Studies on dihydropyridines. II. Synthesis of 4,7-dihydropyrazolo(3,4-b)pyridines with vasodilating and antihypertensive activities.

Abstract

A series of 4-aryl-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate derivatives (72-149) was prepared and the compounds were tested for Ca-blocking activity in isolated guinea pig portal vein, antihypertensive activity in spontaneously hypertensive rats, and coronary vasodilating effect in isolated guinea pig heart. A number of derivatives had potent antihypertensive and coronary vasodilating activities. The structure-activity relationships of the series indicated that a 3cyclopentyl or 3-cyclohexyl substituent and a hydrophobic 5-ester moiety with moderate bulkiness were effective for increasing the pharmacological potencies.

Synthesis of Pyrido[1,2-a]indole Malonates and Amines through Aryne Annulation

“…Hz, 1 H), 7.57 (s, 1 H), 7.29 (d, J = 8.3 Hz, 1 H), 4.40 (q, J = 7.2 Hz, 2 H), 4.32 (q, J = 7.1 Hz, 2 H), 1.35 (m, 6 H); 13 C NMR (100 MHz, CDCl 3 ) δ 166.4, 164.0, 151.2, 149.8, 139.5, 137.8, 129.9, 127.2, 122.1, 62.1, 61.7, 14.3, 14.2; HRMS (EI) calcd for C 13 H 15 BrNO 4 328.0184, found 328.0186. Dimethyl 2-[(5-Bromopyridin-2-yl)methylene]malonate(25). The product was isolated as a white solid: mp 96−99 °C;1 H NMR (400 MHz, CDCl 3 ) δ 8.66 (s, 1 H), 7.86 (dd, J = 8.2, 2.3 Hz, 1 H), 7.61 (s, 1 H), 7.29 (d, J = 8.3 Hz, 1 H), 3.90 (s, 3 H), 3.86 (s, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ 166.9, 164.3, 151.4, 149.5, 139.6, 138.6, 129.0, 127.4, 122.3, 53.1, 52.8; HRMS (EI) calcd for [M + H] + (M = C 11 H 10 BrNO 4 ) 299.9866, found 299.9870.…”

Design, Synthesis, and Pharmacological Properties of New Heteroarylpyridine/Heteroarylpyrimidine Derivatives as CB2 Cannabinoid Receptor Partial Agonists

“…All chemicals and reagents were purchased from Aldrich (Sigma-Aldrich) or Lancaster (Alfa Aesar, Johnson Matthey Company). The 5-aminopyrazoles were prepared by known procedures: 1,3-dimethyl-1 H -pyrazol-5-amine ( 11a ), 3-ethyl-1-methyl-1 H -pyrazol-5-amine ( 11b ), 3- tert -butyl-1-methyl-1 H -pyrazol-5-amine ( 11c ), 1-methyl-3-phenyl-1 H -pyrazol-5-amine ( 11d ), 3-(4-chlorophenyl)-1-methyl-1 H -pyrazol-5-amine ( 11e ), 1-methyl-1 H -pyrazol-5-amine ( 11f ) …”

A convenient synthesis of pyrazolo[3,4-b]pyridine nucleosides by convenient ring-closure procedures. X-Ray crystal and molecular structure of 4-amino-1 -(β-D-ribofuranosyl)-1,7-dihydropyrazolo[3,4-b]pyridin-6-one

“…For a number of years, we'g2 and others3-I2 have been interested in the pyrazolo[3,4-b]pyridines as potential specific antagonists of nucleic acid metabolism, and in more recent years have evaluated derivatives of this ring system as substrate inhibitors of purine-requiring enzymes. Although several polysubstituted derivatives of this heterocycle have been synthesized [13][14][15][16][17][18][19] as medicinal agents, such as etazolate, tracatolate, and cartazolate, only a few nucleosides possessing this ring system are known. '-4 This may be due to the confusion and c o r r e ~t i o n s ~* ~* ~* ' ' over the identity of the pyrazolo[3,4blpyridine ring-closure product obtained from various pyrazole derivatives, and also due to the tedious preparation' of the precursor 5-amino-l-benzylpyrazole (17).…”

“…Although several polysubstituted derivatives of this heterocycle have been synthesized [13][14][15][16][17][18][19] as medicinal agents, such as etazolate, tracatolate, and cartazolate, only a few nucleosides possessing this ring system are known. '-4 This may be due to the confusion and c o r r e ~t i o n s ~* ~* ~* ' ' over the identity of the pyrazolo[3,4blpyridine ring-closure product obtained from various pyrazole derivatives, and also due to the tedious preparation' of the precursor 5-amino-l-benzylpyrazole (17). Recently, we described a rather long but regio-and stereo-selective synthesis of compounds (1) and (2) from the amine (17) in several steps.…”