Orally active 4-amino-5-diarylurea-furo[2,3-d]pyrimidine derivatives as anti-angiogenic agent inhibiting VEGFR2 and Tie-2
Orally active 4-amino-5-diarylurea-furo[2,3-d]pyrimidine derivatives as anti-angiogenic agent inhibiting VEGFR2 and Tie-2
复制标题
DOI：
10.1016/j.bmcl.2006.12.077
复制
发表时间：
2007-03-15
影响因子：
2.7
通讯作者：
Ozawa, Kazunori
中科院分区：
文献类型：
--
作者：
Miyazaki, Yasushi;Tang, Jun;Ozawa, Kazunori
在我们努力开发 VEGFR2 和 Tie-2 双重抑制剂作为癌症治疗的抗血管生成剂的过程中，我们发现 4-amino-5-(4-((2-氟-5-(三氟甲基)苯基)-氨基羰基氨基)苯基)呋喃[2,3-d]嘧啶 (8a) 在酶和细胞水平上对 VEGFR2 和 Tie-2 具有很强的抑制活性。化合物8a通过口服给药表现出高药代动力学暴露，并且通过每日一次口服给药在小鼠HT-29异种移植模型中显示出显着的肿瘤生长抑制和抗血管生成活性。 (c) 2006 Elsevier Ltd. 保留所有权利。
During our effort to develop dual VEGFR2 and Tie-2 inhibitors as anti-angiogenic agents for cancer therapy, we discovered 4-amino-5-(4-((2-fluoro-5-(trifluoromethyl)phenyl)-aminocarbonylamino)phenyl)furo[2,3-d]pyrimidine (8a) possessing strong inhibitory activity at both the enzyme and cellular level against VEGFR2 and Tie-2. Compound 8a demonstrated high pharmaco-kinetic exposure through oral administration, and showed marked tumor growth inhibition and anti-angiogenic activity in mouse HT-29 xenograft model via once-daily oral administration. (c) 2006 Elsevier Ltd. All rights reserved.