Antibacterial activities heterocycles

Interposition of a methylene group between the phenyl ring and the heterocycle leads to the benzyldiami nopyrimidines, a class of compounds notable for their antibacterial activity. Condensation of hydrocinnamate 54 with ethyl formate leads to the hydroxymethylene derivative 55. In this case, too, the heterocyclic ring is formed by reaction with guanidine. This sequence probably involves initial addition-elimination to the forniyl carbon to form 56 cyclization in this case involves simple amide formation. Tautomerization then affords the hydroxy derivative 57. This is converted to tetroxoprim (58) by first... 

Further development in the chemistry of oxazolidinone antibacterials was based mainly on the assumption that the 4-pyridyl moiety of one of Dupont s lead compounds, E-3709, might be amenable to replacement by suitably saturated heterocyclic bioisosteres [48]. This assumption was based on an example in which successful replacement of the piperazine ring system in the quinolone antibacterials, such as ciprofloxacin, with a pyridine fragment, such as seen in Win-57273, results in improvement of both the antibacterial and the pharmacokinetic profiles of the compounds. Similarly, as in the case of ciprofloxacin and Win-57273, it was predicted that the presence of a small but highly electron-withdrawing fluorine atom would be tolerated at the meta position(s) of the central phenyl ring, and would confer enhanced antibacterial activity and/or other desirable properties to the targeted oxazolidinones, as shown in Fig. 3. 

Later on, it was demonstrated that these heterocycles can undergo Diels-Alder reactions in the presence of an electrophile (Ss or Mel) and dienophiles <2002T1573, 2003HAC560>. These phosphoms-containing heterocycles were found to produce, upon reaction with tricarbonyl(cycloheptatriene)molybdenum(0) or tricarbonyl(mesitylene) tungsten(O), cr-complexes of the type L2M(CO)4 or I,(M(CO)( instead of 7t-complexes <1998EJI1079>. Some derivatives of this heterocycle were also found to display remarkable antibacterial activity <2005BML937>. 

Antibacterial activity is retained when the relatively complex amide side chains are replaced by a simple heterocycle amidine. The required reagent (7-2) is prepared by reaction of azepine formamide (7-1) with oxalyl chloride. Condensation of the product with 6-APA (2-4) leads to the formation of the amidine and thus amdinocillin (7-3) [11]. 

As a consequence of the increased resistance of bacteria to classical /3-lactam antibiotics, several strategies devoted to the synthesis of new bi- and polycyclic /3-lactam derivatives have been developed, giving rise to a large number of compounds featuring enhanced antibacterial activity or better resistance toward /3-lactamases. It is the aim of this section to extend previous accounts on this subject in CHEC(1984) and CHEC-II(1996) and to summarize several recent methodologies concerning the preparation of these fused heterocycles. 

Penicillin V is a narrow-spectrum penicillin and has similar antibacterial activity to benzylpenicillin. It is active against many streptococcal infections, but it is inactivated by penicillinases. Flucloxacillin is a penicillinase-resistant antibiotic and is effective against infections caused by penicillin-resistant staphylococci. In comparison to penicillin V, attachment of carbocyclic/heterocyclic ring directly to the C6 carbonyl group confers resistance to beta-lactamases due to steric hindrance around the amide group. 

In the second section of the volume, N-hclerocycles such as phenothiazines, phenoxazines, dihydropyridines, and related compounds are shown also to have interesting biological activity including antitumor activity, vermicide, antibacterial activity, and antischizophrenic activity (i.e. chlorpromazine of the phenothiazine family and its analogs). The activity of phenothiazine and compounds such as phenoxazines and related heterocycles, and also recent bioactive mesoionic heterocycles will be discussed. 

Cephalosporin derivatives containing a pyrrole ring in the A -acyl chain, such as compound 8, show significant antibacterial activity, similar to that of cefalexin <2000PHA568>. l-Butyl-4-(2-phenyl-17f-indol-3-yl)-2-azetidinones of the type 9 <2004HAC494> and several new spiro indoline-based heterocycles 10 <2004BMC2483> show interesting antibacterial activity. 

The Influence of Chemical Constitution on Antibacterial Activity. Part IV. A Survey of Heterocyclic Bases with special reference to Benzoquinolines, Phenanthri-dines, Benzacridines, Quinolines and Pyridines. 

Thiazolidinones are an important group of heterocycles found in numerous natural products and pharmaceuticals known for their antitumor, COX-2 inhibition, anti-HIV and antibacterial activities [140],... 

Applications of MCR-Derived Heterocycles in Drug Discovery Table 6 Antibacterial activities of select pyrazolo-pyrido-pyrimidine-diones... 

Recent analyses of a Free-Wilsontype have included the in vitro inhibitory activity of a series of heterocyclic compounds against K. pneumonia (197). Other applications of the Free-Wilson approach have included studies on the antimycobacterial activity of 4-alkyl-thiobenzanilides, the antibacterial activity of fluoronapthyridines, and the benzodiazepine receptor-binding ability of some non-benzodi-apzepine compounds such as 3-X-imidazo-[l,2-6]pyridazines, 2-phenylimidazo[l,2-o ]pyri-dines,2-(alkoxycarbony)imidazo[2,l-p]benzo-thiazoles, and 2-arylquinolones(198-200). 

C.S. Cooper and co-workers synthesized several quinolones containing five- and six-membered heterocyclic substituents at the 7-position and tested their antibacterial activities. The 1,4-diketone substrate was prepared via the oxidative coupling of isopropenyl acetate and an acetophenone derivative. The Paai-Knorr furan synthesis was conducted in the presence of p-TsOH. 

Thiazolidinone and their derivatives are important heterocyclic compounds due to their broad biological activities such as anti-inflammatory, antiprohferative, anticyclooxygenases (COX-1 and COX-2), antihistaminic, and antibacterial activities. More importantly, some of the 2,3-diaryl-l,3-thiazolidin-4-ones were found to be highly effective against HlV-1 replication. 

Procedures for the synthesis of compounds containing a five-membered heterocycle with a linearly fused 1,8-naphthyridine fragment (thiazolo[5,4-Z>]- (1979CPB410), imidazolo[4,5-Z>]-, triazolo[4,5-Z>]- (1980CPB235), oxazolo[5,4-/ ]-, thiadiazolo[5,4-b]-, isothiazolo[5,4-Z>]-, pyrazolo[3,4-Z>]-, thieno[2,3-Z>]-, furo[2,3-/ ]-l,8-naphthyridines (1980CPB761, 1984CPB4914)) were described and the antibacterial activity of these compounds was studied. 

Cephamydns, A family of fJ-lactam antibiotics produced by various Streptomyces species. Detection and production Stapley et at.. Antimicrvb. Ag. Chemother. 2, 122 (1972). Chemical characterization Miller et al, ibid. 132. Cephamycins A, B, and C have been isolated, tha latter being identical to a Streptomyces clavullgerus metabolite Nagarajan et ah. J. Am. Chem. Soc. 93, 2308 (1971). Structures Albers -Sehoenberg et ah, Tetrahedron Letters 1972, 2911- Antibacterial activity studies Miller et ah, dmimi-crob. Ag. Chemother. 2, 281, 287 (1972) Daoust et al. ibid. 3, 254 (1973). Review of syntheses T. Hiraoka et ah. Heterocycles 8, 719 (1977). 

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