公开(公告)号：US06809097B1

公开(公告)日：2004-10-26

申请号：US09254440

申请日：1999-03-09

申请人： Andrew Peter Thomas ,  Laurent Francois Andre Hennequin ,  Patrick Ple

发明人： Andrew Peter Thomas ,  Laurent Francois Andre Hennequin ,  Patrick Ple

IPC分类号： C07D21522

CPC分类号： C07D215/233 ,  C07D215/44 ,  C07D215/48 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/12 ,  C07D417/12 ,  C07D471/04

摘要： Compounds of the formula (I): wherein: R2 represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; n is an integer from 0 to 5; Z represents —O—, —NH—, —S— or —CH2—; G1 represents phenyl or a 5-10 membered heteroaromatic cyclic or bicyclic group; Y1, Y2, Y3 and Y4 each independently represents carbon or nitrogen; R1 represents fluoro or hydrogen; m is an integer from 1 to 3; R3 represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C1-3alkyl, —NR4R5 (wherein R4 and R5, can each be hydrogen or C1-3alkyl), or a group R6—X1— wherein X1 represents —CH2— or a heteroatom linker group and R6 is an alkyl, alkenyl or alkynyl chain optionally substituted by for example hydroxy, amino, nitro, alkyl, cycloalkyl, alkoxyalkyl, or an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring, which alkyl, alkenyl or alkynyl chain may have a heteroatom linker group, or R6 is an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring and salts thereof, in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals such as humans, processes for the preparation of such derivatives, pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient and compounds of formula I. The compounds of formula I and the pharmaceutically acceptable salts thereof 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： 式（I）的化合物：其中：R 2表示羟基，卤代，C 1-3烷基，C 1-3烷氧基，C 1-3烷酰氧基，三氟甲基，氰基，氨基或硝基; n为0〜5的整数， Z表示-O - ， - NH - ， - S-或-CH 2 - ; G 1表示苯基或5-10元杂芳族环状或双环基团; Y 1，Y 2，Y 3和Y 4各自独立地表示碳或氮; R 1表示氟或氢; m为1〜3的整数; R 3表示氢，羟基，卤代，氰基，硝基，三氟甲基，C 1-3烷基，-NR 4 R 5（其中R 4和R 5各自可以是氢或C 1-3烷基 ）或基团R 6 -X 1 - ，其中X 1表示-CH 2 - 或杂原子连接基团，R 6是任选被例如羟基，氨基， ，硝基，烷基，环烷基，烷氧基烷基或选自吡啶酮，苯基和杂环的任选取代的基团，该烷基，烯基或炔基链可具有杂原子连接基团，或R 6为任选取代的基团， 吡啶酮，苯基和杂环及其盐在制备用于在温血动物如人类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，制备这些衍生物的方法，药物 含有式I化合物或其药学上可接受的盐的组合物具有活性 式I化合物和式I化合物及其药学上可接受的盐抑制VEGF在治疗许多疾病状态（包括癌症和类风湿性关节炎）中的价值的性质。

公开(公告)号：US06362340B1

公开(公告)日：2002-03-26

申请号：US09856810

申请日：2001-05-25

申请人： Tuan-Phat Dang

发明人： Tuan-Phat Dang

IPC分类号： C07D21522

CPC分类号： C07D215/233 ,  C07D215/56

摘要： The invention concerns a method for preparing 4-hydroquinolines and/or tautomeric compounds. More particularly, the invention concerns 5,7-dichloro-4-quinolines and/or its tautomeric compounds. The method is characterized in that it consists in heating a 4-hydroquinolinecarboxylic acid, its derivatives or precursors, at a temperature not more than 200° C. in the presence of a base.

摘要翻译： 本发明涉及一种制备4-氢喹啉和/或互变异构化合物的方法。 更具体地，本发明涉及5,7-二氯-4-喹啉和/或其互变异构化合物。 该方法的特征在于其在碱存在下，在不高于200℃的温度下加热4-氢喹啉羧酸，其衍生物或前体。