21543-49-7Relevant academic research and scientific papers
Synthesis and analgesic activity of secondary amine analogues of pyridylmethylamine and positional isomeric analogues of ABT-594
Zhang, Chuan-Xin,Ge, Ze-Mei,Cheng, Tie-Ming,Li, Run-Tao
, p. 2013 - 2016 (2006)
A series of highly sterically hindered secondary amine analogues of pyridylmethylamine (7a-f, 8a-c) and positional isomeric analogues of ABT-594 (9a-c) were synthesized and evaluated for their in vivo analgesic activity. The compounds 7a and 7d show potent analgesic activity and lower toxicity. Some interesting structure-activity relationships have been revealed.
Ultrasounds-mediated 10-seconds synthesis of chalcones as potential farnesyltransferase inhibitors
Farce, Amaury,Ghinet, Alina,Homerin, Germain,Nica, Adrian Sorin,Dubois, Jo?lle
supporting information, (2020/04/10)
A broad range of chalcones and derivatives were easily and rapidly synthesized, following Claisen-Schmidt condensation of (hetero)aryl ketones and (hetero)aryl aldehydes using a ultrasound probe. A comparison was made with classical magnetic stirring experiments, and an optimization study was realized, showing lithium hydroxide to be the best basic catalyst of the studied condensations. By-products of the reactions (β-hydroxy-ketone, diketones, and cyclohexanols) were also isolated. All compounds were evaluated in vitro for their ability to inhibit human farnesyltransferase, a protein implicated in cancer and rare diseases and on the NCI-60 cancer cell lines panel. Molecules showed inhibitory activity on the target protein and cytostatic effect on different cell lines with particular activity against MCF7, breast cancer cells.
New-type compound and preparation method and application thereof
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Paragraph 0043-0046; 0050, (2019/05/02)
The invention relates to a new-type compound. A structural formula of the new-type compound is as shown in a formula (1). The invention further provides a method for preparing the above new-type compound. The invention further provides an application of the above new-type compound or pharmaceutically acceptable salt thereof, a solvate or a drug compound for preparing a drug for treating a diseaserelated to activation of a hedgehog passage. The provided above new-type compound can be used for preparing the drug for treating the disease related to the activation of the hedgehog passage. The new-type compound is particularly capable of inhibiting growth of medulloblastoma well, and can be used for preparing a drug for treating medulloblastoma related diseases.
MUSCARINIC M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
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Page/Page column 40, (2018/03/25)
The present invention relates to compounds of formula (I), or their isotopic forms, stereoisomers, tautomers or pharmaceutically acceptable salt (s) thereof as muscarinic M1 receptor positive allosteric modulators (M1 PAMs). The present invention describes the preparation, pharmaceutical composition and the use of compound formula (I).
INHIBITORS OF HEPATITIS C VIRUS POLYMERASE
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Paragraph 578; 581, (2016/10/11)
The present invention provides, among other things, compounds represented by the general Formula I: (I) and pharmaceutically acceptable salts thereof, wherein L and A (and further substituents) are as defined in classes and subclasses herein and compositions (e.g., pharmaceutical compositions) comprising such compounds, which compounds are useful as inhibitors of hepatitis C virus polymerase, and thus are useful, for example, as medicaments for the treatment of HCV infection.
Design, synthesis, and characterization of α-ketoheterocycles that additionally target the cytosolic port Cys269 of fatty acid amide hydrolase
Otrubova, Katerina,Cravatt, Benjamin F.,Boger, Dale L.
supporting information, p. 1079 - 1089 (2014/03/21)
A series of α-ketooxazoles incorporating electrophiles at the C5 position of the pyridyl ring of 2 (OL-135) and related compounds were prepared and examined as inhibitors of fatty acid amide hydrolase (FAAH) that additionally target the cytosolic port Cys269. From this series, a subset of the candidate inhibitors exhibited time-dependent FAAH inhibition and noncompetitive irreversible inactivation of the enzyme, consistent with the targeted Cys269 covalent alkylation or addition, and maintained or enhanced the intrinsic selectivity for FAAH versus other serine hydrolases. A preliminary in vivo assessment demonstrates that these inhibitors raise endogenous brain levels of anandamide and other FAAH substrates upon intraperitoneal (i.p.) administration to mice, with peak levels achieved within 1.5-3 h, and that the elevations of the signaling lipids were maintained >6 h, indicating that the inhibitors effectively reach and remain active in the brain, inhibiting FAAH for a sustained period.
CARBAMATE/UREA DERIVATIVES CONTAINING PIPERIDIN AND PIPERAZIN RINGS AS H3 RECEPTOR INHIBITORS
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Paragraph 0501-0502, (2014/09/03)
The invention relates to compound of the formula I (I) or a salt thereof, wherein the substituents are as defined in the specification; to its preparation and to medicaments comprising it for treating diseases connected to tehinhibition of H3 receptor.
SUBSTITUTED PYRIMIDINIUM COMPOUNDS AND DERIVATIVES FOR COMBATING ANIMAL PESTS
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Page/Page column 79; 80, (2014/10/29)
The present invention relates to substituted pyrimidinium compounds of formula (I), to the stereoisomers, salts, tautomers and N-oxides thereof and to compositions comprising such compounds. The invention also relates to methods and uses of these substituted pyrimidinium compounds and of compositions thereof, for combating and controlling animal pests. Furthermore the invention relates also to pesticidal methods of applying such substituted pyrimidinium compounds. The substituted pyrimidinium compounds of the present invention are defined by the following general formula (I) wherein X, Y, Z, R1, R2, A and Het are defined as in the description.
Rational design of fatty acid amide hydrolase inhibitors that act by covalently bonding to two active site residues
Otrubova, Katerina,Brown, Monica,McCormick, Michael S.,Han, Gye W.,O'Neal, Scott T.,Cravatt, Benjamin F.,Stevens, Raymond C.,Lichtman, Aron H.,Boger, Dale L.
supporting information, p. 6289 - 6299 (2013/06/26)
The design and characterization of α-ketoheterocycle fatty acid amide hydrolase (FAAH) inhibitors are disclosed that additionally and irreversibly target a cysteine (Cys269) found in the enzyme cytosolic port while maintaining the reversible covalent Ser241 attachment responsible for their rapid and initially reversible enzyme inhibition. Two α-ketooxazoles (3 and 4) containing strategically placed electrophiles at the C5 position of the pyridyl substituent of 2 (OL-135) were prepared and examined as inhibitors of FAAH. Consistent with the observed time-dependent noncompetitive inhibition, the cocrystal X-ray structure of 3 bound to a humanized variant of rat FAAH revealed that 3 was not only covalently bound to the active site catalytic nucleophile Ser241 as a deprotonated hemiketal, but also to Cys269 through the pyridyl C5-substituent, thus providing an inhibitor with dual covalent attachment in the enzyme active site. In vivo characterization of the prototypical inhibitors in mice demonstrates that they raise endogenous brain levels of FAAH substrates to a greater extent and for a much longer duration (>6 h) than the reversible inhibitor 2, indicating that the inhibitors accumulate and persist in the brain to completely inhibit FAAH for a prolonged period. Consistent with this behavior and the targeted irreversible enzyme inhibition, 3 reversed cold allodynia in the chronic constriction injury model of neuropathic pain in mice for a sustained period (>6 h) beyond that observed with the reversible inhibitor 2, providing effects that were unchanged over the 1-6 h time course monitored.
CARBAMATE/ UREA DERIVATIVES CONTAINING PIPERIDIN AND PIPERAZIN RINGS AS H3 RECEPTOR INHIBITORS
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Page/Page column 46; 47, (2013/04/24)
The invention relates to compound of the formula I (I) or a salt thereof, wherein the substituents are as defined in the specification; to its preparation and to medicaments comprising it for traeting diseases connected to tehinhibition of H3 receptor.
