558443-28-0Relevant articles and documents
Improved Synthesis of MDL 73811 - A Potent AdoMetDC Inhibitor and Anti-Trypanosomal Compound
Brockway, Anthony J.,Cosner, Casey C.,Volkov, Oleg A.,Phillips, Margaret A.,De Brabander, Jef K.
, p. 2065 - 2068 (2016/07/06)
An improved synthesis of MDL 73811 - a potent AdoMetDC (S-adenosylmethionine decarboxylase) inhibitor and anti-trypanosomal compound with in vivo activity - has been completed in four steps from commercially available 2′,3′-O-isopropylideneadenosine. Util
Discovery of novel small molecule orally bioavailable C-X-C chemokine receptor 4 antagonists that are potent inhibitors of T-tropic (X4) HIV-1 replication
Skerlj, Renato T.,Bridger, Gary J.,Kaller, Al,McEachern, Ernest J.,Crawford, Jason B.,Zhou, Yuanxi,Atsma, Bem,Langille, Jonathon,Nan, Susan,Veale, Duane,Wilson, Trevor,Harwig, Curtis,Hatse, Sigrid,Princen, Katrien,De Clercq, Erik,Schols, Dominique
supporting information; experimental part, p. 3376 - 3388 (2010/09/05)
The redesign of azamacrocyclic CXCR4 chemokine receptor antagonists resulted in the discovery of novel, small molecule, orally bioavailable compounds that retained T-tropic (CXCR4 using, X4) anti-HIV-1 activity. A structure-activity relationship (SAR) was determined on the basis of the inhibition of replication of X4 HIV-1 NL4.3 in MT-4 cells. As a result of lead optimization, we identified (S)-N′-((1H-benzo[d]imidazol-2-yl)methyl)- N′-(5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine (AMD070) 2 as a potent and selective antagonist of CXCR4 with an IC50 value of 13 nM in a CXCR4 125I-SDF inhibition binding assay. Compound 2 inhibited the replication of T-tropic HIV-1 (NL4.3 strain) in MT-4 cells and PBMCs with an IC50 of 2 and 26 nM, respectively, while remaining noncytotoxic to cells at concentrations exceeding 23 μM. The pharmacokinetics of 2 was evaluated in rat and dog, and good oral bioavailability was observed in both species. This compound represents the first small molecule orally bioavailable CXCR4 antagonist that was developed for the treatment of HIV-1 infection.
CHEMICAL COMPOUNDS
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Page/Page column 91, (2010/10/20)
The present invention provides novel compounds that demonstrate protective effects on target cells from HIV infection in a manner as to bind specifically to the chemokine receptor, and which affect the binding of the natural ligand or chemokine to a receptor such as CXCR4 and/or CCR5 of a target cell.
Chemokine receptor binding heterocyclic compounds with enhanced efficacy
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, (2008/06/13)
The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).
New Methodology for the Synthesis of Protected, Primary Pentadienylamines
Connel, Richard D.,Helquist, Paul,Akermark, Bjoern
, p. 3359 - 3370 (2007/10/02)
The utility of forming N-tert-butoxycarbonyl- (Boc) and N-phthalimido-protected primary 2(E),4(E)-pentadienylamines from aldehydes and ketones is described.When diethyl -2-buten-1-yl>phosphonate (33E) is treated with s
