Synthesis of 2-[{4-(t-amino-1-yl) but-2-yn-1-yl }oxy]-1,3-benzothiazole derivatives as H3-antagonists
Journal Title: IOSR Journal of Pharmacy (IOSRPHR) - Year 2014, Vol 4, Issue 9
Abstract
Aminoacetylenicoxybenzothiazole derivatives were synthesized from the reaction of 2- hydroxybenzothiazole with 3-bromoprop-1-yne to generate 2-(prop-2-ynl-1-yloxy)-1,3-benzothiazole (RM-1). A mixture of 2-(prop-2-yn-1-yloxy)-1,3-benzothiazole, paraformaldehyde, cyclic amine and cuprous chloride catalytic amount, in peroxide-free dioxane through Mannich reaction yielded the desired aminoacetylenicoxybenzothiazoles (RM- 2-7). The mp, IR, 1H-NMR, 13C-NMR and elemental analysis were consistent with the assigned structures. The design of these compounds as H3 antagonists was based on the rationalization for the important criteria needed to overlap effectively with H3 receptor to induce antagonistic activity. These criteria are: 1) The basic amino group for ionic binding. 2) The acetylenic group for electrostatic interaction. 3) The 2-butyne provide the appropriate distance between the basic nitrogen and benzthiazole. 4) Oxy ether to provide hydrogen bonding with H3 receptor and 5) benzothiazole group found in H3 antagonists and many other biologically active compounds. The docking results showed that all the designed compounds have a good H3 receptor antagonism especially RM-7 which have -6 (kcal/mol). These results provide a good lead to design more effective H3 antagonists in managing Alzheimer's and other diseases like depression, epilepsy, schizophrenia and many other CNS disorders.
Authors and Affiliations
Ragheed Al- Rahmani , Elham Al-kaissi , Tawfeeq Arafat , Mohammad Ghattas , Zuhair Muhi-eldeen
Keywords
Related Articles
- EP ID EP163094
- DOI -
- Views 86
- Downloads 0
Assessment of Good Pharmacy Practice (GPP) in Pharmacies of Community Settings in India
: Good Pharmacy Practice (GPP) is at the very heart of the profession of Pharmacy; indeed it is the very essence of the profession. Moreover, it expresses our covenant with the patient not only to ‘do no harm’ bu...
Hepatoprotective effects of simvastatin on paracetamol -induced hepatic damage in rats
ABSTRACT: This study was designed to investigate the possibility of statins hepatoprotection in paracetamol toxicicity. Paracetamol hepatotoxicity was associated with significant decrease in the serum total&nb...
Monitoring histological changes in oral mucosa using AgNORs as biomarkers for oxygenic stress in smokers and COPD patients
Background: It is well known that tobacco smoke causes cellular proliferation and chronic obstructive pulmonary disease (COPD), but changes in buccal mucosa cells in smokers and COPD patients remains unknown. Ai...
The Preventive Effects of N-Acetylcysteine on Tacrolimus Induced Nephrotoxicity
Tacrolimus exhibits its nephrotoxic effect in relation to its inhibition of one of the antioxidant enzymes named catalase. Glutathione peroxidase catalysesa similar reaction done by catalase. The factor which increases G...
Protective Potential of Aqueous Leaf Exract of Vernonia amygdalina in Cyclophosphamide – Induced Myelotoxicity
Cyclophosphamide (CP) is among the most widely used alkylating anti-cancer agents in chemotherapy. Myelotoxicity is one of its dose-limiting adverse effects. The aim of the present study, therefore, was to investigate th...