| Affiliation: | 1. Department of Medicinal Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States;2. Department of Medicinal Chemistry, Merck Research Laboratories, 320 Bent Street, Cambridge, MA 02141, United States;3. Department of Drug Design, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States;4. Department of Bone, Respiratory, Immunology, and Dermatology, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States |
| Abstract: | We disclose further optimization of hydantoin TNF-α convertase enzyme (TACE) inhibitors. SAR with respect to the non-prime region of TACE active site was explored. A series of biaryl substituted hydantoin compounds was shown to have sub-nanomolar Ki, good rat PK, and good selectivity versus MMP-1, -2, -3, -7, -9, and -13. |
