公开(公告)号：WO0179173A2

公开(公告)日：2001-10-25

申请号：PCT/GB0101682

申请日：2001-04-12

Applicant: CELLTECH R&D LTD ,  NORMAN TIMOTHY JOHN ,  PORTER JOHN ROBERT ,  HUTCHINSON BRIAN WOODSIDE ,  RATCLIFFE ANDREW JAMES ,  HEAD JOHN CLIFFORD ,  ALEXANDER RIKKI PETER ,  LANGHAM BARRY JOHN ,  WARRELLOW GRAHAM JOHN ,  ARCHIBALD SARAH CATHERINE ,  LINSLEY JANEEN MARSHA

Inventor： NORMAN TIMOTHY JOHN ,  PORTER JOHN ROBERT ,  HUTCHINSON BRIAN WOODSIDE ,  RATCLIFFE ANDREW JAMES ,  HEAD JOHN CLIFFORD ,  ALEXANDER RIKKI PETER ,  LANGHAM BARRY JOHN ,  WARRELLOW GRAHAM JOHN ,  ARCHIBALD SARAH CATHERINE ,  LINSLEY JANEEN MARSHA

IPC: A61K31/198 ,  A61K31/223 ,  A61K31/4375 ,  A61K31/4409 ,  A61K31/4436 ,  A61K31/4545 ,  A61K31/472 ,  A61P1/04 ,  A61P3/10 ,  A61P11/06 ,  A61P17/00 ,  A61P17/02 ,  A61P17/06 ,  A61P19/02 ,  A61P19/08 ,  A61P19/10 ,  A61P21/00 ,  A61P25/28 ,  A61P29/00 ,  A61P37/06 ,  A61P43/00 ,  C07C229/36 ,  C07D213/81 ,  C07D217/22 ,  C07D409/12 ,  C07D471/04 ,  A61K31/44 ,  C07C225/20

CPC classification number: C07D213/81 ,  C07C229/36 ,  C07C2601/10 ,  C07D217/22 ,  C07D471/04

Abstract: Enamine derivatives of formula (1) are described. In said formula , R a group Ar L Ar Alk- in which Ar is an aromatic or heteroaromatic group, L is a covalent bond or a linker atom or group, Ar is an arylene or heteroarylene group and Alk is a chain -CH2-CH(R)-, -CH=C(R)- or (a) in which R is a carboxylic acid or a derivative or biostere thereof; R is a hydrogen atom or a C1-6alkyl group; Cy is a cycloaliphatic or heterocycloaliphatic ring in which X is a N atom or a C(R ) group; R is a oxo, thioxo, or imino group; R and R are each a hydrogen atom or optional substituent; provided that Cy is not a cyclobutenedione group; and the salts, solvates, hydrates and N-oxides thereof. The compounds are able to inhibit the binding of integrins to their ligands and are of use in the prophylaxis and treatment of immune or inflammatory disorders, or disorders involving the inappropriate growth or migration of cells.

Abstract translation: 描述式（1）的烯胺衍生物。 在所述式中，R 1，Ar 1，Ar 2，Ar 2 Al，其中Ar 1是芳族或杂芳族基团，L 2是共价键或连接原子或 基团，Ar 2是亚芳基或亚杂芳基，Alk是链-CH 2 -CH（R） - ， - CH = C（R） - 或（a）其中R是羧酸或衍生物或生物固体 物; R 2是氢原子或C 1-6烷基; Cy是其中X是N原子或C（R））基团的脂环族或杂脂环族环; R x是氧代，硫代或亚氨基; R w和R z各自为氢原子或任选的取代基; 只要Cy不是环丁烯二酮基团; 及其盐，溶剂合物，水合物和N-氧化物。 这些化合物能够抑制整联蛋白与其配体的结合，并且可用于预防和治疗免疫或炎性疾病或涉及细胞不适当生长或迁移的病症。

公开(公告)号：AT270266T

公开(公告)日：2004-07-15

申请号：AT00987574

申请日：2000-12-22

Applicant: CELLTECH R&D LTD

Inventor： LANGHAM BARRY JOHN ,  ALEXANDER RIKKI PETER ,  HEAD JOHN CLIFFORD ,  LINSLEY JANEEN MARSHA ,  PORTER JOHN ROBERT ,  ARCHIBALD SARAH CATHERINE ,  WARRELLOW GRAHAM JOHN

IPC: C07C229/34 ,  C07C229/36 ,  C07D471/04 ,  C07C225/20 ,  C07C229/46 ,  C07D295/12 ,  A61K31/13 ,  A61K31/435 ,  A61P29/00

Abstract: Squaric acid derivatives of formula (1) are described:whereinR1 is a group Ar1Ar2Alk- in whichAr1 is an optionally substituted aromatic or heteroaromatic group;Ar2 is an optionally substituted phenylene or nitrogen-containing six-membered heteroarylene group; and Alk is a chain-CH2-CH(R)-, -CH=C(R)-,in which R is a carboxylic acid (-CO2H) or a derivative or biostere thereof;R2 is a hydrogen atom or a C1-6 alkyl group;L1 is a covalent bond or a linker atom or group;n is zero or the integer 1;Alk1 is an optionally substituted aliphatic chain;R3 is a hydrogen atom or an optionally substituted heteroaliphatic, cycloaliphatic, heterocycloaliphatic, polycycloaliphatic, heteropolycycloaliphatic, aromatic or heteroaromatic group: and the salts, solvates, hydrates and N-oxides thereof.The compounds are able to inhibit the binding of integrins to their ligands and are of use in the prophylaxis and treatment of immune or inflammatory disorders, or disorders involving the inappropriate growth or migration of cells.

公开(公告)号：ES2223639T3

公开(公告)日：2005-03-01

申请号：ES00987574

申请日：2000-12-22

Applicant: CELLTECH R&D LTD

Inventor： LANGHAM BARRY JOHN ,  ALEXANDER RIKKI PETER ,  HEAD JOHN CLIFFORD ,  LINSLEY JANEEN MARSHA ,  PORTER JOHN ROBERT ,  ARCHIBALD SARAH CATHERINE

IPC: C07C229/34 ,  C07C229/36 ,  C07D471/04 ,  C07C225/20 ,  C07C229/46 ,  C07D295/12 ,  A61K31/13 ,  A61K31/435 ,  A61P29/00

Abstract: Un compuesto de fórmula (1): en la que R1 es un grupo Ar1Ar2Alk- en el que: Ar1 es un grupo aromático o heteroaromático opcionalmente sustituido; Ar2 es un grupo fenileno opcionalmente sustituido o un grupo heteroarileno de seis miembros que contiene nitrógeno; y Alk es una cadena en la que R es un ácido carboxílico (-CO2H) o un derivado o bióstero del mismo; R2 es un átomo de hidrógeno o un grupo alquilo C1-6; L1 es un enlace covalente o un átomo o grupo de engarce; n es cero o el número entero 1; Alk1 es una cadena alifática opcionalmente sustituida; R3 es un átomo de hidrógeno o un grupo heteroalifático, cicloalifático, heterocicloalifático, policicloalifático, heteropolicicloalifático, aromático o heteroaromático opcionalmente sustituido; y las sales, solvatos, hidratos y N-óxidos del mismo.

公开(公告)号：AU5088900A

公开(公告)日：2000-12-18

申请号：AU5088900

申请日：2000-05-26

Applicant: CELLTECH R&D LTD

Inventor： LANGHAM BARRY JOHN ,  ALEXANDER RIKKI PETER ,  HEAD JOHN CLIFFORD ,  LINSLEY JANEEN MARSHA ,  PORTER JOHN ROBERT ,  ARCHIBALD SARAH CATHERINE ,  WARRELOW GRAHAM JOHN

IPC: A61K31/198 ,  A61K31/223 ,  A61K31/381 ,  A61K31/4375 ,  A61K31/4409 ,  A61K31/472 ,  A61K31/505 ,  A61P7/00 ,  A61P29/00 ,  A61P37/00 ,  A61P43/00 ,  C07B61/00 ,  C07C229/34 ,  C07C229/36 ,  C07C233/55 ,  C07C233/81 ,  C07C235/16 ,  C07C235/24 ,  C07C235/56 ,  C07C235/64 ,  C07C235/84 ,  C07C237/40 ,  C07C255/57 ,  C07C271/22 ,  C07C271/28 ,  C07C271/58 ,  C07D213/79 ,  C07D213/81 ,  C07D215/42 ,  C07D217/22 ,  C07D239/34 ,  C07D239/42 ,  C07D239/88 ,  C07D239/94 ,  C07D241/42 ,  C07D241/44 ,  C07D295/135 ,  C07D333/40 ,  C07D333/70 ,  C07D471/04 ,  C07D295/12 ,  A61K31/122 ,  A61K31/44

Abstract: Squaric acid Derivatives of formula (1) are described: wherein R1 is an integrin binding group; R2 is a hydrogen atom or a C1-6alkyl group; L1 is a covalent bond or a linker atom or group; n is zero or the integer 1; Alk1 is an optionally substituted aliphatic chain; R3 is a hydrogen atom or an optionally substituted heteroaliphatic, cycloaliphatic, heterocycloaliphatic, polycycloaliphatic, polyheterocycloaliphatic, aromatic or heteroaromatic group: and the salts, solvates, hydrates and N-oxides thereof. The compounds are able to inhibit the binding of integrins to their ligands and are of use in the prophylaxis and treatment of immune of inflammatory disorders, or disorders involving the inappropriate growth or migration of cells.

公开(公告)号：CA2410640A1

公开(公告)日：2001-12-06

申请号：CA2410640

申请日：2001-05-30

Applicant: CELLTECH R&D LTD

Inventor： LINSLEY JANEEN MARSHA ,  ALEXANDER RIKKI PETER ,  LANGHAM BARRY JOHN ,  ARCHIBALD SARAH CATHERINE ,  WARRELOW GRAHAM JOHN ,  PORTER JOHN ROBERT ,  HEAD JOHN CLIFFORD

IPC: A61K31/472 ,  A61K31/4725 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/55 ,  A61K31/551 ,  A61P29/00 ,  A61P37/00 ,  C07D217/22 ,  C07D217/24 ,  C07D401/12 ,  C07D401/14 ,  C07D413/12 ,  C07D417/12 ,  C07D487/08 ,  C07D403/12

Abstract: 3-Substituted isoquinoline containing squaric acids of formula (1) are described wherein Ar1 is a 3-substituted isoquinolin-1-yl group; L2 is a covalent bond or a linker atom or group; Ar2 is an optionally substituted aromatic or heteroanomatic chain; Alk is a chain (a), (b), (c) or (d) in whi ch R is a carboxylic acid (-CO2H) or a derivative or biostere thereof; R1 is a hydrogen atom or a C1-6alkyl group; L1 is a covalent bond or a linker atom o r group; Alk1 is an optionally substituted aliphatic chain; n is zero or the integer 1; R2 is a hydrogen atom or an optionally substituted heteroaliphati c, cycloaliphatic, heterocycloaliphatic, polycycloaliphatic, heteropolycycloaliphatic, aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof. The compounds are able to inhibit t he binding of integrins to their ligands and are of use in the prophylaxis and treatment of immune or inflammatory disorder or disorders involving the inappropriate growth or migration of cells.

公开(公告)号：CA2409617A1

公开(公告)日：2001-12-06

申请号：CA2409617

申请日：2001-05-30

Applicant: CELLTECH R&D LTD

Inventor： LANGHAM BARRY JOHN ,  HEAD JOHN CLIFFORD ,  WARRELLOW GRAHAM JOHN ,  LINSLEY JANEEN MARSHA ,  PORTER JOHN ROBERT ,  ARCHIBALD SARAH CATHERINE ,  ALEXANDER RIKKI PETER

IPC: C07D487/08 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/55 ,  A61K31/551 ,  A61P1/04 ,  A61P3/10 ,  A61P11/06 ,  A61P17/06 ,  A61P19/02 ,  A61P25/28 ,  A61P29/00 ,  A61P37/00 ,  A61P37/06 ,  A61P43/00 ,  C07D471/04 ,  C07D519/00 ,  C07D221/00 ,  A61K31/435

Abstract: 2,7-Naphthyridine containing squaric acids of formula (1) are described, wherein Ar1 is an optionally substituted 2,7-naphthridin-1-yl group; L2 is a covalent bond or a linker atom or group; Ar2 is an optionally substituted aromatic or heteroaromatic chain; Alk is a chain (2) in which R is a carboxylic acid (-CO2H) or a derivative or biostere thereof; R1 is a hydroge n atom or a C1-6alkyl group; L1 is a covalent bond or a linker atom or group; Alk1 is an optionally substituted aliphatic chain; n is zero or the integer 1; R2 is a hydrogen atom or an optionally substituted heteroaliphatic, cycloaliphatic, heterocycloaliphatic, polycycloaliphatic, heteropolycycloaliphatic, aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof. The compounds are able to inhibit t he binding of integrins to their ligands and are of use in the prophylaxis and treatment of immuno or inflammatory disorders or disorders involving the inappropriate growth or migration of cells.

公开(公告)号：CA2375218A1

公开(公告)日：2000-12-07

申请号：CA2375218

申请日：2000-05-26

Applicant: CELLTECH R&D LTD

Inventor： LANGHAM BARRY JOHN ,  PORTER JOHN ROBERT ,  LINSLEY JANEEN MARSHA ,  HEAD JOHN CLIFFORD ,  ALEXANDER RIKKI PETER ,  ARCHIBALD SARAH CATHERINE ,  WARRELLOW GRAHAM JOHN

IPC: A61K31/198 ,  A61K31/223 ,  A61K31/381 ,  A61K31/4375 ,  A61K31/4409 ,  A61K31/472 ,  A61K31/505 ,  A61P7/00 ,  A61P29/00 ,  A61P37/00 ,  A61P43/00 ,  C07B61/00 ,  C07C229/34 ,  C07C229/36 ,  C07C233/55 ,  C07C233/81 ,  C07C235/16 ,  C07C235/24 ,  C07C235/56 ,  C07C235/64 ,  C07C235/84 ,  C07C237/40 ,  C07C255/57 ,  C07C271/22 ,  C07C271/28 ,  C07C271/58 ,  C07D213/79 ,  C07D213/81 ,  C07D215/42 ,  C07D217/22 ,  C07D239/34 ,  C07D239/42 ,  C07D239/88 ,  C07D239/94 ,  C07D241/42 ,  C07D241/44 ,  C07D295/135 ,  C07D333/40 ,  C07D333/70 ,  C07D471/04 ,  C07D295/12 ,  A61K31/122 ,  A61K31/44

Abstract: Squaric acid Derivatives of formula (1) are described: wherein R1 is an integrin binding group; R2 is a hydrogen atom or a C1-6 alkyl group; L1 is a covalent bond or a linker atom or group; n is zero or the integer 1; Alk1 is an optionally substituted aliphatic chain; R3 is a hydrogen atom or an optionally substituted heteroaliphatic, cycloaliphatic, heterocycloaliphatic , polycycloaliphatic, polyheterocycloaliphatic, aromatic or heteroaromatic group: and the salts, solvates, hydrates and N-oxides thereof. The compounds are able to inhibit the binding of integrins to their ligands and are of use in the prophylaxis and treatment of immune or inflammatory disorders, or disorders involving the inappropriate growth or migration of cells.