- Development of a Zinc-Mediated Approach to a 2,3- cis-Pyrrolidine Arginase Inhibitor
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This manuscript outlines the development activities toward a robust synthesis of cis-2,3-pyrrolidine via tandem zinc-enolate cyclization/Negishi coupling that proceeds with high diastereoselectivity. The methodology facilitated a gram-scale delivery of the target API and eliminated the need for costly chiral resolutions and inefficient protecting group manipulations. A series of DFT experiments provided a transition-state model that agrees closely with the experimental observations and provides a more in-depth understanding of the observed selectivity.
- He, Cyndi Qixin,Lyons, Thomas W.,Martinot, Theodore A.,Qi, Ji,Shao, Guangxin
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- Synthesis of the Enantiomers of Tedanalactam and the First Total Synthesis and Configurational Assignment of (+)-Piplaroxide
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Highlighting the recently established methodology for the direct synthesis of glycidic amides from tertiary allyl amines, the synthesis of the enantiomers of tedanalactam were completed in two steps from the corresponding chiral dihydropiperidine. Additio
- Romero-Ibaez, Julio,Xochicale-Santana, Leonardo,Quintero, Leticia,Fuentes, Lilia,Sartillo-Piscil, Fernando
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- Immunomodulation by IAP inhibitors
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The present invention is directed to immune adjuvants containing IAP inhibitors, including Smac mimetics. The invention further provides pharmaceutical compositions and vaccines containing an IAP inhibitor and an antigen. Methods of enhancing an immune re
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Page/Page column 34; 35; 36
(2017/12/27)
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- Substituted Indazoles as Nav1.7 Blockers for the Treatment of Pain
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The genetic validation for the role of the Nav1.7 voltage-gated ion channel in pain signaling pathways makes it an appealing target for the potential development of new pain drugs. The utility of nonselective Nav blockers is often li
- Frost, Jennifer M.,Degoey, David A.,Shi, Lei,Gum, Rebecca J.,Fricano, Meagan M.,Lundgaard, Greta L.,El-Kouhen, Odile F.,Hsieh, Gin C.,Neelands, Torben,Matulenko, Mark A.,Daanen, Jerome F.,Pai, Madhavi,Ghoreishi-Haack, Nayereh,Zhan, Cenchen,Zhang, Xu-Feng,Kort, Michael E.
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p. 3373 - 3391
(2016/05/19)
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- (Indazol-4-YL) Hexahydropyrrolopyrrolones and Methods of Use
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Compounds of formula (I) and pharmaceutically acceptable salts, esters, amides, or radiolabelled forms thereof, wherein GAr, L1, Z1 and Z2 are as defined in the specification, are useful in treating conditions or disorders prevented by or ameliorated by voltage-gated sodium channels, e.g., Nav 1.7 and/or Nav 1.8. Methods for making the compounds are disclosed. Also disclosed are pharmaceutical compositions of compounds of formula (I), and methods for using such compounds and compositions.
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Paragraph 0304
(2016/10/04)
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- NOL3 IS A PREDICTOR OF PATIENT OUTCOME
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The present invention features a method for determining the prognosis for survival of a cancer patient. Methods for measuring the level of NOL3 expression in a cancer cell-containing sample from a patient, and comparing the level of NOL3 expression in the
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Page/Page column 16-17
(2010/08/03)
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- Organic compounds
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Novel compounds that inhibit the binding of the Smac protein to Inhibitor of Apoptosis Proteins (IAPs) of the formula I
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Page/Page column 20-21
(2008/06/13)
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- Novel constrained CCK-B dipeptoid antagonists derived from pipecolic acid
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A new series of 4-substituted pipecolic acid derivatives was prepared and incorporated into dipeptoids. The resulting products behave as moderately potent CCK-B antagonists but their constrained structure and its comparison with structurally related compounds yield valuable information about the conformational requirements for optimal recognition of the CCK-B receptor by antagonists.
- Bellier, Bruno,Da Nascimento, Sophie,Meudal, Herve,Gincel, Edith,Roques, Bernard P.,Garbay, Christiane
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p. 1419 - 1424
(2007/10/03)
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- Asymmetric synthesis of (2S,3S)- and (2S,3R)-3-prolinomethionines: 3-Methylsulfanylmethyl-pyrrolidine-2-carboxylic acids
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The synthesis of 3-prolinomethionine can be easily achieved in a diastereoselective and enantioselective way via zinc-enolate cyclisation. After transmetallation by CuCN.2LiCl, the zinc-copper derivative was reached with S-methyl methanesulfonothioate leading in a 'one-pot' procedure, to N-(α-methylbenzyl)-3-prolinomethinine benzyl ester. The α-methylbenzyl group was transformed in vinyl-oxycarbonyl and tertiobutyl-oxycarbonyl groups successively. Reprotonation of cis Voc prolinomethionine enolate at low temperature yielded the enantiomerically pure trans diastereoisomer.
- Karoyan, Philippe,Chassaing, Gerard
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p. 2025 - 2032
(2007/10/03)
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