Synthesis and Evaluation of Some Novel 2-Amino-4-Aryl Thiazoles for
Gangadhar B. Gundlewad
and Bhagwan R. Patil
Department of Chemistry, Shri Shivaji College, Parbhani, Maharashtra 431401, India
Department of Chemistry, Sharda Mahavidyalaya, Parbhani, Maharashtra 431401, India
Received May 12, 2017
Published online 21 January 2018 in Wiley Online Library (wileyonlinelibrary.com).
A series of novel 2-amino-4-aryl thiazoles were synthesized from α-chloroacetophenone and thiourea at
room temperature using acetone as solvent. The structures of synthesized compounds were conﬁrmed by
spectral data. All the compounds were evaluated for antitubercular activity by macro broth dilution method
against Mycobacterium Tuberculosis H37Rv as standard strain. The synthesized compound displays notable
J. Heterocyclic Chem., 55, 769 (2018).
In recent years, the interest in synthesis of biologically
active heterocyclic compounds is greatly increased. The
heterocycles containing nitrogen and sulfur atom has
acquired more importance in medicinal chemistry. The
thiazole ring is a part of many potent biologically
active molecules such as Sulfathiazole (Antimicrobial
drug), Tiazofurin (Antineoplastics drug), and Ritonavir
(Antiretroviral drug). This class of compounds has
various medicinal applications like antibiotics , photo
sensitizers , antibacterial , antitubercular [4,5],
antifungal , anti-HIV , and anti-inﬂammatory .
Some thiazole derivatives have found applications in
drug development for the treatment of allergies ,
hypertension , and schizophrenia . Amino
thiazoles are also used as ligands of estrogen receptors .
Several methods for the synthesis of thiazole and its
derivatives were developed by Hantzsch, Tchernic,
Cook Helborn, Gabriel, and other groups [13,14].
Other methods developed by different workers, from
α-haloketone and thioamide using β-cyclodextrin as catalyst
, by the reaction of acetophenone with thiourea using
as catalyst , from α-bromoketone, primary amine
and phenylisothiocynate in presence of catalytic amount of
triethylamine , 2-aminothiazole derivatives were
synthesized from α-bromoketone, thiourea catalytic amount
of ammonium chloride , ring expansion of
1-arylmethyl-2-(thiocynatomethyl)aziridine with an acyl
chloride in presence of TiCl
Tuberculosis (TB) is a highly contagious infectious disease.
According to World Health Organization, one-third of world’s
population is currently infected with TB . In 2015, there is
an estimated 10.4 million of new (incident) TB cases
worldwide and an estimated 1.4 million TB deaths,
additional 0.4 million deaths resulting from TB disease
among people living with HIV . Currently, TB is treated
with the combination of ﬁrst line antitubercular drugs like
rifampicin, isoniazid, ethambutal, and Pyrazinamide for 6 to
8 months. The organism Mycobacterium Tuberculosis
shows resistance to isoniazid and rifampicin. Totally, drug
resistant TB and possibility of infection with HIV is a
serious problem. The earlier mentioned drugs have side
effects like hepatotoxicity, breathlessness, pruritus, hyper
pigmentation nausea, vomiting, and diarrhea.
The ﬁrst line antitubercular agent Pyrazinamide is a
nicotinamide analog. Pyrazinamide kill the dormant
nongrowing tubercle bacilli of low metabolism activity
when administered with isoniazid or rifampicin. This is
never used alone, because of these side effects of current
drugs and the serious threats of TB, the search of new
effective anti-TB drug against the resistant strains having
fever or no side effects has gaining more importance.
It was found that the biological activity of thiazole increases
with increase in lipophilic character of the molecule, it is an
important parameter related to membrane permeation in
biological system . The halogen substituted aromatic
substituents at fourth position increases lipophilic nature. In
addition, the amino group at second position of thiazole
would be essential element for hydrogen bonding .
Therefore, the present study was designed to synthesize
such scaffold and to evaluate their antitubercular activity.
RESULT AND DISCUSSION
The reaction of α-chloroacetophenone and thiourea in
acetone at room temperature gives 2-amino-4-arylthizole.
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