53525-60-3Relevant academic research and scientific papers
NAPHTHO[2,1 -D]THIAZOLE DERIVATIVES, COMPOSITIONS THEREOF AND METHODS OF TREATING DISORDERS
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Paragraph 0144, (2021/05/29)
The present application relates to the compounds of formula (I) that inhibit CDK9, pharmaceutical compositions thereof and methods of making and using the same.
Structure Kinetics Relationships and Molecular Dynamics Show Crucial Role for Heterocycle Leaving Group in Irreversible Diacylglycerol Lipase Inhibitors
Janssen, Antonius P.A.,Van Hengst, Jacob M.A.,Béquignon, Olivier J.M.,Deng, Hui,Van Westen, Gerard J.P.,Van Der Stelt, Mario
, p. 7910 - 7922 (2019/10/11)
Drug discovery programs of covalent irreversible, mechanism-based enzyme inhibitors often focus on optimization of potency as determined by IC50-values in biochemical assays. These assays do not allow the characterization of the binding activity (Ki) and reactivity (kinact) as individual kinetic parameters of the covalent inhibitors. Here, we report the development of a kinetic substrate assay to study the influence of the acidity (pKa) of heterocyclic leaving group of triazole urea derivatives as diacylglycerol lipase (DAGL)-α inhibitors. Surprisingly, we found that the reactivity of the inhibitors did not correlate with the pKa of the leaving group, whereas the position of the nitrogen atoms in the heterocyclic core determined to a large extent the binding activity of the inhibitor. This finding was confirmed and clarified by molecular dynamics simulations on the covalently bound Michaelis-Menten complex. A deeper understanding of the binding properties of covalent serine hydrolase inhibitors is expected to aid in the discovery and development of more selective covalent inhibitors.
PREPARATION METHOD OF DEXMEDETOMIDINE INTERMEDIATE
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Paragraph 0023, (2016/10/11)
The present invention discloses a preparation method of 2,3-dimethyl phenyl-1-trityl-imidazole-4-ketone. In accordance with this method, imidazole-4-ethyl formate is used as a raw material; ethyl formate is used for amino protection, 1-trityl-1H-imidazole
BENZENE SULFONAMIDES AS CCR9 INHIBITORS
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Page/Page column 96; 97, (2015/07/15)
The present invention relates to compounds useful as CCR9 modulators, to compositions containing them, to methods of making them, and to methods of using them. In particular, the present invention relates to compounds capable of modulating the function of the CCR9 receptor by acting as partial agonists, antagonists or inverse agonists. Such compounds may be useful to treat, prevent or ameliorate a disease or condition associated with CCR9 activation, including inflammatory and immune disorder diseases or conditions such as inflammatory bowel diseases (IBD).
(SUBSTITUTED ARALKYL) HETEROCYCLIC COMPOUNDS
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, (2008/06/13)
A (substituted-aralkyl)heterocyclic compound of the formula I wherein R1 is an azido, carbamoyl, cyano, formyl, hy-droxy or nitro radical, a 1-6C 1-hydroxyalkyl, alkoxy, alkylcarbamoyl, alkylthio, alkylsulphinyl or alkylsulphonyl radical, a 2-cyanoethyl radical, optionally bearing one to four 1-6C alkyl substituents, or a 2-6C alkanoyl, halogenoalkanoyl, alkanoyloxy, alkanoylamino, dialkylcarbamoyl or alkoxycarbonyl radical; R2 and R3, which may be the same or different, are each a hydrogen atom, a 1-6C alkyl, dueterioalkyl or halogenoalkyl radical, or a phenyl or phenyl(l-6C alkyl) radical, in each of which the phenyl may optionally bear one or more substituents; or R2 and R3, together with the carbon atom to which they are attached, may form a 3- to 6-membered ring; or R1R2R3C- is a 1,1-dicyanoethyl or trifluoromethylsulphonyl radical; R4 is a hydrogen or halogen atom, a cyano or nitro radical or a 1-6C alkyl or halogenoalkyl radical; R5 has any of the values de-fined above for the group RIR2R3C but is not necessarily the same as R1R2R3C, or has any of the values de-fined above for R4 but is not necessarily the same as R4, or is a carbamoyl, 1-pyrrolidinyl-carbonyl, piperidino-carbonyl, morpholinocarbonyl or nitro radical, a 1-6C alkoxy or halogenoalkoxy radical or a 2-6C alkanoyl or alkoxy-carbonyl radical; A is a methylene or ethylene radical optionally bearing one or more substituents selected from deuterium and halogen atoms, carbamoyl, cyano and hydroxy radicals, 1-6C alkyl and alkoxy radicals, and 2-6C alkanoyloxy radicals provided that when A is linked to R through a nitrogen atom thereof, it may not bear a hydroxy, alkoxy or alkanoyloxy sub-stituent on the carbon atom adjacent to such nitrogen atoms; and R6is a lH-l,2,4-triazol-l-yl, 4H-l,2,4-triazol-4-yl, IH-imidazol-1-yl, 5-cyano-lH-imidazol-l-yl, 3-pyridyl or 5-pyrimidinyl radical, or a IH-imidazol-1-yl radical, bearing at the 5-position thereof a 1-6C alkyl substituent which is itself optionally substituted by one or more carbamoyl, cyano, hydroxy or 2-6C alkoxycar-bonyl radicals; and provided that when R2, R3, R4 and R5 are hydrogen, A is a methylene radical and R6 is a 3-pyridyl radical, R1 is not a cyano, hydroxy or hydroxymethyl radical, and when R1 is a hydroxy radical, R3, R4 and R5 are hydrogen, A is a methylene radical and R6 is 3-pyridyl, R2 is not a methyl or a 2-chloro-1-methylethyl radical, and provided that when R1 is a methoxycarbonyl radical, R2, R3, R4 and R5 are hydrogen and A is a methylene radical, Ri is not a IH-imidazol-a1-yl radical; and the pharmaceutically acceptable acid addition salts thereof
New Synthesis of 2-Nitroimidazoles
Davis, Dwight P.,Kirk, Kenneth L.,Cohen, Louis A.
, p. 253 - 256 (2007/10/02)
1-Triphenylmethylimidazoles are treated with n-butyllithium in tetrahydrofuran at 0 deg C to form the 2-lithio derivatives.The latter species react with n-propyl nitrate to give 1-trityl-2-nitroimidazoles which, after acid hydrolysis, provide the correspondine 2-nitroimidazoles. 2-Nitroimidazole was obtained from imidazole from overall yields of 27-35percent; 4-methyl-2-nitroimidazole was obtained in 40percent overall yield from 4-methylimidazole.Imidazole-4,5-dicarboxylic acid was converted, in several steps, to 1-tritylimidazole-4-methanil, and the latter compound was transformed into 2-nitroimidazole-4-methanol in an overall yield of 18percent.Protection of the hydroxymethyl function was found to be unnecessary during carbanion formation and nitration.Attempts to nitrate 1-methylimidazole or 1-methoxymethylimidazole by the same procedure failed.
Imidazole derivatives with potential biological activity
Belgodere,Bossio,Parrini,Pepino
, p. 1051 - 1056 (2007/10/02)
A series of 1-substituted imidazole-5-carbohydroxamic acids Ia, Ib and Ie were prepared from the corresponding 5-methoxycarbonyl imidazoles (IX) obtained by a univocal synthesis starting with the reaction of the amines (III) with ethylchloroacetate. On treatment of 4(5)-methoxycarbonyl imidazoles (XI) with alkylar halides (X), on the contrary, mixtures of 1-substituted-4(or 5)-methoxycarbonyl imidazoles were obtained that, when separated by thin-layer chromatography, gave the carbohydroxamic acids Ia, Ib, Id and Ie and IIa→f. The structures of the imidazole derivatives were obtained by means of IR, NMR and UV spectra. On carrying out tests of biological activity on these compounds, it had been found that the 5-carbohydroxamic acids possess, compared to the 4-carbohydroxamic ones, a greater activity. Particularly Ib and Ib-HCl seem fairly active against Klebsiella pneumoniae and Clostridium bifermentans, Ib-HCl against Bacillus subtilis, too.
