公开(公告)号：US4745116A

公开(公告)日：1988-05-17

申请号：US945751

申请日：1986-12-23

申请人： Alexander Krantz ,  Robin Spencer ,  Tim Tam ,  Teng J. Liak

发明人： Alexander Krantz ,  Robin Spencer ,  Tim Tam ,  Teng J. Liak

IPC分类号： C07D265/26 ,  C07F9/6533 ,  A61K31/535 ,  C07D265/36

CPC分类号： C07D265/26 ,  C07F9/65335

摘要： 2-Oxy-4H-3,1-benzoxazin-4-ones, useful as serine protease inhibitors, represented by the formula: ##STR1## and the pharmaceutically acceptable acid addition salts thereof, wherein:a is an integer of 1 to 4;A is a bond, or alkylene having one to eight carbon atoms;R is hydrogen, phenyl, imidazolyl or cycloalkyl having three to six carbon atoms, wherein the phenyl, imidazolyl or cycloalkyl ring is optionally substituted with 1 to 3 substituents independently selected from the group consisting of lower alkyl having one to four carbon atoms, lower alkoxy having one to four carbon atoms, --N(R.sup.1).sub.2, --NO.sub.2, halo or lower alkylthio having one to four carbon atoms, and,each R' is independently selected from the group consisting of hydroxy, benzyloxy, lower alkyl having one to six atoms, lower alkenyl having two to six carbon atoms, lower alkoxy having one to six carbon atoms, lower alkylthio or halo-lower alkyl having one to six carbon atoms, halo, --NO.sub.2, --N(R.sup.1).sub.2, --NR.sup.1 CO.sub.2 R.sup.2, --NR.sup.1 COR.sup.2, and --NR.sup.1 C(O)N(R.sup.1).sub.2,in whicheach R.sup.1 is independently hydrogen or lower alkyl having one to four carbon atoms, or together form a piperidine or a piperazine ring optionally substituted at the ring nitrogen by lower alkyl having one to four carbon atoms or --CH.sub.2 CH.sub.2 OH;each R.sup.2 is independently lower alkyl having one to four carbon atoms,A is an alkylene group if R is hydrogen,or a pharmaceutically acceptable acid addition salt thereof.

摘要翻译： 2-氧代-4H-3,1-苯并恶嗪-4-酮，其可用作丝氨酸蛋白酶抑制剂，由下式表示：其中：a为1的整数 到4; A是键或具有1-8个碳原子的亚烷基; R是氢，苯基，咪唑基或具有3至6个碳原子的环烷基，其中苯基，咪唑基或环烷基环任选地被1至3个独立地选自具有1至4个碳原子的低级烷基，低级烷氧基 具有1-4个碳原子的-N（R 1）2，-NO 2，卤素或具有1至4个碳原子的低级烷硫基，并且每个R'独立地选自羟基，苄氧基，具有一个至 六个原子，具有2-6个碳原子的低级烯基，具有1-6个碳原子的低级烷氧基，具有1-6个碳原子的低级烷硫基或卤代低级烷基，卤素，-NO 2，-N（R 1）2，-NR 1 CO 2 R 2， -NR1COR2和-NR1C（O）N（R1）2，其中每个R1独立地是氢或具有1-4个碳原子的低级烷基，或者一起形成在环氮上被低级烷基任意取代的哌啶或哌嗪环 具有1-4个碳原子或-CH 2 CH 2 OH; 每个R 2独立地是具有1-4个碳原子的低级烷基，如果R是氢，则A是亚烷基，或其药学上可接受的酸加成盐。

公开(公告)号：US4665070A

公开(公告)日：1987-05-12

申请号：US748631

申请日：1985-06-25

申请人： Alexander Krantz ,  Robin Spencer ,  Tim Tam ,  Teng J. Liak

发明人： Alexander Krantz ,  Robin Spencer ,  Tim Tam ,  Teng J. Liak

IPC分类号： C07D265/24 ,  A61K31/535 ,  A61K31/536 ,  A61P43/00 ,  C07D265/18 ,  C07D265/26 ,  C07F9/6533 ,  C07D265/36

CPC分类号： C07D265/26 ,  C07F9/65335

摘要： 2-Oxy-4H-3,1-benzoxazin-4-ones represented by the formula: ##STR1## and the pharmaceutically acceptable acid addition salts thereof, wherein: a is an integer of 0-4;A is a bond, or alkylene having one to eight carbon atoms;R is hydrogen, phenyl, imidazolyl or cycloalkyl having three to six carbon atoms, wherein the phenyl, imidazolyl or cycloalkyl ring is optionally substituted with 1-3 substituents independently selected from the group consisting of lower alkyl having one to four carbon atoms, lower alkoxy having one to four carbon atoms, --N(R.sup.1).sub.2, --NO.sub.2, halo or lower alkylthio having one to four carbon atoms, and,each R' is independently selected from the group consisting of lower alkyl having one to six atoms, lower alkenyl having two to six carbon atoms, lower alkoxy having one to six carbon atoms,lower alkylthio or halo-lower alkyl having one to four carbon atoms, halo, --NO.sub.2, --N(R.sup.1).sub.2, ##STR2## --NR.sup.1 COR.sup.2, and ##STR3## in which each R.sup.1 is independently hydrogen or lower alkyl having one to four carbon atoms, or together form a piperidine or a piperazine ring optionally substituted at the ring nitrogen by lower alkyl having one to four carbon atoms or --CH.sub.2 CH.sub.2 OH,each R.sup.2 is independently lower alkyl having one to four carbon atoms,A is an alkylene group if R is hydrogen,and the pharmaceutically acceptable acid addition salts thereof are useful as serine protease inhibitors in humans and animals.

摘要翻译： 由式（I）表示的2-氧代-4H-3,1-苯并恶嗪-4-酮及其药学上可接受的酸加成盐，其中：a为0-4的整数; A是键或具有1-8个碳原子的亚烷基; R是氢，苯基，咪唑基或具有3至6个碳原子的环烷基，其中苯基，咪唑基或环烷基环任选地被1-3个独立地选自具有1-4个碳原子的低级烷基，低级烷氧基 具有1-4个碳原子的-N（R 1）2，-NO 2，卤代或低级烷硫基，每个R'独立地选自具有1-6个原子的低级烷基，低级烷基 具有2-6个碳原子的烯基，具有1-6个碳原子的低级烷氧基，具有1-4个碳原子的低级烷硫基或卤代低级烷基，卤素，-NO 2，-N（R 1）2，-NR 1 COR 2和 其中每个R 1独立地为氢或具有1-4个碳原子的低级烷基，或者一起形成哌啶或哌嗪环，其任选在环氮上被具有1-4个碳原子的低级烷基或-CH 2 CH 2 OH取代，每个R 2 独立地是低级烷基 g为1-4个碳原子，如果R为氢，则A为亚烷基，其药学上可接受的酸加成盐可用作人和动物中的丝氨酸蛋白酶抑制剂。

公开(公告)号：US4657893A

公开(公告)日：1987-04-14

申请号：US673996

申请日：1984-11-26

申请人： Alexander Krantz ,  Robin Spencer ,  Tim Tam

发明人： Alexander Krantz ,  Robin Spencer ,  Tim Tam

IPC分类号： A61K31/535 ,  A61K38/00 ,  C07C273/18 ,  C07C275/42 ,  C07D265/22 ,  C07D265/24 ,  C07K5/078 ,  A61K37/02 ,  C07D265/06

CPC分类号： C07C265/16 ,  C07C273/1827 ,  C07D265/24 ,  C07K5/06165 ,  A61K38/00

摘要： Novel 2-amino-4H-3,1-benzoxazin-4-ones represented by the formula ##STR1## wherein R.sup.1, R.sup.2, R.sup.3 and X are defined herein are useful as enzyme inhibitors in animals.

摘要翻译： 式中，R1，R2，R3和X表示的新颖的2-氨基-4H-3,1-苯并恶嗪-4-酮可用作动物体内的酶抑制剂。