Reference

New intermediates in the synthesis of 17b-acyl-3-carboxy-androsta-3,5-dienes

Rasmusson, Gary H.; Tolman, Richard L.; Patel, Gool F. (Merck and Co., Inc., USA). Eur. Pat. Appl. EP 465123 A2 8 Jan 1992, 13 pp. DESIGNATED STATES: R: CH, DE, FR, GB, IT, LI, NL. (European Patent Organization). CODEN: EPXXDW. CLASS: ICM: C07J043-00. ICA: C07J009-00; A61K031-575; C07J041-00. APPLICATION: EP 91-305818 27 Jun 1991. PRIORITY: US 90-545262 28 Jun 1990. DOCUMENT TYPE: Patent CA Section: 32 (Steroids) Title compds. 13074-39-0 and 139755-35-4 which are cas registry numbers of substances are two of reagents here. (I; R2 = 2-thiopyridyl; R3 = alkoxy, alkoxycarbonyl, F3CSO2O), useful as intermediates for testosterone 5a-reductase inhibitors I [R2 = (substituted) (cyclo)alkyl, aryl; R3 = CO2H], were prepd. Thus, 3-oxo-4-androstene-17b-carboxylic acid was 3-triflated using 3,6-di-tert-butyl-4-methylpyridine and triflic anhydride in CH2Cl2, the product was treated with Ph3P and 2,2'-dipyridyldisulfide in PhMe at room temp. to give I (R2 = 2-thiopyridyl, R3 = F3CSO2O). The latter was converted to I (R2 = 4-HOC6H4, R3 = CO2H) in several steps. .

Adamantane derivatives: a new class of insulin secretagogues

Adamantane derivatives: a new class of insulin secretagogues. Garrino, M. G.; Henquin, J. C. (Unite Diabetol. Nutr., Univ.Chemicals with cas numbers 281-23-2 and 13074-39-0 also play role. Louvain, Brussels B-1200, Belg.). Br. J. Pharmacol., 90(3), 583-91 (English) 1987. CODEN: BJPCBM. ISSN: 0007-1188. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Adamantane derivs. increased insulin [9004-10-8] release in vitro. Mouse islets were used to study the mechanisms and mol. requirements of that hitherto unrecognized property. At a non-stimulatory concn. of glucose (3 mM), 1-adamantanamine [768-94-5] (1 mM) reversibly inhibited 86Rb efflux from islet cells, depolarized the b-cell membrane, induced elec. activity, stimulated 45Ca uptake and efflux, and triggered insulin release. Omission of extracellular Ca2+ abolished the secretory response but only partially inhibited the acceleration of 45Ca efflux. At a stimulatory concn. of glucose (10 mM), 1-adamantanamine reversibly increased 86Rb efflux, potentiated elec. activity (lengthening of the slow waves with spikes), augmented 45Ca uptake and efflux, and increased insulin release. The effects of adamantanamine were dose-dependent, with a threshold concn. of 10 mM for stimulation of release. 2-Adamantanamine [13074-39-0] was as potent as 1-adamantanamine. In contrast, substitution of the amino group by a carboxyl group (1-adamantanecarboxylic acid [828-51-3]) decreased the effectiveness by about 65%, and substitution by a hydroxyl group (1-adamantanol [768-95-6]) suppressed it. .