Selective thromboxane synthetase inhibitors. 4. 2-(1H-Imidazol-1-ylmethyl)benzo[b]furan-, -benzo[b]thiophene-, -indole- and -naphthalenecarboxylic acids

Abstract

The preparation of a series of 2-(1H-imidazol-1-ylmethyl)-substituted carboxylic acids of benzo[b]furan, benzo-[b]thiophene, indole, and naphthalene is described. All compounds showed a similar level of activity as TxA2 synthetase inhibitors in vitro, having IC50 values between 1 and 7 X 10(-8) M. In the cases examined, compounds had, at most, only negligible activity against PGI2 synthetase, cyclooxygenase, and steroid 11 beta-hydroxylase. The benzo[b]thiophenes generally showed the greatest potency in vivo, and compounds 72, 73, and 75 caused almost complete inhibition of thromboxane production for 6 h after oral administration of 0.5 mg/kg to conscious dogs. In the case of 73 and 75, thromboxane production was still inhibited by 80% after 24 h.

Synthesis of N-Alkenylated Heterocycles via T3P-Promoted Condensation with Ketones

“…6,13,14 N-Alkenyl heterocycles are an interesting and underexplored class of compounds 15 where notable members of this family include the steroidal N-(1-cycloalkenyl) heterocycles galeterone 16 (a) and VNPP433−3β 17 (b) used for the treatment of castrateresistant prostate cancer (Figure 1). 18 Moreover, their utility extends beyond the anticancer field as demonstrated by vinpocetine, 19 a derivative of the alkaloid vincamine with a strong vasodilatory effect that is used for the treatment of stroke, and rolafragel, 20 (d), a selective inhibitor of thromboxane-A synthase for the treatment of vasospasm and thrombosis. Finally, it is worth mentioning that poly(N-vinylindole)s have also been reported as promising semiconducting and photosensitive materials.…”

“…Consequently, organic chemists are continuously developing new synthetic methodologies devoted to introducing substituents or constructing these rings. − Despite these advances, the selective N -functionalization of indoles , and other NH -heterocycles − is an ongoing challenge , and the development of new and efficient methods is highly desirable. ,, N -Alkenyl heterocycles are an interesting and underexplored class of compounds where notable members of this family include the steroidal N -(1-cycloalkenyl) heterocycles galeterone (a) and VNPP433–3β (b) used for the treatment of castrate-resistant prostate cancer (Figure ). Moreover, their utility extends beyond the anticancer field as demonstrated by vinpocetine, a derivative of the alkaloid vincamine with a strong vasodilatory effect that is used for the treatment of stroke, and rolafragel,(d), a selective inhibitor of thromboxane-A synthase for the treatment of vasospasm and thrombosis. Finally, it is worth mentioning that poly( N -vinylindole)s have also been reported as promising semiconducting and photosensitive materials. , …”

“…20 = +23.51°(c 1.17, CH 2 Cl 2 ); HRMS (ESI+) m/z [M = C 33 H 33 N 2 O 4 ]: [M + H] + calcd 521.2440, found 521.2430.…”

De Novo and Divergent Synthesis of Highly Functionalized Furans by Cascade Reactions of 2‐Hydroxy‐1,4‐diones with Nucleophiles

“…The first one is by the functionalization of a-substituted furan derivatives, including furfuralcohola nd a-halogenatedf uran, among others. One example is the acid-catalyzed dehydration of furfuralcohol derivatives [3] to form carbocation intermediates that can trap an umber of electron-rich substrates, which allows the functionalization at the a positiono ft he furan skeletont o form new CÀC, CÀO, and CÀNb onds (Scheme 1a). However, substituted furfuralcohols and a-halogenated furans are difficult to access, which restricts the application of this route.…”

“Abnormal” bromination reaction selectivity of 5-diarylamino-2-methylbenzo[b]thiophene caused by a “non-planar” conjugated model: Synthesis and theoretical calculation

“…According to the experiments in literatures [9][10][11][12][13][14][15][16][17][18], 5-substituted-2-methylbenzo [b]thiophene derivatives (Fig. 1a) generally had a fixed active position named as ''normal'' position (3-position of thiophene ring), whatever the 5-substituent was electron-accepting or electron-donating group (Table 1) [9][10][11][12][13][14][15][16][17][18]. The relatively higher activity of electrophilic substitution of thiophene ring may be the reasonable explanation for the selectivity.…”