公开(公告)号：US06576785B1

公开(公告)日：2003-06-10

申请号：US09570728

申请日：2000-05-12

申请人： Kousuke Tani ,  Shuichi Ohuchida

发明人： Kousuke Tani ,  Shuichi Ohuchida

IPC分类号： C07C40500

CPC分类号： C07C405/00

摘要： A &ohgr;-cycloalkyl-prostaglandin E2 derivatives of the formula (I) wherein R is carboxy or hydroxymethyl; R1 is oxo, methylene or halogen atom; R2 is H, OH or C1-4 alkoxy; R3 is H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted by 1-3 of substituent selected from halogen atom, C1-4 alkoxy, C3-7 cycloalkyl, phenyl, or phenyl substituted by 1-3 of substituent selected from halogen atom, C1-4 alkyl, C1-4 alkoxy, nitro, trifluoromethyl; n is 0-4; and non-toxic salt thereof, prodrug thereof and cyclodextrin clathrate thereof can strongly bind on EP2 subtype receptor. Therefore, they are useful for prevention and/or treatment of immune disease (autoimmune disease, organ transplantation, etc.), asthma, abnormal bone formation, neuron cell death, liver damage, abortion, premature birth or retina neuropathy of glaucoma etc.

摘要翻译： 式（I）的ω-环烷基 - 前列腺素E2衍生物，其中R是羧基或羟甲基; R1是氧代，亚甲基或卤素原子; R2是H，OH或C1-4烷氧基; R 3为H，C 1-8烷基，C 2-8烯基，C 2-8炔基，C 1-8烷基，C 2-8烯基或被1-3个选自卤素原子，C 1-4烷氧基， C 3-7环烷基，苯基或被1-3个选自卤素原子，C 1-4烷基，C 1-4烷氧基，硝基，三氟甲基的取代基取代的苯基; n为0-4;其无毒盐，其前药和环糊精包合物可以强烈结合EP2亚型受体。 因此，它们可用于预防和/或治疗青光眼等免疫疾病（自身免疫性疾病，器官移植等），哮喘，异常骨形成，神经细胞死亡，肝损伤，流产，早产或视网膜神经病变等。

公开(公告)号：US06110969A

公开(公告)日：2000-08-29

申请号：US18565

申请日：1998-02-04

申请人： Kousuke Tani ,  Shuichi Ohuchida

发明人： Kousuke Tani ,  Shuichi Ohuchida

IPC分类号： C07C405/00 ,  A61K31/5575

CPC分类号： C07C405/00

摘要： A .omega.-cycloalkyl-prostaglandin E.sub.2 derivatives of the formula (I) ##STR1## wherein R is carboxy or hydroxymethyl; R.sup.1 is oxo, methylene or halogen atom; R.sup.2 is H, OH or C1-4 alkoxy; R.sup.3 is H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted by 1-3 of substituent selected from halogen atom, C1-4 alkoxy, C3-7 cycloalkyl, phenyl, or phenyl substituted by 1-3 of substituent selected from halogen atom, C1-4 alkyl, C1-4 alkoxy, nitro, trifluoromethyl; n is 0-4; and non-toxic salt thereof, prodrug thereof and cyclodextrin clathrate thereof can strongly bind on EP.sub.2 subtype receptor. Therefore, they are useful for prevention and/or treatment of immune disease (autoimmune disease, organ transplantation, etc.), asthma, abnormal bone formation, neuron cell death, liver damage, abortion, premature birth or retina neuropathy of glaucoma etc.

摘要翻译： 式（I）的ω-环烷基 - 前列腺素E2衍生物，其中R为羧基或羟甲基; R1是氧代，亚甲基或卤素原子; R2是H，OH或C1-4烷氧基; R 3为H，C 1-8烷基，C 2-8烯基，C 2-8炔基，C 1-8烷基，C 2-8烯基或被1-3个选自卤素原子，C 1-4烷氧基， C 3-7环烷基，苯基或被1-3个选自卤素原子，C 1-4烷基，C 1-4烷氧基，硝基，三氟甲基的取代基取代的苯基; n为0-4; 其无毒盐，其前药和环糊精包合物可以强烈结合EP2亚型受体。 因此，它们可用于预防和/或治疗青光眼等免疫疾病（自身免疫性疾病，器官移植等），哮喘，异常骨形成，神经细胞死亡，肝损伤，流产，早产或视网膜神经病变等。

公开(公告)号：US06235780B1

公开(公告)日：2001-05-22

申请号：US09356674

申请日：1999-07-19

申请人： Shuichi Ohuchida ,  Kousuke Tani

发明人： Shuichi Ohuchida ,  Kousuke Tani

IPC分类号： A61K31215

CPC分类号： A61K31/557

摘要： (wherein R1 is OH etc.; X is Cl, F; R2 is H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl which may be substituted; n is 0-4.), non-toxic salts thereof or cyclodextrin clathrates thereof can strongly bind on EP2 subtype receptor. Therefore, they are useful for the prevention and/or treatment of immunological diseases (autoimmune diseases, post-transplantation graft rejection etc.), asthma, abnormal bone formation, neuronal cell death, hepatopathy, abortion, premature birth or retina neuropathy (e.g. glaucoma) etc.

摘要翻译： （其中R1为OH等; X为Cl，F; R2为H，C1-8烷基，C2-8烯基，可被取代的C2-8炔基; n为0-4），无毒性盐 或其环糊精包合物可以强烈结合EP2亚型受体。 因此，它们可用于预防和/或治疗免疫疾病（自身免疫疾病，移植后移植排斥反应等），哮喘，异常骨形成，神经元细胞死亡，肝病，流产，早产或视网膜神经病变（例如青光眼 ）等

公开(公告)号：US06262293B1

公开(公告)日：2001-07-17

申请号：US09582348

申请日：2000-06-23

申请人： Kousuke Tani ,  Shuichi Ohuchida

发明人： Kousuke Tani ,  Shuichi Ohuchida

IPC分类号： C07C10500

CPC分类号： C07C405/00

摘要： &ohgr;-Cycloalkyl-prostaglandin E2 derivatives of formula (I) (wherein all symbols are as defined in the description); and non-toxic salts thereof, prodrugs thereof and cyclodextrin clathrates thereof. Compounds of formula (I) strongly bind on the EP2 subtype receptor. Therefore, they are useful for prevention and/or treatment of immunological diseases (autoimmune diseases, organ transplantation etc.), asthma, abnornmal bone formation, neuronal cell death, liver damage, abortion, premature birth or retina neuropathy of glaucoma etc.

摘要翻译： 式（I）的ω-环烷基 - 前列腺素E2衍生物（其中所有符号如说明书中所定义）;及其无毒盐，其前药和环糊精包合物。式（I）化合物强烈结合EP2亚型 受体。 因此，它们可用于预防和/或治疗青光眼等免疫疾病（自身免疫性疾病，器官移植等），哮喘，异常骨形成，神经元细胞死亡，肝损伤，流产，早产或视网膜神经病变等。

公开(公告)号：US06790866B2

公开(公告)日：2004-09-14

申请号：US10207078

申请日：2002-07-30

申请人： Shuichi Ohuchida ,  Yuuki Nagao

发明人： Shuichi Ohuchida ,  Yuuki Nagao

IPC分类号： A61K3144

CPC分类号： C07D213/80 ,  C07C233/18 ,  C07C233/75 ,  C07C311/08 ,  C07C311/10 ,  C07C311/11 ,  C07C311/13 ,  C07C311/14 ,  C07C311/17 ,  C07C311/21 ,  C07C311/29 ,  C07C313/06 ,  C07C323/67 ,  C07C2601/02 ,  C07C2601/08 ,  C07C2601/14 ,  C07D307/64 ,  C07D307/68 ,  C07D333/34 ,  C07D333/38

摘要： The sulfonamide or carboamide derivatives of the formula (I) and a pharmaceutical composition which comprise them as an active ingredient: (wherein A ring, B ring is carbocyclic ring, heterocyclic ring; Z1 is —COR1, —CH═CH—COR1 etc.; Z2 is H, alkyl etc.; Z3 is single bond, alkylene; Z4 is SO2, CO; Z5 is alkyl, phenyl, heterocyclic ring etc.; R2 is CONR8, O, S, NZ6, Z7-alkylene, alkylene etc.; R3 is H, alkyl, halogen, CF3 etc.; R4 is H, (substituted) alkyl etc.; n, t is 1-4). The compounds of the formula (I) can bind to receptors of PGE2 and show antagonistic activity against the action thereof or agonistic activity. Therefore, they are considered to be useful as medicine for inhibition of uterine contraction, analgesics, antidiarrheals, sleep inducers, medicine for increase of vesical capacity or medicine for uterine contraction, cathartic, suppression of gastric acid secretion, antihypertensive or diuretic agents.

摘要翻译： 式（I）的磺酰胺或氨基酰胺衍生物和包含它们作为活性成分的药物组合物：其中A环，B环为碳环，杂环; Z 1为-COR 1，-CH = CH-COR 1等; Z 2是H，烷基等; Z 3是单键，亚烷基; Z 4是SO 2，CO; Z 5是烷基，苯基，杂环 环等; R 2是CONR 8，O，S，NZ 6，Z 7 - 亚烷基，亚烷基等; R 3是H，烷基，卤素，CF 3等; R 式（I）化合物可以与PGE2的受体结合，对其作用或激动作用具有拮抗作用。 因此，它们被认为可用作抑制子宫收缩，止痛剂，止泻药，睡眠诱导剂，用于增加膀胱能力的药物或用于子宫收缩的药物，通气，抑制胃酸分泌，抗高血压药或利尿剂的药物。

公开(公告)号：US06235777B1

公开(公告)日：2001-05-22

申请号：US09078577

申请日：1998-05-14

申请人： Shuichi Ohuchida ,  Yuuki Nagao ,  Takayuki Maruyama

发明人： Shuichi Ohuchida ,  Yuuki Nagao ,  Takayuki Maruyama

IPC分类号： A61K3121

CPC分类号： C07C311/19 ,  C07C2601/14 ,  C07C2601/16 ,  C07C2601/18 ,  C07C2602/42 ,  C07C2602/44

摘要： A benzenesulfonamide compound of the formula (I) (R1 is hydroxy, C1˜4 alkoxy, NR6R7 (each R6 and R7 is, independently, H or C1˜4 alkyl.); R2 is H, C1˜4 alkyl; R3, R4 are C1˜4 alkyl, halogen trifluoromethyl; R5 is H, C1˜4 alkyl, halogen, trifluoromethyl; Y is cis-vinylene, trans-vinylene; and the symbol (i) is single bond, double bond.), non-toxic salt thereof or cyclodextrin clathrate thereof and an antagonist of EP1 receptor which is a prostaglandin E2 receptor subtype comprising it as an active ingredient. The present invention compounds of the of the formula (I) can bind strongly to EP1 receptor which is a prostaglandin E2 receptor subtype and scarcely bind to the other receptor subtypes. Therefore, they are considered to be useful as antipyretic agents, as analgesics or as treating agent for pollakiuria having little side effect.

摘要翻译： 式（I）的苯磺酰胺化合物（R 1是羟基，C 1-4烷氧基，NR 6 R 7（各R 6和R 7独立地是H或C 1-4烷基）; R 2是H，C 1-4烷基; R 3，R 4 是C1〜4烷基，卤素三氟甲基; R5是H，C1〜4烷基，卤素，三氟甲基; Y是顺式亚乙烯基，反式亚乙烯基;符号（i）是单键，双键），无毒 其盐或环糊精包合物和作为前列腺素E2受体亚型的EP1受体的拮抗剂，其包含其作为活性成分。本发明式（I）的化合物可以强烈地与作为前列腺素E2受体的EP1受体结合 亚型，几乎不结合其他受体亚型。 因此，它们被认为可用作解热剂，作为止痛剂或作为尿酸治疗剂具有很小的副作用。

公开(公告)号：US07176240B2

公开(公告)日：2007-02-13

申请号：US10194247

申请日：2002-07-15

申请人： Shuichi Ohuchida ,  Kazuo Kishimoto ,  Narito Tateishi ,  Hiroyuki Ohno

发明人： Shuichi Ohuchida ,  Kazuo Kishimoto ,  Narito Tateishi ,  Hiroyuki Ohno

IPC分类号： A01N37/00 ,  A61K31/20 ,  A61K31/19 ,  A61K31/231 ,  C07C63/04

CPC分类号： C07D213/75 ,  A61K31/19 ,  C07C53/21 ,  C07C69/612 ,  C07C69/63 ,  C07C69/708 ,  C07C233/05 ,  C07C233/11 ,  C07C233/25 ,  C07C233/47 ,  C07C233/54 ,  C07C323/52 ,  C07D295/185

摘要： The compound of the formula (I): wherein R1 is alkyl substituted by fluorine(s); R2 is hydroxy, alkoxy, alkoxy substituted by phenyl, NR3R4, in which R3, R4 is (i) hydrogen, (ii) alkyl, (iii) phenyl, (iv) phenyl substituted by alkoxy or carboxyl, (v) heterocyclic ring containing nitrogen atom, (vi) alkyl substituted by phenyl, phenyl substituted by alkoxy or carboxyl, heterocyclic ring containing nitrogen atom, (vii) the nitrogen bonded to R3 and R4, taken together a saturated heterocyclic ring or amino acid residues; and non-toxic salts thereof and acid addition salts thereof. The compounds of the present invention of the formula (I) and the compounds of the formula (X): wherein n is 0 or 1, R11 is hydrogen and chlorine, R5 is R7—CH2— or R8, or R5 and R11, taken together is alkylidene; R6 is hydroxy, alkoxy, alkoxy substituted by phenyl, NR9R10, in which R9, R10 is (i) hydrogen, (ii) alkyl, (iii) phenyl, (iv) phenyl substituted by alkoxy or carboxyl, (v) heterocyclic ring containing nitrogen atom, (vi) alkyl substituted by phenyl, phenyl-substituted by alkoxy or carboxyl, heterocyclic ring containing nitrogen atom, (vii) the nitrogen bonded to R9 and R10, taken together a saturated heterocyclic ring or amino acid residues, R7 is (i) F—(CH2)m— or F3C—CH2—, (ii) alkyl substituted by chlorine, (iii) alkyl substituted by alkoxy, cycloalkyl, phenyl, phenoxy; R8 is alkyl, alkenyl, alkoxy, alkylthio, cycloalkyl, phenyl, phenoxy; non-toxic salts and acid addition salts thereof are useful for prevention and/or treatment for neurodegenerarive disease (Alzheimer's disease etc.) and neuronal dysfunction by stroke or traumic injury (Multiple sclerosis etc.) etc.

公开(公告)号：US5411974A

公开(公告)日：1995-05-02

申请号：US265734

申请日：1994-06-27

申请人： Masaaki Toda ,  Shuichi Ohuchida ,  Hiroyuki Ohno

发明人： Masaaki Toda ,  Shuichi Ohuchida ,  Hiroyuki Ohno

IPC分类号： C07D207/08 ,  C07D277/04 ,  C07D405/04 ,  C07D417/06 ,  A61K31/425

CPC分类号： C07D207/08 ,  C07D277/04 ,  C07D405/04 ,  C07D417/06

摘要： Heterocyclic compounds of the general formula: ##STR1## wherein, Z represents methylene group or sulfur atom, R represents a general formula:G--E--D--B--A--.

摘要翻译： 具有以下通式的杂环化合物：其中Z表示亚甲基或硫原子，R表示通式：G-E-D-B-A-。

公开(公告)号：US5384414A

公开(公告)日：1995-01-24

申请号：US107576

申请日：1993-08-18

申请人： Shuichi Ohuchida ,  Masaaki Toda ,  Tsumoru Miyamoto

发明人： Shuichi Ohuchida ,  Masaaki Toda ,  Tsumoru Miyamoto

IPC分类号： C07D311/72 ,  C07D311/92 ,  C07D311/04

CPC分类号： C07D311/92 ,  C07D311/72

摘要： Benzopyran derivatives of the formula: ##STR1## wherein R.sup.1a is hydrogen, C1-4 alkyl or C1-4 alkoxy; or two R.sup.1a taken together with 7th- and 8th-carbon to which they are attached form a C6 carbocyclic ring;R.sup.2a is hydrogen, C1-4 alkyl or C1-4 alkoxy;R.sup.3a is hydrogen, C2-4 acyl or benzoyl;na is 1-3;Ya is C1-7 alkylene, C2-7 alkenylene or C2-7 alkynylene;Ma isi) bond orii) a group of the formula: --Da--Ba--;Da isi) --O-- orii) --S--;Ba isi) C1-4 alkylene orii) a group of the formula: ##STR2## Za is i) bond,ii) --OCO--,iii) CONR.sup.9a --,iv) --COO--,v) --NR.sup.9a CO--,vi) --O-- orvii) --NH--CO--NH--;Wa is a group of the formula: --W1a--Aa--W2 a--;Aa isi) bond orii) a group of the formula: --Ea-- .circle.Ga --;Ea isi) bond,ii) --O-- oriii) --S--; .circle.Ga is C4-10 carbocyclic or heterocyclic ring; or C4-10 carbocyclic or heterocyclic ring substituted by one to three C1-4 alkyl, C1-4 alkoxy, halogen, a group of the formula: --COOR.sup.7a, trihalomethyl or acetamido;W1a and W2a each, independently, isi) bondii) C1-4 alkylene,iii) C2-4 alkenylene oriv ) C2-4 alkynylene;R.sup.4a is hydrogen or C1-4 alkyl;R.sup.5a is hydrogen, C1-4 alkyl or amino;R.sup.6a is hydrogen, C1-4 alkyl, C1-4 alkoxy, halogen, a group of the formula: --COOR.sup.8a, trihalomethyl or acetoamido;R.sup.7a is hydrogen or C1-4 alkyl;R.sup.8a is hydrogen or C1-4 alkyl;R.sup.9a is hydrogen, C1-4 alkyl or benzyl; with a proviso, and the pharmaceutically acceptable acid addition salts thereof possess the inhibitory activity on Maillard reaction and an antioxidizing effect.

摘要翻译： 下式的苯并吡喃衍生物：其中R 1a是氢，C 1-4烷基或C 1-4烷氧基; 或两个R 1a与它们所连接的第七和第八碳一起形成C6碳环; R 2a是氢，C 1-4烷基或C 1-4烷氧基; R3a是氢，C2-4酰基或苯甲酰基; na是1-3; Ya是C 1-7亚烷基，C 2-7亚烯基或C 2-7亚炔基; Ma是i）键或ii）下式的基团：-Da-Ba-; Da为i）-O-或ii）-S-; b）i）C1-4亚烷基或ii）下式的基团：Za是i）键，ii）-OCO-，iii）CONR9a - ，iv）-COO-，v）-NR9aCO-，vi ）-O-或vii）-NH-CO-NH-; Wa是下列基团：-W1a-Aa-W2a-; Aa是i）键或ii）下式的基团：-Ea-＆Cir＆Ga - ; Ea为i）键，ii）-O-或iii）-S-; ＆cir＆Ga是C4-10碳环或杂环; 或被一至三个C 1-4烷基取代的C 4-10碳环或杂环，C 1-4烷氧基，卤素，下式基团：-COOR 7 a，三卤代甲基或乙酰氨基; W1a和W2a各自独立地是i）键合ii）C 1-4亚烷基，iii）C 2-4亚烯基或iv）C 2-4亚炔基; R4a是氢或C1-4烷基; R5a是氢，C1-4烷基或氨基; R 6a是氢，C 1-4烷基，C 1-4烷氧基，卤素，下式基团：-COOR 8 a，三卤甲基或乙酰胺基; R 7a是氢或C 1-4烷基; R 8a是氢或C 1-4烷基; R9a是氢，C1-4烷基或苄基; 并且其药学上可接受的酸加成盐具有对美拉德反应的抑制活性和抗氧化作用。

公开(公告)号：US5340832A

公开(公告)日：1994-08-23

申请号：US107314

申请日：1993-08-17

申请人： Masaaki Toda ,  Shuichi Ohuchida ,  Hiroyuki Ohno

发明人： Masaaki Toda ,  Shuichi Ohuchida ,  Hiroyuki Ohno

IPC分类号： A61K31/40 ,  A61K31/401 ,  A61K31/4025 ,  A61K31/435 ,  A61K31/44 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61P25/28 ,  C07D207/08 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  A61K31/52

CPC分类号： C07D207/08 ,  C07D405/12

摘要： A novel prolinal derivative of the general formula: ##STR1## [wherein A represents alkylene or alkenylene group of from 1 to 8 carbon atom(s) or a saturated hydrocarbon ring of from 3 to 7 carbon atoms, R represents hydrogen atom, phenyl group, benzyl group, alkyl group of from 1 to 8 carbon atom(s) or cycloalkyl group of from 3 to 7 carbon atoms,B represents alkylene group of from 1 to 8 atom(s) unsubstituted or substituted by phenyl group or benzyl group, or a single bond,D represents carbocyclic or heterocyclic ring unsubstituted or substituted by from one to three of halogen atom, alkyl or alkoxy group of from 1 to 4 carbon atom(s), nitro group or trifluoromethyl group.]possess inhibitory activity on prolyl endopeptidase, and therefore are useful for treating and/or preventing agent as a amnesia.

摘要翻译： 一种新颖的通式如下的流延衍生物：其中A表示1至8个碳原子的亚烷基或亚烯基或3至7个碳原子的饱和烃环，R表示氢原子 苯基，苄基，1〜8个碳原子的烷基或3〜7个碳原子的环烷基，B表示1〜8个未被取代或被苯基取代或被苯基取代的亚烷基， 苄基或单键，D表示未被取代或被1至3个卤素原子，1至4个碳原子的烷基或烷氧基，硝基或三氟甲基取代的碳环或杂环。]具有抑制性 对脯氨酰内肽酶的活性，因此可用于治疗和/或预防药物作为遗忘。