Design, synthesis, and progress toward optimization of potent small molecule antagonists of CC chemokine receptor 8 (CCR8)

被引：34

作者：

Ghosh, S

Elder, A

Guo, JP

Mani, U

Patane, M

Carson, K

Ye, Q

Bennett, R

Chi, S

Jenkins, T

Guan, B

Kolbeck, R

Smith, S

Zhang, C

LaRosa, G

Jaffee, B

Yang, H

Eddy, P

Lu, C

Uttamsingh, V

Horlick, R

Harriman, G

Flynn, D

机构：

[1] Millennium Pharmaceut, Dept Med Chem, Cambridge, MA 02139 USA

[2] Millennium Pharmaceut, Dept Pharmacol, Cambridge, MA 02139 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 09期

关键词：

D O I：

10.1021/jm050965z

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

Activation of CCR8 by its ligand CCL1 may play an important role in diseases such as asthma, multiple sclerosis, and cancer. The study of small molecule CCR8 antagonists will help establish the validation of these hypotheses. We report the design, synthesis, and progress toward optimization of potent small molecule CCR8 antagonists identified from a high-throughput screen. These analogues exhibit good potency in binding and chemotaxis assays, show good selectivity versus the hERG channel, and have good eADME ( early absorption, distribution, metabolism, and excretion) profiles.

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收藏

页码：2669 / 2672

页数：4

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