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Nitrocyclopropane formation has been successfully carried out by reaction of bromonitromethane with electrophilic alkenes bearing two electron-withdrawing groups in the α- and β-positions, and in the presence of potassium carbonate as base. The method allows good yields and moderate to satisfactory diastereoselectivity with linear alkenes, while shows the complete formation of the exo-product with N-alkylmaleimides.

Azabicyclo[3.1.0]amine analogues of anacardic acid (16a, 16b, 18a, 18b, 19 and 19b) were synthesized from anacardic acid and tested for their antibacterial activity against Gram positive and Gram negative bacteria. Most of the compounds are having potency at par with ampicillin and inferior with other standard drugs.

A novel series of HDAC inhibitors demonstrating class I subtype selectivity and good oral bioavailability is described. The compounds are potent enzyme inhibitors (IC50 values less than 100 nM), and improved activity in cell proliferation assays was achieved by modulation of polar surface area (PSA) through the introduction of novel linking groups. Employing oral pharmacokinetic studies in mice, comparing drug levels in spleen to plasma, we selected compounds that were tested for efficacy in human tumor xenograft studies based on their potential to distribute into tumor. One compound, 21r (CHR-3996), showed good oral activity in these models, including dose-related activity in a LoVo xenograft. In addition 21r showed good activity in combination with other anticancer agents in in vitro studies. On the basis of these results, 21r was nominated for clinical development.

The simple and in-expensive amidine base, N.N-diethylacetamidine, has been prepared and utilized in the construction of bicyclic hetero compound, 4 and employed for further reduction of amidic carbonyl groups of 4 by using NaBH 4I2-THF condition which is an efficient and commercially viable method to prepare 5 towards the synthesis of amino moiety I, in Trovafloxacin 2 an antibacterial agent.

The mechanism for the hepatotoxicity of trovafloxacin remains unresolved. Trovafloxacin contains a cyclopropylamine moiety which has a potential to be oxidized to reactive intermediate(s) although other putative elements may exist. In this study, a drug model of trovafloxacin containing the cyclopropylamine substructure was synthesized. Chemical oxidation of the drug model by K3Fe(CN)6 and NaClO revealed that both oxidants oxidize this drug model to a reactive α,β-unsaturated aldehyde, 11. The structure of 11 was fully elucidated by LC/MS/MS and NMR analysis. These results suggested that P450s with heme-iron center and myeloperoxidase generating hypochlorous acid in the presence of chloride ion are capable of bioactivating the cyclopropylamine moiety of trovafloxacin. This deleterious metabolism may lead to eventual hepatotoxicity.

Trovafloxacin acid salts are prepared via the hydrolysis of imine intermediates using mineral acid including, but not limited to, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, nitric acid, sulfuric acid, phosphoric acid, hydrochloric ac

Trovafloxacin, a novel broad spectrum antibacterial, contains the unusual (1α,5α,6α)-3-azabicyclo[3.1.0]hexane ring system. The prototype of the industrial synthesis of this ring system and possible mechanistic pathways to exclusive formation of the exo or 6α-nitro derivative 4 are described, which leads to the key 6a-nitro-3-azabicyclo[3.1.0]hexane intermediate 10. The synthesis of 6a-amino-3-azabicyclo[3.1.0]hexane 16 and useful protected cxo 6-amino derivatives 15 and 17 follows from 10. These can be coupled with the 7-chloronaphthyridone 18 to yield protected trovafloxacin compounds 20-22 in good yield. The ethyl ester of trovafloxacin 21 can also be accessed from the product of coupling 19, derived from 18 and the exo 6-nitro-3-azabicyclo[3.1.0]hexane compound 12. Removal of protecting groups from 20-22 with methanesulfonic acid yields trovafloxacin mesylate from which trovafloxacin zwitterion 1 can be liberated with base treatment. Zwitterion l can also be prepared directly from 16 tosylate salt and naphthyridone-2-carboxylic acid 26. The Royal Society of Chemistry 2000.

A process for preparing a compound of formula (I) wherein R is C1-C6 alkyl, C3-C6 cycloalkyl or benzyl, and wherein the phenyl moiety of said benzyl group is optionally substituted by one or more substituents each independently selected from halo, nitro, C1-C6 alkyl, C1-C6 alkoxy, amino and trifluoromethyl, which comprises adding a solution comprising a compound of formula (II), a halonitromethane and an organic solvent selected from acetone, dimethylformamide, dimethylacetamide, acetonitrile, dimethylsulfoxide, N-methylpyrrolidinone and dimethoxyethane. In formula (II), wherein R is as defined above, to a mixture comprising a base and an organic solvent, said organic solvent being as defined above and the said base being selected from potassium carbonate, sodium carbonate, cesium carbonate, trisodium phosphate, and potassium fluoride, so that a compound of formula (I) is produced, any excess base being eliminated from the reaction mixture prior to recovery of the product (I).

Antibacterial quinolone carboxylic acids and naphthyridone carboxylic acids, having an external amino group attached to their 7-substituent are prepared without the use, and subsequent removal, of blocking groups on the external amino group. In a preferre

A process for preparing a compound of the formula wherein R1, m, o and p are described below, which comprises adding a base of the formula wherein R2, R3 and R4 are as described below, to a solution comprising a compound of the formula wherein R1, m, o an

This invention relates to novel processes and intermediates for the preparation of pharmaceutically acceptable acid salts, of the formula

A process for preparing a compound of the formula wherein R1, m, o and p are described below, which comprises adding a base of the formula wherein R2, R3and R4are as described below, to a solution comprising a c

This invention relates to compounds of the formulae STR1 wherein R and X are defined as below. These compounds are useful as intermediates in the syntheses of azabicyclo quinoline carboxylic acids having antibacterial activity.

This invention relates to novel processes for preparing compounds of the formulae STR1 wherein R and X defined as below. Compounds of the formulae VII are useful as intermediates in the syntheses of azabicyclo quinoline carboxylic acids having antibacteri