Bradykinin 1 antagonist

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]. 

J. Knolle, G. Breipohl, S. Henke, K. Wirth, B. Scholkens, New and Highly Potent Bradykinin Antagonists , Agents Actions 1992, Suppl. 38, 559-564. 

Bradykinin antagonists of the B2 receptor are currently in development and may find utility in the treatment of pain associated with burns and such chronic inflammatory disorders as arthritis, asthma, and chronic pain. 

In addition to the deductions one might make about a receptor binding site on the basis of receptor binding data from conformationally constrained ligands as previously described, models of bradykinin and bradykinin antagonists bound to their respective sites on the receptor as complimentary aspects of the overall strategy are also valuable. Unfortunately, due to the nature of the bradykinin... 

The results of the receptor binding assay performed using this compound, IA, are shown in Table 4 where it is clear that affinity to the human B2 receptor is improved with respect to compound I. This data is supportive of the notion that the C-terminal residue(s) in this new series of bradykinin antagonist compounds interact with a hydrophobic environment, perhaps within the transmembrane domain of the receptor as previously suggested. 

Kyle DJ, Blake PR, Hicks RP. In Burch RM, ed. Bradykinin Antagonists Basic and Clinical Research. New York Marcel Dekker, 1991 131-146. 

Coupling of a benzyl bromide and a resin-bound stannane in the presence of a protected guanidine (Scheme 51), en route to solid-phase synthesis of bradykinin antagonists, is also reported in this patent.101... 

Griesbacher and Lembeck (1992) used the isolated guinea-pig ileum for analysis of bradykinin antagonists. 

Grant (2) prepared sulfonylquinoxalone derivatives, (III), as bradykinin antagonists, which were used to relieve adverse symptoms, associated with bradykinin disorders including pain, inflammation, bronchoconstriction, and cerebral edema. 

G. Kotovych, The importance of the N-terminal beta-turn in bradykinin antagonists,/. Biomd. Struct. Dyn. 2000, 18, 249-260. 

Stewart, J. M. (1995) Bradykinin antagonists developments and applications. Biopolymers 37, 143-155. 

Chan, D., Gera, L., Stewart, J., et al. (2002) Bradykinin antagonist dimer, CU210, inhibits the growth of human lung eaneer eell lines by a biased agonist mechanism. Proc. Natl. Acad. Sci. USA 99, 4608 613. 

De Castro, L.F.P. and Reissmann, S. (1995). QSAR in Bradykinin Antagonists. Inhibition of the Bradykinin Induced Contraction of the Isolated Rat Uterus and Guinea Pig Ileum. Quant.-Struct.-Act.Relat, 14,249-257. 

Other examples are symmetrical bradykinin antagonists and symmetrical lexitropsins (netropsine, distamycine), active against HTV-I viruses. Non-symmetrical polymethylenic thromboxane synthetase inhibitors are described by Press et al The compounds contain a thiophene-2-carboxamide moiety, separated from an imidazole ring by 3-8 methylene units. Surprisingly, whereas most of the compounds show... 

C12a. Chryssanthou, C. Kalberer, J., Jr., Kooperstein, S., and Antopol, W., Studies on dysbarism. II. Influence of bradykinin and bradykinin-antagonists on decompression sickness in mice. Aerospace Med. 36, 741-746 (1964). 

C. Clinical Role Although it has no therapeutic application, bradykinin may play a role in the antihypertensive action of angiotensin-converting enzyme inhibitors, as previously noted (Chapter 11 Figure 11-4). At present there are no clinically important bradykinin antagonists. 

Bock MG, Longmore J (2000) Bradykinin antagonists new opportunities. Curr Opin Chem Biol 4 401 06... 

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