Development of a prostaglandin D2 receptor antagonist : discovery of a new chemical lead

A series of N-(p-alkoxy)benzoyl-5-methoxy-2-methylindole-3-acetic acids and N-(p-butoxy)benzoyl-2-methylindole-4-acetic acid were discovered as new chemical leads for a prostaglandin D2 (PGD2) receptor antagonist. Most of them exhibited PGD2 receptor binding and blocked cyclic adenosine 3',5�...

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Veröffentlicht in:	European journal of medicinal chemistry 2005-05, Vol.40 (5), p.505-519
Hauptverfasser:	TORISU, Kazuhiko, KOBAYASHI, Kaoru, IWAHASHI, Maki, EGASHIRA, Hiromu, NAKAI, Yoshihiko, OKADA, Yutaka, NANBU, Fumio, OHUCHIDA, Shuichi, NAKAI, Hisao, TODA, Masaaki
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Area Under Curve Binding, Competitive - physiology Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents CHO Cells Cricetinae Cyclic AMP - antagonists & inhibitors Cyclic AMP - metabolism Half-Life Indoleacetic Acids - chemical synthesis Indoleacetic Acids - chemistry Indoleacetic Acids - pharmacokinetics Indomethacin - analogs & derivatives Indomethacin - chemistry Indomethacin - pharmacokinetics Magnetic Resonance Spectroscopy Male Medical sciences Mice Pharmacology. Drug treatments Rats Receptors, Immunologic - antagonists & inhibitors Receptors, Immunologic - metabolism Receptors, Prostaglandin - antagonists & inhibitors Receptors, Prostaglandin - metabolism Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Structure-Activity Relationship
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Zusammenfassung:	A series of N-(p-alkoxy)benzoyl-5-methoxy-2-methylindole-3-acetic acids and N-(p-butoxy)benzoyl-2-methylindole-4-acetic acid were discovered as new chemical leads for a prostaglandin D2 (PGD2) receptor antagonist. Most of them exhibited PGD2 receptor binding and blocked cyclic adenosine 3',5'-monophosphate (cAMP) formation in vitro. In particular, 2-methylindole-4-acetic acid analog 1 showed markedly increased receptor affinity and cAMP antagonist activity. Chemistry and structure activity relationship (SAR) data are also presented.
ISSN:	0223-5234 1768-3254
DOI:	10.1016/j.ejmech.2004.11.011