143224-83-3Relevant academic research and scientific papers
Nonpeptidic lysosomal modulators derived from Z-Phe-Ala-diazomethylketone for treating protein accumulation diseases
Viswanathan, Kishore,Hoover, Dennis J.,Hwang, Jeannie,Wisniewski, Meagan L.,Ikonne, Uzoma S.,Bahr, Ben A.,Wright, Dennis L.
, p. 920 - 924 (2013/01/15)
Lysosomes are involved in protein turnover and removing misfolded species, and their enzymes have the potential to offset the defect in proteolytic clearance that contributes to the age-related dementia Alzheimer's disease (AD). The weak cathepsin B and L
Design, biologic evaluation, and SAR of novel pseudo-peptide incorporating benzheterocycles as HIV-1 protease inhibitors
He, Meizi,Zhang, Hang,Yao, Xiaojian,Eckart, Michael,Zuo, Elizabeth,Yang, Ming
scheme or table, p. 174 - 180 (2011/03/20)
A series of novel HIV-1 protease inhibitors based on the (hydroxyethylamino)-sulfonamide isostere incorporating substituted phenyls and benzheterocycle derivatives bearing rich hydrogen bonding acceptors as P 2 ligands were synthesized. Prolonged chain linking the benzhereocycle to the carbonyl group resulted in partial loss of binding affinities. Introduction of a small alkyl substituent with appropriate size to the -CH2- of P1-P2 linkage as a side chain resulted in improved inhibitory potency, and in this study, isopropyl was the best side chain. Replacement of the isobutyl substituent at P 1′group with phenyl substituent decreased the inhibitory potency. One of the most potent inhibitor, compound 23 showing high affinity to HIV-1 protease with an IC50 value of 5 nm, also exhibited good anti-SIV activity (EC50 = 0.8 μm) with low toxicity (TC 50 > 100 μm). The flexible docking of inhibitor 23 to HIV-1 protease active site rationalized the interactions with protease.
COMPOUNDS FOR LYSOSOMAL MODULATION AND METHODS OF USE
-
, (2009/12/02)
Compounds useful for promoting lysosomal processes and thereby ameliorating the disruption of cellular and functional integrity induced by Aβ and other protein and glycoconjugate species are provided. Methods for the treatment of neurodegenerative disease
Succinoylamino hydroxyethylamino sulfonyl urea derivatives useful as retroviral protease inhibitors
-
Page column 34, (2010/01/30)
Succinoylamino hydroxyethylamino sulfonyl urea derivatives of the formula: wherein the substituents are as defined in the specification, are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.
Aminodiol HIV Protease Inhibitors. 1. Design, Synthesis, and Preliminary SAR
Barrish, Joel C.,Gordon, Eric,Alam, Masud,Lin, Pin-Fang,Bisacchi, Gregory S.,et al.
, p. 1758 - 1768 (2007/10/02)
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).
