Nonsteroidal progesterone receptor ligands (I): synthesis and SAR of new tetrahydronaphthofuranone derivatives.
We have synthesized a series of nonsteroidal progesterone receptor (PR) ligands, tetrahydronaphthofuranones, structurally based on the fungal metabolite PF1092C. Structure-activity relationship studies revealed that substituents at the 6- and 7-positions were critical for PR binding affinity and for agonist or antagonist activity. Compounds in this series, exemplified by 19i, exhibited high affinity and high specificity for PR over other steroid hormone receptors and acted as selective PR antagonists. Further modification of PF1092C may generate compounds of potential pharmacological interest.
Pharmaceutical Research Department, Meiji Seika Kaisha, Ltd., Yokohama 222-8567, Japan. rie_shinei@meiji.co.jp
Rie
R
Shinei
Ken-ichi
K
Kurihara
Kiyoshi
K
Tanabe
Yuji
Y
Tabata
Yasushi
Y
Kurata
Shigeru
S
Hoshiko
Tsuneo
T
Okonogi
D002460:Cell Line; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D009284:Naphthols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D005663:Furans; D006727:Hormone Antagonists; D008024:Ligands; D009284:Naphthols; C106750:PF 1092C; D011980:Receptors, Progesterone; D012717:Sesquiterpenes; D013764:Tetrahydronaphthalenes