公开(公告)号：US06479531B1

公开(公告)日：2002-11-12

申请号：US09831385

申请日：2001-08-02

申请人： Sarkis Barret Kalindjian ,  Ildiko Maria Buck ,  Ian Duncan Linney ,  Paul Trevor Wright ,  Iain Mair McDonald ,  Katherine Isobel Mary Steel ,  Robert Antony David Hull ,  Sonia Patricia Roberts ,  John David Gaffen ,  Jeremy Gilbert Vinter ,  Martin Keith Walker ,  James Whyte Black ,  Gillian Fairfull Watt ,  Elaine Anne Harper ,  Nigel Paul Shankley ,  Matthew John Tozer ,  David John Dunstone ,  Michael John Pether ,  Elliot James Lilley ,  David Andrew Sykes ,  Caroline Minli Rachel Low ,  Eric Peter Griffin ,  Laurence Wright

发明人： Sarkis Barret Kalindjian ,  Ildiko Maria Buck ,  Ian Duncan Linney ,  Paul Trevor Wright ,  Iain Mair McDonald ,  Katherine Isobel Mary Steel ,  Robert Antony David Hull ,  Sonia Patricia Roberts ,  John David Gaffen ,  Jeremy Gilbert Vinter ,  Martin Keith Walker ,  James Whyte Black ,  Gillian Fairfull Watt ,  Elaine Anne Harper ,  Nigel Paul Shankley ,  Matthew John Tozer ,  David John Dunstone ,  Michael John Pether ,  Elliot James Lilley ,  David Andrew Sykes ,  Caroline Minli Rachel Low ,  Eric Peter Griffin ,  Laurence Wright

IPC分类号： C07D40306

CPC分类号： C07D233/64 ,  C07D207/34 ,  C07D233/88 ,  C07D233/90 ,  C07D263/34 ,  C07D277/56 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D403/12 ,  C07D405/04

摘要： Compounds of formula (I) and their pharmaceutically acceptable salts are ligands at gastrin and/or cholecystokinin receptors. X and Y are independently ═N—, —N(R5)—═CH—, —S— or —O—. n is from 1 to 4; R1 is H or C1 to C15 hydrocarbyl R2 is selected from H, Me, Et, Pr and OH, R3 is selected from H, Me, Et and Pr; or (when n is greater than 1) each R3 is independently selected from H, Me, Et and Pr, or two R3 groups on neighbouring carbon atoms are linked to form a C3 to C6 carbocylic ring, or R2 and R3 on the same carbon atom together represent an ═O group; R4 is C1 to C15 hydrocarbyl Z is —(NR7)a—CO—(NR8)b— (wherein a is 0 or 1, b is 0 or 1, —CO—NR7—CH2—CO—NR8—, —CO—O—, —CH2—CH2—, —CH═CH—, —CH2—NR8— or a bond; Q is —R9V, or (II), (wherein R9 is —CH2—; —CH2—CH2—; or (III), R9 and R8, together with the nitrogen atom to which R8 is attached, form a piperidine or pyrrolidine ring which is substituted by V; V is —CO—NH—SO2—Ph, —SO2—NH—CO—Ph, —CH2OH, or a group of the formula —R10U, (wherein U is —COOH, tetrazolyl, —CONHOH— or —SO3H; and R10 is a bond; C1 to C6 hydrocarbylene, —O—(C1 to C3 alkylene)—; —SO2NR11—CHR12—; —CO—NR11—CHR12—, or —NH—(CO)c—CH2—, c being 0 or 1).

摘要翻译： 式（I）化合物及其药学上可接受的盐是胃泌素和/或胆囊收缩素受体的配体。 X和Y独立地为= N-，-N（R 5） - = CH - ， - S-或-O-。 n为1至4; R1为H或C1至C15烃基R2选自H，Me，Et，Pr和OH，R3选自H，Me，Et和Pr; 或（当n大于1时），每个R 3独立地选自H，Me，Et和Pr，或相邻碳原子上的两个R 3基团连接形成C 3至C 6碳环，或在相同碳上的R 2和R 3 原子一起代表a = O组; R4为C1〜C15烃基Z为 - （NR7）a-CO-（NR8）b-（其中a为0或1，b为0或1，-CO-NR7-CH2-CO-NR8-，-CO- O，-CH 2 -CH 2 - ， - CH = CH - ， - CH 2 -NR 8 - 或键; Q为-R 9 V或（II）（其中R 9为-CH 2 - ; -CH 2 -CH 2 - III），R9和R8与R8所连接的氮原子一起形成被V取代的哌啶或吡咯烷环; V是-CO-NH-SO 2-Ph，-SO 2 -NH-CO-Ph， -CH 2 OH或式-R 10 U的基团（其中U为-COOH，四唑基，-CONHOH-或-SO 3 H; R 10为键; C 1至C 6亚烃基，-O-（C 1至C 3亚烷基） - ; -SO2NR11-CHR12-; -CO-NR11-CHR12-或-NH-（CO）c-CH2-，c为0或1）。

公开(公告)号：US06878734B2

公开(公告)日：2005-04-12

申请号：US10275741

申请日：2001-05-04

申请人： Sarkis Barret Kalindjian ,  Ildiko Maria Buck ,  Katherine Isobel Mary Steel ,  Paul Trevor Wright ,  Matthew John Tozer ,  Michael John Pether ,  Caroline Minli Rachel Low

发明人： Sarkis Barret Kalindjian ,  Ildiko Maria Buck ,  Katherine Isobel Mary Steel ,  Paul Trevor Wright ,  Matthew John Tozer ,  Michael John Pether ,  Caroline Minli Rachel Low

IPC分类号： A61K31/42 ,  A61K45/06 ,  A61P1/04 ,  C07D233/54 ,  C07D403/04 ,  C07D413/04 ,  C07D417/04 ,  A61K31/415 ,  C07D233/06 ,  C07D237/08 ,  C07D247/02 ,  C07D405/04 ,  C07D413/02

CPC分类号： C07D233/64 ,  A61K31/42 ,  A61K45/06 ,  C07D403/04 ,  C07D413/04 ,  C07D417/04 ,  A61K2300/00

摘要： Ligands for the gastrin and cholecystokinin (CCK) receptors are provided, together with methods for preparing such ligands, and compounds which are useful intermediates in such methods. Pharmaceutical compositions comprising such ligands, methods for preparing such pharmaceutical compositions, and methods of treatment using these compositions also are provided. The ligands have the formula (I): where n is from 1 to 3; X and Y are independently ═N— or —N(R5)— where R5 is selected from the group consisting of H, Me, Et, Pr, Bn, —OH and —CH2COOR6, where R6 represents H, Me, Et, Pr or Bn; R1 is H or a C1-C15 saturated carbocylic ring optionally substituted with OMe, NMe2, CF3, Me, F, Cl, Br or I where up to three H atoms may optionally be replaced by halogen atoms; R2 is selected from H, Me, Et, Pr and OH, each R2 being independently selected from H, Me, Et, Pr and OH when n is greater than 1; R3 is selected from the group consisting of H, Me, Et and Pr when n is 1; or, when n is greater than 1, each R3 is independently selected from the group consisting of H, Me, Et and Pr, or two R3 groups on neighbouring carbon atoms are linked to form a C3 to C6 carbocylic ring, or two R3 groups are absent from neighbouring carbon atoms which are linked by a double bond; or R2 and R3 on the same carbon atom together represent an ═O group; R4 is H or a C3 to C10 alicyclic ring where up to three H atoms may optionally be replaced by halogen atoms; Z is selected from the group consisting of: Q is a 6-membered aromatic carbocycle substituted with 1 or 2 V groups and optionally substituted with 1, 2 or 3 T groups; V is selected from the group consisting of —CO—NH—SO2—Ph, —SO2—NH—CO—Ph, —CH2OH, or a group of the formula —R7U, where U is selected from the group consisting of —COOH, tetrazolyl, —CONHOH and —SO3H; and R7 is selected from the group consisting of a bond; C1 to C6 hydrocarbylene, optionally substituted by hydroxy, amino or acetamido; —O—(C1 to C3 alkylene)-; —SO2NR8—CHR9—; —CO—NR8—CHR9—, where R8 and R9 are independently selected from H and methyl; and —NH—(CO)c—CH2—, where c is 0 or 1.