The design and synthesis of related molecules that are more effective, more selective, and less toxic than aspirin are important objectives of biomedical research.Keep reading other articles of 4430-31-3. COA of Formula: https://www.ambeed.com/products/4430-31-3.html.
Chemistry involves the study of all things chemical – chemical processes, chemical compositions and chemical manipulation – in order to better understand the way in which materials are structured, how they change and how they react in certain situations. COA of Formula: https://www.ambeed.com/products/4430-31-3.html.
Three-dimensional quantitative structure-activity relationship methods, the comparative molecular field analysis (CoMFA) and the comparative molecular similarity indices analysis (CoMSIA), were applied using a training set of 45 ligands of the (alpha4)(2)(beta2)(3) nicotinic acetylcholine receptor (nAChR). All compounds are related to (-)-epibatidine, (-)-cytisine, (+)-anatoxin-a, and (-)-ferruginine, and additionally, novel diazabicyclo[4.2.1]nonane- and quinuclidin-2-ene-based structures were included. Their biological data have been determined by utilizing the same experimental protocol. Statistically reliable models of good predictive power (CoMFA r(2) = 0.928, q(2) = 0.692, no. of components = 3; CoMSIA r(2) = 0.899, q(2) = 0.701, no. of components = 3) were achieved. The results obtained were graphically interpreted in terms of field contribution maps. Hence, physicochemical. determinants of binding, such as steric and electrostatic and, for the first time, hydrophobic, hydrogen bond donor, and hydrogen bond acceptor properties, were mapped back onto the molecular structures of a set of nAChR modulators. In particular, changes in the binding affinity of the modulators as a result of modifications in the aromatic ring systems could be rationalized by the steric, electrostatic, hydrophobic, and hydrogen bond acceptor properties. These results were used to guide the rational design of new nAChR ligands such as 48-52 and 54, which were subsequently synthesized for the first time and tested. Key steps of our synthetic approaches were successfully applied Stille and Suzuki cross-coupling reactions. Predictive r(2) values of 0.614 and 0.660 for CoMFA and CoMSIA, respectively, obtained for 22 in part previously unknown ligands for the (alpha4)(2)(beta2)(3) subtype, demonstrate the high quality of the 3D QSAR models.
The design and synthesis of related molecules that are more effective, more selective, and less toxic than aspirin are important objectives of biomedical research.Keep reading other articles of 4430-31-3. COA of Formula: https://www.ambeed.com/products/4430-31-3.html.
Reference:
Quinuclidine – Wikipedia,
,Quinuclidine | C7H13N | ChemSpider