公开(公告)号：CA2492430A1

公开(公告)日：2004-01-22

申请号：CA2492430

申请日：2003-07-16

Applicant: CELLTECH R&D LTD

Inventor： BAILEY STUART ,  BRAND STEPHEN ,  BROWN JULIEN ALISTAIR

IPC: A61K31/4375 ,  A61K31/496 ,  A61K31/5377 ,  A61P1/04 ,  A61P3/10 ,  A61P9/00 ,  A61P11/06 ,  A61P17/00 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P29/00 ,  A61P37/06 ,  A61P43/00 ,  C07D471/04 ,  C07D221/00

Abstract: Phenylalanine enamide derivatives of formula (1) are described, wherein R1is a -CH(CH3)2, -(CH2)2CH3; -CH2C(CH3)3, -CH2CH2OH, -CH2CH2OCH3, -CH2CH2OCH2CH2OH , - CH2CH2OCH2CH2OCH3, formula (A) group; and the salts, solvates and N-oxides thereof. Compounds according to the invention are potent and selective inhibitors of .alpha.4 integrins. The compounds are of use in modulating cel l adhesion and in particular are of use in the prophylaxis and treatment of diseases or disorders including inflammation in which the extravasation of leukocytes plays a role and the invention extends to such a use and to the u se of the compounds for the manufacture of a medicament for treating such diseases or disorders.

公开(公告)号：NO20033710L

公开(公告)日：2003-10-22

申请号：NO20033710

申请日：2003-08-20

Applicant: CELLTECH R&D LTD

Inventor： BAILEY STUART ,  BROWN JULIEN ALISTAIR ,  BRAND STEPHEN ,  JOHNSON JAMES ANDREW ,  PORTER JOHN ROBERT ,  HEAD JOHN CLIFFORD

IPC: A61K31/198 ,  A61K31/4375 ,  A61K31/44 ,  A61K31/4406 ,  A61K31/497 ,  A61P3/10 ,  A61P9/00 ,  A61P17/00 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P29/00 ,  A61P37/00 ,  A61P37/06 ,  A61P43/00 ,  C07C229/34 ,  C07C229/46 ,  C07C233/82 ,  C07C321/22 ,  C07C323/30 ,  C07D213/81 ,  C07D213/89 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D471/04

Abstract: Phenylalanine enamide derivatives of formula (1) are described: wherein R 1 , R x , R y , R z , X and V are as defined in claim 1. The compounds are able to inhibit the 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：NO20033710D0

公开(公告)日：2003-08-20

申请号：NO20033710

申请日：2003-08-20

Applicant: CELLTECH R&D LTD

Inventor： BAILEY STUART ,  BROWN JULIEN ALISTAIR ,  BRAND STEPHEN ,  JOHNSON JAMES ANDREW ,  PORTER JOHN ROBERT ,  HEAD JOHN CLIFFORD

IPC: A61K31/198 ,  A61K31/4375 ,  A61K31/44 ,  A61K31/4406 ,  A61K31/497 ,  A61P3/10 ,  A61P9/00 ,  A61P17/00 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P29/00 ,  A61P37/00 ,  A61P37/06 ,  A61P43/00 ,  C07C229/34 ,  C07C229/46 ,  C07C233/82 ,  C07C321/22 ,  C07C323/30 ,  C07D213/81 ,  C07D213/89 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D471/04 ,  C07D

Abstract: Phenylalanine enamide derivatives of formula (1) are described: wherein R 1 , R x , R y , R z , X and V are as defined in claim 1. The compounds are able to inhibit the 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：NZ540232A

公开(公告)日：2007-06-29

申请号：NZ54023202

申请日：2002-01-18

Applicant: CELLTECH R&D LTD

Inventor： BAILEY STUART ,  BROWN JULIEN ALISTAIR ,  BRAND STEPHEN ,  JOHNSON JAMES ANDREW ,  PORTER JOHN ROBERT ,  HEAD JOHN CLIFFORD

IPC: A61K31/198 ,  A61K31/4375 ,  A61K31/44 ,  A61K31/4406 ,  A61K31/497 ,  A61P3/10 ,  A61P9/00 ,  A61P17/00 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P29/00 ,  A61P37/00 ,  A61P37/06 ,  A61P43/00 ,  C07C229/34 ,  C07C229/46 ,  C07C233/82 ,  C07C321/22 ,  C07C323/30 ,  C07D213/81 ,  C07D213/89 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D471/04 ,  C07C229/36

Abstract: Disclosed are phenylalanine enamide derivatives of formula (1) wherein: R1 is a group Ar1L2Alk- as defined in the specification; X is an -N(R2)- group wherein R2 is H or C1-6alkyl; V is O; Rx, Ry and Rz may be the same or different and each represent L1(Alk1)n(R3)v as defined in the specification; n is zero or 1; and v is 1, 2 or 3. Compounds of the type disclosed are selective inhibitors of alpha-4 integrins.

公开(公告)号：AR040579A1

公开(公告)日：2005-04-13

申请号：ARP030102550

申请日：2003-07-16

Applicant: CELLTECH R&D LTD

Inventor： BROWN JULIEN ALISTAIR ,  BAILEY STUART ,  BRAND STEPHEN

IPC: A61K31/4409 ,  A61P1/04 ,  A61P3/10 ,  A61P7/00 ,  A61P9/00 ,  A61P11/06 ,  A61P17/00 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P29/00 ,  A61P37/06 ,  C07D213/81 ,  A61K31/44

Abstract: Se describen derivados de fenilalanina enamida de fórmula (1) donde R1 es un grupo -CH3, -(CH2)3CH3, -CH2CH2OH, -CH2CH2OCH3, -CH2CH2OCH2CH2OH, -CH2CH2OCH2CH2OCH3, o como se muestra en los restos de fórmulas (2) y (3) y sus sales, solvatos y N-óxidos. Los compuestos de acuerdo con la presente son inhibidores potentes y selectivos de las alfa4-integrinas. Los compuestos son útiles en la modulación de la adhesión celular y en particular son útiles para la profilaxis y tratamiento de enfermedades o desórdenes que incluyen inflamaciones en las que la extravasación de los leucocitos desempena un papel, y la presente se extiende a dicho uso y al uso de los compuestos para la fabricación de un medicamento para el tratamiento de dichas enfermedades o desórdenes.

公开(公告)号：CA2492381A1

公开(公告)日：2004-01-22

申请号：CA2492381

申请日：2003-07-16

Applicant: CELLTECH R&D LTD

Inventor： BAILEY STUART ,  BROWN JULIEN ALISTAIR ,  BRAND STEPHEN

IPC: A61K31/4409 ,  A61P1/04 ,  A61P3/10 ,  A61P7/00 ,  A61P9/00 ,  A61P11/06 ,  A61P17/00 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P29/00 ,  A61P37/06 ,  C07D213/81 ,  C07D413/12 ,  C07D401/12 ,  A61K31/44 ,  A61K31/4433 ,  A61K31/444

Abstract: Phenylalanine enamide derivatives of formula (1) are described: wherein R1 i s a -CH3, -(CH2)3CH3, -CH2CH20H, -CH2CH20CH3, -CH2CH20CH2CH20H, - CH2CH20CH2CH20CH3, Formula (II) group; and the salts, solvates and N-oxides thereof. Compounds according to the invention are potent and selective inhibitors of oA integrins. The compounds are of use in modulating cell adhesion and in particular are of use in the prophylaxis and treatment of diseases or disorders including inflammation in which the extravasation of leukocytes plays a role and the invention extends to such a use and to the u se of the compounds for the manufacture of a medicament for treating such diseases or disorders.

公开(公告)号：HU0303160A2

公开(公告)日：2003-12-29

申请号：HU0303160

申请日：2002-01-18

Applicant: CELLTECH R&D LTD

Inventor： BAILEY STUART ,  BRAND STEPHEN ,  BROWN JULIEN ALISTAIR ,  HEAD JOHN CLIFFORD ,  JOHNSON JAMES ANDREW ,  PORTER JOHN ROBERT

IPC: A61K31/198 ,  A61K31/4375 ,  A61K31/44 ,  A61K31/4406 ,  A61K31/497 ,  A61P3/10 ,  A61P9/00 ,  A61P17/00 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P29/00 ,  A61P37/00 ,  A61P37/06 ,  A61P43/00 ,  C07C229/34 ,  C07C229/46 ,  C07C233/82 ,  C07C321/22 ,  C07C323/30 ,  C07D213/81 ,  C07D213/89 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D471/04

Abstract: Phenylalanine enamide derivatives of formula (1) are described: wherein R 1 , R x , R y , R z , X and V are as defined in claim 1. The compounds are able to inhibit the 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：SK286991B6

公开(公告)日：2009-09-07

申请号：SK10322003

申请日：2002-01-18

Applicant: CELLTECH R&D LTD

Inventor： BAILEY STUART ,  BROWN JULIEN ALISTAIR ,  BRAND STEPHEN ,  JOHNSON JAMES ANDREW ,  PORTER JOHN ROBERT ,  HEAD JOHN CLIFFORD

IPC: C07D213/00 ,  A61K31/198 ,  A61K31/4375 ,  A61K31/44 ,  A61K31/4406 ,  A61K31/497 ,  A61P3/10 ,  A61P9/00 ,  A61P17/00 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P29/00 ,  A61P37/00 ,  A61P37/06 ,  A61P43/00 ,  C07C229/00 ,  C07C229/34 ,  C07C229/46 ,  C07C233/82 ,  C07C321/22 ,  C07C323/30 ,  C07D213/81 ,  C07D213/89 ,  C07D401/00 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D471/00 ,  C07D471/04

Abstract: Disclosed are phenylalanine enamide derivatives of formula (1), wherein R1 is a group Ar1L2Ar2Alk- and the salts, solvates, hydrates and N-oxides thereof, pharmaceutical composition comprising said compounds, ethyl (2S)-2-(2-bromo-3oxo- spiro[3.5]non-1-en-1-ylamino)-3-{4-[(3,5- dichloroisonicotinoyl)amino]phenyl}propanoate, pharmaceutical composition comprising said compound and the use of ethyl (2S)-2-(2-bromo-3oxo-spiro[3.5]non-1-en-1-ylamino)-3-{4-[(3,5- dichloroisonicotinoyl)amino]phenyl}propanoate for preparing medicines for the treatment and/or prevention of rheumatoid arthritis, multiple sclerosis, asthma or inflammatory bowel diseases.

公开(公告)号：AT367390T

公开(公告)日：2007-08-15

申请号：AT03740814

申请日：2003-07-16

Applicant: CELLTECH R&D LTD

Inventor： BROWN JULIEN ALISTAIR ,  BAILEY STUART ,  BRAND STEPHEN

IPC: C07D471/04 ,  A61K31/4375 ,  A61K31/496 ,  A61K31/5377 ,  A61P1/04 ,  A61P3/10 ,  A61P9/00 ,  A61P11/06 ,  A61P17/00 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P29/00 ,  A61P37/06 ,  A61P43/00 ,  C07D221/00

Abstract: Phenylalanine enamide derivatives of formula (1) are described:wherein R is a -CH(CH3)2, -(CH2)2CH3, -CH2C(CH3)3, -CH2CH2OH, -CH2CH2OCH3, -CH2CH2OCH2CH2OH, -CH2CH2OCH2CH2OCH3,group; and the salts, solvates and N-oxides thereof.Compounds according to the invention are potent and selective inhibitors of alpha4 integrins. The compounds are of use in modulating cell adhesion and in particular are of use in the prophylaxis and treatment of diseases or disorders including inflammation in which the extravasation of leukocytes plays a role and the invention extends to such a use and to the use of the compounds for the manufacture of a medicament for treating such diseases or disorders.

公开(公告)号：NZ528134A

公开(公告)日：2005-09-30

申请号：NZ52813402

申请日：2002-01-18

Applicant: CELLTECH R&D LTD

Inventor： BAILEY STUART ,  BROWN JULIEN ALISTAIR ,  BRAND STEPHEN ,  JOHNSON JAMES ANDREW ,  PORTER JOHN ROBERT ,  HEAD JOHN CLIFFORD

IPC: A61K31/198 ,  A61K31/4375 ,  A61K31/44 ,  A61K31/4406 ,  A61K31/497 ,  A61P3/10 ,  A61P9/00 ,  A61P17/00 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P29/00 ,  A61P37/00 ,  A61P37/06 ,  A61P43/00 ,  C07C229/34 ,  C07C229/46 ,  C07C233/82 ,  C07C321/22 ,  C07C323/30 ,  C07D213/81 ,  C07D213/89 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D471/04 ,  C07C229/36

Abstract: Phenylalanine enamide derivatives of formula (I) are described: wherein R1 is a group Ar1L2Ar2Alk- in which: Ar1 is an optionally substituted aromatic or heteroaromatic group; L2 is a covalent bond or a linker atom or group; Ar2 is an optionally substituted arylene or heteroarylene group; and Alk is a chain -CH2-CH(R)-, -CH=C(R)- or -CH(CH2R)- X is an -N(R2) group; V is an oxygen (O) or sulphur (S) atom; RX and RY are joined together to form an optionally substituted spiro linked cycloaliphatic or heterocycloaliphatic group; and RZ represents a halogen atom, or, -L1(Alk1)n(R3)v in which L is a covalent bond or a linker atom or group, Alk1 is an optionally substituted aliphatic or heteroaliphatic chain, R3 is a hydrogen or halogen atom or group selected from -OR3a [where R3a is a hydrogen atom or an optionally substituted alkyl or cycloalkyl], SR3a, -CN or an optionally substituted cycloaliphatic, heterocycloaliphatic, polycycloaliphatic, heteropolycycloaIiphatic, aromatic or heteroaromatic group, n is zero or the integer 1 and v is the integer 1, 2 or 3 provided that when n is zero and L is a covalent bond v is the integer 1; and the salts, solvates, hydrates and N-oxides thereof. Furthermore compounds of formula (I) are able to inhibit the binding of integrins to their ligands and described is the use of compounds of formula (I) for the manufacture of a medicament for the treatment and/or prevention of immuno or inflammatory disorders or disorders involving the inappropriate growth or migration of cells.