Invention Grant
- Patent Title: Macrocyclic quinazoline derivatives as antiproliferative agents
- Patent Title (中): 大环喹唑啉衍生物作为抗增殖剂
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Application No.: US10558007Application Date: 2004-05-25
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Publication No.: US07648975B2Publication Date: 2010-01-19
- Inventor: Eddy Jean Edgard Freyne , Timothy Pietro Suren Perera , Peter Jacobus Johannes Antonius Buijnsters , Marc Willems , Gaston Stanislas Marcella Diels , Werner Constant Johan Embrechts
- Applicant: Eddy Jean Edgard Freyne , Timothy Pietro Suren Perera , Peter Jacobus Johannes Antonius Buijnsters , Marc Willems , Gaston Stanislas Marcella Diels , Werner Constant Johan Embrechts
- Applicant Address: BE Beerse
- Assignee: Janssen Pharmaceutica N.V.
- Current Assignee: Janssen Pharmaceutica N.V.
- Current Assignee Address: BE Beerse
- Priority: WOPCT/EP03/05723 20030527; WOPCT/EP03/10266 20030915; WOPCT/EP03/51061 20031218
- International Application: PCT/EP2004/005621 WO 20040525
- International Announcement: WO2004/105765 WO 20041209
- Main IPC: A01N43/00
- IPC: A01N43/00 ; A61K31/33 ; C07D487/00 ; C07D491/00 ; C07D513/00

Abstract:
The present invention concerns the compounds of formula (I) the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Z represents O, CH2, NH or S; in particular Z represents NH; Y represents —C3-9alkyl-, —C3-9alkenyl-, —C3-9alkynyl-, —C3-7alkyl-CO—NH— optionally substituted with amino, mono- or di(C1-4alkyl)amino or C1-4 alkyloxycarbonylamino-, —C3-7alkenyl-CO—NH— optionally substituted with amino, mono- or di(C1-4alkyl)amino- or C1-4alkyloxycarbonylamino-, C1-5alkyl-oxy-C1-5alkyl-, —C1-5alkyl NR13—, —C1-5alkyl-, —C1-5alkyl-NR14—CO—C1-5alkyl-, —C1-5alkyl-CO NR15—C1-5alkyl-, —C1-6alkyl-CO—NH—, —C1-6alkyl-NH—CO—, —C1-3alkyl-NH—CS-Het20-, —C1-3alkyl-NH—CO-Het20, —C1-2alkyl-CO-Het21-CO—, -Het22-CH2—CO—NH—C1-3alkyl-, —CO—NH—C1-6alkyl-, —NH—CO—C1-6alkyl-, —CO—C1-7alkyl-, —C1-7alkyl-CO—, —C1-6alkyl-CO—C1-6alkyl-, —C1-2alkyl-NH—CO—CR16R17—NH—, —C1-2alkyl-CO—NH—CR18R19—CO—, —C1-2alkyl-CO—NR20—C1-3alkyl-CO—, C1-2alkyl-NR21—CH2—CO—NH—C1-3alkyl-, or NR22—CO—C1-3alkyl-NH—, X1 represents a direct bond, O or —O—C1-2alkyl-, CO, —CO—C1-2alkyl-, NR11, —NR11—C1-2alkyl-, —CH2—, —O—N═CH— or —C1-2alkyl-; X2 represents a direct bond, O, —O—C1-2alkyl-, CO, —CO—C1-2alkyl-, NR12, —NR12—C1-2alkyl-, —CH2—, —O—N═CH— or —C1-2alkyl-. The growth inhibitory effect anti-tumour activity of the present compounds has been demonstrated in vitro, in enzymatic on the receptor tyrosine kinase EGFR.
Public/Granted literature
- US20060247237A1 Macrocyclic quinazoline derivatives as antiproliferative agents Public/Granted day:2006-11-02
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