143935-61-9

Upstream product

• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 68030-64-8 (1S)-2-(tert-butylcarbamoyl)pyrrolidine-1-carboxylic acid tert-butyl ester 

Downstream Products

• 165522-26-9 1-<(2R,3S)-3-amino-2-hydroxy-4-phenylbutyryl>-N-tert-butyl-L-prolinamide 
• 153380-43-9 (S)-N-tert-butyl-1-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutanoyl]pyrrolidine-2-carboxamide 
• 143934-31-0 (S)-N-tert-butyl-3-[(2S,3S)-3-[(S)-2-(tert-butoxycarbonyl)aminosuccinamyl]amino-2-hydroxy-4-phenylbutanoyl]pyrrolidine-2-carboxamide 
• 139694-65-8 (S)-N-tert-butyl-3-[(2S,3S)-2-hydroxy-3-[(S)-2-benzyloxycarbonylaminosuccinamyl]amino-4-phenylbutanoyl]pyrrolidine-2-carboxamide 
• 141171-77-9 (S)-N-tert-butyl-3-[(2S,3S)-3-[(S)-2-(1-naphthoxyacetyl)aminosuccinamyl]amino-2-hydroxy-4-phenylbutanoyl]pyrrolidine-2-carboxamide 
• 141171-79-1 (S)-N-tert-butyl-3-[(2S,3S)-3-[(S)-2-(2-naphthoxyacetyl)aminosuccinamyl]amino-2-hydroxy-4-phenylbutanoyl]pyrrolidine-2-carboxamide 
• 153380-41-7 (S)-2-Amino-N¹-[(1S,2S)-1-benzyl-3-((S)-2-tert-butylcarbamoyl-pyrrolidin-1-yl)-2-hydroxy-3-oxo-propyl]-succinamide 
• 139758-12-6 1-<(2R,3S)-3-(N²-benzyloxycarbonyl-L-asparaginyl)amino-2-hydroxy-4-phenylbutyryl>-N-tert-butyl-L-prolinamide 

Relevant academic research and scientific papers

Structure-activity relationship of orally potent tripeptide-based HIV protease inhibitors containing hydroxymethylcarbonyl isostere

We designed and synthesized a new class of peptidomimetic human immunodeficiency virus protease inhibitors containing a unique unnatural amino acid, allophenylnorstatine [Apns; (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid], with a hydroxymethylcarbonyl isostere as the active moiety. From a structure-activity relationship study of HIV-1 protease inhibition, enzyme selectivity for other aspartyl proteases, the antiviral activity and pharmacokinetics in rats, 24c (KNI-227) and 24d (KNI-272, our first clinical candidate) were found to be selective and orally potent HIV protease inhibitors. Moreover, an improvement of the pharmacokinetic features of KNI-272 provided two long-lasting and highly bioavailable compounds (24g: JE-2178,h: JE-2179).

KNI-102, a novel tripeptide HIV protease inhibitor containing allophenylnorstatine as a transition-state mimic

HIV-1 protease inhibitors containing allophenylnorstatine (Apns; (2S,3S)-3-amino-2-hydroxy-4-phenyl-butyric acid]-Pro (syn distereomer) as a transition-state mimic were established to be potent and highly selective. Z-Asn-Apns-Pro-NHBu(t) (KNI-102) is the only tripeptide exhibiting substantial anti-HIV activity and may be of minimum size for potent, selective inhibition of HIV protease. Ready availability due to its simple chemical structure and stability should make it valuable for studies of the development of metabolically stable anti-AIDS drugs.