Angiotensin amide

Chemical Name L-asparaginyl-L-arginvI-L-valvl-L-tyrosyl-L-valyl-L-histidvI-L-protyl-L-phenylalanine 

L-Asparaginyl -L-arginyl -L-valyl -L-tyrosyl-L-valyl -L-histidyl -L-prolyl -L-phenylalanine methyl ester trihydrochloride Sodium hydroxide 

48 mg (0.042 mmol) of L-asparaginyl-L-arginyl-L-valyl-L-tyrosyl-L-valyl-L-histidyl-L-prolyl-L-phenylalanine methyl ester trihydrochloride are suspended I n 0.5 ml of methanol, and treated gradually In the course of one hour with 03 ml of N-caustic soda solution (about 7 equivalents) so that the pH value of the solution is maintained between 10.5 and 11.5. After a further 30 minutes the solution is freed from methanol under vacuum at room temperature, adjusted with 1 N-acetic acid to pH 7.4 and lyophilized. The residual mixture of free peptide and inorganic salts (79 mg) is fractionated by countercurrent distribution in the system butanol/0.1 N-ammonium hydroxide. The pure octapeptide is obtained as a colorless powder which is soluble in water and methanol, more sparingly soluble in ethanol, and insoluble in acetone. 

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L-Asparaginyl-L-arginyl-L-valyl-L-tyrosyl-L-valyl-L-histidyl-L-prolyl-L-phenylalanine methyl ester trihydrochloride Angiotensin amide Atropic acid ethyl ester Tilidine HCI Atropine... 

Much of the recent work on the use of anodic amide oxidation reactions has focused on the utility of these reactions for functionalizing amino acids and for synthesizing peptide mimetics [13]. For example, in work related to the cyclization strategy outlined in Scheme 3, the anodic amide oxidation reaction has been used to construct a pair of angiotensin-converting enzyme inhibitors [14]. The retrosynthetic analysis for this route is outlined in Scheme 4. In this work, the anodic oxidation reaction was used to functionalize either a proline or a pipercolic add derivative and then the resulting methoxylated amide used to construct the bicyclic core of the desired inhibitor. A similar approach has recently been utilized to construct 6,5-bicyclic lactam building blocks for... 

Some drugs possessing amide bonds, such as prilocaine, and of course, peptides, can be hydrolyzed by peptidases and inactivated in this manner. Peptidases are also of pharmacological interest because they are responsible for the formation of highly reactive cleavage products (fibrin, p. 146) and potent mediators (angiotensin 11, p. 124 bradykinin, enkephalin, p. 210) from biologically inactive peptides. 

Peptides make up the largest group among the neurosecretions. Many peptide hormones—e.g., thyroliberin (TRH) and angiotensin 11—simultaneously act as transmitters. Most neuropeptides are small (3-15 AA). At their N-terminus, many of them have a glutamate residue that has been cyclized to form pyroglutamate (5-oxoproline, [Pg.352]

Reaction of the imidazole (7-4) with the benzofuran derivative (6-7) leads to the displacement of the benzylic halogen and the formation of the alkylation product (8-1). Treatment of that intermediate with trifluoroacetic acid breaks open the urethane to afford the corresponding free amine. This is allowed to react with ttiflic anhydride to afford the trifluoromethyl sulfonamide (8-2). The ester group on the imdidazole is then saponified, and the newly formed acid is reacted with carbonyl diimidazole. Reaction with ammonia converts the activated carboxyl group to the amide. There is thus obtained the angiotensin antagonist saprisartan (8-3) [6]. 

Amine 567 and its amides are useful diuretics (81GEP3029871). Compound 570 has antiarrhythmic activity (92PJC131). Compounds 573-575 were prepared as potent, active angiotensin II receptor antagonists (94JMC2371). 

Reduction of the carbonyl in the r >[CO-CH2-NH] link 7 (R1 = H) results in the (hy-droxy)ethyleneamino or r >[CH(OH)-CH2-NH] link 8 (R1 = H), which has proved to be a very potent analogue of the tetrahedral hydrated intermediate of the scissile amide bond. It has been widely used for the design of various inhibitors of HIV protease 141,142 14 154 and ACE, 155-157 and to synthesize angiotensin II, III, and IV analogues. 158,159 Indeed, the chirality of the hydroxylated carbon is critical for HIV protease inhibition, but separation of the epimers may be difficult. Therefore, the stereoselective synthesis from epoxides has been actively investigated. An example of a C-methylated tp[CMe(OH)-CH2-NH] link, obtained from an epoxide with chromatographic separation of the epimers, has also been described. 157 Most of the [(hydroxy)ethyleneamino] peptides have been prepared by solution procedures, but two examples of solid-phase synthesis have been reported. A theoretical study of the (hydroxy)ethyleneamino replacement for the amide bond has been carried out on a HIV protease inhibitor. 160 ... 

Additional p-Lhienylbenzyl amides, (I), effective as angiotensin-(l-7) receptors agonists were prepared by the author (3) in earlier investigations. 

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