Discovery of a Potent and Orally Bioavailable Dual Antagonist of CC Chemokine Receptors 2 and 5.
Percy H Carter, Gregory D Brown, Robert J Cherney, Douglas G Batt, Jing Chen, Cheryl M Clark, Mary Ellen Cvijic, John V Duncia, Soo S Ko, Sandhya Mandlekar, Ruowei Mo, David J Nelson, Jian Pang, Anne V Rose, Joseph B Santella, Andrew J Tebben, Sarah C Traeger, Songmei Xu, Qihong Zhao, Joel C Barrish
Author Information
Percy H Carter: Departments of Discovery Chemistry, Lead Discovery & Optimization, Preclinical Candidate Optimization, Molecular Discovery Technologies, and Disease Sciences & Biology, Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543, United States.
Gregory D Brown: Departments of Discovery Chemistry, Lead Discovery & Optimization, Preclinical Candidate Optimization, Molecular Discovery Technologies, and Disease Sciences & Biology, Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543, United States.
Robert J Cherney: Departments of Discovery Chemistry, Lead Discovery & Optimization, Preclinical Candidate Optimization, Molecular Discovery Technologies, and Disease Sciences & Biology, Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543, United States.
Douglas G Batt: Departments of Discovery Chemistry, Lead Discovery & Optimization, Preclinical Candidate Optimization, Molecular Discovery Technologies, and Disease Sciences & Biology, Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543, United States.
Jing Chen: Departments of Discovery Chemistry, Lead Discovery & Optimization, Preclinical Candidate Optimization, Molecular Discovery Technologies, and Disease Sciences & Biology, Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543, United States.
Cheryl M Clark: Departments of Discovery Chemistry, Lead Discovery & Optimization, Preclinical Candidate Optimization, Molecular Discovery Technologies, and Disease Sciences & Biology, Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543, United States.
Mary Ellen Cvijic: Departments of Discovery Chemistry, Lead Discovery & Optimization, Preclinical Candidate Optimization, Molecular Discovery Technologies, and Disease Sciences & Biology, Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543, United States.
John V Duncia: Departments of Discovery Chemistry, Lead Discovery & Optimization, Preclinical Candidate Optimization, Molecular Discovery Technologies, and Disease Sciences & Biology, Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543, United States.
Soo S Ko: Departments of Discovery Chemistry, Lead Discovery & Optimization, Preclinical Candidate Optimization, Molecular Discovery Technologies, and Disease Sciences & Biology, Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543, United States.
Sandhya Mandlekar: Departments of Discovery Chemistry, Lead Discovery & Optimization, Preclinical Candidate Optimization, Molecular Discovery Technologies, and Disease Sciences & Biology, Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543, United States.
Ruowei Mo: Departments of Discovery Chemistry, Lead Discovery & Optimization, Preclinical Candidate Optimization, Molecular Discovery Technologies, and Disease Sciences & Biology, Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543, United States.
David J Nelson: Departments of Discovery Chemistry, Lead Discovery & Optimization, Preclinical Candidate Optimization, Molecular Discovery Technologies, and Disease Sciences & Biology, Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543, United States.
Jian Pang: Departments of Discovery Chemistry, Lead Discovery & Optimization, Preclinical Candidate Optimization, Molecular Discovery Technologies, and Disease Sciences & Biology, Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543, United States.
Anne V Rose: Departments of Discovery Chemistry, Lead Discovery & Optimization, Preclinical Candidate Optimization, Molecular Discovery Technologies, and Disease Sciences & Biology, Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543, United States.
Joseph B Santella: Departments of Discovery Chemistry, Lead Discovery & Optimization, Preclinical Candidate Optimization, Molecular Discovery Technologies, and Disease Sciences & Biology, Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543, United States.
Andrew J Tebben: Departments of Discovery Chemistry, Lead Discovery & Optimization, Preclinical Candidate Optimization, Molecular Discovery Technologies, and Disease Sciences & Biology, Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543, United States.
Sarah C Traeger: Departments of Discovery Chemistry, Lead Discovery & Optimization, Preclinical Candidate Optimization, Molecular Discovery Technologies, and Disease Sciences & Biology, Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543, United States.
Songmei Xu: Departments of Discovery Chemistry, Lead Discovery & Optimization, Preclinical Candidate Optimization, Molecular Discovery Technologies, and Disease Sciences & Biology, Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543, United States.
Qihong Zhao: Departments of Discovery Chemistry, Lead Discovery & Optimization, Preclinical Candidate Optimization, Molecular Discovery Technologies, and Disease Sciences & Biology, Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543, United States.
Joel C Barrish: Departments of Discovery Chemistry, Lead Discovery & Optimization, Preclinical Candidate Optimization, Molecular Discovery Technologies, and Disease Sciences & Biology, Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543, United States.
We describe the hybridization of our previously reported acyclic and cyclic CC chemokine receptor 2 (CCR2) antagonists to lead to a new series of dual antagonists of CCR2 and CCR5. Installation of a γ-lactam as the spacer group and a quinazoline as a benzamide mimetic improved oral bioavailability markedly. These efforts led to the identification of 13d, a potent and orally bioavailable dual antagonist suitable for use in both murine and monkey models of inflammation.
