Agonists design

F. R., Astruc-Diaz, F., Thompson, . M., Cavasotto, C. N., Naguib, M. (2009) 2,3-Dihydro-1-benzofuran derivatives as a series of potent selective cannabinoid receptor 2 agonists design, synthesis, and binding mode prediction through ligand-steered modeling. ChemMedChem 4, 1615-1629. 

Bury, Y. et al. (2001) Molecular evaluation of vitamin D3 receptor agonists designed for topical treatment of skin diseases. The Journal of Investigative Dermatology, 116, 785-792. 

Cl-1017, a functionally Mj-selective muscarinic agonist design, synthesis, and preclinical pharmacology... 

PPARy phosphorylation, whereas the differences in their agonistic potency conld explain the differences in their side effects [27]. With this new knowledge, effective and safe PPARy agonists designed as antidiabetic compounds must maximise the inhibition of PPARy phosphorylation at Ser273 while reducing the PPARy transactivation activity. 

Y C, M G Bures, A A Danaher, J DeLazzer, I Lico and P A Pavlik 1993. A Fast New Approach to irmacophore Mapping and its Application to Dopaminergic and Benzodiazepine Agonists. mal of Computer-A ided Molecular Design 7 83-102. 

FIGURE 5.15 Different modes of response measurement, (a) Real time shows the time course of the production of response such as the agonist-stimulated formation of a second messenger in the cytosol, (b) The stop-time mode measures the area under the curve shown in panel A. The reaction is stopped at a designated time (indicated by the dotted lines joining the panels) and the amount of reaction product is measured. It can be seen that in the early stages of the reaction, before a steady state has been attained (i.e., a plateau has not yet been reached in panel A), the area under the curve is curvilinear. Once the rate of product formation has attained a steady state, the stop-time mode takes on a linear character. 

Perez, M., Pauwels, P. J., Fourrier, C., Chopin, P., Valentin, J.-P., John, G. W., Marien, M., and Halazy, S. (1998). Dimerization of sumatriptan as an efficienct way to design a potent, centrally and orally active 5-HT1B agonist. Bioorg. Med. Chem. Lett. 8 675-680. 

General Procedure A function is fit to both sets of data points and a set of responses are chosen that have data points for at least one of the curves within the range of the other curve. A metameter of the fitting function is then used to calculate the concentrations of agonist for the other curve that produce the designated responses from the first curve. 

Aim This method is designed to measure the affinity of an antagonist that produces insurmountable antagonism (depression of maximal response to the agonist) but also shifts the curve to the right by a measurable amount. 

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