Javid H. Zaidi

Synthesis and antimalarial activity of novel chiral and achiral benzenesulfonamides bearing 1, 3, 4-oxadiazole moieties

A series of new benzenesulfonamides, most of which are chiral, incorporating 1, 3, 4-oxadiazole and amino acid moieties have been synthesized. Some of these compounds were screened for antimalarial activity and also evaluated for their ability to inhibit hem polymerization. The electrophoretic analysis indicated that one compound was effective in inhibiting the degradation of hemoglobin. The synthesized compounds were tested in mice infected with Plasmodium berghei. These derivatives have the potential for the development of novel antimalarial lead compounds.

An efficient approach to prepare ether and amide-based self-catalyzed phthalonitrile resins

Phthalonitrile polymers with amide and ortho-, meta-, and para-substituted ether linkages in the backbone were synthesized successfully and their thermal properties were investigated. The monomer building blocks for these polymers were cured without the addition of catalysts due to the self-catalyzing nature of the monomers amino group. The ether and amide functionalities in the chain enhanced their processability without compromising thermal stability. The resins exhibited a low complex viscosity over a wide processing window between the monomer melting temperature and the polymer cure temperature, with the processing temperature range varying significantly for para-, ortho-, and meta-substituted polymer architectures. All three systems exhibited high thermal and thermo-oxidative stability. The high char yields, which ranged from 66–75% at 900 °C under nitrogen atmosphere, and the high glass transition temperatures of the polymers indicate a high crosslinking density in the network structure.

Synthesis and Biological Studies of Novel Neurotensin(8–13) Mimetics

Novel neurotensin (NT) (8-13) (Arg(8)-Arg(9)-Pro(10)-Tyr(11)-Ile(12)-Leu(13)) mimetics 3, 4 were designed by adopting all intrinsic functional groups of the native neurotensin(8-13) and using a substituted indole as a template to mimic the pharmacophore of NT(8-13). Biological studies at subtype 1 of the NT receptor showed that 3 has a 55 and 580 nM binding affinity at rat and human neurotensin receptors, respectively. As a comparison, compounds 5 and 6 were also synthesized. The binding difference between 3, 4 and 5, 6 argues the importance of the carboxylic group in achieving higher potency NT(8-13) mimetics.

Synthesis, Anti-HIV, and Antifungal Activity of New Benzensulfonamides Bearing the 2,5-Disubstituted-1,3,4-Oxadiazole Moiety

A series of novel chiral and achiral N-[1-(1,3,4-oxadiazol-2ylthio)alkyl]-4-methyl/chloro/methoxybenzenesulfonamides 5a–l were prepared by the reaction of 4-(4-methyl, chloro, methoxyphenylsulfonamido)alkyl carboxylic acid hydrazides 4a–l with CS2 and KOH. Another series of new secondary benzenesulfonamides 10a–j and bis-benzenesulfonamides 11a–j have been synthesized by a new approach using Et3N and dimethylaminopyridine. All synthesized compounds were characterized by physical, microanalytical, and spectral data. Some of the synthesized compounds were screened in vitro for their anti–HIV and antifungal activities.

A bifunctional anthraquinone synthon

Abstract Commercially available anthrarufin has been converted into a bifunctional reagent which will be useful for the preparation of anthraquinone C-glycosides.

Carbonic anhydrase inhibitors. Inhibition of human tumor-associated isozymes IX and cytosolic isozymes I and II with some 1,3,4-oxadiazole-thiols

A series of chiral 1,3,4-oxadiazole-5-thiols incorporating 2-substituted-benzenesulfonamide moieties has been prepared from amino acids, via the ester and carbohydrazide intermediate, followed by cyclization with carbon disulfide. Some of these compounds have been investigated for the inhibition of three physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the human cytosolic hCA I and II, and the human, transmembrane, tumor-associated isozyme hCA IX. All these compounds showed weak (millimolar) affinity for the three isozymes, except two carbohydrazides and two heterocyclic thiols which selectively inhibited the tumor-associated isozyme with inhibition constants around 10 μM. Such compounds constitute interesting lead molecules for the possible design of CA IX-selective inhibitors.

Synthesis of dithioacetals and oxathioacetals with chiral auxiliaries

Abstract One‐pot synthesis of dithioacetals as well as an efficient method for oxathioacetal is reported. Additionally, some chiral auxiliaries were used to synthesize enantiomerically pure dithioacetals and oxathioacetals.

A CONVENIENT PREPARATION OF N-BUTYL CHLOROMETHYL ETHER AND ITS USE IN ORTHO-DIRECTED METALATION OF PHENOLS

Abstract A simple preparation of n-butyl chloromethyl ether is described which can be extended to other alkyl chloromethyl ethers. n-Butoxymethyl ether derived from n-butyl chloromethyl ether and phenol were used to assess the effectiveness of n-butoxymethyl group in ortho-metalation.

Dienone–phenol rearrangements of bicyclic cyclohexa-2,5-dienones; confirmation of a multistage mechanism

Two mechanisms are well established for the dienone–phenol rearrangements of bicyclic cyclohexadienones of the 4a-alkyl-5,6,7,8-tetrahydronaphthalen-2(4aH)-one type, of which the 4a-methyl compound (1) and the steroidal 1,4-dien-3-ones are examples. They involve, for (1), either a direct alkyl shift from C-4a to C-4 and deprotonation to give a 4-alkyl-5,6,7,8-tetrahydro-2-naphthol or a shift of the 4a,5-bond from C-4a to C-8a with formation of a spiran intermediate and further ring migration from C-8a to C-1 to from a 4-alkyl-5,6,7,8-tetrahydro-1-naphthol. A further mechanism, for which there was little strong evidence, involves an alkyl shift from one angular position, C-4a, to the other, C-8a, followed by further ring migrations via a spiran intermediate to give an additional route to the 4-alkyltetrahydro-2-naphthol product. The products of rearrangement of 3,4a-and 1,4a-dimethyl-5,6,7,8-tetrahydronaphthalen-2(4aH)-ones in aqueous sulphuric acid, and in acetic anhydride with sulphuric acid catalysis, have been studied critically. The use of quantitative 13C n.m.r. spectroscopy confirms the identity and ratios of products deduced using 1H n.m.r. spectroscopy and other techniques. The results show that the third, suspect, mechanism does indeed operate, and that it contributes significantly to the formation of 4-alkyltetrahydro-2-naphthol products from both dienones.

Rational design of novel neurotensin mimetics: Discovery of a pharmacologically unprecedented agent exhibiting concentration-dependent dual effects as antagonist and full agonist

SummaryWe report the rational design of novel neurotensin mimetics through use of the Multiple Template Approach. This approach is based on our notion that a flexible peptide can be replaced by a partially flexible molecule, identified through testing a comparatively small number of molecules possessing a different intrinsic availability of conformations of the native peptide. The Multiple Template Approach has culminated in the discovery of a pharmacologically unprecedented agent, which behaves as a neurotensin antagonist at low concentration and as a full neurotensin agonist at high concentration.