cas 98730-77-9, 1-(hydroxymethyl)cyclopropanecarbonitrile

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Articles about 98730-77-9Total 23 be found

Article title
Article abstract
Author
Journal number and time
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Structure-Based Design of Potent and Orally Active Isoindolinone Inhibitors of MDM2-p53 Protein-Protein Interaction
Inhibition of murine double minute 2 (MDM2)-p53 protein-protein interaction with small molecules has been shown to reactivate p53 and inhibit tumor growth. Here, we describe rational, structure-guided, design of novel isoindolinone-based MDM2 inhibitors. MDM2 X-ray crystallography, quantum mechanics ligand-based design, and metabolite identification all contributed toward the discovery of potent in vitro and in vivo inhibitors of the MDM2-p53 interaction with representative compounds inducing cytostasis in an SJSA-1 osteosarcoma xenograft model following once-daily oral administration.
Chessari, Gianni,Hardcastle, Ian R.,Ahn, Jong Sook,Anil, Burcu,Anscombe, Elizabeth,Bawn, Ruth H.,Bevan, Luke D.,Blackburn, Timothy J.,Buck, Ildiko,Cano, Celine,Carbain, Benoit,Castro, Juan,Cons, Ben,Cully, Sarah J.,Endicott, Jane A.,Fazal, Lynsey,Golding, Bernard T.,Griffin, Roger J.,Haggerty, Karen,Harnor, Suzannah J.,Hearn, Keisha,Hobson, Stephen,Holvey, Rhian S.,Howard, Steven,Jennings, Claire E.,Johnson, Christopher N.,Lunec, John,Miller, Duncan C.,Newell, David R.,Noble, Martin E. M.,Reeks, Judith,Revill, Charlotte H.,Riedinger, Christiane,St. Denis, Jeffrey D.,Tamanini, Emiliano,Thomas, Huw,Thompson, Neil T.,Vinkovi?, Mladen,Wedge, Stephen R.,Williams, Pamela A.,Wilsher, Nicola E.,Zhang, Bian,Zhao, Yan
supporting information
p. 4071 - 4088
(2021/05/04)

Synthesis of Spirocyclic β- and γ-Sultams by One-Pot Reductive Cyclization of Cyanoalkylsulfonyl Fluorides
One-pot intramolecular cyclization of novel sp3-enriched cyanoalkylsulfonyl fluorides into spirocyclic β- or γ-sultams is disclosed. The method relies on nitrile group reduction followed by sulfonylation of amino group thus formed upon mild con
Stepannikova, Kateryna O.,Vashchenko, Bohdan V.,Grygorenko, Oleksandr O.,Gorichko, Marian V.,Cherepakha, Artem Yu.,Moroz, Yurii S.,Volovenko, Yulian M.,Zhersh, Serhii
p. 6530 - 6540
(2020/05/25)

SALT OF LSD1 INHIBITOR AND A POLYMORPH THEREOF
Provided are a compound III serving as an LSD1 inhibitor and a crystal form thereof, as well as use of the compound and the crystal form thereof in preparation of a medicament for treating an LSD1 related disease.
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Paragraph 0041-0043

(2021/10/15)

ISOINDOLINONE INHIBITORS OF THE MDM2-P53 INTERACTION HAVING ANTICANCER ACTIVITY
The invention provides a compound of formula (I): (I) or tautomer or a solvate or a pharmaceutically acceptable salt thereof, wherein the various substituents are as defined in the claims. Also provided are pharmaceutical compositions containing the compounds of formula (I), processes for making the compounds and the medical uses of the compounds.
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Page/Page column 183; 184

(2017/05/07)

Enantioselective C-H Functionalization-Addition Sequence Delivers Densely Substituted 3-Azabicyclo[3.1.0]hexanes
An enantioselective C-H functionalization route to perfluoroalkyl-containing 3-azabicyclo[3.1.0]hexanes is disclosed. A modular and bench-stable diazaphospholane ligand enables highly enantioselective Pd(0)-catalyzed cyclopropane C-H functionalization using trifluoroacetimidoyl chlorides as electrophilic partners. In turn, the resulting cyclic ketimine products react smoothly with a broad variety of nucleophiles in one-pot processes enabling the rapid and modular construction of heavily substituted pyrrolidines.
Pedroni, Julia,Cramer, Nicolai
supporting information
p. 12398 - 12401
(2017/09/25)

PYRIMIDINE AND TRIAZINE DERIVATIVES AND THEIR USE AS AXL INHIBITORS
Compounds of the general formula(I): (I) processes for the preparation of these compounds, compositions containing these compounds, and the uses of these compounds.
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Page/Page column 94

(2016/07/05)

NOVEL COMPOUNDS
Disclosed are novel retinoid-related orphan receptor gamma (RORγ) modulators and their use in the treatment of diseases mediated by RORγ.
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Page/Page column 66

(2015/12/17)

NOVEL ANTIVIRAL PYRROLOPYRIDINE DERIVATIVES AND METHOD FOR PREPARING THE SAME
The present invention relates to a pyrrolopyridine derivative represented by the Chemical Formula I, and a racemate or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and relates to an antiviral composition including the same as an active ingredient. The compound of the Chemical Formula I has excellent antiviral activity and selectivity for wild type and resistant HIV-1, and thereby is useful as a therapeutic agent for acquired immune deficiency syndrome (AIDS).
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Paragraph 0347; 0351; 0352

(2014/09/16)

NOVEL ANTIVIRAL PYRROLOPYRIDINE DERIVATIVE AND A PRODUCTION METHOD FOR SAME
The present invention relates to a pyrrolopyridine derivative represented by the Chemical Formula I, and a racemate or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and relates to an antiviral composition including the same as an active ingredient. The compound of the Chemical Formula I has excellent antiviral activity and selectivity for wild type and resistant HIV-1, and thereby is useful as a therapeutic agent for acquired immune deficiency syndrome (AIDS).
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Paragraph 0328; 0332; 0333

(2014/12/09)

PHENYL-HETEROARYL AMINE COMPOUNDS AND THEIR USES
The present invention provides a compound of formula (I): and pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, or racemates thereof. Also provided are methods of treating a disease or condition mediated by CDK9 using the compounds of Formula I, and pharmaceutical compositions comprising such compounds
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Page/Page column 72

(2012/06/01)

3-(AMINOARYL)-PYRIDINE COMPOUNDS
The present invention provides a compound of formula (I): and pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, or racemates thereof. Also provided are pharmaceutical compositions containing these compounds and methods of treating a disease or condition mediated by CDK9 using these compounds and compositions.
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Page/Page column 79

(2012/06/01)

PYRIMIDINE BIARYL AMINE COMPOUNDS AND THEIR USES
The present invention provides a pyrimidine compound of formula (I): wherein one of X and Y but not both is N, and pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tantomers, diastereomers, deuterated versions, or racemates thereof. These compounds inhibit the activity of CDK9 and are thus useful as pharmaceuticals. Also provided are methods of treating a disease or condition mediated by CDK9 using the compounds of Formula I and isomers thereof, and pharmaceutical compositions comprising such compounds
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Page/Page column 77

(2012/08/08)

PYRIDINE BIARYL AMINE COMPOUNDS AND THEIR USES
The present invention provides a compound of formula (I): and pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, or racemates thereof. These compounds inhibit the activity of CDK9 and are thus useful as pharmaceuticals. Also provided are methods of treating a disease or condition mediated by CDK9 using the compounds of Formula I and isomers thereof, and pharmaceutical compositions comprising such compounds.
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Page/Page column 87

(2012/08/08)

Compounds and Compositions as Protein Kinase Inhibitors
The present invention provides compounds of Formula I or II: wherein R1, R1b, R2, R3, R4, R5, R6 and R7 are defined herein. The compounds of Formula (I) or (II) and pharmaceutical compositions thereof are useful for the treatment of B-Raf-associated diseases.
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(2011/04/14)

1-(4-UREIDOBENZOYL)PIPERAZINE DERIVATIVES
The present invention relates to 1-(4-ureidobenzoyl)piperazine derivatives having the general Formula I (We bring to your attention that formula I is not provided on this electronic version as it is provided in the abstract of the paper copy) Wherein Rsu
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Page/Page column 22

(2010/04/06)

4, 6-DISUBSTITUTED 2-AMINO-PYRIMIDINES AS HISTAMINE H4 RECEPTOR MODULATORS
The present invention relates to substituted heterocyclic compounds of Formula (I) or pharmaceutically acceptable salts or N-oxides or quaternary ammonium salts thereof wherein constituent members are provided hereinwith, as well as their compositions and methods of use, which are histamine H4 receptor inhibitors/antagonists useful in the treatment of histamine H4 receptor-associated conditions or diseases or disorders including, for example, inflammatory diseases or disorders, pruritus, and pain.
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Page/Page column 151-152

(2010/07/09)

Discovery and optimization of piperidyl benzamide derivatives as a novel class of 11β-HSD1 inhibitors
Discovery and optimization of a piperidyl benzamide series of 11β-HSD1 inhibitors is described. This series was derived from a cyclohexyl benzamide lead structures to address PXR selectivity, high non-specific protein binding, poor solubility, limited in
Rew, Yosup,McMinn, Dustin L.,Wang, Zhulun,He, Xiao,Hungate, Randall W.,Jaen, Juan C.,Sudom, Athena,Sun, Daqing,Tu, Hua,Ursu, Stefania,Villemure, Elisia,Walker, Nigel P.C.,Yan, Xuelei,Ye, Qiuping,Powers, Jay P.
scheme or table
p. 1797 - 1801
(2009/12/07)

N-BENZYL,N'-ARYLCARBONYLPIPERAZINE DERIVATIVES
The present invention relates to N-benzyl,N′-arylcarbonylpiperazine derivatives having the general formula I to pharmaceutical compositions comprising the same, and to the use of a these N-benzyl,N′-arylcarbonylpiperazine derivatives for the manufacture o
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Page/Page column 17

(2009/10/30)

N-BENZYL, N'-ARYLCARBONYLPIPERAZINE DERIVATIVES AS LXR MODULATORS
The present invention relates to N-benzyl,N'-arylcarbonylpiperazine derivatives having the general Formula (I) to pharmaceutical compositions comprising the same, and to the use of a these N-benzyl,N'-arylcarbonylpiperazine derivatives for the manufacture
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Page/Page column 30

(2009/04/25)

Distinctive molecular inhibition mechanisms for selective inhibitors of human 11β-hydroxysteroid dehydrogenase type 1
11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the NADPH dependent interconversion of inactive cortisone to active cortisol. Excess 11β-HSD1 or cortisol leads to insulin resistance and metabolic syndrome in animal models and in humans. Inhibiting 11β-HSD1 activity signifies a promising therapeutic strategy in the treatment of Type 2 diabetes and related diseases. Herein, we report two highly potent and selective small molecule inhibitors of human 11β-HSD1. While compound 1, a sulfonamide, functions as a simple substrate competitive inhibitor, compound 2, a triazole, shows the kinetic profile of a mixed inhibitor. Co-crystal structures reveal that both compounds occupy the 11β-HSD1 catalytic site, but present distinct molecular interactions with the protein. Strikingly, compound 2 interacts much closer to the cofactor NADP+ and likely modifies its binding. Together, the structural and kinetic analyses demonstrate two distinctive molecular inhibition mechanisms, providing valuable information for future inhibitor design.
Tu, Hua,Powers, Jay P.,Liu, Jinsong,Ursu, Stefania,Sudom, Athena,Yan, Xuelei,Xu, Haoda,Meininger, David,DeGraffenreid, Michael,He, Xiao,Jaen, Juan C.,Sun, Daqing,Labelle, Marc,Yamamoto, Hiroshi,Shan, Bei,Walker, Nigel P.C.,Wang, Zhulun
experimental part
p. 8922 - 8931
(2009/04/06)

ARYL SULFONAMIDE COMPOUNDS AND USES RELATED THERETO
The present invention provides Aryl Sulfonamide Compounds having the formula: (I); and prodrugs or pharmaceutically acceptable salts or prodrugs thereof. The Aryl Sulfonamide Compounds are useful for treating diabetes, obesity, and other diseases and disorders.
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Page/Page column 78

(2010/02/12)

PYRIMIDINEDIONE, PYRIMIDINETRIONE, TRIAZINEDIONE AND TETRAHYDROQUINAZOLINEDIONE DERIVATIVES AS ALPHA1-ADRENERGIC RECEPTOR ANTAGONISTS
Compounds of Formula I: STR1 where R 5 is a group selected from Formulae (a), (b), (c) and (d): STR2 and the pharmaceutically acceptable salts and N-oxides thereof, are α 1-adrenergic receptor antagonists useful for the treatment of diseases involving directly or indirectly an obstruction of the lower urinary tract, such as benign prostatic hyperplasia.
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(2008/06/13)

Pyrimidinedione, pyrimidinetrione, triazinedione, tetrahydroquinazolinedione derivatives as alpha-1-adrenergic receptor antagonists
The present invention relates to novel α1-adrenoceptor antagonists of the formula I*(formula 01)* in which: R1 is acetylamino, amino, cyano, trifluoroacetylamino, halo, hydro, hydroxy, nitro, methylsulfonylamino, 2-propynyloxy, a group selected from (C1-6)alkyl, (C3-6)cycloalkyl, (C3-6)cycloalkyl(C1-4)alkyl, (C1-6)alkyloxy, (C3-6)cycloalkyloxy, (C3-6)cycloalkyl(C1-4)alkyloxy and (C1-4)alkylthio (which group is optionally further substituted with one to three halo atoms) or a group selected from aryl, aryl(C1-4)alkyl, heteroaryl, heteroaryl(C1-4)alkyl, aryloxy, aryl(C1-4)alkyloxy, heteroaryloxy and heteroaryl(C1-4)alkyloxy (which aryl and heteroaryl are optionally further substituted with one to two radicals independently selected from halo and cyano); R2 is cyano, halo, hydro, hydroxy or a group selected from (C1-6)alkyl and (C1-6)alkyloxy (which group is optionally further substituted with one to three halogen atoms);R3 and R4 are both hydro or methyl or together are ethylene; and R5 is a group selected from Formulae (a), (b), (c) and (d):*(formula 02)* in which: X is C(O), CH2 or CH(OH); Y is CH2 or CH(OH); Z is N or C(R9), wherein R9 is hydro, (C1-6)alkyl or hydroxy; R6 is hydro, a group selected from (C1-6)alkyl, (C3-6)cycloalkyl, (C3-6)cycloalkyl(C1-4)alkyl (which group is optionally further substituted with one to three halo atoms) or a group selected from aryl, heteroaryl, aryl(C1-4)alkyl and heteroaryl(C1-4)alkyl (which aryl and heteroaryl are optionally further substituted with one to three radicals selected from halo, cyano, (C1-6)alkyloxy, (C1-6)alkyl and aryl); R7 is (C1-6)alkanoyl, carbamoyl, cyano, di(C1-6)alkylamino, halo, hydro, hydroxy, hydroxyiminomethyl, (C1-6)alkylsulfonyl, (C1-6)alkylthio, a group selected from (C1-6)alkyl, (C3-6)cycloalkyl,(C1-6)alkyloxy and (C1-6)alkyloxy(C1-4)alkyl (which group is optionally further substituted with one to three radicals selected from halo, hydroxy or (C1-6)alkyloxy) or a group selected from aryl, heteroaryl, aryl(C1-4)alkyl and heteroaryl(C1-4)alkyl (which aryl and heteroaryl are optionally further substituted with one to three radicals selected from halo, cyano, (C1-6)alkyloxy, (C1-6)alkyl and aryl) or R7 and R9 together are tetramethylene; and each R8 is independently hydro, hydroxy, methyl or ethyl; and the pharmaceutically acceptable salts and N-oxides thereof.
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(2008/06/13)