Yogesh T. Naliapara

SYNTHESIS AND QSAR STUDIES OF 4-SUBSTITUTED PHENYL-2,6-DIMETHYL-3,5-BIS-N-(SUBSTITUTED PHENYL) CARBAMOYL-1,4-DIHYDROPYRIDINES AS POTENTIAL ANTITUBERCULAR AGENTS

Synthesis and QSAR studies of the title compounds have resulted in the identification of structural and physicochemical parameters (MR, sigma(o), sigma(m), sigma(p)) contributing to antitubercular activity. Among these, carbamoyl phenyl ring substituted at 3 and 4 position with NO(2) group or 2 position with Cl or OCH(3) group shows >90% inhibition against H(37)Rnu comparable to other substituted phenyls.

Synthesis and biological activity of stable and potent antitumor agents, aniline nitrogen mustards linked to 9-anilinoacridines via a urea linkage

To improve the chemical stability and therapeutic efficacy of N-mustard, a series of phenyl N-mustard linked to DNA-affinic 9-anilinoacridines and acridine via a urea linker were synthesized and evaluated for antitumor studies. The new N-mustard derivatives were prepared by the reaction of 4-bis(2-chloroethyl)aminophenyl isocyanate with a variety of 9-anilinoacridines or 9-aminoacridine. The antitumor studies revealed that these agents exhibited potent cytotoxicity in vitro without cross-resistance to taxol or vinblastine and showed potent antitumor therapeutic efficacy in nude mice against human tumor xenografts. It also showed that 24d was capable of inducing marked dose-dependent levels of DNA cross-linking by comet assay and has long half-life in rat plasma.

Water Mediated Construction of Trisubstituted Pyrazoles/Isoxazoles Library Using Ketene Dithioacetals

A small molecule library of alkyl, sulfone, and carboxamide functionalized pyrazoles and isoxazoles has been developed via a rapid sequential condensation of various alpha-acylketene dithioacetals (1a-o) with hydrazine hydrate or hydroxylamine hydrochloride, followed by oxidation of sulfide to sulfone using water as the reaction medium. An efficient and safe oxidation of sulfides (4/5a-o) to the corresponding sulfones (6/7a-o) using sodium per borate system in aqueous medium is reported. The concise and two step synthesis of trisubstituted pyrazoles and isoxazoles was investigated under variety of reaction condition. The newly developed methodology has the advantage of excellent yield and chemical purity with short reaction time using water as a solvent.

Novel DNA-directed alkylating agents: Design, synthesis and potent antitumor effect of phenyl N-mustard-9-anilinoacridine conjugates via a carbamate or carbonate linker

A series of phenyl N-mustard-9-anilinoacridine conjugates via a carbamate or carbonate linker was synthesized for antitumor evaluation. The carbamate or carbonate linker is able to lower the reactivity of the phenyl N-mustard pharmacophore and thus, these conjugates are rather chemically stable. The in vitro studies revealed that these derivatives possessed significant cytotoxicity with IC(50) in sub-micromolar range in inhibiting human lymphoblastic leukemia (CCRF-CEM), breast carcinoma (MX-1), colon carcinoma (HCT-116) and human non-small cell lung cancer (H1299) cell growth in vitro. Compounds 10a, 10b, 10e, 10i, and 15a were selected for evaluating their antitumor activity in nude mice bearing MX-1 and HCT-116 xenografts. Remarkably, total tumor remission was achieved by these agents with only one cycle of treatment. Interestingly, no tumor relapse was found in mice treated with 10a over 129 days. This agent is capable of inducing DNA interstrand cross-linking in human non-small lung cancer H1299 cells in a dose dependent manner by modified comet assay and has a long half-life in rat plasma.

Synthesis, Characterization, Crystal, and Molecular Structure Analysis of 3,4-dihydro-6-(2-hydroxyphenyl)-5-nitro-4-phenylpyrimidin-2(1H)-one

A novel nitro and 2-hydroxyphenyl functionalized pyrimidinone at C5 and C6, respectively, has been synthesized using 1-(2-hydroxyphenyl)-2-nitroethanone, benzaldehyde, urea, and etidronic acid as a catalyst is described. The synthesized compound characterized by spectroscopic techniques and finally confirmed by X-ray diffraction studies. The molecule crystallizes in the monoclinic crystal class in the space group P21/c with cell parameters a = 11.1070(10)Å, b = 8.8210(4)Å, c = 15.1110(13)Å, β = 106.193(2)°, and Z = 4. The pyrimidine ring adopts flattened boat conformation.

Synthesis and X-ray structure conformation of novel unsymmetrical 1,4-dihydropyridine

Methyl 2,6-dimethyl-5-(2-methylphenylcarbamoyl)-4-(3-nitrophenyl)-1,4-dihydropyridine-2-carboxylate (3) was prepared by known Hantzch method and its structure was elucidated by X-ray diffraction method.

Water Mediated Synthesis of N′-Arylmethylene-4,5,6,7-tetrahydro-2H-indazole-3-carbohydrazide Library

A novel two-step synthesis of 4,5,6,7-tetrahydro-2H-indazole-3-carbohydrazide has been developed. The library of N′-arylmethylene-4,5,6,7-tetrahydro-2H-indazole-3-carbohydrazide was generated by coupling of hydrazide to various aromatic and heterocyclic aldehydes in water media at ambient temperature with great flexibility regarding reaction time and yield.

SYNTHESIS AND CHARACTERIZATION OF n-BUTYL 4-(3,4-DIMETHOXYPHENYL)-6-METHYL-2-THIOXO-1,2,3,4 TETRAHYDROPYRIMIDINE-5-CARBOXYLATE NANOCRYSTALLINE PARTICLES BY WATER/OIL MICROEMULSION METHOD

Various pyrimidine derivatives are well known for their different pharmaceutical applications. The n-butyl 4-(3, 4-dimethoxyphenyl)-6-methyl-2-thioxo-1,2,3,4 tetrahydropyrimidine-5-carboxylate (n-butyl THPM) was synthesized by using n-butylacetoacetate. The n-butyl acetoacetate was obtained by transesterification of ethyl acetoacetate with n-butyl alcohol using Biginelli condensation. The synthesized powder was used to obtain the nanoparticles of n-butyl THPM by using water/oil microemulsion technique. The average particle size was calculated from the powder XRD pattern by applying Scherrers formula. The nanoparticles of n-butyl THPM were observed by Transmission Electron Microscope (TEM). The diameter of the nanoparticles varied from 15 nm to 65 nm. The nanoparticles were also characterized by FT–IR spectroscopy, TG–DTA–DSC and mass spectroscopy. The n-butyl THPM nanoparticles were stable up to 280°C. Thermodynamic and kinetic parameters of decomposition were obtained by applying Coats and Redfern relation to the thermogram. The dielectric study was carried out in the frequency range of 50 Hz to 5 MHz. The dielectric constant, dielectric loss and ac conductivity decreased as the frequency of applied field increased.