Synthesis and characterization of new biologically active 2‐(1,3‐disubstituted pyrazolyl)chromones and corresponding pyrimidine, thiopyrimidine, pyrazolyl derivatives

Abstract

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Synthesis of Chromone-Related Pyrazole Compounds

“…These chromone-pyrazole dyads 8 can have the pyrazole substituent linked by the carbon atoms C-5, C-4 or C-3 at carbon C-2 of the chromone scaffold, depending on the pyrazole used as substituent at the 3-position of the starting material 7 . In 2004, Gill and coworkers described the synthesis of 2-(1,3-/1,3,5-di/tri-substituted-pyrazol-5-yl)chromones [ 8 ], which were obtained in moderate to good yields (50–83%) by cyclization of the appropriate 1-(2-hydroxyaryl)propane-1,3-diones 7 in refluxing ethanol with a catalytic amount of hydrochloric acid (step (i), Scheme 1 ). Only two of the nine derivatives of 7 presented moderate phosphodiesterase IV enzyme inhibition activity [ 8 ].…”

“…In 2004, Gill and coworkers described the synthesis of 2-(1,3-/1,3,5-di/tri-substituted-pyrazol-5-yl)chromones [ 8 ], which were obtained in moderate to good yields (50–83%) by cyclization of the appropriate 1-(2-hydroxyaryl)propane-1,3-diones 7 in refluxing ethanol with a catalytic amount of hydrochloric acid (step (i), Scheme 1 ). Only two of the nine derivatives of 7 presented moderate phosphodiesterase IV enzyme inhibition activity [ 8 ]. Following a slightly different procedure, using glacial acetic acid instead of ethanol, along with a catalytic amount of hydrochloric acid, Karale and coworkers prepared 2-{( E )-2-[1-(4-fluorophenyl)-3-(thiophen-2-yl)-1 H -pyrazol-4-yl]vinyl}chromones [ 9 ], in moderate yields (52–65%) (step (ii), Scheme 1 ).…”

“…This selective and fast procedure, involving an excess of hydrazine hydrate in refluxing ethanol, was applied to a wide variety of 2-substituted chromones 97 to afford several 3(5)-(2-hydroxyaryl)-5(3)-substituted pyrazoles 98 . The substitution at carbon C-2 of the chromone unit can include polyfluoroalkyl [ 62 , 63 ], 1-isopropyl-1 H -indazol-3-yl [ 64 ], 4-(allyloxy)-3-methoxyphenyl-1-yl [ 65 ], 4-chloro-3,4-difluorophenyl-1-yl [ 66 ], 1-aryl-3-(benzofuran-2-yl/naphthalen-3-yl/phenyl/pyridin-3/4-yl, thiophen-2-yl/3-bromothiophen-2-yl)pyrazol-4-yl [ 18 , 19 , 20 , 21 , 67 , 68 , 69 , 70 ], 1-methyl-3-propyl-4-substituted pyrazol-5-yl [ 8 ], 2-(3-methylthiophen-2-yl)-1,3-thiazol-5-yl [ 71 ] substituents (step (i), Scheme 31 ). Using a 5-methyl-3-phenylisoxazol-4-yl group as C-2 substituent, the reaction occurs in the presence of glacial acetic acid to afford 3(5)-(2-hydroxyaryl)-5(3)-(5-methyl-3-phenylisoxazol-4-yl)-1 H -pyrazoles, in good yields (59–83%) (step (ii), Scheme 31 ) [ 72 ].…”

“…Replacing ethanol by another alcohol as solvent, a series of 2-(5-aryl-1,2,3-triazol-4-yl)chromones in methanol (step (iii), ( Scheme 31 ) or 2-[2-(quinoxalin-2-one-3-yl)methylidene-chromones in n -butanol (step (iv), Scheme 31 ) undergo condensation with hydrazine hydrate to furnish 5(3)-(5-aryl-1,2,3-triazol-4-yl)-3(5)-(2-hydroxyaryl)-1 H -pyrazoles [ 73 ] or 3(5)-(2-hydroxy-aryl)-5(3)-[2-(quinoxalin-2-one-3-yl)methylidene]-1 H -pyrazoles [ 74 ], respectively. Biological evaluation of a wide range of 3(5)-(2-hydroxyaryl)pyrazoles 96 were performed, mainly as antimicrobial and antioxidant agents [ 8 , 18 , 19 , 20 , 21 , 64 , 65 , 66 , 67 , 70 , 71 , 72 ].…”

Synthesis and characterization of some important indazolyl derivatives

“…Chromones having heterocyclic substituents at the 2-position have been reported to possess antitumor, antibacterial and antifungal activities and also to exhibit good phosphodiesterase IV inhibition activity and some flavones have potential HIV-integrase inhibition activity [17][18][19][20]39].…”