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.
Important Role for Phylogenetically Invariant PP2Acα Active Site and C-Terminal Residues Revealed by Mutational Analysis in Saccharomyces cerevisiae