Diketo Analogues and Their Significance

Diketo Analogues and Their SignificanceINTRODUCTIONMedicinal chemistry is the branch of science, which has remarkable value for synthesis of novel drugs with intense healthful natural action. It concerns with discovery, development, designation and interpretation of mode of action of biologically mobile compounds at molecular level.The molecular biological revolution and progressive mapping of human genome have created a new biochemical and biostructural world order.1These developments have provided new challenges and opportunities for drug research in general and drug design in particular. Pure entire compounds, natural or synthetic products are the chief source of agents for the cure, the mitigation or the prevention of disease today. The major objectives of the medicinal chemists are transformation of pathobiochemical and physiological data into a chemical language with the aim of designing molecules interacting specifically with the derailed or degenerating processes in the diseased organisms.The development of chemotherapy during past 60 years even out one of most important therapeutic advances in history of medicine and antimicrobic drugs are the greatest contribution of present century to therapeutics2. Potential therapeutic targets are being disclosed with increasing frequency and the exponential growth will continue during the next decades.In this situation there is a indispensableness for rapid and effective target validation and for accelerated lead discovery procedures. organic fertiliser chemists are increasingly directing their attention towards synthetic aspects of biomolecules and biologically active compounds, biosynthesized by plants and animals.Many important biochemical compounds and drugs of natural origin contain heterocyclic ring structures. Many of them are employed in treatment of more infectious diseases due to their specific activity, but their use in treatment is attributed to their inherent toxicity to various pathogens.D IKETO ANALOGUES AND THEIR SIGNIFICANCEAntibacterialThe quinolones3 are well know synthetic antibacterial agents with di keto moiety some examples are Ciprofloxacin (1) Norfloxacin (2).Boteva4 et al synthesized some Halogen Substituted 4,5-dibenzoyl-1-phenyl-1H-pyrrole-2,3-dione derivatives (2-6) evaluated for Antibacterial Activity.Anti HIVThe first report of a company of compounds that inhibit HIV integrase appeared in 1992. Aurin tricarboxylic acids and derivatives were determined to inhibit 3 processing of viral cDNA with moderate iC50 values of 10-50micromolar.Thus the 1st pharmacophore with integrase inhibitory activity was determined i.e. aromatic rings with multiple hydroxyl substituents positioned on same ring or present close together in a 3D space if rings stack on top of each other. Since then considerable amount of work has been carried out in developing potential drop inhibitors of integrase victorious the above compounds as leads.Presently there is only one FDA ap proved drug used as integrase inhibitor i.e. Raltegravir or Isentress, (7) approved in 2007. Elvitegravir (8) is another potential integrase inhibitor which is in phase III clinical trial5.THIOPHENE ANALOGS AND THEIR SIGNIFICANCEThiophene (9) and its derivatives are an important class of heterocyclic compounds possessing broad biological activities, such as anti-inflammatory6, analgesic6, antioxidant7, antitubercular8, antidepressant9, sedative9, antiamoebic10, oral analgesic11, antimetabolite12, and cancer drug properties13.AntimicrobialsThiophene analogues have been known as antibacterials. In the year 2007 Stephane et al14 reported the synthesis and antibacterial activity of arylbenzothiophenes (10) and diarylthiophenes. (11)(10) (11)In the year 2010 Kavitha P N et al15 reported the antimicrobial activity of 3- amino-2- mercapto-5,6,7,8-tetrahydrobenzo(b)thieno2,3-dpyrimidin-4(3H)-ones (12-17) by utilise B. subtilus, K. pneumonia and A. niger.Desai Akshay et al16 reported the s ynthesis of 2-thiophene-2- ethylthioureido-4- morpholino-6-(aryl) ureido-s-triazines.(18-23) These analogs were evaluated for their antimicrobial activity using S. typhi, C. albicans.Bhuiyan Md. Mosharef Hossain et al17 reported synthesis of 4-hydrazino-2- mehylthio-5-ethyl-6- methylthieno 2,3-d pyrimidine (24) which is evaluated as antimicrobial agent by using B.cereus, V.cholerae, A.alternate.(24)Shiradkar M. et al18 reported synthesis of N-3-(substituted)-7H- 1,2,4 triazolo 3,4-b 1,3,4 thiadiazine / thiadiazol-4,5,6,7- tetrahydrobenzob thiophenes (25-32) as good antimicrobial agents by using E.coli, S.aureus, A.nigar.Ahmed M. M. et al19 reported synthesis of 4-(substituted)-7-cyano- 6-phenyl aminothieno 3,2-d pyrimidins (33-34) and evaluated as good antimicrobial agents by using B.subtilis and St.aureus, compared with eccentric drug Amoxicillin.The 6-methyl-2-phenyl-3-(substituted)-3H-thieno3,2-d pyrimidin-4-ones (35-38) has been reported by Chander Mohan et al20 and evaluated f or antimicrobial activity by using B. subtilis, E.coli, P.aeruginosa compared with standard drug Ciprofloxacin.Bhuiyan Md. Mosharef Hossain et al21 reported synthesis of thieno3,2-e imidazo1,2-c pyrimidin-2(3H)ones (39) which was evaluated for antimicrobial activity against B. cereus, S.typhi and A.alternatacompare to reference drugs ampicillin with Nystatin.(39)Shetty Nitin kumar et al22 reported synthesis of 8,9,10,11-tetrahydro1benzothieno3,2-e 1,2,4triazolo 1,5- cpyrimidine -8-ones (40-42) and evaluated for antibacterial activity against B. subtilis comparable to ampicilin.References Larsen PK, Liljefors T, Madsen U, editors. 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