公开(公告)号：US20050215574A1

公开(公告)日：2005-09-29

申请号：US10508675

申请日：2003-03-26

申请人： Robert Bradbury ,  Laurent Francois Hennequin ,  Jason Kettle

发明人： Robert Bradbury ,  Laurent Francois Hennequin ,  Jason Kettle

IPC分类号： C07D491/056 ,  A61K31/517 ,  A61K31/5377 ,  A61P9/10 ,  A61P13/08 ,  A61P17/06 ,  A61P35/00 ,  A61P35/02 ,  A61P43/00 ,  C07D239/94 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D491/04

CPC分类号： C07D401/12 ,  C07D403/12

摘要： The invention concerns quinazoline derivatives of Formula (I) wherein each of Q1, Z, R1 and Q2 have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours which are sensitive to inhibition of erbB receptor tyrosine kinases.

摘要翻译： 本发明涉及式（I）的喹唑啉衍生物，其中Q 1，Z，R 1和Q 2 2中的每一个具有定义的任何含义 在说明中; 其制备方法，含有它们的药物组合物及其在制备用于预防或治疗对erbB受体酪氨酸激酶抑制敏感的肿瘤中的抗增殖剂的药物中的用途。

公开(公告)号：US20070037837A1

公开(公告)日：2007-02-15

申请号：US10572048

申请日：2004-09-15

申请人： Laurent Francois Hennequin ,  Bernard Barlaam ,  Robert Bradbury

发明人： Laurent Francois Hennequin ,  Bernard Barlaam ,  Robert Bradbury

IPC分类号： A61K31/517

CPC分类号： C04B35/632 ,  A61K31/517 ,  C07D401/12

摘要： The invention concerns quinazoline derivatives of Formula (I): wherein each of R1, R2, X1, R5 and m have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours which are sensitive to inhibition of EGF and erbB receptor tyrosine kinases.

摘要翻译： 本发明涉及式（I）的喹唑啉衍生物：其中R 1，R 2，X 1，R 5， / SUP>和m具有描述中定义的任何含义; 其制备方法，含有它们的药物组合物及其在制备用于预防或治疗对EGF和erbB受体酪氨酸激酶的抑制敏感的肿瘤中作为抗增殖剂的药物中的用途。

公开(公告)号：US20070066633A1

公开(公告)日：2007-03-22

申请号：US11600752

申请日：2006-11-17

申请人： Laurent Francois Hennequin ,  Elaine Sophie Stokes

发明人： Laurent Francois Hennequin ,  Elaine Sophie Stokes

IPC分类号： A61K31/517 ,  C07D403/02

CPC分类号： C07D401/12 ,  C07D239/94 ,  C07D403/12 ,  C07D417/12

摘要： The invention concerns compounds of the formula (I): wherein ring A is phenyl or a 5- or 6-membered heterocyclic ring as defined herein; Z is —O—, —NH— or —S—; m is an integer from 0 to 5 inclusive; R1 is hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, C1-3alkyl, C1-3alkoxy, C1-3alkylthio, or —NR5R6 (wherein R5 and R6, which may be the same or different, are hydrogen or C1-3alkyl); R2 is hydrogen, hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, trifluoromethyl, amino or nitro; R3 is hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; provided that when ring A is a 5- or 6-membered heterocyclic ring, at least one R3 is either hydroxy or halogeno; X1 is —O—, —CH2—, —S—, —SO—, —SO2—, —NR7—, —NR7CO—, —CONR7—, —SO2NR7— or —NR7SO2—, (wherein R7 is hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl); and R4 is selected from a number of groups defined herein comprising an C2-5alkylene, C3-5alkenylene or C3-5alkynylene chain wherein each methylene group (other than that of the α-carbon) is optionally substituted by 1 substituent independently selected from hydroxy, halogeno, amino and C1-4alkanoyloxy; provisos are as defined herein. The invention also relates to pharmaceutical compositions comprising a compound of formula (I), to the use of a compound of formula (I) in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in a warm-blooded animal and to a method for producing an antiangiogenic and/or vascular permeability reducing effect in a warm-blooded animal in need of such treatment. The compounds are useful in disease states such as cancer, rheumatoid arthritis and psoriasis.

公开(公告)号：US20070043009A1

公开(公告)日：2007-02-22

申请号：US10573090

申请日：2004-09-13

申请人： Laurent Francois Hennequin ,  Christopher Halsall

发明人： Laurent Francois Hennequin ,  Christopher Halsall

IPC分类号： A61K31/33

CPC分类号： C04B35/632 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14

摘要： The invention concerns quinazoline derivatives of the Formula (I); wherein each of R1, R2, W, X1, X2, Z, a and b are as defined in the description; processes for their preparation; pharmaceutical compositions containing them and their use in the manufacture of a medicament for providing an anti-proliferative effect. The quinazoline derivatives of Formula (I) are expected to be useful in the treatment of diseases such as certain cancers mediated by erbB receptor tyrosine kinases, particularly EGFR tyrosine kinase.

摘要翻译： 本发明涉及式（I）的喹唑啉衍生物; 其中R 1，R 2，W，X 1，X 2，Z，a和b中的每一个 如说明书中所定义; 其准备过程; 含有它们的药物组合物及其在制备用于提供抗增殖作用的药物中的用途。 预期式（I）的喹唑啉衍生物可用于治疗诸如由erbB受体酪氨酸激酶，特别是EGFR酪氨酸激酶介导的某些癌症的疾病。

公开(公告)号：US20090156821A1

公开(公告)日：2009-06-18

申请号：US11882604

申请日：2007-08-02

申请人： Laurent Francois Hennequin

发明人： Laurent Francois Hennequin

IPC分类号： C07D471/02

CPC分类号： C07D401/14 ,  C07D403/12 ,  C07D471/04 ,  C07D491/04

摘要： The invention relates to compounds of the formula (I): wherein ring C is as defined herein, for example indolyl, indazolyl or azaindolyl; Z is —O—, —NH— or —S—; n is 0-5; m is 0-3; R1 and R2 are defined herein including groups: (i) Q1X1 wherein Q1 and X1 are as defined herein; (ii) Q15W3 wherein Q15 and W3 are as defined herein, (iii) Q21W4C1-5alkylX1— wherein Q21, W4 and X1 are as defined herein, (iv) Q28C1-5alkylX1—, Q28C2-5alkenylX1— or Q28C2-5alkynylX1— wherein Q28 and X1 are as defined herein and (v) Q29C1-5alkylX1—, Q29C2-5alkenylX1— or Q29C2-5alkynylX1— wherein Q29 and X1 are as defined herein; R2 can also be 6,7-methylenedioxy or 6,7-ethylenedioxy; and salts thereof; their use in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in warm?blooded animals; processes for the preparation of such compounds; intermediates used in such processes; processes for making such intermediates; pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof and methods of treating disease states involving angiogenesis by administering a compound of formula I or a pharmaceutically acceptable salt thereof. The compounds of formula I inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

摘要翻译： 本发明涉及式（I）的化合物：其中环C如本文所定义，例如吲哚基，吲唑基或氮杂吲哚基; Z是-O - ， - NH-或-S-; n为0-5; m为0-3; R1和R2在本文中定义为包括：（i）Q1X1，其中Q1和X1如本文所定义; （ii）其中Q15和W3如本文所定义的Q15W3，（iii）Q21W4C1-5烷基X1-，其中Q21，W4和X1如本文所定义，（iv）Q28C1-5烷基X1-，Q28C2-5烯基X1-或Q28C2-5炔基X1-，其中Q28 和X 1如本文所定义，和（v）Q29C1-5烷基X1-，Q29C2-5烯基X1-或Q29C2-5炔基X1-，其中Q29和X1如本文所定义; R2也可以是6,7-亚甲二氧基或6,7-亚乙二氧基; 及其盐; 它们在制备用于在温血动物中产生抗血管生成和/或血管通透性降低作用的药物中的用途; 制备这些化合物的方法; 在这些过程中使用的中间体; 制造这种中间体的方法; 含有式I化合物或其药学上可接受的盐的药物组合物和通过给予式I化合物或其药学上可接受的盐治疗涉及血管生成的疾病状态的方法。 式I的化合物抑制VEGF的作用，其在治疗许多疾病状态（包括癌症和类风湿性关节炎）中是有价值的。