139976-34-4Relevant academic research and scientific papers
Reduced amide bond peptidomimetics. (4S)-N-(4-amino-5-[aminoalkyl]aminopentyl)-N′-nitroguanidines, potent and highly selective inhibitors of neuronal nitric oxide synthase
Hah,Roman,Martásek,Silverman
, p. 2667 - 2670 (2001)
Selective inhibition of the isoforms of nitric oxide synthase (NOS) could be therapeutically useful in the treatment of certain disease states arising from the overproduction of nitric oxide. Recently, we reported nitroarginine-containing dipeptide amides (Huang, H; Martasek, P.; Roman, L. J.; Masters, B. S. S.; Silverman, R. B. J. Med. Chem. 1999, 42, 3147.) and some peptidomimetic analogues (Huang, H; Martasek, P.; Roman, L. J.; Silverman, R.B. J. Med Chem. 2000, 43, 2938.) as potent and selective inhibitors of neuronal NOS (nNOS). Here, reduced, amide bond pseudodipeptide analogues are synthesized and evaluated for their activity. The deletion of the carbonyl group from the amide bond either preserves or improves the potency for nNOS. Significantly, the selectivities for nNOS over eNOS (endothelial NOS); and iNOS (inducible NOS) are greatly increased in these series. The most potent nNOS inhibitor among these compounds is (4S)-N-(4-amino-5-[aminoethyl]aminopentyl)-N′-nitroguanidine (7) (Ki = 120 nM), which also shows the highest selectivity over eNOS (greater than 2500-fold) and 320-fold selectivity over iNOS. The reduced amide bond is an excellent surrogate of the amide bond, and it will facilitate the design of new potent and selective inhibitors of nNOS.
Atom-economical synthesis of the N(10)-C(17) fragment of cyclotheonamides via a novel Passerini reaction-deprotection-acyl migration strategy1
Owens, Timothy D.,Semple, J. Edward
, p. 3301 - 3304 (2001)
Equation presented A novel variant of the atom-economical Passerini reaction between suitably protected argininal, dipeptide isonitrile, and proline components afforded adduct 13. Orthogonal N-deprotection of 13 led, via a smooth O-to N-acyl migration, to 14, which constitutes the N(10)-C(17) fragment of the cyclotheonamide family of serine protease inhibitors. Each reaction in this three-step protocol proceeds in good yield and under very mild conditions.
Selective neuronal nitric oxide synthase inhibitors
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Page/Page column 9; 23, (2009/01/24)
Peptidomimetic compositions for selective inhibition of neuronal nitric oxide synthase.
Aromatic heterocyclic derivatives as enzyme inhibitors
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Page column 44-45, (2010/02/04)
The present invention discloses peptide aldehydes which are potent and specific inhibitors of thrombin, their pharmaceutically acceptable salts, pharmaceutically acceptable compositions thereof, and methods of using them as therapeutic agents for disease states in mammals characterized by abnormal thrombosis.
