公开(公告)号：US4399147A

公开(公告)日：1983-08-16

申请号：US872635

申请日：1978-01-26

申请人： Masaki Hayashi ,  Yoshinobu Arai ,  Yoshitaka Konishi ,  Katsuichi Shimoji ,  Shuichi Ohuchida ,  Hirohisa Wakatsuka ,  Hiroyuki Ito

发明人： Masaki Hayashi ,  Yoshinobu Arai ,  Yoshitaka Konishi ,  Katsuichi Shimoji ,  Shuichi Ohuchida ,  Hirohisa Wakatsuka ,  Hiroyuki Ito

IPC分类号： C07D307/935 ,  A61K31/34 ,  A61K31/343 ,  A61P43/00 ,  C07C405/00 ,  C07D307/937 ,  A61K31/557

CPC分类号： C07D307/937 ,  C07C405/00

摘要： Prostaglandin I.sub.2 analogues of the formula: ##STR1## [wherein X represents trans-vinylene or an ethylene group unsubstituted or substituted by a bromine atom at the C-5 position, Y represents trans-vinylene or ethylene, R.sup.1 represents hydrogen or an alkyl group containing from 1 to 12 carbon atoms, R.sup.2 represents hydrogen or methyl or ethyl, R.sup.3 represents a single bond or an alkylene group containing from 1 to 4 carbon atoms, R.sup.4 represents hydrogen, an alkyl group containing from 1 to 8 carbon atoms, a cycloalkyl group containing from 4 to 7 carbon atoms unsubstituted or substituted by at least one alkyl group containing from 1 to 8 carbon atoms, or a phenyl or phenoxy group unsubstituted or carrying at least one substituent selected from halogen atoms, the trifluoromethyl group and alkyl groups containing from 1 to 3 carbon atoms, and the wavy line attached to the carbon atoms in positions 6, 11 and 15 depicted in the formula represents .alpha.- or .beta.-configuration or mixtures thereof] are new compounds possessing pharmacological properties typical of prostaglandins, for example PGI.sub.2, and are more stable than PGI.sub.2.

摘要翻译： 前列腺素I2类似物，具有下式：其中X表示反式亚乙烯基或未被取代或被C-5位上的溴原子取代的亚乙基，Y表示反式亚乙烯基或亚乙基，R 1表示氢或烷基 含有1至12个碳原子，R 2表示氢或甲基或乙基，R 3表示单键或含有1至4个碳原子的亚烷基，R 4表示氢，含有1至8个碳原子的烷基，环烷基 含有未取代或被至少一个含有1至8个碳原子的烷基取代的4至7个碳原子的基团，或未取代或携带至少一个选自卤素原子的取代基的苯基或苯氧基，三氟甲基和含有 1至3个碳原子，并且连接在式中描述的6,11和15位的碳原子上的波浪线代表α-或β-构型或其混合物] 是具有典型的前列腺素的药理学性质的新化合物，例如PGI 2，并且比PGI2更稳定。

公开(公告)号：US4178367A

公开(公告)日：1979-12-11

申请号：US878571

申请日：1978-02-16

申请人： Hayashi Masaki ,  Yoshinobu Arai ,  Yoshitaka Konishi ,  Katsuichi Shimoji ,  Shuichi Ohuchida ,  Hiroyuki Ito ,  Hirohisa Wakatsuka

发明人： Hayashi Masaki ,  Yoshinobu Arai ,  Yoshitaka Konishi ,  Katsuichi Shimoji ,  Shuichi Ohuchida ,  Hiroyuki Ito ,  Hirohisa Wakatsuka

IPC分类号： C07C405/00 ,  C07D307/937 ,  C07F9/40 ,  A61K31/34 ,  C07D307/93

CPC分类号： C07D307/937 ,  C07C405/00 ,  C07F9/4018

摘要： Prostaglandin I.sub.2 analogues of the formula: ##STR1## (wherein Y represents trans-vinylene or ethylene, R.sup.1 represents hydrogen or an alkyl group containing from 1 to 12 carbon atoms, R.sup.2 represents hydrogen, methyl or ethyl, R.sup.3 represents a single bond, or an alkylene group containing from 1 to 4 carbon atoms, R.sup.4, R.sup.5 and R.sup.6, which may be the same or different, each represent hydrogen or an alkyl group containing from 1 to 8 carbon atoms, n represents 3, 4, 5 or 6, the wavy line attached to the carbon atoms in positions 11 and 15 depicted in the formula represents .alpha.- or .beta.-configuration or mixtures thereof, and the double bond between C.sub.6 -C.sub.6 is Z or E) are new compounds possessing pharmacological properties typical of prostaglandins, for example PGI.sub.2.

摘要翻译： 前列腺素I2类似物具有下式：其中Y表示反式亚乙烯基或亚乙基，R 1表示氢或含有1至12个碳原子的烷基，R 2表示氢，甲基或乙基，R 3表示单键， 或含有1至4个碳原子的亚烷基，可以相同或不同的R 4，R 5和R 6各自表示氢或含有1至8个碳原子的烷基，n表示3,4,5或6 连接在式中描述的位置11和15处的碳原子的波浪线代表α-或β-构型或其混合物，并且C6-C6之间的双键是Z或E）是具有典型的药理学性质的新化合物 前列腺素，例如PGI2。

公开(公告)号：US4207332A

公开(公告)日：1980-06-10

申请号：US944164

申请日：1978-09-20

申请人： Masaki Hayashi ,  Yoshinobu Arai ,  Katsuichi Shimoji ,  Yoshitaka Konishi ,  Shuichi Ohuchida ,  Shinsuke Hashimoto

发明人： Masaki Hayashi ,  Yoshinobu Arai ,  Katsuichi Shimoji ,  Yoshitaka Konishi ,  Shuichi Ohuchida ,  Shinsuke Hashimoto

IPC分类号： C07D307/935 ,  A61K31/34 ,  A61K31/343 ,  A61P43/00 ,  C07C405/00 ,  C07D307/937 ,  C07D307/93

CPC分类号： C07D307/937 ,  C07C405/00

摘要： Prostaglandin analogues of the general formula: ##STR1## [wherein Y represents ethylene or trans-vinylene, R.sup.1 represents a group --C.sub.m H.sub.2m COOR.sup.5, --C.sub.n H.sub.2n OR.sup.6 or ##STR2## (wherein R.sup.5 represents an alkyl group containing from 1 to 4 carbon atoms, R.sup.6 represents a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms, R.sup.7 and R.sup.8, which may be the same or different, each represents an alkyl group containing from 1 to 4 carbon atoms, m represents an integer of from 1 to 12 and n represents an integer of from 2 to 12), R.sup.2 represents a hydrogen atom or a methyl or ethyl group, R.sup.3 represents a single bond, or an alkylene group containing from 1 to 4 carbon atoms, R.sup.4 represents a hydrogen atom, an alkyl group containing from 1 to 8 carbon atoms, a cycloalkyl group containing from 4 to 7 carbon atoms in the ring, which may be unsubstituted or substituted by at least one alkyl group containing from 1 to 8 carbon atoms, or represents a phenyl or phenoxy group which may be unsubstituted or substituted by at least one chlorine atom, trifluoromethyl group or alkyl group containing from 1 to 3 carbon atoms, the wavy line attached to the carbon atoms in positions 11 and 15 represents .alpha.- or .beta.-configuration, or mixtures thereof, and the double bond between C.sub.5 -C.sub.6 is Z] and cyclodextrin clathrates thereof, and, when R.sup.1 represents a group ##STR3## in which n, R.sup.7 and R.sup.8 are as hereinbefore defined, non-toxic acid addition salts thereof, are new compounds and possess characteristic prostaglandin-like properties.

摘要翻译： 前列腺素类似物具有以下通式：其中Y表示亚乙基或反式亚乙烯基，R1表示基团-CmH2mCOOR5，-CnH2nOR6或其中R5表示含有1至4个碳原子的烷基，R6表示 含有1至4个碳原子的氢原子或烷基，可以相同或不同的R 7和R 8各自表示含有1至4个碳原子的烷基，m表示1至12的整数，m表示1至12的整数， n表示2〜12的整数），R2表示氢原子或甲基或乙基，R3表示单键或含有1〜4个碳原子的亚烷基，R4表示氢原子，烷基 含有1至8个碳原子的环烷基，环中含有4至7个碳原子的环烷基，其可以是未取代的或被至少一个含有1至8个碳原子的烷基取代，或表示苯基或苯氧基， 可以是未取代的或未取代的 由至少一个氯原子，三氟甲基或含有1至3个碳原子的烷基取代，连接到位置11和15的碳原子的波浪线表示α或β构型，或其混合物，双键 C5-C6之间是Z]和环糊精包合物，当R1代表其中n，R7和R8如上所定义的基团“IMAGE”时，其无毒的酸加成盐是新的化合物，并且具有特征性的前列腺素 - 像属性。

公开(公告)号：US4232009A

公开(公告)日：1980-11-04

申请号：US14082

申请日：1979-02-22

申请人： Masaki Hayashi ,  Yoshinobu Arai ,  Shuichi Ohuchida ,  Shinsuke Hashimoto

发明人： Masaki Hayashi ,  Yoshinobu Arai ,  Shuichi Ohuchida ,  Shinsuke Hashimoto

IPC分类号： C07D307/935 ,  A61K31/34 ,  A61K31/343 ,  A61K31/557 ,  A61K47/48 ,  A61P1/04 ,  A61P7/02 ,  A61P9/00 ,  A61P9/12 ,  A61P15/04 ,  A61P43/00 ,  C07C405/00 ,  C07D307/937 ,  A61K31/70 ,  A61K31/58

CPC分类号： C07D307/937 ,  A61K47/48969 ,  B82Y5/00 ,  C07C405/00

摘要： Prostaglandin I.sub.2 analogues of the formula: ##STR1## [wherein Y represents ethylene or trans-vinylene, R.sup.1 represents hydrogen, alkyl of 1 to 12 carbon atoms, aralkyl of 7 to 12 carbon atoms, cycloalkyl of 4 to 7 carbon atoms optionally substituted by at least one alkyl group containing from 1 to 4 carbon atoms, phenyl unsubstituted or substituted by at least one chlorine atom, trifluoromethyl group, alkyl group containing from 1 to 4 carbon atoms or phenyl group, a --C.sub.m H.sub.2m COOR.sup.4 group (wherein m is an integer from 1 to 12 and R.sup.4 represents alkyl of 1 to 4 carbon atoms), a C.sub.n H.sub.2n OR.sup.5 group (wherein n is an integer from 2 to 12 and R.sup.5 represents hydrogen or alkyl of 1 to 4 carbon atoms), or a ##STR2## (wherein n is as hereinbefore defined and R.sup.6 and R.sup.7 each represent alkyl of 1 to 4 carbon atoms), R.sup.2 represents hydrogen, methyl or ethyl, X represents a --C.sub.p H.sub.2p --group (wherein p is an integer from 2 to 8) or a ##STR3## (wherein R.sup.8 represents a single bond, or alkylene of 1 to 4 carbon atoms, R.sup.9 represents a single bond or alkylene of 1 to 8 carbon atoms, and q is an integer from 3 to 6), R.sup.3 represents chlorine or fluorine, the wavy line attached to the carbon atoms in positions 11 and 15 represents .alpha.- or .beta.-configuration or mixtures thereof, and the double bond between C.sub.5 -C.sub.6 is Z] and cyclodextrin clathrates thereof and, when appropriate non-toxic salts, including acid addition salts, thereof, are new compounds possessing prostaglandin-like activity.

摘要翻译： 具有下式的前列腺素I2类似物：其中Y表示亚乙基或反式亚乙烯基，R 1表示氢，1至12个碳原子的烷基，7至12个碳原子的芳烷基，4至7个碳原子的环烷基， 至少一个含有1至4个碳原子的烷基，未被取代或被至少一个氯原子取代的苯基，三氟甲基，含有1至4个碳原子的烷基或苯基，-C m H 2 mCOOR 4基团（其中m是 1〜12的整数，R 4表示碳原子数1〜4的烷基），C n H 2n O 5基（n为2〜12的整数，R 5表示氢或碳原子数为1〜4的烷基） 其中n如上所定义，R 6和R 7各自表示1至4个碳原子的烷基），R 2表示氢，甲基或乙基，X表示-C p H 2p基团（其中p是2至8的整数） IMAGE>（其中R8表示单键或1至4个碳原子的亚烷基，R9 表示1〜8个碳原子的单键或亚烷基，q为3〜6的整数），R3表示氯或氟，11和15位上与碳原子相连的波浪线表示α或β构型 或其混合物，C5-C6之间的双键为Z]和环糊精包合物，当合适的无毒盐（包括其酸加成盐）为具有前列腺素样活性的新化合物时。

公开(公告)号：US4234597A

公开(公告)日：1980-11-18

申请号：US20339

申请日：1979-03-14

申请人： Masaki Hayashi ,  Shuichi Ohuchida ,  Yoshinobu Arai

发明人： Masaki Hayashi ,  Shuichi Ohuchida ,  Yoshinobu Arai

IPC分类号： C07D209/94 ,  A61K31/557 ,  A61P7/02 ,  A61P9/00 ,  A61P9/10 ,  A61P43/00 ,  C07C405/00 ,  C07D209/52 ,  A61K31/40

CPC分类号： C07C405/00 ,  C07C405/0041 ,  C07D209/52

摘要： Prostaglandin I.sub.2 analogues of the formula: ##STR1## [wherein R.sup.1 represents hydrogen, alkyl of 1 to 12 carbon atoms, aralkyl of 7 to 12 carbon atoms, cycloalkyl of 4 to 7 carbon atoms optionally substituted by alkyl of 1 to 4 carbon atoms, phenyl optionally substituted by chlorine, trifluoromethyl, alkyl of 1 to 4 carbon atoms or phenyl, or represents a group --C.sub.p H.sub.2p COOR.sup.5, --C.sub.q H.sub.2q OR.sup.6 or ##STR2## (wherein R.sup.5, R.sup.7 and R.sup.8 represent alkyl of 1 to 4 carbon atoms, R.sup.6 represents hydrogen or alkyl of 1 to 4 carbon atoms, p represents an integer of from 1 to 12, and q represents an integer of from 2 to 12), R.sup.2, R.sup.3 and R.sup.4, represent hydrogen or alkyl of 1 to 8 carbon atoms, B represents a single bond, or alkylene of 1 to 4 carbon atoms, n represents 3, 4, 5 or 6, and the symbol represents a single or double bond] and, when appropriate, non-toxic salts, including acid addition salts, thereof are new compounds possessing pharmacological properties typical of the prostaglandins.

摘要翻译： 具有下式的前列腺素I2类似物：其中R 1表示氢，1至12个碳原子的烷基，7至12个碳原子的芳烷基，4至7个碳原子的环烷基，任选被1至4个碳原子的烷基取代 任选被氯，三氟甲基，1-4个碳原子的烷基或苯基取代的苯基，或代表基团-CpH2pCOOR5，-CqH2qOR6或者其中R5，R7和R8代表1-4个碳原子的烷基，R6代表 氢或1〜4个碳原子的烷基，p表示1〜12的整数，q表示2〜12的整数），R2，R3和R4表示氢或碳原子数为1〜8的烷基，B 表示单键，或1〜4个碳原子的亚烷基，n表示3,4,5或6，符号表示单键或双键]，适当时包括无毒盐，包括其酸加成盐 是具有典型的前列腺素的药理学特性的新化合物。

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：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：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：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。