Antagonist analogs activity

Furthermore, we believe that our hypothesis regarding design of antagonist analogs with prolonged activity offers a potentially useful approach to peptide drug design. 

Rekasi Z, Schally AV (1993) A method for evaluation of activity of antagonistic analogs growth hormone-releasing hormone in a superfusion system. Proc Natl Acad Sci USA 90 2146-2149... 

Table 2.4 Binding and Cyclase Activity of Selected Antagonist Analogs of PTH with Bone-Derived ROS 17/2.8 Cells...

The Ca +-channel antagonists, the 1,4-dihydropyridines (DHPs), represent a remarkably successful group of cardiovascular drugs that have antihypertensive, antiangi-nal, and antiarrhythmic properties (167). Nifedipine (Fig. 10.8) was the first member of the DHP family a structure that embraces both Ca -channel antagonists and activators (168), which was followed by the synthesis of a number of analogs with a prolonged duration cf action and enhanced vascular selectivity (167). 

The development of a glucagon antagonist which lowers blood glucose levels in diabetic animals [66] illustrates the importance of careful binding studies in conjunction with full dose-response analysis of activity. In addition these studies provide another illustration of the manner in which steric changes which cause conformational perturbations apparently can lead to antagonist analogs. 

Sanofi-Synthelabo researchers discovered pyrazole 53 and analogs to have potent Cannabinoid receptor-1 (CB-1) antagonist/inverse agonist activity and have progressed 53 into development for treatment of obesity and alcohol dependence. The synthesis of 53 was accomplished by heating the diketone sodium salt 51 with the aryl hydrazine hydrochloride in acetic acid to provide the intermediate 52, which was further derivatized... 

Inhibition of human multidrug resistance P-glycoprotein 1 was investigated by analogs of a potent. 5-opioid antagonist, including (35, 1 lu5)-3-[(4-hydroxy-2,6-dimethylphenyl)methyl]-11,11 u-dihydro-2//-pyrazino[l, 1-b] isoquinoline-l,4(3//,6//)-dione (OIMIIO). Opioid antagonist activity of... 

Figure 1. Structure of (+)-anatoxin-a and two analogs with agonist and noncompetitive antagonist activity, respectively.

Attaching some short peptidic sequences to adamantane makes it possible to design novel antagonists. The bradykinin antagonist, which is used as an anticancer agent, is an example. The adamantane-based peptidic bradykinin analog was utilized in strucmre-activity relationship (SAR) studies on the bradykinin receptors and showed a potent activity in inhibition of bradykinin-induced cytokine release and stimulation of histamine release [142]. 

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