higashiyama ,  Masayuki Sato ,  Yukinori Masuda

发明人： Keizo Tanikawa ,  Yoshimasa Kamikawaji ,  Keisuke Odoi ,  Tsutomu Higashiyama ,  Masayuki Sato ,  Yukinori Masuda

IPC分类号： C07D231/38 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07F9/6558 ,  A61K31/415 ,  A61K31/44

CPC分类号： C07D231/38 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07F9/65583

摘要： Pyrazole compounds of formula �1! and their tautomers and salts: ##STR1## (wherein R.sup.1 is an alkyl group, etc.; R.sup.2 is a carboxyl group, etc.; R.sup.3 is a halogen atom, an alkyl group, a phenyl group, etc.; R.sup.4, R.sup.5 and R.sup.6 each are a hydrogen atom, a halogen atom, etc.; R.sup.7 is a carboxyl group, a 5-tetrazolyl group, etc.; X is a nitrogen atom, etc.; Y and Z each are CH, a nitrogen atom, etc.; A and E each are a methylene group, etc.; D is a phenyl group, etc.; G is a covalent bond, etc.). The compounds of the invention have an antagonistic effect against angiotensin II and are useful for prevention and remedy of hypertension, congestive cardiac insufficiency, chronic renal insufficiency, aldosteronism, hyper-intraocular pressure, etc.

公开(公告)号：US5721264A

公开(公告)日：1998-02-24

申请号：US525555

申请日：1995-09-29

申请人： Keizo Tanikawa ,  Yoshimasa Kamikawaji ,  Keisuke Odoi ,  Tsutomu Higashiyama ,  Masayuki Sato ,  Yukinori Masuda

发明人： Keizo Tanikawa ,  Yoshimasa Kamikawaji ,  Keisuke Odoi ,  Tsutomu Higashiyama ,  Masayuki Sato ,  Yukinori Masuda

IPC分类号： C07D231/38 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07F9/6558 ,  A61K31/415

CPC分类号： C07D231/38 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07F9/65583

摘要： Pyrazole compounds of formula �1! and their tautomers and salts: ##STR1## (wherein R.sup.1 is an alkyl group, etc.; R.sup.2 is a carboxyl group, etc.; R.sup.3 is a halogen atom, an alkyl group, a phenyl group, etc.; R.sup.4, R.sup.5 and R.sup.6 each are a hydrogen atom, a halogen atom, etc.; R.sup.7 is a carboxyl group, a 5-tetrazolyl group, etc.; X is a nitrogen atom, etc.; Y and Z each are CH, a nitrogen atom, etc.; A and E each are a methylene group, etc.; D is a phenyl group, etc.; G is a covalent bond, etc.). The compounds of the invention have an antagonistic effect against angiotensin II and are useful for prevention and remedy of hypertension, congestive cardiac insufficiency, chronic renal insufficiency, aldosteronism, hyper-intraocular pressure, etc.

摘要翻译： PCT No.PCT / JP94 / 00587第 371 1995年9月29日第 102（e）1995年9月29日PCT PCT 1994年4月7日PCT公布。 公开号WO94 / 22838 日期：1994年10月13日式[1]吡唑化合物及其互变异构体和盐：其中R1是烷基等; R2是羧基等; R3是卤素原子， 烷基，苯基等; R4，R5和R6各自为氢原子，卤素原子等; R7为羧基，5-四唑基等; X为氮原子， Y和Z各自为CH，氮原子等; A和E各自为亚甲基等; D为苯基等; G为共价键等）。 本发明化合物对血管紧张素II具有拮抗作用，可用于预防和治疗高血压，充血性心功能不全，慢性肾功能不全，醛固酮增多症，超眼压等。

公开(公告)号：US5817828A

公开(公告)日：1998-10-06

申请号：US999493

申请日：1997-12-29

申请人： Keizo Tanikawa ,  Yoshimasa Kamikawaji ,  Keisuke Odoi ,  Tsutomu Higashiyama ,  Masayuki Sato ,  Yukinori Masuda

发明人： Keizo Tanikawa ,  Yoshimasa Kamikawaji ,  Keisuke Odoi ,  Tsutomu Higashiyama ,  Masayuki Sato ,  Yukinori Masuda

IPC分类号： C07D231/38 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07F9/6558 ,  A61K31/415

CPC分类号： C07D231/38 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07F9/65583

摘要： Pyrazole compounds of formula �1! and their tautomers and salts: ##STR1## (wherein R.sup.1 is an alkyl group, etc.; R.sup.2 is a carboxyl group, etc.; R.sup.3 is a halogen atom, an alkyl group, a phenyl group, etc.; R.sup.4, R.sup.5 and R.sup.6 each are a hydrogen atom, a halogen atom, etc.; R.sup.7 is a carboxyl group, a 5-tetrazolyl group, etc.; X is a nitrogen atom, etc.; Y and Z each are CH, a nitrogen atom, etc.; A and E each are a methylene group, etc.; D is a phenyl group, etc.; G is a covalent bond, etc.). The compounds of the invention have an antagonistic effect against angiotensin II and are useful for prevention and remedy of hypertension, congestive cardiac insufficiency, chronic renal insufficiency, aldosteronism, hyper-intraocular pressure, etc.

公开(公告)号：US5840909A

公开(公告)日：1998-11-24

申请号：US998669

申请日：1997-12-29

申请人： Keizo Tanikawa ,  Yoshimasa Kamikawaji ,  Keisuke Odoi ,  Tsutomu Higashiyama ,  Masayuki Sato ,  Yukinori Masuda

发明人： Keizo Tanikawa ,  Yoshimasa Kamikawaji ,  Keisuke Odoi ,  Tsutomu Higashiyama ,  Masayuki Sato ,  Yukinori Masuda

IPC分类号： C07D231/38 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07F9/6558 ,  A61K31/415

CPC分类号： C07D231/38 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07F9/65583

摘要： Pyrazole compounds of formula �1! and their tautomers and salts: ##STR1## (wherein R.sup.1 is an alkyl group, etc.; R.sup.2 is a carboxyl group, etc.; R.sup.3 is a halogen atom, an alkyl group, a phenyl group, etc.; R.sup.4, R.sup.5 and R.sup.6 each are a hydrogen atom, a halogen atom, etc.; R.sup.7 is a carboxyl group, a 5-tetrazolyl group, etc.; X is a nitrogen atom, etc.; Y and Z each are CH, a nitrogen atom, etc.; A and E each are a methylene group, etc.; D is a phenyl group, etc.; G is a covalent bond, etc.). The compounds of the invention have an antagonistic effect against angiotensin II and are useful for prevention and remedy of hypertension, congestive cardiac insufficiency, chronic renal insufficiency, aldosteronism, hyper-intraocular pressure, etc.

摘要翻译： 式[1]的吡唑化合物及其互变异构体和盐：其中R1是烷基等; R2是羧基等; R3是卤素原子，烷基， 苯基等; R4，R5和R6分别是氢原子，卤素原子等; R7是羧基，5-四唑基等; X是氮原子等; Y和 Z各自为CH，氮原子等; A和E各自为亚甲基等; D为苯基等; G为共价键等）。 本发明化合物对血管紧张素II具有拮抗作用，可用于预防和治疗高血压，充血性心功能不全，慢性肾功能不全，醛固酮增多症，超眼压等。

公开(公告)号：US20100105636A1

公开(公告)日：2010-04-29

申请号：US12651849

申请日：2010-01-04

申请人： Taiji FURUKAWA ,  Osamu Yamada ,  Hiroo Matsumoto ,  Toru Yamashita ,  Yukinori Masuda

发明人： Taiji FURUKAWA ,  Osamu Yamada ,  Hiroo Matsumoto ,  Toru Yamashita ,  Yukinori Masuda

IPC分类号： A61K31/675 ,  A61K31/551 ,  A61K31/4545

CPC分类号： A61K31/675

摘要： There is provided a T-type calcium channel blocker that is a compound of formula (1), a pharmaceutically acceptable salt thereof or a solvate thereof: wherein Ar1 is phenyl group, pyridyl group, furyl group or 2,1,3-benzoxadiazol-4-yl group; nitrogen-containing hetero ring moiety is 1,4-dihydropyridine ring or pyridine ring; Z is a group of formula (2) or CO2R2; Ra and Rb are independently of each other C1-6alkyl group, ANR8R9, CH2OANR8R9, or the like; in case where the nitrogen-containing hetero ring moiety is 1,4-dihydropyridine ring, R1 is C1-6alkyl group, ANR8R9, AN(CH2CH2)2NR8, AN(CH2CH2)2O, AOR8 or benzyl group; R3 is hydrogen atom, C1-20alkyl group, ANR8R9, a group of formula or the like.

摘要翻译： 提供了式（1）化合物，其药学上可接受的盐或其溶剂化物的T型钙通道阻断剂：其中Ar1是苯基，吡啶基，呋喃基或2,1,3-苯并恶二唑-2-基， 4-基; 含氮杂环部分为1,4-二氢吡啶环或吡啶环; Z是式（2）或CO 2 R 2的基团; R a和R b彼此独立地为C 1-6烷基，ANR 8 R 9，CH 2 OANR 8 R 9等; 在含氮杂环部分为1,4-二氢吡啶环的情况下，R 1为C 1-6烷基，ANR 8 R 9，AN（CH 2 CH 2）2 NR 8，AN（CH 2 CH 2）2 O，AOR 8或苄基; R3是氢原子，C1-20烷基，ANR8R9，式等基团。

公开(公告)号：US20070129335A1

公开(公告)日：2007-06-07

申请号：US10580532

申请日：2004-11-25

申请人： Taiji Furukawa ,  Osamu Yamada ,  Hiroo Matsumoto ,  Toru Yamashita ,  Yukinori Masuda

发明人： Taiji Furukawa ,  Osamu Yamada ,  Hiroo Matsumoto ,  Toru Yamashita ,  Yukinori Masuda

IPC分类号： A61K31/675 ,  A61K31/551 ,  A61K31/496 ,  A61K31/455 ,  A61K31/4439 ,  C07D403/02

CPC分类号： A61K31/675

摘要： There is provided a T-type calcium channel blocker that is a compound of formula (1), a pharmaceutically acceptable salt thereof or a solvate thereof. wherein Ar1 is phenyl group, pyridyl group, furyl group or 2,1,3-benzoxadiazol-4-yl group; nitrogen-containing hetero ring moiety is 1,4-dihydropyridine ring or pyridine ring; Z is a group of formula (2) or CO2R2; Ra and Rb are independently of each other C1-6alkyl group, ANR8R9, CH2OANR8R9, or the like; in case where the nitrogen-containing hetero ring moiety is 1,4-dihydropyridine ring, R1 is C1-6alkyl group, ANR8R9, AN(CH2CH2)2NR8, AN(CH2CH2)2O, AOR8 or benzyl group; R3 is hydrogen atom, C1-20alkyl group, ANR8R9, a group of formula or the like.

摘要翻译： 提供了一种T型钙通道阻断剂，其是式（1）的化合物，其药学上可接受的盐或其溶剂化物。 其中Ar 1是苯基，吡啶基，呋喃基或2,1,3-苯并二唑-4-基; 含氮杂环部分为1,4-二氢吡啶环或吡啶环; Z是式（2）或CO 2 R 2的基团; R a a和R b彼此独立地是C 1-6烷基，ANR 8 R 12 > 9 ，CH 2，OANR 8，9，9等等; 在含氮杂环部分为1,4-二氢吡啶环的情况下，R 1为C 1-6烷基，ANR 8 O AN（CH 2 CH 2 CH 2）2 NR 8，其中R 1，R 2， AN（CH 2 CH 2）2 O，AOR 8或苄基; R 3是氢原子，C 1-20烷基，ANR 8 R 9，式 或类似物。

公开(公告)号：US07563782B2

公开(公告)日：2009-07-21

申请号：US10549510

申请日：2004-03-29

申请人： Yukinori Masuda ,  Taiji Furukawa

发明人： Yukinori Masuda ,  Taiji Furukawa

IPC分类号： A61K31/675 ,  C07F9/02

CPC分类号： C07F9/657181 ,  A61K31/675 ,  C07F9/59 ,  C07F9/65583

摘要： There is provided a T-type calcium channel blocker that is optically active 1,4-dihydropyridine compound, a pharmaceutically acceptable salt thereof or a solvate thereof, of formula (1) wherein R1 and R2 are independently of each other C1-6 alkyl group or R1 and R2 together form —CR5R6—CR7R8, —CR5R6—CR7R8—CR9R10— or —CR5R6—CR7R8—CR9R10—CR11R12—, etc., X1 and X2 are independently of each other O or NR13, Ar is optionally substituted phenyl group, etc., Ra and Rb are independently of each other C1-6alkyl group, —L2—NR16R17, CH2O—L2—NR16R17CN, —L2—N(CH2CH2)2NR16 or NR16R17, etc., Y is C1-20 alkyl group, —L3—NR18R19 and * is absolute configuration of R.

摘要翻译： 提供了式（1）的光学活性1,4-二氢吡啶化合物，其药学上可接受的盐或其溶剂合物的T型钙通道阻断剂，其中R 1和R 2彼此独立地为C 1-6烷基 或者R1和R2一起形成-CR5R6-CR7R8，-CR5R6-CR7R8-CR9R10-或-CR5R6-CR7R8-CR9R10-CR11R12-等，X1和X2彼此独立地为O或NR13，Ar为任选取代的苯基 等等，R a和R b彼此独立地为C 1-6烷基，-L 2 -NR 16 R 17，CH 2 O-L 2 -NR 16 R 17 CN，-L 2 -N（CH 2 CH 2）2 NR 16或NR 16 R 17等，Y为C 1-20烷基， -L3-NR18R19和*是R的绝对构型。