Novel Gonadotrophin Inhibitors in the 19-Norsteroid Series

Potential antifertility agents. 1. Substituted diaryl derivatives of benzo[b]thiophenes, benzo[b]furans, 1H-2-benzothiapyrans, and 2H-1-benzothiapyrans

“…J-E C32H36N202S-2HC1 C,6 H, Cl, N °A, Me2CO; B, SkellysolveB; C,n-BuOH; D, EtOH; E,H20; F, C6H6; G, CH2C12; H, EtOAc; I,CHC13; J, GPrOH. 6 Anal, results for indicated elements are within ±0.4% of the theor values unless otherwise noted. c Cf.…”

“…The N02 group then was modified through reduction and subsequent acylation to yield benzo [b]thiophenes 3i-3j. Scheme II is related to work by Middleton in which 2-carboxy-substituted benzo [b]thiophenes were prepared from the reaction of mercaptoacetic acid with 2-chloro-5-nitrobenzophenone followed by cyclization.10 It was hoped that the 5aminobenzo [b ¡thiophene 3i might serve as a precursor to the 5-OH-substituted relative which had proved (8) Similar syntheses of benzo [6 ]thiophenes have been reported previously. Cf.…”

“…A series of 2,3-diarylbenzo [6 ]furans has been reported by Grover, et al,n to possess antifertility activity. A similar series of compounds was synthesized independently in these laboratories111 using a synthetic approach (cf.…”

Bc → BCD → Abcd

“…It was shown in the early 1960's by Perelman and co-workers [59] and by Fried and associates [74] that the introduction of a A 4>9 -bisdehydro system in the 19-norsteroids resulted in the preparation of exceptionally potent oral antiestrogens. These compounds could be synthesized by a one-step bromination of A 5(10) -3-ketosteroids in pyridine solution (as illustrated in the conversion of 55 to 57, Scheme 10-5).…”

Fluorine-Containing Steroids

“…Compared with 17a-ethinyl-19-nortestosterone, its L15-10 analogue (Enovid) had 2-3 times more anti-gonadotropin potency, but only 0.1 times the progestational potency. A number of 17a-trifluoropropynyl or 17a-trifl.uorovinyl androstene derivatives have been described which possess both types of biological activity (FRIED et al, 1961).…”