Discovery of a potent, selective and orally bioavailable 3,9-diazaspiro[5.5]undeca-2-one CCR5 antagonist

Replacement of the cyclic carbamate in our previously disclosed 1-oxa-3,9-diazaspiro[5.5]undecan-2-one template led to the discovery of two novel series of 3,9-diazaspiro[5.5]undecane and undeca-2-one CCR5 antagonists. The synthesis, SAR, and antiviral activities of these two series are described. One compound (32) was found to have attractive combination of antiviral potency, selectivity, and pharmacokinetic profile. The asymmetric synthesis of 32 was also accomplished and both enantiomers were equally potent.

Graphical abstractTwo novel series of 3,9-diazaspiro[5.5]undecane and undeca-2-one CCR5 antagonists were discovered. The synthesis, SAR, and antiviral activities of these two series are described. Compound 32 was found to have attractive combination of antiviral potency, selectivity, and pharmacokinetic profile.Figure optionsDownload full-size imageDownload as PowerPoint slide