122665-97-8Relevant articles and documents
Development of a bulk enabling route to maraviroc (UK-427,857), a CCR-5 receptor antagonist
Haycock-Lewandowski, Sarah J.,Wilder, Alexander,Ahman, Jens
, p. 1094 - 1103 (2008)
A bulk enabling synthesis of the CCR-5 receptor antagonist, Maraviroc (UK-427,857) (1), is presented. Synthesis of the three key fragments, β-amino ester 3,4,4-difluorohexanecarboxylic acid (2), and 1,3,4-triazole-substituted tropane fragment 4 are described. Coupling strategies for these fragments are discussed and described, including synthetic challenges, protection strategies, impurity generation, and final scale-up of the developed route to 1.
Exploration of bivalent ligands targeting putative mu opioid receptor and chemokine receptor CCR5 dimerization
Arnatt, Christopher K.,Falls, Bethany A.,Yuan, Yunyun,Raborg, Thomas J.,Masvekar, Ruturaj R.,El-Hage, Nazira,Selley, Dana E.,Nicola, Anthony V.,Knapp, Pamela E.,Hauser, Kurt F.,Zhang, Yan
, p. 5969 - 5987 (2016)
Modern antiretroviral therapies have provided HIV-1 infected patients longer lifespans and better quality of life. However, several neurological complications are now being seen in these patients due to HIV-1 associated injury of neurons by infected microglia and astrocytes. In addition, these effects can be further exacerbated with opiate use and abuse. One possible mechanism for such potentiation effects of opiates is the interaction of the mu opioid receptor (MOR) with the chemokine receptor CCR5 (CCR5), a known HIV-1 co-receptor, to form MOR–CCR5 heterodimer. In an attempt to understand this putative interaction and its relevance to neuroAIDS, we designed and synthesized a series of bivalent ligands targeting the putative CCR5–MOR heterodimer. To understand how these bivalent ligands may interact with the heterodimer, biological studies including calcium mobilization inhibition, binding affinity, HIV-1 invasion, and cell fusion assays were applied. In particular, HIV-1 infection assays using human peripheral blood mononuclear cells, macrophages, and astrocytes revealed a notable synergy in activity for one particular bivalent ligand. Further, a molecular model of the putative CCR5–MOR heterodimer was constructed, docked with the bivalent ligand, and molecular dynamics simulations of the complex was performed in a membrane-water system to help understand the biological observation.
Initial synthesis of UK-427,857 (Maraviroc)
Price, David A.,Gayton, Simon,Selby, Matthew D.,Ahman, Jens,Haycock-Lewandowski, Sarah,Stammen, Blanda L.,Warren, Andrew
, p. 5005 - 5007 (2005)
The initial synthesis of UK-427,857 (Maraviroc) is described including the preparation of 4,4-difluorocyclohexanoic acid and amide coupling utilizing a polymer supported reagent.
USP30 INHIBITORS
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, (2018/12/13)
The application relates to phenyl- or naphthylsulfonamide derivatives of the structural formula (I). The compounds are described as inhibitors of USP30 (ubiquitin specific peptidase 30) useful for the treatment of conditions involving mitochondrial defects including neurodegenerative diseases such as Alzheimer's and Parkinson's or a neoplastic disease such as leukemia.
Asymmetric Mannich Reaction and Construction of Axially Chiral Sulfone-Containing Styrenes in One Pot from α-Amido Sulfones Based on the Waste-Reuse Strategy
Li, Dongmei,Tan, Yu,Peng, Lei,Li, Shan,Zhang, Nan,Liu, Yidong,Yan, Hailong
supporting information, p. 4959 - 4963 (2018/08/24)
A simultaneous asymmetric Mannich reaction and the construction of axially chiral sulfone-containing styrenes in one pot from α-amido sulfones based on the waste-reuse strategy was demonstrated. A series of chiral β-amino diesters and axially chiral sulfone-containing styrenes with various functional groups were synthesized in good to excellent yields and enantioselectivities under mild conditions. In addition, this protocol has been successfully applied to synthesize the anti-HIV drug Maraviroc and chiral trichloro derivatives.
A 4, 4 - difluoro-cyclohexyl preparation of formic acid method
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Paragraph 0029; 0030; 0031; 0032; 0033; 0034, (2017/08/25)
The invention relates to a preparation and purification process of a compound 4,4-difluorocyclohexanecarboxylic acid represented in the formula (I). The preparation and purification process is characterized in that a method comprises steps represented in an equation shown in the specification. The processing method has the characteristics of easiness in operation, facilitation of industrial production of 4,4-difluorocyclohexanecarboxylic acid and environmental protection.
Substituted imidazo[1,2-b]pyridazines as protein kinase inhibitors
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, (2016/09/13)
The present invention provides protein kinase having one of the following structures (I), (II) or (III): or a stereoisomer, prodrug, tautomer or pharmaceutically acceptable salt thereof, wherein R, R1, R2 and X are as defined herein. Compositions and methods for using the same in the treatment of cancer, autoimmune, inflammatory and other Pim kinase-associated conditions are also disclosed.
N-Acyl-N'-(pyridin-2-yl) Ureas and Analogs Exhibiting Anti-Cancer and Anti-Proliferative Activities
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, (2014/09/30)
Described are compounds of Formula I which find utility in the treatment of cancer, autoimmune diseases and metabolic bone disorders through inhibition of c-FMS (CSF-1R), c-KIT, and/or PDGFR kinases. These compounds also find utility in the treatment of other mammalian diseases mediated by c-FMS, c-KIT, or PDGFR kinases.
HETEROCYCLIC PROTEIN KINASE INHIBITORS
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, (2013/03/26)
The present invention provides protein kinase having one of the following structures (I), (II) or (III): or a stereoisomer, prodrug, tautomer or pharmaceutically acceptable salt thereof, wherein R, R1, R2 and X are as defined herein. Compositions and methods for using the same in the treatment of cancer, autoimmune, inflammatory and other Pim kinase-associated conditions are also disclosed.
SUBSTITUTED ISOINDOLONES AND THEIR USE AS METABOTROPIC GLUTAMATE RECEPTOR POTENTIATORS
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Page/Page column 18, (2009/05/29)
The present invention is directed to compounds of formula I: wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and n are as defined for formula I in the description. The invention also relates to processes for the preparation of the compounds and to new intermediates employed in the preparation, pharmaceutical compositions containing the compounds, and to the use of the compounds in therapy.
