160232-54-2

Upstream product

• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 165727-45-7 tert-butyl ((2S,3S)-4-chloro-3-hydroxy-1-phenylbutan-2-yl)carbamate 
• 102123-74-0 (S)-tert-butyl (4-chloro-3-oxo-1-phenylbutan-2-yl)carbamate 
• 67729-36-6 Boc-Phe-O-COO-isoBu 
• 60398-41-6 (3S)-tert-butyl 1-benzyl-3-diazo-2-oxopropylcarbamate 
• 98760-08-8 (1-oxiranyl-2-phenylethyl)carbamic acid tert-butyl ester 
• 74-89-5 methylamine 

Downstream Products

• 162539-71-1 {(1S,2R)-1-Benzyl-3-[((S)-3-tert-butoxycarbonylamino-2-oxo-4-phenyl-butyl)-methyl-amino]-2-hydroxy-propyl}-carbamic acid tert-butyl ester 
• 733744-92-8 (S)-2-[3-((2R,3S)-3-tert-Butoxycarbonylamino-2-hydroxy-4-phenyl-butyl)-3-methyl-ureido]-4-methyl-pentanoic acid methyl ester 
• 1031361-56-4 1,1-dimethylethyl [(1S,2R)-2-hydroxy-3-(methyl{[(phenylmethyl)oxy]carbonyl}amino)-1-(phenylmethyl)propyl]carbamate 
• 160231-30-1 C₂₄H₃₃N₃O₆S 

Relevant academic research and scientific papers

Synthesis and in vivo antimalarial evaluation of novel hydroxyethylamine derivatives

A series of hydroxyethylamines has been synthesized from the reaction of (2S,3S )Boc-phenylalanine epoxide with alkyl amines in good yields and evaluated for their in vivo antimalarial activity in mice. Compound 4g presented better activity then the reference artesunate in percentage of inhibition of parasitemia in treated P. berghei-infected mice and compare to the activity of artesunate in the survival of mice 14 days after infection. In addiction, no hemolytic activity was found, which supports that inhibition of parasitemia is due to antimalarial activity. The compound 4g inhibited the differentiation to schizonts suggesting that parasite metabolism is a possible target of 4g. These results indicate that this class of compound possesses promising perspectives for the development of new antimalarial drugs.

Second generation of hydroxyethylamine BACE-1 inhibitors: Optimizing potency and oral bioavailability

BACE-1 inhibition has the potential to provide a disease-modifying therapy for the treatment of Alzheimer's disease. Optimization of a first generation of BACE-1 inhibitors led to the discovery of novel hydroxyethylamines (HEAs) bearing a tricyclic nonprime side. These derivatives have nanomolar cell potency and are orally bioavailable.

Probing pockets S2-S4′ of the γ-secretase active site with (hydroxyethyl)urea peptidomimetics

(Hydroxyethyl)urea peptidomimetics are potent inhibitors of γ-secretase that are accessible in a few synthetic steps. Systematic alteration of P2-P4′ revealed that the corresponding S2-S4′ active site pockets accommodate a variety of substituents, consistent with the fact that this protease cleaves a variety of single-pass membrane proteins; however, phenylalanine is not well tolerated at P2′. A compound spanning P2-P3′ was identified as a low nM inhibitor of γ-secretase activity both in cells and under cell-free conditions.

HYDROXYETHYLAMINE DERIVATIVES FOR THE TREATMENT OF ALZHEIMER'S DISEASE

The present invention relates to novel hydroxyethylamine compounds of formula (I): (I) having Asp2 (-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated-amyloid levels or-amyloid deposits, particularly Alzheimer's disease.

TRICYCLIC INDOLE DERIVATIVES AND THEIR USE IN THE TREATMENT OF ALZHEIMER’S DISEASE

The present invention relates to novel hydroxyethylamine compounds having Asp2 (β-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated β- amyloid levels or β-amyloid deposits, particularly Alzheimer's disease.

Aminodiol HIV Protease Inhibitors. 1. Design, Synthesis, and Preliminary SAR

A series of HIV protease inhibitors containing a novel C2 symmetrical "aminodiol" core structure were prepared from amino acid starting materials.The ability of the aminodiols to inhibit HIV replication in cell culture is comparable to their ability to inhibit the isolated enzyme, a result compatible with good cell membrane penetration by this class of compounds.Optimization of the structure-activity in this series led to aminodiol 9a (Ki = 100 nM; ED50(HIV-1) = 80 nM) containing P1/P1' benzyl and P2/P2' Boc substituents.Compound 9a is a selective inhibito r of HIV protease versus other aspartyl proteases such as human renin, human cathepsin D, and porcine pepsin.In addition, 9a is equipotent against HIV-1 and HIV-2 in cell culture and demonstrates similar activity in infected T-lymphocytes and PBMCs.After iv and oral administration in rats, 9a displayed significant oral bioavailability (ca. 40percent) and a promising plasma elimination half-life (4 h).