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Substituted N-(3,5-dichlorobenzenesulfonyl)-L-prolyl-phenylalanine analogues as potent VLA-4 antagonists |
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| Authors: | Kopka Ihor E Young David N Lin Linus S Mumford Richard A Magriotis Plato A MacCoss Malcolm Mills Sander G Van Riper Gail McCauley Ermengilda Egger Linda E Kidambi Usha Schmidt John A Lyons Kathryn Stearns Ralph Vincent Stella Colletti Adria Wang Zhen Tong Sharon Wang Junying Zheng Song Owens Karen Levorse Dorothy Hagmann William K |
| Affiliation: | Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. ihor_kopka@merck.com |
| Abstract: | A series of substituted N-(3,5-dichlorobenzenesulfonyl)-L-prolyl- and alpha-methyl-L-prolyl-phenylalanine derivatives was prepared as VLA-4/VCAM antagonists. The compounds showed excellent potency with a wide variety of neutral, polar, electron withdrawing or donating groups on the phenylalanine ring (IC50 approximately 1 nM). Heteroaryl ring substitution for phenylalanine was also well tolerated. Pharmacokinetic studies in rat were performed on a representative set of compounds in both series. |
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