Chemistry Synopsis

SYNO PS IS OF T HE TH ES IS TO BE SUBM ITT ED TO BHA VN AG AR UNI VE RS IT Y FOR Ph .D . DE GR EE IN CHEMI ST RY

FACULTY

: SCIENCE

TITLE

: BIO-ACTIVE HETEROCYCLIC COMPOUNDS AS POTENTIAL ANTIMICROBIAL AGENTS

NAME OF THE CANDIDATE

: SHIHORA PRASHANT NANUBHAI

NAME OF THE GUIDE

: PROF. NISHEETH C. DESAI

REGISTRATION NUMBER

: 963

DATE OF REGISTRATION

: 16/04/2005

PLACE OF WORK

: DEPARTMENT OF CHEMISTRY, BHAVNAGAR UNIVERSITY, BHAVNAGAR-364 002, (INDIA)

BIO-ACTIVE HETEROCYCLIC COMPOUNDS AS POTENTIAL ANTIMICROBIAL AGENTS

Medicinal and bio-organic chemistry is concerned with the design, synthesis, and analysis of the relationship between molecular structure and biological activity for compounds that can be used for the cure or treatment of disease. Heterocyclic chemistry is fundamental to biology and medicine. It is not farfetched to say that we are living in the age of Heterocyclic chemistry. The emergence of drug resistant bacteria has posed a growing challenge to the search for new chemical entities. Yet, from the viewpoint of drug discovery it is critical to realize that, despite the importance of drug knowledge, it is not an exclusive tool. Rather, it is a tool that must be used with the techniques of combinatorial chemistry, structural biology, high throughput screening, siRNA, in silico design & related technologies. The dynamics of drug development is one of the defining characteristics of pharmaceutical industry. Despite its importance to industry, there is little information on how long it takes for particular drugs to go through human clinical trials and the probabilities of successful completion. Useful drugs like risperidone, pyrethrin, isoniazide, rotenone, AZT, strychnine, reserpine, some antihistamines, ergot alkaloids, caffeine, cocaine and barbiturates are heterocyclic compounds. Recently some non-nucleoside heterocyclic compounds like nivirapine, TIBO, BHAP, PETT and HEPT have been used as anti-HIV agents. The latest anticancer drug is Fludarabine, which contain heterocyclic framework in the structure.

Looking to the importance of heterocyclic compounds in medicinal chemistry, we have synthesized the following heterocyclic compounds and screened for their in vitro antimicrobial activity. Heterocyclic compounds like 4-oxo-quinazoline, 4-oxo-thiazolidin, 5-oxo-imidazole, 1,2,4-triazol and their derivatives have been found to possess strong hypnotic, anaesthetic, analgesic, sedative, antifungal, antitubercular, anticonvulsant, CNS-depressant, anti-HIV, anticancer and antibacterial activities.

Part-I Section 1: N-{5-[(aryl)methylene]-2-(2-hydroxyphenyl]-4-oxo(1,3thiazolidin-3-yl)}{4-[2-(4-methylphenyl)-4-oxo(3-hydro quinazolin-3-yl)] phenyl}carboxamides. Section 2: N-{5-[(aryl)methylene]-2-(4-hydroxyphenyl]-4-oxo(1,3thiazolidin-3-yl)}{4-[2-(4-methylphenyl)-4-oxo(3-hydro quinazolin-3-yl)]phenyl}carboxamides. Section 3: N-{5-[(aryl)methylene]-2-(4-fluorophenyl]-4-oxo(1,3thiazolidin-3-yl)}{4-[2-(4-methylphenyl)-4-oxo(3-hydro quinazolin-3-yl)]phenyl}carboxamides. Section 4: N-{5-[(aryl)methylene]-2-(4-chlorophenyl]-4-oxo(1,3thiazolidin-3-yl)}{4-[2-(4-methylphenyl)-4-oxo(3-hydro quinazolin-3-yl)]phenyl}carboxamides.

Part-II Section 5: N-{4-[(aryl)methylene]-5-oxo-2-phenyl(2-imidazolinyl)} {4-[2(3-nitrophenyl)-4-oxo(3-hydroquinazolin-3-yl)]phenyl} carboxamides. Section 6: N-{4-[(aryl)methylene]-5-oxo-2-phenyl(2-imidazolinyl)} {4-[2(4-nitrophenyl)-4-oxo(3-hydroquinazolin-3-yl)]phenyl} carboxamides. Section 7: N-{4-[(aryl)methylene]-5-oxo-2-phenyl(2-imidazolinyl)}-2-(1phenyl(3H-1,2,4-triazol-3-yloxy))acetamides. Section 8: {4-[(Diethoxythioxophosphino)amino]phenyl}-n-{4-[(aryl) methylene]-5-oxo-2-phenyl(2-imidazolinyl)}carboxamides.

Part-III Section 9: Phenyl-N-{5-naphthal-3-sulfanyl(1,2,4-triazol-4-yl)} carboxamides. Section 10: Phenyl-N-{5-[(4-chlorophenoxy)methyl]-3-sulfanyl(1,2,4triazol-4-yl)}carboxamides. Section 11: Phenyl–N–{5–(2–naphthyloxyacetyl)-3–sulfanyl(1,2,4–triazole4-yl)}carboxamides. Section 12: Phenyl–N–{5–[(3-nitrophenyl)methyl]–3–sulfanyl(1,2,4–triazole4-yl)}carboxamides.

Part-I : Structures of the synthesized compounds O

OH

O

O

NH

O

NH

N

N O

N

N

OH

S

S

O

N

N

Ar

CH 3

Section : 1

Section : 2 F

O O

Cl

O

NH

O

N

N

Ar

CH 3

N

N

S

O

NH

S

O

N

N

Ar

CH 3

CH 3

Section : 3

Ar

Section : 4 Where Ar = Different aryl group

Part-II : Structures of the synthesized compounds

Ar

O

O

O

O O

Ar

O N

N N

N

N

NH

N

N

NH

R

N

Where R = 4-Nitrophenyl NO2

Section : 5 Ar

O

Section : 6

O CH2

N

N

NH

Ar

O

O

O

N

NH

N

N

NH

N

S

N

Section : 7

P

OC2H5 OC2H5

Section : 8 Where Ar = Different aryl group

Part-III : Structures of the synthesized compounds SH O Ar

N NH

N

N

SH

Ar

N

O

Section : 9

N

N

Cl

Section :10 SH O Ar

N

O

N

NH

Ar

N N

N

CH2

CH2

NO2

Section : 11

NH

CH2

SH O

N

O

Section : 12

NH

Where Ar = Different aryl group

Part-IV: Biological evaluation and characterization The study in part four is divided into following two sections. Section A: This section deals with the biological evaluation of the compounds synthesised in part I, II and III. Section B: In this section we will discuss the spectroscopic analysis of the compounds reported in part I, II and III.

Signature of the guide

Signature of the candidate

Prof. Nisheeth C. Desai

Shihora Prashant Nanubhai

Date: 29/06/2007 Place: BHAVNAGAR