Background:
Thienopyrimidines are the bioisoster of quinazoline and unlike quinazoline
exist in three isomeric forms corresponding to the three possible types annulation of thiophene to the
pyrimidine ring viz thieno[2,3-d] pyrimidine, thieno[3,2-d] pyrimidine and thieno[3,4-d]pyrimidine.
Heterocyclic containing the thienopyrimidinone moiety exhibits various pronounced activities such as
anti-hypertensive, analgesic and anti-inflammatory, antiviral, platelet aggregation inhibitory, antiprotozoal
bronchodilatory, phosphodiesterase inhibitory, antihistaminic, antipsychotic and antimicrobial activity.
Objective:
Synthesis of novel 3(N,N-dialkylamino)alkyl/phenyl substituted thieno[2,3-d]pyrimidinones
as H1-anti-histaminic and antimicrobial agents.
Methods:
A series of 3-[(N,N-dialkylamino)alkyl/phenyl]-2-(1H)thioxo-5,6,7,8-tetrahydrobenzo(b)
thieno(2,3-d)pyrimidine-4(3H)-ones[4a-d], their oxo analogous [5a-d] and 3-[(N,N-dialkylamino)alkyl]-
2-chlorophenyl-5,6,7,8-tetrahydrobenzo(b)thieno(2,3-d)pyrimidine- 4 (3H)-ones[6a-d]derivative were
synthesized from 2-amino-4,5,6,7-tetrahydrobenzo(b)thiophene-3-carboxylic acid by nucleophilic substitution
of different N,N-dialkyl alkylene/phenylene diamines on activated 3-acylchloride moiety followed
by cyclocondensation with carbon disulfide and ethanolic potassium hydroxide to get [4a-d] and
in second reaction by condensation with 4-chlorobenzoyl chloride to get [6a-d] by single pot novel innovative
route. The oxo analogous [5a-d] were prepared by treating derivatives [4a-d] with potassium
permagnate in ethanolic KOH. The synthesized compound were evaluated for H1-antihistaminic and
antimicrobial activities.
Results:
All synthesized compounds exhibited significant H1-antihistaminic activity by in vitro and in
vivo screening methods and data were verified analytically and statistically. The compound 4a, 4b, 5a
and 5b showed significant H1-antihistaminiic activity than the reference standard chlorpheniramine
maleate. The compound 6d, 6c, 5c and 4c exhibited significant antimicrobial activity.
In vivo screening to identify genes mutated in Mycobacterium tuberculosis that alter bacterial sensitivity to antibiotics specifically in the in vivo environment