Twelve in vitro oxygenated metabolites of 3a,4,5,6,7,7a- hexahydro-3-(l-methyl-5-nitro-lH-imidazol-2-yl) -1,2-benzisoxazole (MK-0436) were produced by incubation of this antiprotozoal agent with the postmitochondriai supernatant (S9) fraction isolated from the livers of rats treated with phenoba...

The effect of liver enzymes (S9) on the mutagenic response of nitroimidazoles and nitrofurans in the Ames test was evaluated with strain TA100. A diminished response was observed with a 5-nitroimidazole and 5-nitrofurans when the S9 preparation was incorporated in the agar layer. Preincubation w...

The antiprotozoal drug 3a,4,5,6,7,7a‐hexahydro‐3‐(1‐methyl‐5‐nitro‐1 H‐imidazol‐2‐yl)‐1,2‐benzisoxazole (I), which exhibits activity against trypanosomiasis, is also antibacterial in vivo. Since the urine from a dog dosed with I showed a broader spectrum of antibacterial activity tha...

Metabolite fractions from the urine of a dog dosed with 3a,4,5,6,7,7a-hexahydro-3-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,2-benzisoxazole (MK-0436) were obtained by the use of high-performance liquid chromatography. These fractions were of suitable purity for structural elucidation. Data obtained ...

1H-NMR and MS were employed to identify 13 rat urinary metabolites of 14C-labeled cis-3a,4,5,6,7,7a-hexahydro-3-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,2-benzisoxazole (MK-0436). The major free (unconjugated) metabolite was cis-3a,4,5,6,7,7a-hexahydro-3-carboxamido-1,2-benzisoxazole; it was also t...

A new general method for the synthesis of substituted and annelated 1,2-benzisoxazoles has been developed by cycloaromatization of ∝-oxoketene dithioacetals with 3-methyl-5-lithiomethylisoxazole.

The transformation of hydroxyl group in benzyl or allyl alcohols to trifluoromethyl was achieved via the reaction of the corresponding alkyloxydiphenylphosphine and CuCF3, generated in situ from methyl fluorosulfonyldifluoroacetate and CuI, under mild conditions. A plausible mechanism was propos...

A series of 17 novel tetra substituted thiophenes was designed, synthesized, and screened for anti-inflammatory activity in carrageenin induced rat paw edema model, an acute in vivo model. The lead molecule selected was Tenidap, a dual COX/LOX inhibitor. Compounds I (43%), III (60%), IV (60%), a...

Alkylation of ethyl 4-(2,5-dimethylthiophen-3-yl)-3-oxobutanoate with 2-aryl-4-bromoacetyl-5-methyl-1,3-oxazole followed by decar-boxylation–cyclization of the intermediate diketo ester affords the title photochromic compounds. Relationship between the fluorescent characteristics, thermal stabi...

Presence of basic calcium phosphate in knee joints of osteoarthritis patients could be prevented by inhibiting tissue non-specific alkaline phosphatase (TNAP) activity. Levamisole or the L stereoisomer of tetramisole (a known TNAP inhibitor) has been used as a treatment for curing rheumatoid art...

A facile [3 + 2] cycloaddition / aromatization cascade reaction with broad substrate scopes in up to 94% isolated yield was disclosed herein. This tandem approach was accomplished by employing isoquinolines and bromoacetyl derivatives with methyl perfluoroalk-2-ynoates as readily available start...

A facile, convenient and one-pot three-component method has been outlined for the synthesis of title compounds by treating equimolar amounts of 3-(2-bromoacetyl)-2H-chromen-2-one (2) with 2-cyanothioacetamide (3) and various aryl/heteryl aldehydes (5 or 7) independently. The effect of solvent an...

The conformational study of some 2-(2′-haloacetyl)-5-substituted five-membered heteroaromatic compounds Z-CH2C(O)(C4H2X)Y bearing a halogen (Z = Cl or Br) at the 2′-position and (Y = NO2, H, Me or Cl) substituents at the 5-position of the heteroaromatic ring for X = NMe, O and S was performed ...

Reactant incompatibility is a common problem in organic chemistry. In this study we investigate the use of concentrated aqueous dispersions of mesoporous oxides to overcome incompatibility in the Friedel–Crafts reaction between sodium salicylate and 4-tert-butylbenzyl chloride. The mesoporous m...

Treatment of benzylic bromides with Zn and LiCl, followed by the reaction with i-butyl nitrite gave N-arylmethyl-N-arylmethyleneamine N-oxides in moderate yields. The present reaction is a novel and simple method for the preparation of nitrones from benzylic bromides, although the yields are mod...

Three alternative methods for the synthesis of the optically active heptanoate (6), a key intermediate in the preparation of a highly potent and tissue selective HMG Co-A reductase inhibitor are described.

This paper describes a simple chromatographic technique on Sephadex LH20 for the separation of vitamin D3 sulfate from free vitamin D3 and its metabolites. This technique has been used in the study of vitamin D3 sulfate metabolism in rats. Seven hours after injection of vitamin D3 sulfate (35S o...

Twenty four hours after dosing of pregnant rats with 3H vitamin D3 i.v. the sulfoconjugate was detected only in the kidney. In contrast, 24 or 48 hours after 3H vitamin D3 i.v. dosing the vitamin D3 sulfoconjugate was detected in the plasma, liver, kidney and mammary glands of lactating mother rats.

1,1-Bis(trifluoromethyl)alkyl isocyanates obtained from perfluoroisobutene (PFIB) react with aroyl(arylsulfonyl)hydrazines. Twenty eight prospective biologically active polyfluorinated 1,4-substituted semicarbazides were synthesized. The structure of each new product was confirmed by analytical ...

Piperazine derivatives of 5(6)-substituted-(1H-benzimidazol-2-ylthio)acetic acids were synthesized by using two methods and studied for antihelminthic activity.The antiparasitic screening showed that compounds 18–24 exhibited higher activity against Trichinella spiralis in vitro in comparison t...