Pyrrolidine inhibitors of human cytosolic phospholipase A2. Part 2: synthesis of potent and crystallized 4-triphenylmethylthio derivative 'pyrrophenone'

K Seno; T Okuno; K Nishi; Y Murakami; K Yamada; S Nakamoto; T Ono

doi:10.1016/s0960-894x(01)00003-8

Pyrrolidine inhibitors of human cytosolic phospholipase A2. Part 2: synthesis of potent and crystallized 4-triphenylmethylthio derivative 'pyrrophenone'

Bioorg Med Chem Lett. 2001 Feb 26;11(4):587-90. doi: 10.1016/s0960-894x(01)00003-8.

Authors

K Seno¹, T Okuno, K Nishi, Y Murakami, K Yamada, S Nakamoto, T Ono

Affiliation

¹ Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan. kaoru.seno@shionogi.co.jp

PMID: 11229777
DOI: 10.1016/s0960-894x(01)00003-8

Abstract

We synthesized a potent and crystallized human cytosolic phospholipase A2alpha inhibitor, pyrrophenone (6) which inhibits the isolated enzyme with an IC50 value of 4.2 nM. Pyrrophenone shows potent inhibition of arachidonic acid release, prostaglandin E2, thromboxane B2, and leukotriene B4 formation in human whole blood. The magnitudes of prostaglandin E2 and thromboxane B2 inhibition are the same as those of indomethacin.

MeSH terms

Arachidonic Acid / metabolism
Crystallization
Cytosol / enzymology
Dinoprostone / biosynthesis
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
Humans
Phospholipases A / antagonists & inhibitors*
Phospholipases A2
Pyrrolidines / chemical synthesis*
Pyrrolidines / pharmacology
Thromboxane B2 / biosynthesis

Substances

Enzyme Inhibitors
Pyrrolidines
Arachidonic Acid
Thromboxane B2
Phospholipases A
Phospholipases A2
Dinoprostone