公开(公告)号：US4530919A

公开(公告)日：1985-07-23

申请号：US574765

申请日：1984-01-27

申请人： John L. Belletire

发明人： John L. Belletire

IPC分类号： C07C57/30 ,  C07C57/58 ,  C07C59/64 ,  C07C59/66 ,  C07C62/30 ,  C07C62/32 ,  C07C62/34 ,  C07D311/58 ,  C07D335/06 ,  C07F7/18 ,  A61K31/35

CPC分类号： C07C62/30 ,  C07C57/30 ,  C07C57/58 ,  C07C59/64 ,  C07C59/66 ,  C07C62/32 ,  C07C62/34 ,  C07D311/58 ,  C07D335/06 ,  C07F7/18

摘要： A series of substituted phenylacetic acid compounds and their derivatives, including the pharmacologically acceptable base salts of said acids, have been found to be active as oral hypoglycemic agents. Preferred member compounds include 6-ethoxy-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid, 6-benzyloxy-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid, chroman-4-carboxylic acid, p-chlorophenylacetic acid, o-methylphenylacetic acid, o-methoxyphenylacetic acid, p-methoxyphenylacetic acid and .alpha., .alpha.-di(4-methoxyphenyl)acetic acid. Synthetic routes leading to those member compounds which are novel per se are described in some detail.

摘要翻译： 已经发现一系列取代的苯乙酸化合物及其衍生物，包括所述酸的药理学上可接受的碱盐，其作为口服降糖药具有活性。 优选的成员化合物包括6-乙氧基-1,2,3,4-四氢化萘-1-羧酸，6-苄氧基-1,2,3,4-四氢萘-1-羧酸，苯并二氢吡喃-4-羧酸，p 邻苯甲基苯乙酸，邻甲氧基苯基乙酸，对甲氧基苯基乙酸和α，α-二（4-甲氧基苯基）乙酸。 导致本身是新颖的那些成员化合物的合成路线被详细描述。

公开(公告)号：US4414220A

公开(公告)日：1983-11-08

申请号：US353514

申请日：1982-03-01

申请人： John L. Belletire

发明人： John L. Belletire

IPC分类号： C07D209/44 ,  C07D211/10 ,  C07D213/38 ,  C07D213/53 ,  C07D213/82 ,  C07D295/02 ,  C07D295/073 ,  C07D295/096 ,  C07D295/135 ,  C07D295/155 ,  C07D307/52 ,  C07D307/68 ,  A61K31/445 ,  C07D401/10

CPC分类号： C07D213/53 ,  C07D209/44 ,  C07D211/10 ,  C07D213/38 ,  C07D213/82 ,  C07D295/02 ,  C07D295/073 ,  C07D295/096 ,  C07D295/135 ,  C07D295/155 ,  C07D307/52 ,  C07D307/68 ,  Y10S514/866

摘要： A series of organic diamine base compounds derived from either an aromatic, alicyclic or heterocyclic ring and possessing, for the most part, an intervening methylene group between the ring and the aforesaid basic moiety have been prepared, including their pharmaceutically acceptable acid addition salts as well as oral pharmaceutical compositions containing same. These particular compounds are found to be useful in therapy as oral hypoglycemic agents. Preferred member compounds include 1,1'-[1,2-phenylenebis(methylene)]bispiperidine, 2,3-dihydro-2-[2-(1-piperidinomethyl)phenylmethyl]-1H-isoindole and 2,3-dihydro-2-[2-(4-morpholinomethyl)phenylmethyl]-1H-isoindole. Alternate methods of preparation are provided and the two principal synthetic routes leading to these compounds are described in some detail.

摘要翻译： 已经制备了一系列衍生自芳族，脂环族或杂环的有机二胺基化合物，并且大部分在环和前述碱性部分之间具有中间的亚甲基，包括其药学上可接受的酸加成盐 作为含有其的口服药物组合物。 发现这些特定化合物可用于作为口服降血糖药的治疗。 优选的成员化合物包括1,1' - [1,2-亚苯基双（亚甲基）]双哌啶，2,3-二氢-2- [2-（1-哌啶基甲基）苯甲基] -1H-异吲哚和2,3-二氢 - 2- [2-（4-吗啉代甲基）苯基甲基] -1H-异吲哚。 提供了替代的制备方法，并且进一步描述了导致这些化合物的两种主要合成途径。

公开(公告)号：US4374148A

公开(公告)日：1983-02-15

申请号：US282762

申请日：1981-07-13

申请人： John L. Belletire

发明人： John L. Belletire

IPC分类号： C07C57/30 ,  C07C57/58 ,  C07C59/64 ,  C07C59/66 ,  C07C62/30 ,  C07C62/32 ,  C07C62/34 ,  C07D311/58 ,  C07D335/06 ,  C07F7/18 ,  A61K31/165 ,  A61K31/19 ,  A61K31/235

CPC分类号： C07D311/58 ,  C07C57/30 ,  C07C57/58 ,  C07C59/64 ,  C07C59/66 ,  C07C62/30 ,  C07C62/32 ,  C07C62/34 ,  C07D335/06 ,  C07F7/18 ,  Y10S514/866

摘要： A series of substituted phenylacetic acid compounds and their derivatives, including the pharmacologically acceptable base salts of said acids, have been found to be active as oral hypoglycemic agents. Preferred member compounds include 6-ethoxy-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid, 6-benzyloxy-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid, chroman-4-carboxylic acid, p-chlorophenylacetic acid, o-methylphenylacetic acid, o-methoxyphenylacetic acid, p-methoxyphenylacetic acid and .alpha.,.alpha.-di(4-methoxyphenyl)acetic acid. Synthetic routes leading to those member compounds which are novel per se are described in some detail.

公开(公告)号：US4210667A

公开(公告)日：1980-07-01

申请号：US31564

申请日：1979-04-19

申请人： Reinhard Sarges ,  John L. Belletire ,  Rodney C. Schnur

发明人： Reinhard Sarges ,  John L. Belletire ,  Rodney C. Schnur

IPC分类号： A61K31/37

CPC分类号： A61K31/37

摘要： Preparations useful as aldose reductase inhibitors and as therapeutic agents for the treatment of chronic diabetic complications are disclosed. The preparations contain substituted and unsubstituted coumarin-4-carboxylic or acetic acid derivatives as the active ingredients.

摘要翻译： 公开了用作醛糖还原酶抑制剂和用作治疗慢性糖尿病并发症的治疗剂的制剂。 制剂含有取代和未取代的香豆素-4-羧酸或乙酸衍生物作为活性成分。

公开(公告)号：US4210663A

公开(公告)日：1980-07-01

申请号：US959023

申请日：1978-11-08

申请人： John L. Belletire

发明人： John L. Belletire

IPC分类号： A61K31/35 ,  A61K31/352 ,  A61K31/38 ,  A61K31/382 ,  A61P3/08 ,  A61P3/10 ,  A61P25/00 ,  A61P27/02 ,  A61P27/12 ,  C07D311/04 ,  C07D311/22 ,  C07D311/58 ,  C07D311/92 ,  C07D335/06 ,  C07F7/18

CPC分类号： C07D335/06 ,  C07D311/04 ,  C07D311/22 ,  C07D311/58 ,  C07D311/92 ,  C07F7/1856 ,  Y10S514/866

摘要： Novel halogen-substituted benzopyran-4-carboxylic acids, benzothiopyran-4-carboxylic acids and derivatives thereof useful as aldose reductase inhibitors and as therapeutic agents for the treatment of chronic diabetic complications are disclosed. Specific compounds disclosed include 6-phenyl-8-chloro-3,4-dihydro-2H-1-benzopyran-4-carboxylic acid, 6,7-dichloro-3,4-dihydrobenzothiopyran-4-carboxylic acid, 6-chloro-8-methyl-3,4-dihydro-2H-1-benzopyran-4-carboxylic acid, 6,8-dichloro-3,4-dihydro-2H-1-benzopyran-4-carboxylic acid, 6-fluoro-3,4-dihydro-2H-1-benzopyran-4-carboxylic acid, 6-chloro-3,4-dihydro-2H-1-benzopyran-4-carboxylic acid, 6-chloro-dihydro-2H-naphtho[1,2-b]pyran-4-carboxylic acid, 6-chloro-3,4-dihydro-2H-1-benzothiopyran-4-carboxylic acid and 6-chloro-3,4-dihydro-2H-1-benzopyran-4-acetic acid. Also disclosed are pharmaceutical compositions containing the novel compounds and a method of using the novel compounds for the treatment of chronic diabetic complications.

摘要翻译： 公开了用作醛糖还原酶抑制剂的新型卤素取代的苯并吡喃-4-羧酸，苯并噻喃-4-羧酸及其衍生物，以及用于治疗慢性糖尿病并发症的治疗剂。 所公开的具体化合物包括6-苯基-8-氯-3,4-二氢-2H-1-苯并吡喃-4-羧酸，6,7-二氯-3,4-二氢苯并噻喃-4-羧酸，6-氯 - 8-甲基-3,4-二氢-2H-1-苯并吡喃-4-羧酸，6,8-二氯-3,4-二氢-2H-1-苯并吡喃-4-羧酸，6-氟-3,4-二氢 - 4-二氢-2H-1-苯并吡喃-4-羧酸，6-氯-3,4-二氢-2H-1-苯并吡喃-4-羧酸，6-氯 - 二氢-2H-萘并〔1,2- b]吡喃-4-羧酸，6-氯-3,4-二氢-2H-1-苯并噻喃-4-羧酸和6-氯-3,4-二氢-2H-1-苯并吡喃-4-乙酸 。 还公开了含有新化合物的药物组合物和使用该新化合物治疗慢性糖尿病并发症的方法。

公开(公告)号：US4307108A

公开(公告)日：1981-12-22

申请号：US106577

申请日：1979-12-26

申请人： John L. Belletire ,  Reinhard Sarges

发明人： John L. Belletire ,  Reinhard Sarges

IPC分类号： C07C55/30 ,  C07D209/96 ,  C07D221/20 ,  C07D311/58 ,  C07D333/54 ,  C07D491/10 ,  C07D491/107 ,  C07D495/10 ,  A61K31/40 ,  C07D209/54

CPC分类号： C07D221/20 ,  C07C255/00 ,  C07C55/30 ,  C07D209/96 ,  C07D311/58 ,  C07D333/54 ,  C07D491/10 ,  C07D495/10

摘要： A series of spiro-imide compounds and their base salts with pharmacologically acceptable cations are disclosed. These particular compounds are useful in therapy as agents for the control of certain chronic diabetic complications. Preferred member compounds include 2,3-dihydro-spiro-[1H-indene-1,3'-pyrrolidone]-2',5'-dione, 2,3-dihydro-spiro-[1H-indene-2,3'-pyrrolidine]-2',5'-dione, 3,4-dihydro-spiro-[2H-naphthalene-1,3'-pyrrolidine]-2',5'-dione, 3,4-dihydro-spiro-[2H-naphthalene-1,3'-piperidine]-2',6'-dione, 6-chloro-2,3-dihydro-spiro-[4H-1-benzopyran-4,3'-pyrrolidine]-2',5'-dione and 6,7-dihydro-spiro-[5H-benzo(b)thiophene-4,3'-pyrrolidine]-2',5'-dione. Methods for preparing these compounds from known starting materials are provided.

摘要翻译： 公开了一系列螺酰亚胺化合物及其与药理学上可接受的阳离子的碱盐。 这些特定化合物可用于治疗某些慢性糖尿病并发症的药物。 优选的成员化合物包括2,3-二氢螺 - [1H-茚-1,3'-吡咯烷酮] -2'，5'-二酮，2,3-二氢螺 - [1H-茚-2,3' - 吡咯烷] -2'，5'-二酮，3,4-二氢螺 - [2H-萘-1,3'-吡咯烷] -2'，5'-二酮，3,4-二氢螺 - 2H-萘-1,3'-哌啶] -2'，6'-二酮，6-氯-2,3-二氢 - 螺 - [4H-1-苯并吡喃-4,3'-吡咯烷] -2' 5'-二酮和6,7-二氢 - 螺 - [5H-苯并（b）噻吩-4,3'-吡咯烷] -2'，5'-二酮。 提供了从已知原料制备这些化合物的方法。

公开(公告)号：US4220650A

公开(公告)日：1980-09-02

申请号：US952302

申请日：1978-10-18

申请人： John L. Belletire

发明人： John L. Belletire

IPC分类号： A61K31/135 ,  A61K31/13 ,  A61K31/275 ,  A61K31/34 ,  A61K31/38 ,  A61K31/381 ,  A61K31/395 ,  A61K31/535 ,  A61P3/08 ,  A61P3/10 ,  C07C211/25 ,  C07C211/27 ,  C07C211/29 ,  C07C217/58 ,  C07C255/58 ,  C07D209/44 ,  C07D213/38 ,  C07D213/53 ,  C07D213/82 ,  C07D217/04 ,  C07D295/02 ,  C07D295/073 ,  C07D295/096 ,  C07D295/135 ,  C07D295/155 ,  C07D307/52 ,  C07D307/68 ,  C07D333/20 ,  C07D401/12 ,  A61K31/445 ,  C07D401/10

CPC分类号： C07D213/53 ,  C07D209/44 ,  C07D213/38 ,  C07D213/82 ,  C07D295/02 ,  C07D295/073 ,  C07D295/096 ,  C07D295/135 ,  C07D295/155 ,  C07D307/52 ,  C07D307/68

摘要： A series of organic diamine base compounds derived from either an aromatic, alicyclic or heterocyclic ring and possessing, for the most part, an intervening methylene group between the ring and the aforesaid basic moiety have been prepared, including their pharmaceutically acceptable acid addition salts as well as oral pharmaceutical compositions containing same. These particular compounds are found to be useful in therapy as oral hypoglycemic agents. Preferred member compounds include 1,1'-[1,2-phenylenebis(methylene)]bispiperidine, 2,3-dihydro-2-[2-(1-piperidinomethyl)phenylmethyl]-1H-isoindole and 2,3-dihydro-2-[2-(4-morpholinomethyl)phenylmethyl]-1H-isoindole. Alternate methods of preparation are provided and the two principal synthetic routes leading to these compounds are described in some detail.

摘要翻译： 已经制备了一系列衍生自芳族，脂环族或杂环的有机二胺基化合物，并且大部分在环和前述碱性部分之间具有中间的亚甲基，包括其药学上可接受的酸加成盐 作为含有其的口服药物组合物。 发现这些特定化合物可用于作为口服降血糖药的治疗。 优选的成员化合物包括1,1' - [1,2-亚苯基双（亚甲基）]双哌啶，2,3-二氢-2- [2-（1-哌啶基甲基）苯甲基] -1H-异吲哚和2,3-二氢 - 2- [2-（4-吗啉代甲基）苯基甲基] -1H-异吲哚。 提供了替代的制备方法，并且进一步描述了导致这些化合物的两种主要合成途径。

公开(公告)号：US4181728A

公开(公告)日：1980-01-01

申请号：US961335

申请日：1978-11-16

申请人： Reinhard Sarges ,  John L. Belletire

发明人： Reinhard Sarges ,  John L. Belletire

IPC分类号： A61K31/415 ,  A61K31/4184 ,  A61P3/08 ,  A61P13/02 ,  A61P15/00 ,  A61P25/00 ,  A61P25/24 ,  A61P25/26 ,  A61P27/02 ,  A61P27/12 ,  C07D233/74 ,  C07D235/02 ,  C07D335/00 ,  C07D491/10 ,  C07D491/107 ,  C07D495/10 ,  C12N9/99

CPC分类号： C07D235/02 ,  C07D491/10 ,  C07D495/10 ,  Y10S514/867

摘要： Novel spiro-polycyclicimidazolidinedione derivatives useful as aldose reductase inhibitors and as therapeutic agents for the treatment of chronic diabetic complications are disclosed. The derivatives include 2',3'-dihydro-spiro[imidazolidine-4,4'-[4'H]-naphtho[1,2-b]pyran]-2,5-dione, 2',3'-dihydro-spiro-[imidazolidine-4, 4'-[4'H]-naphtho[1,2-b]thiopyran]-2,5-dione, 1',2',3',4'-tetrahydro-spiro[imidazolidine-4,1'-benz[a]anthracene]2,5-dione, 2',3'-dihydro-spiro[imidazolidine-4,1'phenalene]-2,5-dione, 1',2',3',4'-tetrahydro-spiro[imidazolidine-4,1'-phenanthrene]-2,5-dione, the 2,1 isomers of the 2',3'-dihydro-4'H-pyran and 2',3'-dihydro-4'H-thiopyran derivatives, the 2',3'-dihydro-4'H-anthracenopyran and 2',3'-dihydro-4'H-anthracenothiopyran derivatives, the spiro-4,4' isomer of the tetrahydrophenanthrene derivative, the [b] isomer of the benzanthracene derivative and the mono or disubstituted 2',3'-dihydro-4'H-naphthopyran, 2',3'-dihydro-4'H-naphthothiopyran and tetrahydrophenanthrene derivatives.

摘要翻译： 公开了可用作醛糖还原酶抑制剂和用作治疗慢性糖尿病并发症的治疗剂的新型螺 - 多环咪唑烷二酮衍生物。 衍生物包括2'，3'-二氢 - 螺[咪唑烷-4,4' - [4'H] - 萘并[1,2-b]吡喃] -2,5-二酮，2'，3'-二氢 - 螺 - [咪唑烷-4,4' - [4'H] - 萘并[1,2-b]噻喃] -2,5-二酮，1'，2'，3'，4'-四氢 - 咪唑烷-4,1'-苯并[a]蒽] 2,5-二酮，2'，3'-二氢螺[咪唑烷-4,1'-吩烯] -2,5-二酮，1'，2' 3'，4'-四氢 - 螺[咪唑烷-4,1'-菲] -2,5-二酮，2'，3'-二氢-4'H-吡喃和2'的2,1-异构体， 3' - 二氢-4'H-噻喃衍生物，2'，3'-二氢-4'H-蒽并吡喃衍生物，螺-4,4'异构体 的四氢菲衍生物，苯并蒽衍生物的[b]异构体和一元或二取代的2'，3'-二氢-4'H-萘并吡喃，2'，3'-二氢-4'H-萘并噻吩和四氢菲衍生物。

公开(公告)号：US4471124A

公开(公告)日：1984-09-11

申请号：US564599

申请日：1983-12-22

申请人： John L. Belletire ,  Reinhard Sarges

发明人： John L. Belletire ,  Reinhard Sarges

IPC分类号： C07C55/30 ,  C07D209/96 ,  C07D221/20 ,  C07D311/58 ,  C07D333/54 ,  C07D491/10 ,  C07D495/10 ,  C07D491/107 ,  C07D491/20 ,  C07D495/20

CPC分类号： C07D221/20 ,  C07C255/00 ,  C07C55/30 ,  C07D209/96 ,  C07D311/58 ,  C07D333/54 ,  C07D491/10 ,  C07D495/10

摘要： A series of spiro-imide compounds and their base salts with pharmacologically acceptable cations are disclosed. These particular compounds are useful in therapy as agents for the control of certain chronic diabetic complications. Preferred member compounds include 2,3-dihydro-spiro-[1H-indene-1,3'-pyrrolidone]-2', 5'-dione, 2,3-dihydro-spiro-[1H-indene-2,3'-pyrrolidine]-2',5'-dione, 3,4-dihydro-spiro-[2H-naphthalene-1,3'-pyrrolidine]-2',5'-dione, 3,4-dihydro-spiro-[2H-naphthalene-1,3'-piperidine]-2', 6'-dione, 6-chloro-2,3-dihydro-spiro-[4H-1-benzopyran-4,3'-pyrrolidine]-2',5'-dione and 6,7-dihydro-spiro-[5H-benzo(b)thiophene-4,3'-pyrrolidine]-2',5'-dione. Methods for preparing these compounds from known starting materials are provided.

摘要翻译： 公开了一系列螺酰亚胺化合物及其与药理学上可接受的阳离子的碱盐。 这些特定化合物可用于治疗某些慢性糖尿病并发症的药物。 优选的成员化合物包括2,3-二氢螺 - [1H-茚-1,3'-吡咯烷酮] -2 + 40,5'-二酮，2,3-二氢螺 - [1H-茚-2,3 ' - 吡咯烷] -2'，5'-二酮，3,4-二氢螺 - [2H-萘-1,3'-吡咯烷] -2'，5'-二酮，3,4-二氢 - 螺 - [2H-萘-1,3'-哌啶] -2'，6'-二酮，6-氯-2,3-二氢螺 - [4H-1-苯并吡喃-4,3'-吡咯烷] -2' ，5'-二酮和6,7-二氢 - 螺 - [5H-苯并（b）噻吩-4,3'-吡咯烷] -2'，5'-二酮。 提供了从已知原料制备这些化合物的方法。

公开(公告)号：US4442114A

公开(公告)日：1984-04-10

申请号：US458700

申请日：1983-01-17

申请人： John L. Belletire ,  Reinhard Sarges

发明人： John L. Belletire ,  Reinhard Sarges

IPC分类号： C07C55/30 ,  C07D209/96 ,  C07D221/20 ,  C07D311/58 ,  C07D333/54 ,  C07D491/10 ,  C07D495/10 ,  C07D211/88 ,  A61K31/445

CPC分类号： C07D221/20 ,  C07C255/00 ,  C07C55/30 ,  C07D209/96 ,  C07D311/58 ,  C07D333/54 ,  C07D491/10 ,  C07D495/10 ,  Y10S514/866

摘要： A series of spiro-imide compounds and their base salts with pharmacologically acceptable cations are disclosed. These particular compounds are useful in therapy as agents for the control of certain chronic diabetic complications. Preferred member compounds include 2,3-dihydro-spiro-[1H-indene-1,3'-pyrrolidone]-2',5'-dione, 2,3-dihydro-spiro-[1H-indene-2,3'-pyrrolidine]-2',5'-dione, 3,4-dihydro-spiro-[2H-naphthalene-1,3'-pyrrolidine]-2',5'-dione, 3,4-dihydro-spiro-[2H-naphthalene-1,3'-piperidine]-2',6'-dione, 6-chloro-2,3-dihydro-spiro-[4H-1-benzopyran-4,3'-pyrrolidine]-2',5'-dione and 6,7-dihydro-spiro-[5H-benzo(b)thiophene-4,3'-pyrrolidine]-2',5'-dione. Methods for preparing these compounds from known starting materials are provided.

摘要翻译： 公开了一系列螺酰亚胺化合物及其与药理学上可接受的阳离子的碱盐。 这些特定化合物可用于治疗某些慢性糖尿病并发症的药物。 优选的成员化合物包括2,3-二氢螺 - [1H-茚-1,3'-吡咯烷酮] -2'，5'-二酮，2,3-二氢螺 - [1H-茚-2,3' - 吡咯烷] -2'，5'-二酮，3,4-二氢螺 - [2H-萘-1,3'-吡咯烷] -2'，5'-二酮，3,4-二氢螺 - 2H-萘-1,3'-哌啶] -2'，6'-二酮，6-氯-2,3-二氢 - 螺 - [4H-1-苯并吡喃-4,3'-吡咯烷] -2' 5'-二酮和6,7-二氢 - 螺 - [5H-苯并（b）噻吩-4,3'-吡咯烷] -2'，5'-二酮。 提供了从已知原料制备这些化合物的方法。