Ranjana Aggarwal

Synthesis and pharmacological evaluation of some novel 2-(5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-yl)-4-(coumarin-3-yl)thiazoles.

A series of novel 2-(5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-yl)-4-(coumarin-3-yl)thiazoles (6) were synthesized by condensing 3-(2-bromoacetyl)coumarins (4) with various 5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-thiocarboxamides (5), obtained by the reaction of thiosemicarbazide with trifluoromethyl-β-diketones. All the tested compounds displayed significant to moderate in vivo anti-inflammatory activity when compared to the standard drug indomethacin, and good broad spectrum in vitro antibacterial activity against three Gram-positive and four Gram-negative bacteria when compared with cefixime.

Approaches towards the synthesis of 5-aminopyrazoles

Summary The biological and medicinal properties of 5-aminopyrazoles have prompted enormous research aimed at developing synthetic routes to these heterocyles. This review focuses on the biological properties associated with this system. Various synthetic methods developed up to 2010 for these compounds are described, particularly those that involve the reactions of β-ketonitriles, malononitrile, alkylidenemalononitriles and their derivatives with hydrazines, as well as some novel miscellaneous methods.

REACTION OF HYDRAZINES AND HYDROXYLAMINE WITH TRIFLUOROMETHYL-β-DIKETONES: SYNTHESIS OF TRIFLUOROMETHYLPYRAZOLE AND ISOXAZOLE DERIVATIVES

The reaction of trifluoromethyl-(3-diketones with hydrazines and hydroxylamine finds interesting application in the synthesis of trifluoromethylpyrazole and isoxazole derivatives. The review covers the literature of the reactions mentioned up to 2007. Mechanistic aspects leading to the formation of these heterocycles and their NMR spectral characteristics are also described.

α,α‐Dibromoketones: A Superior Alternative to α‐Bromoketones in Hantzsch Thiazole Synthesis

Abstract α,α‐Dibromoketones (2) have been found to be a superior alternative to the conventionally used α‐bromoketones (1) for performing the Hantzsch thiazole synthesis.1 These crystalline, nonlachrymatory compounds are more reactive than 1 as demonstrated by their reaction with 3,5‐dimethyl‐1‐thiocarboxamide (5).

Synthesis of Some Novel Fluorinated Pyrazolo[3,4‐b]Pyridines

Abstract Reaction of 5‐amino‐3‐substituted pyrazoles (1a–c) and 5‐amino‐1,3‐disubstituted pyrazoles (1d–i) with fluorinated‐β‐diketones (2) results in the formation of the single isomer of pyrazolo[3,4‐b]pyridines (4a–h). A one‐pot procedure for the synthesis of title compounds starting from α‐cyanoacetophenones along with a possible mechanistic pathway for the formation of the title compounds is described.

Synthesis, biological evaluation and molecular modeling study of 5-trifluoromethyl-Δ2-pyrazoline and isomeric 5/3-trifluoromethylpyrazole derivatives as anti-inflammatory agents

Searching for new anti-inflammatory agents, we have prepared a series of potential COX-2 inhibitors, 1-(4,6-dimethylpyrimidin-2-yl)-5-hydroxy-5-trifluoromethyl-Δ(2)-pyrazolines (3) and 1-(4,6-dimethylpyrimidin-2-yl)-3-trifluoromethylpyrazoles (4), by refluxing 2-hydrazino-4,6-dimethylpyrimidine (1) with a number of trifluoromethyl-β-diketones (2) in ethanol. Further dehydration of compounds (3) to the corresponding 1-(4,6-dimethylpyrimidin-2-yl)-5-trifluoromethylpyrazoles (5) was also achieved. Fifteen of these compounds were screened for their anti-inflammatory activity using the carrageenan-induced rat paw edema assay. While all the compounds exhibited significant anti-inflammatory activity (47-76%) as compared to indomethacin (78%), 3-trifluoromethylpyrazoles (4) were found to be the most effective agents (62-76%). To rationalize this anti-inflammatory activity, docking experiments molecular dynamics simulations were performed to study the ability of these compounds to bind into the active site of the COX-2 enzyme.

Iodobenzene Diacetate Mediated Oxidation of N-Substituted Hydrazones of Chalcones: An Efficient Regioselective Synthesis of 1,3,5-Trisubstituted Pyrazoles

Abstract Iodobenzene diacetate, a relatively benign nonmetallic oxidant, has been utilized efficiently for the oxidation of N-substituted hydrazones of chalcones to afford 1,3,5-trisubstituted pyrazoles under mild reaction conditions.

Copper(II) chloride mediated synthesis and DNA photocleavage activity of 1-aryl/heteroaryl-4-substituted-1,2,4-triazolo[4,3-a]quinoxalines.

A new class of photonucleases, 1-aryl/heteroaryl-4-substituted-1,2,4-triazolo[4,3-a]quinoxalines (4) was synthesized in a facile and efficient manner via copper(II) chloride mediated oxidative intramolecular cyclization of 2-(arylidenehydrazino)-3-substituted-quinoxalines (3). DNA cleavage potency of compounds 4a-d (40 μg each) was quantitatively evaluated on supercoiled plasmid ΦX174 under UV irradiation (312 nm, 15 W) without any additive. Compound 4c was found to be the most efficient DNA photocleaver which had converted supercoiled DNA (form I) into the relaxed DNA (form II) at 30 μg and the DNA photocleavage activity increases with increase in concentration of 4c.

Hypervalent Iodine in the Synthesis of Bridgehead Heterocycles: A Facile Route to the Synthesis of 6‐Arylimidazo[2,1‐b]thiazoles Using [Hydroxy(tosyloxy)iodo]benzene

Abstract α‐Tosyloxyketones (2), readily accessible through hypervalent iodine oxidation of enolizable ketones (1) using [hydroxy(tosyloxy)iodo]benzene (HTIB) in acetonitrile, exclusively generates the 6‐arylimidazo[2,1‐b]thiazoles (4) on treatment with commercially available 2‐aminothiazole (3).

A CONVENIENT SYNTHESIS OF 4-SUBSTITUTED-4′-(2-THIENYL)- 2,2′-BITHIAZOLES AS POTENTIAL PHOTOTOXIC AGENTS

Alpha-tosyloxyacetylthiophene (3), obtained by the hypervalent iodine oxidation of 2-acetylthiophene (2) using [hydroxy- (tosyloxy)iodo]benzene (HTIB), on treatment with rubeanic acid exclusively generates 4-(2-thienyl)thiazole-2-thiocarboxamide (4) which upon subsequent treatment with a variety of alpha-tosyloxyketones (5) affords the title compounds (6) in excellent yields.