5897-65-4Relevant academic research and scientific papers
Amino acid derivatives, pharmaceutical compositions containing these compounds and processes for preparing them
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, (2008/06/13)
NPY-antagonistic compounds of the formula STR1 Exemplary are: (A) (R)-N-[[4-(Aminocarbonylaminomethyl)phenyl]methyl]-N 2-bis(4-hydroxyphenyl)acetyl]-argininamide-trifluoracetate;(B) (R)-N-[[4-(Aminocarbonylaminomethyl)phenyl]methyl]-N 2-[bis(4-chlorphenyl)acetyl]-argininamide-trifluoracetate;(C) (R)-N-[[4-Aminocarbonylaminomethyl)phenyl]methyl]-N 2-(diphenylacetyl)-argininamide-trifluoracetate;(D) (R)-N 2-(Diphenylacetyl)-N-[[4-(ethoxycarbonylmethylamino-carbonylaminomethyl) phenyl]methyl]-argininamide-trifluoroacetate;(E) (R,S)-N 5-(Aminoiminomethyl)-N 2-(diphenylacetyl)-N-[(4-hy-droxyphenyl)methyl]-N 5-methyl-ornithinamide-hydrochloride; (F) (R)-N-[[4-(Aminocarbonylmethyl)phenyl]methyl]-N 2-(diphenyl-acetyl)-argininamide-diacetate;(G) (R)-N. sup. 2-(Diphenylacetyl)-N-[[4-(ethylaminocarbonylamino-methyl)-phenyl]methyl]-argininamide-bis-(trifluoroacetate); and,(H) (R)-N. sup.2-(Diphenylacetyl)-N-[[4-(ethoxycarbonylamino-carbonylaminomethyl) phenyl]methyl]-argininamide-trifluoroacetate.
Selective, tight-binding inhibitors of integrin α4β1 that inhibit allergic airway responses
Lin, Ko-Chung,Ateeq, Humayun S.,Hsiung, Sherry H.,Chong, Lillian T.,Zimmerman, Craig N.,Castro, Alfredo,Lee, Wen-Cherng,Hammond, Charles E.,Kalkunte, Sandhya,Chen, Ling-Ling,Pepinsky, R. Blake,Leone, Diane R.,Sprague, Andrew G.,Abraham, William M.,Gill, Alan,Lobb, Roy R.,Adams, Steven P.
, p. 920 - 934 (2007/10/03)
Integrin α4β1 mediates leukocyte recruitment, activation, mediator release, and apoptosis inhibition, and it plays a central role in inflammatory pathophysiology. High-affinity, selective inhibitors of α4β1, based on the Leu-Asp-Val (LDV) sequence from the alternatively spliced connecting segment-1 (CS-1) peptide of cellular fibronectin, are described that employ a novel N-terminal peptide 'cap' strategy. One inhibitor, BIO- 1211, was ~106-fold more potent than the starting peptide and exhibited tight-binding properties (k(off) = 1.4 x 10-4 s-1, K(D) = 70 pM), a remarkable finding for a noncovalent, small-molecule inhibitor of a protein receptor. BIO-1211 was also 200-fold selective for the activated form of α4β1, and it stimulated expression of ligand-induced epitopes on the integrin β1 subunit, a property consistent with occupancy of the receptor's ligand-binding site. Pretreatment of allergic sheep with a 3-mg nebulized dose of BIO-1211 inhibited early and late airway responses following antigen challenge and prevented development of nonspecific airway hyperresponsiveness to carbachol. These results show that highly selective and potent small- molecule antagonists can be identified to integrins with primary specificity for peptide domains other than Arg-Gly-Asp (RGD); they confirm the generality of integrins as small molecule targets; and they validate α4β1 as a therapeutic target for asthma.
