925417-01-2Relevant academic research and scientific papers
Development of inhibitors against mycobacterium abscessus tRNA (m1G37) Methyltransferase (TrmD) Using Fragment-Based Approaches
Whitehouse, Andrew J.,Thomas, Sherine E.,Brown, Karen P.,Fanourakis, Alexander,Chan, Daniel S.-H.,Libardo, M. Daben J.,Mendes, Vitor,Boshoff, Helena I. M.,Floto, R. Andres,Abell, Chris,Blundell, Tom L.,Coyne, Anthony G.
, p. 7210 - 7232 (2019/08/20)
Mycobacterium abscessus (Mab) is a rapidly growing species of multidrug-resistant nontuberculous mycobacteria that has emerged as a growing threat to individuals with cystic fibrosis and other pre-existing chronic lung diseases. Mab pulmonary infections are difficult, or sometimes impossible, to treat and result in accelerated lung function decline and premature death. There is therefore an urgent need to develop novel antibiotics with improved efficacy. tRNA (m1G37) methyltransferase (TrmD) is a promising target for novel antibiotics. It is essential in Mab and other mycobacteria, improving reading frame maintenance on the ribosome to prevent frameshift errors. In this work, a fragment-based approach was employed with the merging of two fragments bound to the active site, followed by structure-guided elaboration to design potent nanomolar inhibitors against Mab TrmD. Several of these compounds exhibit promising activity against mycobacterial species, including Mycobacterium tuberculosis and Mycobacterium leprae in addition to Mab, supporting the use of TrmD as a target for the development of antimycobacterial compounds.
MACROCYCLIC INHIBITORS OF MYELOPEROXIDASE
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Page/Page column 58, (2018/02/03)
The present invention provides compounds of Formula (I): wherein the substituents are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are myeloperoxidase (MPO) inhibitors and/or eosinophil peroxidase (EPX) inhibitors, and may be useful for for the treatment and/or prophylaxis of atherosclerosis, heart failure, chronic obstructive pulmonary disease (COPD), and related diseases.
DUAL NAV1.2/5HT2A INHIBITORS FOR TREATING CNS DISORDERS
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Paragraph 0188, (2018/03/28)
Compounds of formula I: I are disclosed, as are pharmaceutical compositions containing such compounds. Methods of treating neurological or psychiatric disorders in a patient in need are also disclosed. Such disorders include depression, bipolar disorder, pain, schizophrenia, obsessive compulsive disorder, addiction, social disorder, attention deficit hyperactivity disorder, an anxiety disorder, autism, a cognitive impairment, or a neuropsychiatric symptom such as apathy, depression, anxiety, psychosis, aggression, agitation, impulse control disorders, and sleep disorders in neurological disorders such as Alzheimer's and Parkinson's diseases.
TRIAZOLOPYRIDINE INHIBITORS OF MYELOPEROXIDASE
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Page/Page column 72; 73, (2017/10/18)
The present invention provides compounds of Formula (I). wherein A and Z are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are myeloperoxidase (MPO) inhibitors and may be useful for for the treatment and/or prophylaxis of atherosclerosis, heart failure, chronic obstructive pulmonary disease (COPD), and related diseases.
Formamides as Lewis Base Catalysts in SNReactions—Efficient Transformation of Alcohols into Chlorides, Amines, and Ethers
Huy, Peter H.,Motsch, Sebastian,Kappler, Sarah M.
supporting information, p. 10145 - 10149 (2016/08/16)
A simple formamide catalyst facilitates the efficient transformation of alcohols into alkyl chlorides with benzoyl chloride as the sole reagent. These nucleophilic substitutions proceed through iminium-activated alcohols as intermediates. The novel method, which can be even performed under solvent-free conditions, is distinguished by an excellent functional group tolerance, scalability (>100 g) and waste-balance (E-factor down to 2). Chiral substrates are converted with excellent levels of stereochemical inversion (99 %→≥95 % ee). In a practical one-pot procedure, the primary formed chlorides can be further transformed into amines, azides, ethers, sulfides, and nitriles. The value of the method was demonstrated in straightforward syntheses of the drugs rac-Clopidogrel and S-Fendiline.
Aluminium chloride hexahydrate (AlCl3.6H2o): An efficient, facile, mild, and highly chemoselective catalytic deprotection of tert-butyldimethylsilyl (tbs) ethers
Gonzalez-Calderon, Davir,Benitez-Puebla, Luis J.,Gonzalez-Gonzalez, Carlos A.,Garcia-Eleno, Marco A.,Fuentes-Benitez, Aydee,Cuevas-Yanez, Erick,Corona-Becerril, David,Gonzalez-Romero, Carlos
, p. 1258 - 1265 (2014/04/17)
tert-Butyldimethylsilyl (TBS) phenyl / alkyl ethers were cleaved to the corresponding efficiently parent hydroxyl compounds in good yields using catalytic amounts of AlCl3.6H2O by conventional or microwave-assisted heating in methanol or isopropanol solution. Intramolecular and competitive experiments demonstrated the chemoselective deprotection of TBS ethers in the presence of triisopropylsilyl and tert-butyldiphenylsilyl ethers.
A novel chemoselective cleavage of (tert-butyl)(dimethyl)silyl (TBS) ethers catalyzed by Ce(SO4)2·4 H2O
González-Calderón, Davir,González-González, Carlos A.,Fuentes-Benítez, Aydeé,Cuevas-Yá?ez, Erick,Corona-Becerril, David,González-Romero, Carlos
, p. 965 - 972 (2014/08/05)
(tert-Butyl)(dimethyl)silyl (tBuMe2Si; TBS) phenyl/alkyl ethers were efficiently cleaved to the corresponding parent hydroxy compounds in good yields using catalytic amounts of Ce(SO4) 2·4 H2O by microwave-assisted or conventional heating in MeOH. Intramolecular and competitive experiments demonstrated the chemoselective deprotection of TBS ethers in the presence of triisopropylsilyl (iPr3Si; TIPS) and (tert-butyl)(diphenyl)silyl ( tBuPh2Si; TBDPS) ethers. Copyright
Synthesis of the tripeptide domain of sanglifehrins using asymmetric phase-transfer catalysis
White, James D.,Suttisintong, Khomson
, p. 2757 - 2762 (2013/04/23)
The tripeptide (S)-valinyl-(S)-m-hydroxyphenylalanyl-(3S)-piperazate common to immunosuppressant sanglifehrins was synthesized from the constituent amino acid residues in nine steps and 42% overall yield. A key construction was the installation of (S) absolute configuration in m-hydroxyphenylalanine using asymmetric phase-transfer catalysis in the presence of N-(1-naphthyl) cinchonidinium bromide. Cbz-protected (S)-valine was first coupled to the amino group of (S)-m-triisopropylsilyloxyphenylalanine tert-butyl ester, and the resulting dipeptide after ester cleavage was linked to (3S)-methyl piperazate.
Cerium(IV) sulfate tetrahydrate: A catalytic and highly chemoselective deprotection of THP, MOM, and BOM ethers
González-Calderón, Davir,González-González, Carlos A.,Fuentes-Benítez, Aydeé,Cuevas-Yá?ez, Erick,Corona-Becerril, David,González-Romero, Carlos
, p. 7164 - 7166 (2013/12/04)
Tetrahydropyranyl (THP), methoxymethyl (MOM), and benzyloxymethyl (BOM) phenyl/alkyl ethers were efficiently cleaved to the corresponding parent hydroxyl compounds in good yields using catalytic amounts of Ce(SO 4)2·4H2O by microwave-assisted or conventional heating in methanol solution. Intramolecular and competitive experiments demonstrated the chemoselective deprotection of THP ethers in the presence of triisopropylsilyl (TIPS) and tert-butyldiphenylsilyl (TBDPS) phenyl ethers.
HETEROCYCLICALLY SUBSTITUTED ARYL COMPOUNDS AS HIF INHIBITORS
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, (2013/08/14)
The present application relates to novel aryl compounds with heterocyclic substituents, processes for their preparation, their use for treatment and/or prevention of diseases and their use for the preparation of medicaments for treatment and/or prevention
