title: beta-N-Biaryl ether sulfonamide hydroxamates as potent gelatinase inhibitors: part 2. Optimization of alpha-amino substituents.
abstract: The introduction and the optimization of an alpha-amino substituent based on a series of alpha-hydroxy-beta-N-biaryl ether sulfonamide hydroxamates is described. The modification leads to a new series of MMP-2/MMP-9 inhibitors with enhanced inhibitory activities and improved ADME properties. An efficacy study on reducing the ischemia-induced brain edema in the rat transient middle cerebral artery occlusion (tMCAo) model is also demonstrated.
authors: Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 8 Clarke Drive, Cranbury, NJ 08512, USA. syang9@prdus.jnj.com
authors: Shyh-Ming
authors: SM
authors: Yang
authors: Robert H
authors: RH
authors: Scannevin
authors: Bingbing
authors: B
authors: Wang
authors: Sharon L
authors: SL
authors: Burke
authors: Zhihong
authors: Z
authors: Huang
authors: Prabha
authors: P
authors: Karnachi
authors: Lawrence J
authors: LJ
authors: Wilson
authors: Kenneth J
authors: KJ
authors: Rhodes
authors: Bharat
authors: B
authors: Lagu
authors: William V
authors: WV
authors: Murray
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D001929:Brain Edema / Q000139:chemically induced; D004195:Disease Models, Animal; D015195:Drug Design; D018093:Gelatinases / Q000037:antagonists & inhibitors*; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors; D008862:Microsomes, Liver / Q000187:drug effects; D020768:Middle Cerebral Artery / Q000187:drug effects; D015394:Molecular Structure; D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000596:Amino Acids; C097658:CGS 27023A; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011719:Pyrazines; D013449:Sulfonamides; D018093:Gelatinases