Synthesis of novel ageladine A analogs showing more potent matrix metalloproteinase (MMP)-12 inhibitory activity than the natural product.
By employing a previously established synthetic scheme, the synthesis described in the title was carried out in order to explore the substituent effects in the pyrrole ring of ageladine A on MMP-12 inhibitory activity. It became evident that a halogen atom (Br or Cl) at the 2-position and an additional bromine atom at the 4-position are highly effective for improving the inhibitory activity. These studies led us to discover three novel ageladine A analogs (4a, c, o) showing more potent MMP-12 inhibitory activity than the natural product.
Ando
Naoki
N
Discovery Research Laboratories, Kyorin Pharmaceutical Co., Ltd, 2399-1, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan. naoki.andou@mb.kyorin-pharm.co.jp
Terashima
Shiro
S
D047230:Agelas / Q000737:chemistry; D000818:Animals; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
C482289:Ageladine A; D061965:Matrix Metalloproteinase Inhibitors; D011758:Pyrroles; D053508:Matrix Metalloproteinase 12