Inotropic Polyazapentalene Sulmazole Analogues

Abstract

Aryl substituted 1H-imidazo[1,2-a]imidazole 8, imidazo[2,1-b]thiazole 9, 1,4-dihydroimidazo[4,5-d]imidazole 11, and 1(2),4-dihydroimidazo[4,5-c]pyrazoles 12-17 have been prepared. An X-ray crystallographic study confirmed the structure of 8 and showed this analogue to exist as the 1H-tautomer. These heterocycles were evaluated as inotropic agents and analogues 12, 15, and 17 found to display inotropic properties which were less potent in vitro, but more potent in vivo, than those of sulmazole. Structure-activity relationships are discussed.

Discovery of a Potent, Selective T-type Calcium Channel Blocker as a Drug Candidate for the Treatment of Generalized Epilepsies

“…Therefore, we synthesized five-membered heteroaryls as amide isosteres, a few of which are exemplified hereafter (Scheme ). A fused system like a pyrazoloimidazole was built mainly following known literature procedures, leading to compound 32a . Five-membered heteroaryls, either preserving a benzylic position, like triazole 32b , or with the terminal phenyl ring directly linked to the isosteric ring, like oxadiazole 32c , were prepared as well, using standard procedures via intermediates 33 , 34 , and 35 .…”

Ground state and excited state dipole moments of 6,8-diphenylimidazo[1,2-α]pyrazine determined from solvatochromic shifts of absorption and fluorescence spectra

“…Imidazo[1,2-␣]pyrazines [1] are compounds that have drawn attention of many people, due to their remarkable anticancer [2][3][4][5][6][7][8] and antimicrobial [9] in addition to their antihypertensive [10][11][12], antibroncospastic [13][14][15] and inotropic [13,[16][17][18][19][20][21] activities on the cardiovascular system. The cause of great attention on these structures can be attributed to the fact that the chemiluminescent compounds, such as luciferin, from some cypridina, renilla, oplophorus and watasenia species are imidazo[1,2-␣]pyrazine derivatives [22][23][24][25][26][27][28][29][30].…”

Synthesis of Imidazo[4,5-c]pyrazoles via Copper-Catalyzed Amidine Cyclization

“…The use of 4,5-diaminopyrazoles in the synthesis of imidazo­[4,5-c]­pyrazole derivatives is restricted to condensations with aromatic carboxylic acids as well as with carbon disulfide or thiophosgene. The former reactions afford 5-aryl substituted imidazo­[4,5-c]­pyrazoles , and the latter 5-thiones, which are desulfurized with Raney nickel to provide bare heterocycles …”