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.
Keywords: Thieno[2, 3-d]pyrimidinones, H1-antihistaminic, antibacterial activity, antifungal activity, cyclocondensation, bioisoster.
Enhanced Both in vitro and in vivo Kinetics by SLNs Induced Transdermal System of Furosemide: A Novel Approach
Recent Patents on Drug Delivery & Formulation Obstructive Sleep Apnoea Syndrome and Diabetes. Fortuitous Association or Interaction?
Current Diabetes Reviews Peroxisome Proliferator-Activated Receptors and the Control of Fatty Acid Oxidation in Cardiac Hypertrophy
Mini-Reviews in Medicinal Chemistry Renal Blood Flow Dynamics in Inbred Rat Strains Provides Insight into Autoregulation
Current Vascular Pharmacology Buckwheat: A Useful Food and Its Effects on Human Health
Current Nutrition & Food Science Editorial [Hot Topic: The Clinical Management and Treatment of Hypertension, Its Pathophysiology and the Clinical Use of Antihypertensive Drugs (Executive Editor: Gregory Y.H. Lip)]
Current Pharmaceutical Design Atenolol: Differences in Mode of Action Compared with other Antihypertensives.An Opportunity to Identify Features that Influence Outcome?
Current Pharmaceutical Design New Emerging Prospects in the Pharmacotherapy of Hypertension
Cardiovascular & Hematological Agents in Medicinal Chemistry Incretins and Preservation of Endothelial Function
Cardiovascular & Hematological Agents in Medicinal Chemistry Preface [Hot Topic: Treatment of Hypertension, Its Pathophysiology and the Clinical Use of Antihypertensive Drugs (Executive Editor: Gregory Y.H. Lip)]
Current Pharmaceutical Design GPER/GPR30 and Regulation of Vascular Tone and Blood Pressure
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Under Re-organization) The Role of Adipokines in Hypertension and Cardiovascular Disease
Current Hypertension Reviews Renin-Angiotensin-Aldosterone System Antagonists and the Prevention of Type 2 Diabetes Mellitus
Current Pharmaceutical Design Endothelial Dysfunction: Methods of Assessment and Application to Hypertension
Current Pharmaceutical Design Cortical and Putamen Age-Related Changes in the Microvessel Density and Astrocyte Deficiency in Spontaneously Hypertensive and Stroke-Prone Spontaneously Hypertensive Rats
Current Neurovascular Research A Brief Review of Blue- and Bilberries’ Potential to Curb Cardio-Metabolic Perturbations: Focus on Diabetes
Current Pharmaceutical Design Radiological Diagnosis of Renal Thrombosis in Children
Current Pediatric Reviews Cardiovascular Disease in Masked Hypertension: Clinical Implications
Current Hypertension Reviews Drugs Affecting Blood Pressure Variability: An Update
Current Pharmaceutical Design Transient Receptor Potential Channels, the Kidney and Hypertension
Current Hypertension Reviews