公开(公告)号：WO1996011940A1

公开(公告)日：1996-04-25

申请号：PCT/EP1995004026

申请日：1995-10-12

Applicant: GLAXO WELLCOME INC. ,  DEZUBE, Milana ,  HIRST, Gavin, Charles ,  WILLSON, Timothy, Mark ,  SHERRILL, Ronald, George ,  SUGG, Elizabeth, Ellen ,  SZEWCZYK, Jerzy, Ryszard

Inventor： GLAXO WELLCOME INC.

IPC: C07K05/062

CPC classification number: C07D223/16 ,  A61K38/00 ,  C07D243/14 ,  C07D403/06 ,  C07D403/12 ,  C07K5/0222 ,  C07K5/06026 ,  C07K5/06078 ,  C07K5/06104 ,  C07K5/06139 ,  C07K5/06191 ,  C07K5/0821

Abstract: A CCK-A agonist of the general formula (I) R R NCOCH2N(R )COR and physiologically acceptable salts thereof wherein, R is independently C3-6alkyl, C3-6cycloalkyl, C3-6alkenyl, phenyl, -(CH2)pCN or -(CH2)pCOO(C1-4alkyl) and R is independently C3-6alkyl, C3-6cycloalkyl, C3-6alkenyl, benzyl, phenyl or phenyl mono- or disubstituted independently with C1-3alkyl, cyano, hydroxy, dimethylamino, -O(C1-4alkyl), -O(CH2C6H5), -NH(C1-4alkyl), -COO(C1-4alkyl), -N(C1-4alkyl)2 pyrrolidino, morpholino, halogen or C1-3alkyl substituted by one or more fluorine atoms or R is C1-2alkyl and R is phenyl substituted at the 2- or 4-position with chloro, methyl, methoxy or methoxycarbonyl; or R and R together with the nitrogen atom to which they are attached represent the group of formula (II), wherein R is hydrogen or methyl, R represents hydrogen, hydroxy, fluoro dimethylamino, C1-4alkoxy or benzyloxy, and m is zero, 1 or 2; R represents a group selected from C1-6alkyl; phenyl or phenyl substituted by one or two groups independently selected from C1-3alkyl, C1-4alkoxy or halogen; or thiophenyl; R is a group of formula (III) or (IV).

Abstract translation: 通式（I）R 1 R 2 NCOCH 2 N（R 3）COR 4的CCK-A激动剂及其生理学上可接受的盐，其中R 1独立地为C 3-6烷基， C 1-6烯基，苯基， - （CH 2）pCN或 - （CH 2）p COO（C 1-4烷基）和R 2独立地是C 3-6烷基，C 3-6环烷基，C 3-6烯基，苄基， 氰基，羟基，二甲基氨基，-O（C 1-4烷基）， - O（CH 2 C 6 H 5），-NH（C 1-4烷基），-COO（C 1-4烷基）， - N（C 1-4烷基） ）2吡咯烷子基，吗啉代，卤素或被一个或多个氟原子取代的C 1-3烷基或R 1是C 1-2烷基，R 2是在2-或4-位被氯，甲基，甲氧基或 甲氧羰基; 或R 1和R 2与它们所连接的氮原子一起代表式（II）的基团，其中R 7是氢或甲基，R 8表示氢，羟基，氟二甲基氨基 ，C 1-4烷氧基或苄氧基，m为0,1或2; R 3表示选自C 1-6烷基的基团; 苯基或被一个或两个独立地选自C 1-3烷基，C 1-4烷氧基或卤素的基团取代的苯基; 或噻吩基; R 4是式（III）或（IV）的基团。

公开(公告)号：WO1995028391A1

公开(公告)日：1995-10-26

申请号：PCT/EP1995001336

申请日：1995-04-13

Applicant: GLAXO WELLCOME INC. ,  AQUINO, Christopher, Joseph ,  DEZUBE, Milana ,  HENKE, Brad, Richard ,  BRACKEEN, Marcus ,  JEFFS, Peter, Walter ,  SUH, Edward, Martin ,  HIRST, Gavin, Charles ,  SUGG, Elizabeth, Ellen ,  WILLSON, Timothy, Mark ,  MOMTAHEN, Tanya

Inventor： GLAXO WELLCOME INC.

IPC: C07D243/12

CPC classification number: C07D401/04 ,  C07D243/12 ,  C07D401/14 ,  C07D403/06 ,  C07D405/06 ,  C07D409/06 ,  C07D409/14 ,  C07D413/06 ,  C07D471/04

Abstract: 1,5 Benzodiazepine compounds of formula (I), where R is selected from C1-C6alkyl, C3-C6cycloalkyl, phenyl, or substituted phenyl; R is selected from C3-C6alkyl, C3-C6cycloalkyl, C3-C6alkenyl, benzyl, phenylC1-C3alkyl or substituted phenyl; or NR R together form 1,2,3,4-tetrahydroquinoline or benzazepine, mono-, di-, or trisubstituted independently with C1-6alkyl, C1-6alkoxy or halogen substituents; p is an integer 0 or 1; q is an integer 0 or 1; r is an integer 0 or 1; t is an integer 0 or 1, provided that when r is 0 then t is 0; R , R and R are independently hydrogen or C1-6alkyl; R is C1-6alkyl or C1-6alkenyl; R is selected from the group consisting of hydrogen, C1-6alkyl, C1-6cycloalkyl, C1-6alkenyl, phenyl, substituted phenyl, napthyl, heteroaryl, substituted heteroaryl, bicycloheteroaryl or substituted bicycloheteroaryl; or NR R together form a saturated 5, 6 or 7 membered ring optionally interrupted by 1, 2, 3 or 4 N, S or O heteroatoms, with the proviso that any two O or S atoms are not bonded to each other; m is an integer selected from the group of 0, 1, 2, 3 or 4; R and R are selected from a variety of substituents; Z is hydrogen or halogen; novel intermediates, a pharmaceutical composition for treating obesity, gall bladder stasis, disorders of pancreatic secretion, methods for such treatment and processes for preparing compounds of formula (I).

Abstract translation: 1.5式（I）的苯并二氮杂化合物，其中R 1选自C 1 -C 6烷基，C 3 -C 6环烷基，苯基或取代的苯基; R 2选自C 3 -C 6烷基，C 3 -C 6环烷基，C 3 -C 6烯基，苄基，苯基C 1 -C 3烷基或取代的苯基; 或NR 1 R 2一起形成1,2,3,4-四氢喹啉或苯并氮杂，独立地与C 1-6烷基，C 1-6烷氧基或卤素取代基单取代，二取代或三取代; p是整数0或1; q是整数0或1; r为整数0或1; t为整数0或1，条件是当r为0时，t为0; R 3，R 5和R 6独立地是氢或C 1-6烷基; R 4是C 1-6烷基或C 1-6烯基; R 7选自氢，C 1-6烷基，C 1-6环烷基，C 1-6烯基，苯基，取代的苯基，萘基，杂芳基，取代的杂芳基，双环杂芳基或取代的双环杂芳基; 或NR 6 R 7一起形成任选被1,2,3或4个N，S或O杂原子间隔的饱和的5,6或7元环，条件是任何两个O或S原子不结合 对彼此; m是选自0,1,2,3或4的整数; R 8和R 9选自多种取代基; Z是氢或卤素; 新型中间体，用于治疗肥胖的药物组合物，胆囊淤滞，胰腺分泌障碍，这种治疗方法和制备式（I）化合物的方法。

公开(公告)号：WO1995028399A1

公开(公告)日：1995-10-26

申请号：PCT/EP1995001335

申请日：1995-04-13

Applicant: GLAXO WELLCOME INC. ,  AQUINO, Christopher, Joseph ,  DEZUBE, Milana ,  SUGG, Elizabeth, Ellen ,  SHERRILL, Ronald, George ,  WILLSON, Timothy, Mark ,  SZEWCZYK, Jerzy, Ryszard

Inventor： GLAXO WELLCOME INC.

IPC: C07D403/12

CPC classification number: C07D401/04 ,  A61K31/55 ,  A61K31/5513 ,  C07D243/24 ,  C07D403/06 ,  C07D403/12 ,  C07D487/04

Abstract: A method of inducing a Cholescystokinin-A receptor agonist response in a mammal by administering a compound of formula (I), where R is C1-C6alkyl, C3-6cycloalkyl, phenyl, or substituted phenyl; R is C3-6alkyl, C3-6cycloalkyl, C3-6alkenyl, benzyl, phenylC1-3alkyl or substituted phenyl; or NR R together form 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroquinoline or benzazepine mono-, di-, or trisubstituted independently with C1-6alkyl, C1-6alkoxy or halogen substituents; n is an integer selected from the group consisting of 0, 1, 2 or 3; p is the integer 0 or 1; q is the integer 0 or 1; r is the integer 0 or 1, provided that when q is 0 then r is 0; R , R , R and R are selected from a variety of substituents; X is nitrogen, nitroso or R ; m is an integer selected from the group consisting of 0, 1, 2 or 3; Y and Z are hydrogen or halogen, novel intermediates, a pharmaceutical composition for treating obesity, gall bladder stasis, disorders of pancreatic secretion, methods for such treatment and processes for preparing compounds of formula (I).

Abstract translation: 通过施用式（I）化合物，其中R 1是C 1 -C 6烷基，C 3-6环烷基，苯基或取代的苯基，在哺乳动物中诱导Cholescystokinin-A受体激动剂应答的方法; R 2是C 3-6烷基，C 3-6环烷基，C 3-6烯基，苄基，苯基C 1-3烷基或取代的苯基; 或NR 1 R 2一起形成1,2,3,4-四氢喹啉，1,2,3,4-四氢喹啉或苯并氮杂单独，二或三取代为C 1-6烷基，C 1-6烷氧基或 卤素取代基; n是选自0,1,2或3的整数; p是整数0或1; q是整数0或1; r为整数0或1，条件是当q为0时，r为0; R 3，R 4，R 5和R 8选自多种取代基; X是氮，亚硝基或R 8; m是选自0,1,2或3的整数; Y和Z是氢或卤素，新的中间体，用于治疗肥胖的药物组合物，胆囊淤滞，胰腺分泌障碍，这种治疗的方法和制备式（I）化合物的方法。