193542-65-3Relevant academic research and scientific papers
Catalytic Formal Conjugate Addition: Direct Synthesis of δ-Hydroxynitriles from Nitriles and Allylic Alcohols
Thiyagarajan, Subramanian,Sankar, Raman Vijaya,Anjalikrishna, Puthannur K.,Suresh, Cherumuttathu H.,Gunanathan, Chidambaram
, p. 2191 - 2204 (2022/02/14)
Alcohols and nitrile functionalities have widespread applications in biochemical and chemical synthesis. Catalytic transformations involving C-C bond formation relying on unsaturated coupling partners create important pathways for processes in synthetic, material, and medicinal chemistry. The discovery of a simple and selective coupling of nitriles with allylic alcohols catalyzed by a ruthenium pincer complex is described, which tolerates reactive functional groups such as carbamate, sulfonate, olefin, cyano, and trifluoromethyl-substituted benzyl nitriles. Homo allylic alcohols also provided 1,4-addition products following the isomerization of double bonds. Mechanistic studies supported that the allylic alcohols initially undergo selective oxidation by the catalyst to α,β-unsaturated carbonyl compounds followed by 1,4-conjugate addition of benzyl nitriles catalyzed by a base and subsequent catalytic reduction of carbonyl functionality, leading to the formation of δ-hydroxynitrile products. The catalytic cycle of this tandem process is established by density functional theory studies. Remarkably, anipamil drug is successfully synthesized using this catalytic protocol. The utility of the δ-hydroxynitrile products in the synthesis of biologically active molecules and their further functionalization are also demonstrated.
Compounds useful for inhibiting metastasis from cancer and methods using same
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Sheet 6 of 15, (2016/08/03)
The present invention includes compositions that are useful in preventing or treating metastasis in a subject diagnosed with cancer. The present invention also includes methods of preventing or treating metastasis in a subject diagnosed with cancer, where
Methods of Inhibiting Metastasis from Cancer
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, (2012/06/16)
The present invention includes compositions that are useful in preventing or treating metastasis in a subject diagnosed with cancer. The present invention also includes methods of preventing or treating metastasis in a subject diagnosed with cancer, where
Synthesis and structure-activity relationship of the first nonpeptidergic inverse agonists for the human cytomegalovirus encoded chemokine receptor US28
Hulshof, Janneke W.,Casarosa, Paola,Menge, Wiro M. P. B.,Kuusisto, Leena M. S.,Van Der Goot, Henk,Smit, Martine J.,De Esch, Iwan J. P.,Leurs, Rob
, p. 6461 - 6471 (2007/10/03)
US28 is a human cytomegalovirus (HCMV) encoded G-protein-coupled receptor that signals in a constitutively active manner. Recently, we identified 1 {5-(4-(4-chlorophenyl)-4-hydroxy-piperidin-1-yl)-2,2-diphenylpentanenitrile} as the first reported nonpeptidergic inverse agonist for a viral-encoded chemokine receptor. Interestingly, this compound is able to partially inhibit the viral entry of HIV-1. In this study we describe the synthesis of 1 and several of its analogues and unique structure-activity relationships for this first class of small-molecule ligands for the chemokine receptor US28. Moreover, the compounds have been pharmacologically characterized as inverse agonists on US28. By modification of lead structure 1, it is shown that a 4-phenylpiperidine moiety is essential for affinity and activity. Other structural features of 1 are shown to be of less importance. These compounds define the first SAR of ligands on a viral GPCR (US28) and may therefore serve as important tools to investigate the significance of US28-mediated constitutive activity during viral infection.
Discovery of novel non-peptide CCR1 receptor antagonists
Ng, Howard P.,Karen, May,Bauman, John G.,Ghannam, Ameen,Islam, Imadul,Liang, Meina,Horuk, Richard,Hesselgesser, Joseph,Snider, R. Michael,Perez, H. Daniel,Morrissey, Michael M.
, p. 4680 - 4694 (2007/10/03)
Ligands for the CCR1 receptor (MIP-1α and RANTES) have been implicated in a number of chronic inflammatory diseases, most notably multiple sclerosis and rheumatoid arthritis. Because these ligands share a common receptor, CCR1, we sought to discover antagonists for this receptor as an approach to treating these disorders. A novel series of 4-hydroxypiperidines has been discovered by high throughput screening (HTS) which potently inhibits the binding of MIP-1α and RANTES to the recombinant human CCR1 chemokine receptor. The structure-activity relationships of various segments of this template are described as the initial HTS lead 1 was optimized synthetically to the highly potent receptor antagonist 6s. This compound has been shown to have at least 200-fold selectivity for inhibition of CCR1 over other human 7- TM receptors, including other chemokine receptors. In addition, data obtained from in vitro functional assays demonstrate the functional antagonism of compound 6s and structurally related analogues against the CCR1 receptor in a concentration dependent manner. The discovery and optimization of potent and selective CCR1 receptor antagonists represented by compound 6s potentially represent a novel approach to the treatment of chronic inflammatory diseases.
