- ION CHANNEL INHIBITOR COMPOUNDS FOR CANCER TREATMENT
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The present invention concerns a compound of following general formula (I): where: either R is an R1 group and R′ is an -A1-Cy1 group, or R is an -A1-Cy1 group and R′ is an R1 group, R1 particularly being H or (C1-C6)alkyl group;A1 being an —NH— radical or —NH—CH2— radical;Cy1 particularly being a phenyl group,A is a fused (hetero)aromatic ring having 5 to 7 atoms, for use for treating cancer.
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Paragraph 0247; 0248
(2021/01/25)
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- MOF-derived cobalt nanoparticles catalyze a general synthesis of amines
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The development of base metal catalysts for the synthesis of pharmaceutically relevant compounds remains an important goal of chemical research. Here, we report that cobalt nanoparticles encapsulated by a graphitic shell are broadly effective reductive amination catalysts. Their convenient and practical preparation entailed template assembly of cobaltdiamine- dicarboxylic acid metal organic frameworks on carbon and subsequent pyrolysis under inert atmosphere.The resulting stable and reusable catalysts were active for synthesis of primary, secondary, tertiary, and N-methylamines (more than 140 examples).The reaction couples easily accessible carbonyl compounds (aldehydes and ketones) with ammonia, amines, or nitro compounds, and molecular hydrogen under industrially viable and scalable conditions, offering cost-effective access to numerous amines, amino acid derivatives, and more complex drug targets.
- Jagadeesh, Rajenahally V.,Murugesan, Kathiravan,Alshammari, Ahmad S.,Neumann, Helfried,Pohl, Marga-Martina,Radnik, J?rg,Beller, Matthias
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p. 326 - 332
(2017/09/28)
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- Microwave-Enhanced Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)imines
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Microwave irradiation has considerably enhanced the efficiency of the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)imines in isopropyl alcohol catalyzed by a ruthenium complex bearing the achiral ligand 2-amino-2-methylpropan-1-ol. In addition to shortening reaction times for the transfer hydrogenation processes to only 30 min, the amounts of ruthenium catalyst and isopropyl alcohol can be considerably reduced in comparison with our previous procedure assisted by conventional heating, which diminishes the environmental impact of this new protocol. This methodology can be applied to aromatic, heteroaromatic and aliphatic N-(tert-butylsulfinyl)ketimines, leading, after desulfinylation, to the expected primary amines in excellent yields and with enantiomeric excesses of up to 96 %. Microwave irradiation promotes the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)imines in 2-propanol catalysed by a ruthenium complex bearing an achiral β-amino alcohol as ligand. After desulfinylation, α-branched primary amines containing aromatic, heteroaromatic and aliphatic substituents are obtained in excellent yields and with enantiomeric excesses of up to 96 %.
- Pablo, Oscar,Guijarro, David,Yus, Miguel
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p. 7034 - 7038
(2016/02/19)
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- 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
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The present invention relates to novel triazolo [4,3-a]pyridine derivatives of Formula (I), wherein all radicals are as defined in the claims. The compounds according to the invention are positive allosteric modulators of the metabotropic glutamate receptor subtype 2 ("mGluR2"), which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.
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Page/Page column 49-50
(2012/05/31)
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- Chroman and tetrahydroquinoline ureas as potent TRPV1 antagonists
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Novel chroman and tetrahydroquinoline ureas were synthesized and evaluated for their activity as TRPV1 antagonists. It was found that aryl substituents on the 7- or 8-position of both bicyclic scaffolds imparted the best in vitro potency at TRPV1. The most potent chroman ureas were assessed in chronic and acute pain models, and compounds with the ability to cross the blood-brain barrier were shown to be highly efficacious. The tetrahydroquinoline ureas were found to be potent CYP3A4 inhibitors, but replacement of bulky substituents at the nitrogen atom of the tetrahydroisoquinoline moiety with small groups such as methyl can minimize the inhibition.
- Schmidt, Robert G.,Bayburt, Erol K.,Latshaw, Steven P.,Koenig, John R.,Daanen, Jerome F.,McDonald, Heath A.,Bianchi, Bruce R.,Zhong, Chengmin,Joshi, Shailen,Honore, Prisca,Marsh, Kennan C.,Lee, Chih-Hung,Faltynek, Connie R.,Gomtsyan, Arthur
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p. 1338 - 1341
(2011/04/23)
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- Asymmetric synthesis of chiral primary amines by transfer hydrogenation of N -(tert -Butanesulfinyl)ketimines
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(Figure presented) The diastereoselective reduction of (R)-N-(tert- butanesulfinyl)ketimines by a ruthenium-catalyzed asymmetric transfer hydrogenation process in isopropyl alcohol, followed by desulfinylation of the nitrogen atom, is an excellent method to prepare highly enantiomerically enriched α-branched primary amines (up to >99% ee) in short reaction times (1-4 h). (1S,2R)-1-Amino-2-indanol has been shown to be a very efficient ligand to perform this transformation. Ketimines bearing either an aryl or a heteroaryl group and an alkyl group as substituents of the iminic carbon atom are very good substrates for this process. The reduction of a dialkyl ketimine could also be achieved, affording the expected amine with moderate optical purity (69% ee). Some amines which are precursors of very interesting biologically and pharmacologically active compounds have been prepared in excellent yields and enantiomeric excesses.
- Guijarro, David,Pablo, Oscar,Yus, Miguel
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supporting information; experimental part
p. 5265 - 5270
(2010/10/21)
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- 2-Benzimidazolyl-9-(chroman-4-yl)-purinone derivatives as JAK3 inhibitors
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A novel class of Janus tyrosine kinase 3 (JAK3) inhibitors based on a 2-benzimidazoylpurinone core structure is described. Through substitution of the benzimidazoyl moiety and optimization of the N-9 substituent of the purinone, compound 24 was identified incorporating a chroman-based functional group. Compound 24 shows excellent kinase activity, good oral bioavailability and demonstrates efficacy in an acute mechanistic mouse model through inhibition of interleukin-2 (IL-2) induced interferon-γ (INF-γ) production.
- Cole, Andrew G.,Bohnstedt, Adolph C.,Paradkar, Vidyadhar,Kingsbury, Celia,Quintero, Jorge G.,Park, Haengsoon,Lu, Yingchun,You, Ming,Neagu, Irina,Diller, David J.,Letourneau, Jeffrey J.,Shao, Yuefei,James, Ray A.,Riviello, Christopher M.,Ho, Koc-Kan,Lin, Tsung H.,Wang, Bojing,Appell, Kenneth C.,Sills, Matthew,Quadros, Elizabeth,Kimble, Earl F.,Ohlmeyer, Michael H.J.,Webb, Maria L.
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scheme or table
p. 6788 - 6792
(2010/06/12)
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- SUBSTITUTED ARYLAMINE COMPOUNDS AND THEIR USE AS 5-HT6 MODULATORS
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The invention relates to 5-HT6 receptor antagonists. Novel arylamine compounds having the formula: (see formula I) and pharmaceutically acceptable salts and/or esters thereof, wherein - n is 0, 1, 2, 3, or 4; - A, when present is a lower alkyl
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Page/Page column 98
(2008/06/13)
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- 2-AMINO- AND 2-THIO-SUBSTITUTED 1,3-DIAMINOPROPANES
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Disclosed are compounds of the formula: where variables Q, Z, X, R15, R2, R3, and Rc are defined herein. Compounds disclosed herein are inhibitors of the beta-secretase enzyme and are therefore useful in the treatment of Alzheimer’s disease and other diseases characterized by deposition of A beta peptide in a mammal.
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Page/Page column 123-124
(2008/06/13)
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- METHODS OF TREATMENT OF AMYLOIDOSIS USING BI-CYCLIC ASPARTYL PROTEASE INHIBITORS
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The invention relates to novel compounds and methods of treating diseases, disorders, and conditions associated with amyloidosis. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein.
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Page/Page column 128-129; 211-212
(2010/02/14)
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- Cyclic amine derivatives and methods of use
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Selected compounds are effective for treatment of pain and diseases, such as inflammation mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving pain, inflammation, and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
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Page/Page column 39
(2010/02/14)
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- Amino-1,3,5-triazines N-substituted with chiral bicyclic radicals, process for their preparation, compositions thereof, and their use as herbicides and plant growth regulators
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Amino-1,3,5-triazines N-substituted with chiral bicyclic radicals, process for their preparation, compositions thereof, and their use as herbicides and plant growth regulators. The invention relates to an optically active compound of formula (I) or a salt thereof: wherein the various symbols are as defined in the description, to proceses for their preparation, to compositions thereof, and to their use as herbicides or plant growth regulators. The invention also relates to novel intermediates of formula (III), (V) and (XIII) as defined in the description.
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- CYCLIC AMINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF INFLAMMATION-RELATED DISORDERS MEDIATED BY BRADYKININ
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Compounds of formula (I) are effective for treatment of pain and diseases, such as inflammation mediated diseases. The invention encompasses novel compounds, pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving pain, inflammation mediated by Bradykinin. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes wherein q, t, R, Ra, Rb, Rc and R2 are as defined herein.
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- Substituted aryl 1,4-pyrazine derivatives
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Substituted aryl 1,4-pyrazine derivatives and their use in treating anxiety disorders, depression and stress related disorders are disclosed.
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- Catalytic asymmetric hydroboration/amination and alkylamination with rhodium complexes of 1,1′-(2-diarylphosphino-1-naphthyl)isoquinoline
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Catecholboronate esters formed by asymmetric hydroboration of arylalkenes are not directly converted to amines by reaction with hydroxylamine-O-sulfonic acid. Prior conversion to a trialkylborane by reaction with ZnEt2 or MeMgCl permits a subsequent amination reaction to occur with essentially complete retention of configuration, leading to a range of primary α-arylalkylamines in up to 97% enantiomeric excess (ee). Secondary, but not tertiary amines may be formed by a related pathway when in situ generated alkylchloramines are employed as the aminating agent. The catalytic asymmetric hydroboration, β-alkylation and amination steps may be combined in a single stage. Overall, this provides a practical procedure for the synthesis of enantiomerically enriched arylamines, exemplified inter alia by the synthesis of (S)-1,2,3,4-tetrahydro-1-naphthylamine in 95-97% ee and of (R)-N-(cyclohexyl)-1′-(4-methoxyphenyl)ethylamine in 93 % ee.
- Fernandez, Elena,Maeda, Kenji,Hooper, Mark W.,Brown, John M.
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p. 1840 - 1846
(2007/10/03)
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- Phenoxyalkylamines in Semi-rigid Conformation: Synthesis & Pharmacological Activity of N1-(4'-Chromanyl)-N4-arylpiperazines & N1-(2'-Chromanylmethyl)-N4-arylpiperazines
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Synthesis and pharmacological activity of N1-(4'-chromanyl)-N4-arylpiperazines and N1-(chromanylmethyl)-N4-arylpiperazines, cyclic congeners of N1-aryloxyalkyl-N4-arylpiperazines, are reported.None of the compounds of this series shows any significant pharmacological activity.
- Pratap, Ram,Gupta, R. C.,Anand, Nitya
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p. 1063 - 1067
(2007/10/02)
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