公开(公告)号：US4873253A

公开(公告)日：1989-10-10

申请号：US31738

申请日：1987-03-30

申请人： Shosuke Okamoto ,  Yoshio Okada ,  Akiko Okunomiya ,  Taketoshi Naito ,  Yoshio Kimura ,  Morihiko Yamada ,  Norio Ohno ,  Yasuhiro Katsuura ,  Hiroshi Nojima ,  Takashi Shishikura

发明人： Shosuke Okamoto ,  Yoshio Okada ,  Akiko Okunomiya ,  Taketoshi Naito ,  Yoshio Kimura ,  Morihiko Yamada ,  Norio Ohno ,  Yasuhiro Katsuura ,  Hiroshi Nojima ,  Takashi Shishikura

IPC分类号： C07D211/60 ,  C07D211/62 ,  C07D213/64 ,  C07D213/643 ,  C07D213/75 ,  C07D213/80 ,  C07D233/88 ,  C07D239/42 ,  C07D257/06 ,  C07D277/46 ,  C07D295/185

CPC分类号： C07D213/643 ,  C07D211/60 ,  C07D211/62 ,  C07D213/75 ,  C07D213/80 ,  C07D233/88 ,  C07D239/42 ,  C07D257/06 ,  C07D277/46 ,  C07D295/185

摘要： A phenylalanine derivative having the formula (I): ##STR1## wherein A represents ##STR2## B represents ##STR3## wherein m is 0, 1, or 2 and n is 3, 4, or 5; X represents (a) hydroxy, (b) nitro, (c) amino, (d) phenoxy which may be substituted with (i) halogen or (ii) nitro, (e) c.sub.1 -C.sub.4 alkyloxy which may be substituted wit (i) phenyl or (ii) benzoyl, (f) benzoyl, (g) pyridyloxy which may be substituted with (i) halogen or (ii) nitro, or (h) c.sub.1 -C.sub.4 alkyl which may by substituted with halogen;Y represents ##STR4## or --OR.sup.3 wherein R.sup.1 R.sup.2 are independently (a) hydrogen, (b) phenyl which may be substituted with (i) benzoyl, (ii) C.sub.1 -C.sub.4 alkylcarbonyl, (iii) C.sub.1 -C.sub.4 alkyl which may be further substituted with C.sub.1 -C.sub.4 alkoxycarbonyl or hydroxycarbonyl, (iv) C.sub.2 -C.sub.5 alkenyl which may be further substituted with hydroxycarbonyl or C.sub.1 -C.sub.4 alkoxycarbonyl, (v) C.sub.1 -C.sub.4 alkoxycarbonyl, or (vi) amidino, (c) pyridyl which may be substituted with halogen or carboxyl (d) imidazolyl, (e) pyrimidyl, (f) tetrazolyl, (g) thiazolyl which may be substituted with C.sub.1 -C.sub.4 alkyl which may be further substituted with C.sub.1 -C.sub.4 alkoxycarbonyl, (h) C.sub.1 -C.sub.6 alkyl which may be substituted with C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkoxycarbonyl, phenyl, or benzoyl, (i) C.sub.5 -C.sub.7 cycloalkyl which may be substituted with C.sub.1 -C.sub.4 alkoxycarbonyl or (j) R.sup.1 and R.sup.2 may form, with the nitrogen atom attached thereto, (i) pyperazyl which may be substituted on the nitrogen atom with C.sub.1 -C.sub.4 alkyl which may be further substituted with phenyl, (ii) piperidino which may be substituted with carboxyl or C.sub.1 -C.sub.4 alkoxycarbonyl, (iii) pyrrolidyl which may be substituted with C.sub.1 -C.sub.4 alkoxycarbonyl, or (iv) morpholyl; andR.sup.3 represents (a) hydrogen, (b) C.sub.1 -C.sub.6 alkyl which may be substituted with (i) C.sub.1 -C.sub.4 alkoxy, (ii) pehnyl, or (iii) pyridyl, or (c) pyridyl; or a pharmaceutically acceptable acid salt thereof.This phenylalanine derivative is effective as a proteinase.

公开(公告)号：US4895842A

公开(公告)日：1990-01-23

申请号：US912480

申请日：1986-09-29

申请人： Shosuke Okamoto ,  Yoshio Okada ,  Akiko Okunomiya ,  Taketoshi Naito ,  Yoshio Kimura ,  Morihiko Yamada ,  Norio Ohno ,  Yasuhiro Katsuura ,  Yumi Seki

发明人： Shosuke Okamoto ,  Yoshio Okada ,  Akiko Okunomiya ,  Taketoshi Naito ,  Yoshio Kimura ,  Morihiko Yamada ,  Norio Ohno ,  Yasuhiro Katsuura ,  Yumi Seki

IPC分类号： A61K38/00 ,  C07D211/16 ,  C07D211/32 ,  C07D211/62 ,  C07D213/30 ,  C07D213/40 ,  C07D213/64 ,  C07D213/643 ,  C07D213/75 ,  C07D239/42 ,  C07D295/185 ,  C07D307/14 ,  C07D401/12 ,  C07K5/065

CPC分类号： C07D213/30 ,  C07D211/16 ,  C07D211/32 ,  C07D211/62 ,  C07D213/40 ,  C07D213/643 ,  C07D213/75 ,  C07D239/42 ,  C07D295/185 ,  C07D307/14 ,  C07D401/12 ,  C07K5/06078 ,  A61K38/00

摘要： A phenylalanine derivative having the formula (I): ##STR1## where R.sup.1 and R.sup.2 are independently hydrogen provided that both R.sup.1 and R.sup.2 are not hydrogen at the same time;C.sub.1 -C.sub.8 alkyl which may be substituted with hydroxy, hydroxycarbonyl, C.sub.1 -C.sub.4 alkoxycarbonyl, C.sub.1 -C.sub.4 alkylmercapto, C.sub.1 -C.sub.4 alkoxy, carbamoyl, sulfamoyl, pyridyl, or phenyl which may further be substituted with nitro, C.sub.1 -C.sub.4 alkoxy, or halogen;C.sub.6 -C.sub.8 cycloalkyl which may be substituted with hydroxy, C.sub.1 -C.sub.4 alkoxy, hydroxylcarbonyl, C.sub.1 -C.sub.4 alkoxycarbonyl, or C.sub.1 -C.sub.4 alkyl;phenyl which may be substituted with halogen, nitro, trifluoromethyl, C.sub.1 -C.sub.4 alkoxy C.sub.1 C.sub.4 alkylmercapto, C.sub.1 -C.sub.4 alkylcarbonyl, phenylcarbonyl, hydroxycarbonyl, C.sub.1 -C.sub.4 alkoxycarbonyl, carbamoyl, sulfamoyl, amidino, pyridylcarbonyl, or C.sub.1 -C.sub.6 alkyl which may further be substituted with C.sub.1 -C.sub.4 alkylcarbonyl, hydroxycarbonyl, or C.sub.1 -C.sub.4 alkoxycarbonyl;pyridyl which may be substituted with halogen or C.sub.1 -C.sub.4 alkoxy;pyrimidyl;N-benzylazacyclohexyl; andR.sup.1 and R.sup.2 may form with the nitrogen atom attached thereto a ring structure as morpholino; thiomorpholino; piperazino which may be substituted with phenylcarbonyl, benzyl, or C.sub.1 -C.sub.4 alkyl;pyrrolidyl which may be substituted with hydroxycarbonyl or C.sub.1 -C.sub.4 alkoxycarbonyl; andpiperidino substituted with C.sub.1 -C.sub.4 alkyl, phenyl C.sub.1 -C.sub.4 alkyl, phenycarbonyl, or C.sub.1 -C.sub.4 alkoxycarbonyl;X is hydrogen; nitro; amino; or --OZ wherein Z is hydrogen; C.sub.1 -C.sub.4 alkyl; C.sub.2 -C.sub.4 alkenyl; benzyl which may be substituted with halogen, C.sub.1 -C.sub.4 alkyl, nitro, trifluoromethyl, hydroxycarbonyl, C.sub.1 -C.sub.4 alkoxycarbonyl, or cyano; phenylcarbonylmethyl; pyridylmethyl; phenyl which may be substituted with nitro or halogen; pyridyl or pyrimidyl which may be substituted with nitro; phenylsulfonyl which may be substituted with C.sub.1 -C.sub.4 alkyl; or benzyloxycarbonyl which may be substituted with halogen;n is 4 to 10; andthe mark * indicates that the configuration of the carbon may be either one of D-configuration, L-configuration and DL-configuration or a pharmaceutical acceptable salt thereof.This phenylalanine derivative is effective as a proteinase inhibitor.

公开(公告)号：US4764618A

公开(公告)日：1988-08-16

申请号：US65156

申请日：1987-06-19

申请人： Ryoji Kikumoto ,  Yoshikuni Tamao ,  Shinji Tonomura ,  Akira Maruyama ,  Shosuke Okamoto ,  Akiko Okunomiya

发明人： Ryoji Kikumoto ,  Yoshikuni Tamao ,  Shinji Tonomura ,  Akira Maruyama ,  Shosuke Okamoto ,  Akiko Okunomiya

IPC分类号： C07D295/18 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/445 ,  A61K31/451 ,  A61K31/47 ,  A61K38/00 ,  A61P43/00 ,  C07C67/00 ,  C07C239/00 ,  C07C279/04 ,  C07C301/00 ,  C07C311/18 ,  C07D211/14 ,  C07D211/16 ,  C07D211/22 ,  C07D211/46 ,  C07D211/60 ,  C07D211/64 ,  C07D215/36 ,  C07D295/185 ,  C07D319/00 ,  C07D319/22 ,  C07D401/12 ,  C07D405/12 ,  C07K5/072

CPC分类号： C07D295/185 ,  C07D211/16 ,  C07D211/46 ,  C07D211/60 ,  C07D211/64 ,  C07D215/36 ,  C07D401/12 ,  C07D405/12 ,  C07K5/06095 ,  A61K38/00 ,  Y02P20/55

摘要： Novel arginine derivatives represented by the general formula ##STR1## wherein R.sup.1 stands for a naphthalenesulfonyl, a naphthalenecarbonyl, a 1,2,3,4-tetrahydronaphthalenesulfonyl, a 1,2,3,4-tetrahydronaphthalenecarbonyl, a dioxa b-6,7-naphthalenesulfonyl, a dioxa b-6,7-naphthalenecarbonyl, a 1,2,3,4-tetrahydro-8-quinolinesulfonyl, a 1,2,3,4-tetrahydro-8-quinolinecarbonyl, a dibenzofuransulfonyl, a dibenzofurancarbonyl, a fluorenesulfonyl, a fluorenecarbonyl, a dibenzothiophenesulfonyl or a dibenzothiophene, and R.sup.2 stands for a piperidino or a piperazino are disclosed. These arginine derivatives and their pharmaceutically acceptable salts have trypsin-inhibiting activity and useful as a pancreatitis remedy.

摘要翻译： 由通式表示的新型精氨酸衍生物，其中R1代表萘磺酰基，萘羰基，1,2,3,4-四氢萘磺酰基，1,2,3,4-四氢萘羰基，二氧杂环戊烯-6,7- - 萘磺酰基，二恶b-6,7-萘羰基，1,2,3,4-四氢-8-喹啉磺酰，1,2,3,4-四氢-8-喹啉羰基，二苯并呋喃磺酰基，二苯并呋喃羰基， 芴甲酰基，芴羰基，二苯并噻吩磺酰基或二苯并噻吩，R2代表哌啶子基或哌嗪基。 这些精氨酸衍生物及其药学上可接受的盐具有胰蛋白酶抑制活性，可用作胰腺炎治疗。