- Design, synthesis, and progress toward optimization of potent small molecule antagonists of CC chemokine receptor 8 (CCR8)
-
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.
- Ghosh, Shomir,Elder, Amy,Guo, Jianping,Mani, Ukti,Patane, Michael,Carson, Kenneth,Ye, Qing,Bennett, Robert,Chi, Shannon,Jenkins, Tracy,Guan, Bing,Kolbeck, Roland,Smith, Sean,Zhang, Cheng,LaRosa, Gregory,Jaffee, Bruce,Yang, Hua,Eddy, Priya,Lu, Chuang,Uttamsingh, Vinita,Horlick, Robert,Harriman, Geraldine,Flynn, Daniel
-
p. 2669 - 2672
(2007/10/03)
-
- NOVEL DIAZASPIROALKANES AND THEIR USE FOR TREATMENT OF CCR8 MEDIATED DISEASES
-
The invention provides compounds of general formula. [Chemical formula should be inserted here. Please see paper copy] (II) wherein R and R1 are as defined in the specification, processes for their preparation, pharmaceutical compositions conta
- -
-
Page/Page column 24-25
(2008/06/13)
-
- NOVEL DIAZASPIROALKANES AND THEIR USE FOR TREATMENT OF CCR8 MEDIATED DISEASES
-
The invention provides compounds of general formula wherein R and R1 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.
- -
-
Page/Page column 29
(2008/06/13)
-
- NOVEL DIAZASPIROALKANES AND THEIR USE FOR TREATMENT OF CCR8 MEDIATED DISEASES
-
The invention provides compounds of general formula. (II) wherein R and R?1? are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.
- -
-
Page/Page column 24; 25
(2010/11/24)
-
