440125-24-6Relevant articles and documents
Triazolo-peptidomimetics: novel radiolabeled minigastrin analogs for improved tumor targeting
Grob, Nathalie M.,H?ussinger, Daniel,Deupi, Xavier,Schibli, Roger,Behe, Martin,Mindt, Thomas L.
supporting information, p. 4484 - 4495 (2020/06/08)
MG11 is a truncated analog of minigastrin, a peptide with high affinity and specificity toward the cholecystokinin-2 receptor (CCK2R), which is overexpressed by different tumors. Thus, radiolabeled MG11 derivatives have great potential for use in cancer d
Vinyl sulfone-based inhibitors of trypanosomal cysteine protease rhodesain with improved antitrypanosomal activities
Ajayi, Oluwatomi,Collins, Jasmine,Crown, Olamide,Nyamwihura, Rogers,Ogungbe, Ifedayo Victor,Zhang, Huaisheng
supporting information, (2020/05/18)
The number of reported cases of Human African Trypanosmiasis (HAT), caused by kinetoplastid protozoan parasite Trypanosoma brucei, is declining in sub-Saharan Africa. Historically, such declines are generally followed by periods of higher incidence, and one of the lingering public health challenges of HAT is that its drug development pipeline is historically sparse. As a continuation of our work on new antitrypanosomal agents, we found that partially saturated quinoline-based vinyl sulfone compounds selectively inhibit the growth of T. brucei but displayed relatively weak inhibitory activity towards T. brucei's cysteine protease rhodesain. While two nitroaromatic analogues of the quinoline-based vinyl sulfone compounds displayed potent inhibition of T. brucei and rhodesain. The quinoline derivatives and the nitroaromatic-based compounds discovered in this work can serve as leads for ADME-based optimization and pre-clinical investigations.
CALPAIN MODULATORS AND THERAPEUTIC USES THEREOF
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Paragraph 0636, (2018/04/17)
Disclosed herein are small molecule calpain modulator compositions, pharmaceutical compositions, the use and preparation thereof.
1,2,3-Triazoles as amide bond mimics: Triazole scan yields protease-resistant peptidomimetics for tumor targeting
Valverde, Ibai E.,Bauman, Andreas,Kluba, Christiane A.,Vomstein, Sandra,Walter, Martin A.,Mindt, Thomas L.
supporting information, p. 8957 - 8960 (2013/09/02)
The triazole makes the difference: Replacement of amide bonds in the backbone of peptides by 1,4-disubstituted 1,2,3-triazole isosteres affords peptidomimetics with retained receptor affinity and cell-internalization properties, enhanced proteolytic stability, and improved tumor-targeting capabilities. Copyright
Synthesis of new (-)-bestatin-based inhibitor libraries reveals a novel binding mode in the S1 pocket of the essential malaria M1 metalloaminopeptidase
Velmourougane, Geetha,Harbut, Michael B.,Dalal, Seema,McGowan, Sheena,Oellig, Christine A.,Meinhardt, Nataline,Whisstock, James C.,Klemba, Michael,Greenbaum, Doron C.
experimental part, p. 1655 - 1666 (2011/05/16)
The malarial PfA-M1 metallo-aminopeptidase is considered a putative drug target. The natural product dipeptide mimetic, bestatin, is a potent inhibitor of PfA-M1. Herein we present a new, efficient, and high-yielding protocol for the synthesis of bestatin derivatives from natural and unnatural N-Boc-d-amino acids. A diverse library of bestatin derivatives was synthesized with variants at the side chain of either the α-hydroxyβ-amino acid (P1) or the adjacent naturalα-amino acid (P1′). Surprisingly, we found that extended aromatic side chains at the P1 position resulted in potent inhibition against PfA-M1. To understand these data, we determined the X-ray cocrystal structures of PfA-M1 with two derivatives having either a Tyr(OMe) 15 or Tyr(OBzl) 16 at the P1 position and observed substantial inhibitor-induced rearrangement of the primary loop within the PfA-M1 pocket that interacts with the P1 side chain. Our data provide important insights for the rational design of more potent and selective inhibitors of this enzyme that may eventually lead to new therapies for malaria.
AMIDES AS INHIBITORS OF HUMAN SECRETED PHOSPHOLIPASE A2
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Page/Page column 7; 8, (2010/04/03)
Methods and compounds useful for inhibiting a phoshpolipase A2 are provided, the methods comprising contacting the phoshpolipase A2 with a compound having the structure A, or pharmaceutically acceptable salts thereof: wherein R1
Discovery of narlaprevir (SCH 900518): A potent, second generation HCV NS3 serine protease inhibitor
Arasappan, Ashok,Bennett, Frank,Bogen, Stephane L.,Venkatraman, Srikanth,Blackman, Melissa,Chen, Kevin X.,Hendrata, Siska,Huang, Yuhua,Huelgas, Regina M.,Nair, Latha,Padilla, Angela I.,Pan, Weidong,Pike, Russell,Pinto, Patrick,Ruan, Sumei,Sannigrahi, Mousumi,Velazquez, Francisco,Vibulbhan, Bancha,Wu, Wanli,Yang, Weiying,Saksena, Anil K.,Girijavallabhan, Viyyoor,Shih, Neng-Yang,Kong, Jianshe,Meng, Tao,Jin, Yan,Wong, Jesse,McNamkra, Paul,Prongay, Andrew,Madison, Vincent,Piwinski, John J.,Cheng, Kuo-Chi,Morrison, Richard,Malcolm, Bruce,Tong, Xiao,Ralston, Robert,Njoroge, F. George
scheme or table, p. 64 - 69 (2010/12/29)
Boceprevir (SCH 503034), 1, a novel HCV NS3 serine protease inhibitor discovered in our laboratories, is currently undergoing phase III clinical trials. Detailed investigations toward a second generation protease inhibitor culminated in the discovery of narlaprevir (SCH 900518), 37, with improved potency (～10-fold over 1), pharmacokinetic profile and physicochemical characteristics, currently in phase II human trials. Exploration of synthetic sequence for preparation of 37 resulted in a route that required no silica gel purification for the entire synthesis.
Structure-activity relationships of natural and non-natural amino acid-based amide and 2-oxoamide inhibitors of human phospholipase A2 enzymes
Antonopoulou, Georgia,Barbayianni, Efrosini,Magrioti, Victoria,Cotton, Naomi,Stephens, Daren,Constantinou-Kokotou, Violetta,Dennis, Edward A.,Kokotos, George
experimental part, p. 10257 - 10269 (2009/04/12)
A variety of 2-oxoamides and related amides based on natural and non-natural amino acids were synthesized. Their activity on two human intracellular phospholipases (GIVA cPLA2 and GVIA iPLA2) and one human secretory phospholipase (GV
Structure-activity relationship of 2-oxoamide inhibition of group IVA cytosolic phospholipase A2 and group V secreted phospholipase A 2
Six, David A.,Barbayianni, Efrosini,Loukas, Vassilios,Constantinou-Kokotou, Violetta,Hadjipavlou-Litina, Dimitra,Stephens, Daren,Wong, Alan C.,Magrioti, Victoria,Moutevelis-Minakakis, Panagiota,Baker, Sharon F.,Dennis, Edward A.,Kokotos, George
, p. 4222 - 4235 (2008/02/11)
The Group IVA cytosolic phospholipase A2 (GIVA cPLA2) is a key provider of substrates for the production of eicosanoids and platelet-activating factor. We explored the structure-activity relationship of 2-oxoamide-based compounds and
Novel inhibitors of hepatitis C NS3-NS4A serine protease derived from 2-aza-bicyclo[2.2.1]heptane-3-carboxylic acid
Venkatraman, Srikanth,Njoroge, F. George,Wu, Wanli,Girijavallabhan, Viyyoor,Prongay, Andrew J.,Butkiewicz, Nancy,Pichardo, John
, p. 1628 - 1632 (2007/10/03)
Prolonged hepatitis C infection is the leading cause for cirrhosis of the liver and hepatocellular carcinoma. The etiological agent HCV virus codes a single polyprotein of ～3000 amino acids that is processed with the help of a serine protease NS3A to prod
