- Stereoselective Synthesis of New (2 S,3 R)-3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid Analogues Utilizing a C(sp3)-H Activation Strategy and Structure-Activity Relationship Studies at the Ionotropic Glutamate Receptors
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Competitive antagonists for ionotropic glutamate receptors (iGluRs) are highly valuable tool compounds for studying health and disease states in the central nervous system. However, only few subtype selective tool compounds are available and the discovery of antagonists with novel iGluR subtype selectivity profiles remains a profound challenge. In this paper, we report an elaborate structure-activity relationship (SAR) study of the parental scaffold 2,3-trans-3-carboxy-3-phenyl-proline by the synthesis of 40 new analogues. Three synthetic strategies were employed with two new strategies of which one being a highly efficient and fully enantioselective strategy based on C(sp3)-H activation methodology. The SAR study led to the conclusion that selectivity for the NMDA receptors was a general trend when adding substituents in the 5′-position. Selective NMDA receptor antagonists were obtained with high potency (IC50 values as low as 200 nM) and 3-34-fold preference for GluN1/GluN2A over GluN1/GluN2B-D NMDA receptors.
- Bunch, Lennart,Hansen, Jacob C.,Hansen, Kasper B.,Iliadis, Stylianos,Kayser, Silke,Krogsgaard-Larsen, Niels,Larsen, Younes,Moroz, Aleksandra,Nielsen, Birgitte,Pickering, Darryl S.,Staudt, Markus,Syrenne, Jed T.,Temperini, Piero,Yi, Feng
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- Protein quantitative labeling reagent and preparation method and application thereof
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The invention provides a protein quantitative labeling reagent as well as a preparation method and application thereof. According to the protein quantitative labeling reagent provided by the invention, the high reaction activity of a o-phthalaldehyde grou
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Paragraph 0052-0053; 0059-0065
(2020/04/17)
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- HETEROCYCLIC SPIRO-COMPOUNDS AS AM2 RECEPTOR INHIBITORS
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Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: wherein HET, R1, R2, R3, R4, R5, L, L1, X1, X2, X3 and q are as defined herein. The compounds are inhibitors of adrenomedullin receptor subtype 2 (AM2). Also disclosed are the compounds for use in the treatment of diseases modulated AM2, including proliferative diseases such as cancer; pharmaceutical compositions comprising the compounds; methods for preparing the compounds; and intermediates useful in the preparation of the compounds.
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Page/Page column 121-122
(2020/06/05)
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- HETEROCYCLIC SPIRO-COMPOUNDS AS AM2 RECEPTOR INHIBITORS
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Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: wherein R1, R2, R4, R5, R6, R7, R8, R9, R10,Z, X1, X2, X3, L2, HET, n and q are as defined herein. The compounds are inhibitors of adrenomedullin receptor subtype 2 (AM2). Also disclosed are the compounds for use in the treatment of diseases modulated AM2, including proliferative diseases such as cancer; pharmaceutical compositions comprising the compounds; methods for preparing the compounds; and intermediates useful in the preparation of the compounds.
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Page/Page column 148; 161
(2020/06/05)
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- COMPOUNDS
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Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: (I) wherein R1, R2, R3, R4, R5, R6, R8, R9, X, X1, X2, X3, L1 and n are as defined herein. The compounds are inhibitors of adrenomedullin receptor subtype 2 (AM2). Also disclosed are the compounds for use in the treatment of diseases modulated AM2, including proliferative diseases such as cancer; pharmaceutical compositions comprising the compounds; methods for preparing the compounds;and intermediates useful in the preparation of the compounds.
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Page/Page column 278; 279
(2018/12/13)
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- Piperidinone carboxamide indane CGRP receptor antagonists
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The present invention is directed to piperidinone carboxamide indane derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.
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Page/Page column 33
(2016/12/16)
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- Chemiluminescence properties of luminol related o-hydroxybenzimidazole analogues: Experimental and DFT based approach to photophysical properties
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Novel luminol-isoluminol derivatives containing o-hydroxyphenyl benzimidazole unit were synthesized from aromatic aldehydes and diaminophthalates followed by heating under reflux with hydrazine hydrate. The chemiluminescent properties were studied in hydr
- Deshmukh, Mininath S.,Sekar, Nagaiyan
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p. 189 - 199
(2014/10/15)
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- Chemiluminescence properties of luminol related quinoxaline analogs: Experimental and DFT based approach to photophysical properties
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Novel luminol and isoluminol related compounds containing a quinoxaline moiety were synthesized by the reaction of various 1,2-diketones with dimethyl-4,5-diaminophthalate (5) and dimethyl-3,4-diaminophthalate (5′). The UV-Vis absorption and emission spectra of the dyes were studied in solvents of differing polarity and the compounds show solvatofluorism properties. The chemiluminescent properties of the isoluminol and luminol based quinoxaline derivatives were examined and compared with isoluminol and luminol. These compounds produced chemiluminescence by reaction with hydrogen peroxide in the presence of potassium hexacyanoferrate(III) in sodium hydroxide solution. The chemiluminescence intensities of these chemiluminophores were affected by the concentrations of hydrogen peroxide, potassium hexacyanoferrate(III) and sodium hydroxide. These quinoxaline derivatives were found to produce chemiluminescence in the range of 3.2-7.3 and it is 0.57-1.7 times more intensely than isoluminol and luminol, respectively. Density Functional Theory computations have been used for in-depth understanding of structural, molecular, electronic and photophysical parameters of the compounds.
- Deshmukh, Mininath S.,Sekar, Nagaiyan
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- NOVEL TARGETING AGENTS FOR DIAGNOSTIC AND THERAPEUTIC INDICATIONS
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The invention relates to compounds and use thereof in the diagnosis and/or in treatment of medical disorders. In some embodiments, the compounds may be used for detecting a cancer. The compound may include a di-acid moiety. In some embodiments the di-acid moiety comprises a di-carboxylic acid and in some embodiments the di- acid moiety comprises a di-tetrazole.
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Paragraph 00103; 00104
(2013/10/22)
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- PYRIDINE CGRP RECEPTOR ANTAGONISTS
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The present invention is directed to pyridine derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.
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Page/Page column 51; 52; 53
(2013/12/03)
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- ALIPHATIC SPIROLACTAM CGRP RECEPTOR ANTAGONISTS
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The present invention is directed to aliphatic spirolactam derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical\compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.
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Page/Page column 52; 53
(2013/12/03)
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- PROCESS FOR MAKING CGRP RECEPTOR ANTAGONIST
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The invention encompasses a novel process for making 2-[(8R)-8-(3,5-Difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide, which is a CGRP receptor antagonist useful for the treatment of migraine, using an asymmetric phase-transfer catalysis route. The invention also encompasses an efficient and practical synthesis of the (R)-acid intermediate, and generates the benzylic stereocenter in an enantioselective manner.
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Page/Page column 49-50
(2011/02/24)
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- Aromatic compounds
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Disclosed are compounds of formula I wherein A, R1, R2, R3, R4and R5are described in the specification, pharmaceutical formulations comprising these compounds, the use of these compounds are medicaments, the use of these medicaments in the treatment of and/or prevention of diabetes, especially non-insulin dependent diabetes (NIDDM or Type 2 diabetes), as well as methods for treating diabetes comprising administration of these compounds.
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