1. Brief resume of the intended work:

Indolizine is an important ring system in view of its chemical and electronical similarity to indole with a delocalized 10 π -electron aromatic system. This analogy gave rise to an intensive development of indolizine chemistry to obtain biologically active substances.

Various indolizine derivatives have been reported to posses pharmacological activities like Anti fungal1, Analgesic2, , Anti-inflammatory2, CNS depressant3,4,5, Hypoglycemic6, Anti acetylcholine7, 5-HT3 receptor antagonists8, estrogen receptor binding9,Antimicrobial10, Anti cancer11, and Calcium Channel Blocker12 .

Few 1-substituted indolizines have been reported to have antitubercular activities 13, and Indolizines having hydroxyphenylmethyl or Hydroxy alkyl substituents at 1-position have been found most active, but the ring also requires substituents at C-2 and C-3 positions.

Isoniazid, Pyrazinamide, Ethionamide, p-Amino Salicylic Acid are effective against Mycobacterium Tuberculosis14-19.

Considering the antitubercular potential of some Indolizine derivatives, it is planned to synthesize substituted Indolizines and combine chemically with popular antitubercular drugs like Isoniazid, Ethionamide, Pyrazinamide and p-Amino Salicylic Acid, and study the hydrolysis kinetics of these derivatives and also study their comparative Antitubercular activity

2. Materials and method

2.1 Source of the date:

Data were obtained from literature and related articles from libraries of Krupanidhi

college of pharmacy, Indian Institute of Science, publications and journals of medicinal chemistry.

2.2 Scheme of synthesis :

b)

c):

d)

2.3.Method of characterization:

Characterization of compounds will be performed by using modern analytical techniques

Like TLC, Melting point, Elemental Analysis, IR, NMR, Mass spectral data.

2.4Hydrolysis Kinetics:

Hydrolysis values of the Indolizine derivativesat different buffer solutions of PH 1.2 and

7.4 and half life of the drugs to be found out.

2.5 Methods of Screening:

Synthesized compounds will be screened for antitubercular activity according to the methods described in literatures and pharmacopoeias.

3. List of the reference
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J Pharm Sci 1975 Feb; 56(2);225-8.
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7Jorgenson A S, Jacobsen P, Christiansen L B, Bury P S, Kanstrup A, Susan M T at al. Synthesis and estrogen binding affinities of novel pyrrolo(2,1,5 –cd) indolizine derivatives, Bioorg and Med Chem Lett 2000 ; 10 : 2383—6.
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European journal of Medicinal Chemistry 2003 Oct:38(10):867-73.
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14 Merck Index, 14th Edition, 2006; 5186: 7956: 3720.
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17 Foye’s principles of Medicinal Chemistry, fifth edition, 2002; 906-11.
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antitubercular Activity of Hydrazide-Hydrazones. European Journal of Medicinal
Chemistry; volume 41, issue(11) : 2006; 1253-1262.
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Amines. American review of tuberculosis; 1950, 61: 529-34.