137075-21-9Relevant articles and documents
Thioimidazoline based compounds reverse glucocorticoid resistance in human acute lymphoblastic leukemia xenografts
Toscan, Cara E.,Rahimi, Marwa,Bhadbhade, Mohan,Pickford, Russell,McAlpine, Shelli R.,Lock, Richard B.
, p. 6299 - 6312 (2015/06/08)
Glucocorticoids form a critical component of chemotherapy regimens for pediatric acute lymphoblastic leukemia (ALL) and the initial response to glucocorticoid therapy is a major prognostic factor, where resistance is predictive of poor outcome. A high-throughput screen identified four thioimidazoline-containing compounds that reversed dexamethasone resistance in an ALL xenograft derived from a chemoresistant pediatric ALL. The lead compound (1) was synergistic when used in combination with the glucocorticoids, dexamethasone or prednisolone. Synergy was observed in a range of dexamethasone-resistant xenografts representative of B-cell precursor ALL (BCP-ALL) and T-cell ALL. We describe here the synthesis of twenty compounds and biological evaluation of thirty two molecules that explore the structure-activity relationships (SAR) of this novel class of glucocorticoid sensitizing compounds. SAR analysis has identified that the most effective dexamethasone sensitizers contain a thioimidazoline acetamide substructure with a large hydrophobic moiety on the acetamide. This journal is
DERIVATIVES OF UREA AND RELATED DIAMINES, METHODS FOR THEIR MANUFACTURE, AND USES THEREFOR
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Page/Page column 136-137, (2008/06/13)
Compounds of formula (I): Z is >CH-, >C=CH- or >N-, R1 and R2 are optionally substituted and are the same or different, and each represents an aryl group, a heteroaryl group, or Z, R1 and R2 form a fused ring structure of formula: in which A represents a single bond, or linking group, R3 represents hydrogen, a group selected from: -AIkCOOR, -AIkNR7R8, -AIkCONR7R8, -AIkCOR9, -AIkSO2NR10R10', -AIkOR10, and -AIkS(O)nR10, in which AIk is alkyl, R is hydrogen or alkyl, R7 and R8 each represents H, optionally substituted alkyl, alkylaminoalkyl or dialkylaminoalkyl, or CONR7R8 forms an optionally substituted heterocycle, and R10 and R10 are hydrogen atom, optionally substituted alkyl, an alkylaminoalkyl group, an optionally substituted cycle, optionally spaced by an AIk group as defined, Q represents >C=0 or >C=S, R5 is a hydrogen atom or an alkyl, alkoxy, hydroxyalkyl, alkylthio, or thioalkyl group, p is 1, 2 or 3, q is 0, 1 or 2, R6 represents an optionally substituted aryl or heteroaryl group, and salts and esters thereof, are useful as calcimimetics in therapy.
UREA DERIVATIVES USEFUL AS CALCIUM RECEPTOR MODULATORS
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Page/Page column 48; 155-156, (2008/06/13)
The present invention provides compounds of formula (I): in which Y is oxygen or sulphur; R1 and R”1 are optionally substituted aryl, heteroaryl or a fused ring structure, R2and R'2 are each H, or optionally substituted alkyl, alkylaminoalkyl or dialkylaminoalkyl, or R2 and R'2 and their N form a saturated or unsaturated optionally substituted heterocycle, R3 represents a group of formula -(CH2)P-Ar-Rn, wherein p is 0 or 1 and, when p is 1, is optionally substituted, Ar is aryl or heteroaryl, and each R is H, halogen; hydroxyl; trifiuoromethyl; linear and branched alkyl, alkenyl, alkynyl, and alkoxyl groups, all optionally further substituted by one or more of hydroxy groups, halogen atoms, alkoxy groups, amino groups, and alkylthio groups; linear and branched alkoxyl groups; linear and branched thioalkyl groups; aryl groups; aralkyl groups; aralkoxy groups; aryloxy groups; perfluoroalkyl; -CN; -NR4R5, -C(=X)NR4R5,-O-C(=X)NR4R5, -SO2NR4R5, - Alk-NR4R5, -NZC(=X)(NH)qR6, -Alk-NZC(=X)(NH)qR6, -C(=X)R6, -Alk-C(=X)(NH)qR6, -NHSO2R7, -SO2R7, -SOR7, -SR7, or is a saturated or unsaturated heterocyclyl group, and salts and esters thereof, are useful in the treatment of conditions susceptible to modulating ion channels, to a process for their preparation, their application by way of medicaments, and to pharmaceutical compositions containing them.
AZACYCLIC COMPOUNDS AS INHIBITORS OF SENSORY NEURONE SPECIFIC CHANNELS
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Page 50, (2010/02/10)
Compounds of the formula (I), and pharmaceutically acceptable salts thereof, are found to be antagonists of SNS sodium channels. They are therefore useful as analgesic and neuroprotective agents wherein: X is -N- or -CH-; n is from 0 to 3.
(Pyridylcyanomethyl)piperazines as orally active PAF antagonists
Carceller,Almansa,Merlos,Giral,Bartroli,Garcia-Rafanell,Forn
, p. 4118 - 4134 (2007/10/02)
A series of (pyridylcyanomethyl)piperazines was prepared and evaluated for PAF-antagonist activity. Compounds were tested in vitro in a PAF-induced platelet aggregation assay and in vivo in a PAF-induced hypotension test in normotensive rats. Oral activity was ascertained through a PAF-induced mortality test in mice. The main structure-activity trends of the series were established. Activity was mainly found in four skeletons: 1-acyl-4-(3- pyridylcyanomethyl)-piperazine, 1-acyl-4-(4-pyridylcyanomethyl)piperazine, 1- acyl-4-(3-pyridylcyanomethyl)piperidine, and 1-acyl-4-cyano-4-(3- pyridylamino)piperidine. The acyl substituents, diphenylacetyl and 3,3- diphenylpropionyl, provided the most active compounds, and the introduction of an amine or hydroxy group in the 3,3-diphenylpropionyl substituent led to further improvement in oral activity. As a result, three of the most active compounds (100, 114, and 115) have been selected for further pharmacological development.
(cyanomethyl)pyridines useful as PAF antagonists
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, (2008/06/13)
57 The present invention relates to new (cyanomethyl)pyridines of general formula I: wherein Ais nitrogen and Bis -CH-, or Bis nitrogen and Ais -CH-; the group Y-W-represents a group of formula N-CR1(CN)-, N-CH2-CH(CN)-, CH-CH(CN)- or C=C(CN)- wherein R1 is hydrogen or a C1-C6 alkyl group; Rrepresents a group of formula R2CO-,R3R4N-(CH2)nCO- or R5-(CH2)m- wherein R2 represents C1-C15 alkyl, aryl, aryl-(C1-C6)-alkyl, aryl-(C1-C6)-alkenyl, diaryl-(C1-C6)-alkyl, diaryl-(C1-C6)-alkenyl, arylhydroxy-(C1-C6)-alkyl, diarylhydroxy-(C1-C6)-alkyl, aryl-(C1-C6)-alkoxy, diaryl-(C1-C6)-alkoxy, or heteroaryl-(C1-C6)-alkyl group; n is 0, 1, 2 or 3; R3 is hydrogen, C1-C6 alkyl, aryl or aryl-(C1-C6)-alkyl group; R4 is C3-C6 cycloalkyl, aryl, aryl-(C1-C6)-alkyl, diaryl-(C1-C6)-alkyl, aryl-(C1-C6)-alkylcarbonyl or diaryl-(C1-C6)-alkylcarbonyl group; m is 0, 1 or 2; and R5 is aryl-(C1-C6)-alkyl, diaryl-(C1-C6)-alkyl, diaryl-(C1-C6)-alkylcarbonylamino or diaryl-(C1-C6)-alkylaminocarbonyl group. These compounds are potent, orally active PAF antagonists and consequently, useful in the treatment of the diseases in which this substance is involved.