- Monoacylglycerol Lipase Modulators
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Bridged compounds of Formula (I) and Formula (II), pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions associated with MGL modulation, such as those associated with pain, psychiatric disorders, neurological disorders (including, but not limited to major depressive disorder, treatment resistant depression, anxious depression, bipolar disorder), cancers and eye conditions. wherein R2, R3 R4, R5 and R6 are defined herein.
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Paragraph 0410; 0576
(2020/04/24)
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- The 1,2,4-Triazolo[4,3-a]pyrazin-3-one as a Versatile Scaffold for the Design of Potent Adenosine Human Receptor Antagonists. Structural Investigations to Target the A2A Receptor Subtype
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In this work, we describe the identification of the 1,2,4-triazolo[4,3-a]pyrazin-3-one as a new versatile scaffold for the development of adenosine human (h) receptor antagonists. The new chemotype ensued from a molecular simplification approach applied to our previously reported 1,2,4-triazolo[4,3-a]quinoxalin-1-one series. Hence, a set of novel 8-amino-2-aryl-1,2,4-triazolopyrazin-3-one derivatives, featured by different substituents on the 2-phenyl ring (R) and at position 6 (R6), was synthesized with the main purpose of targeting the hA2A adenosine receptor (AR). Several compounds possessed nanomolar affinity for the hA2A AR (Ki = 2.9-10 nM) and some, very interestingly, also showed high selectivity for the target. One selected potent hA2A AR antagonist (12, R = H, R6 = 4-methoxyphenyl) demonstrated some ability to counteract MPP+-induced neurotoxicity in cultured human neuroblastoma SH-SY5Y cells, a widely used in vitro Parkinson's disease model. Docking studies at hAR structures were performed to rationalize the observed affinity data.
- Falsini, Matteo,Squarcialupi, Lucia,Catarzi, Daniela,Varano, Flavia,Betti, Marco,Dal Ben, Diego,Marucci, Gabriella,Buccioni, Michela,Volpini, Rosaria,De Vita, Teresa,Cavalli, Andrea,Colotta, Vittoria
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p. 5772 - 5790
(2017/07/22)
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- Facile, diversity-orientated one-pot synthesis of ethyl 1,5-disubstituted-1H-1,2,4-triazole-3-carboxylates
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Access to the 1,5-disubstituted-1H-1,2,4-triazole-3-carboxamide motif is quite laborious and requires forcing conditions to effect the cyclocondensation step. Herein, we report an efficient and mild one-pot protocol to access this substructure in good che
- Degorce, Sébastien,Delouvrié, Bénédicte,Davey, Paul R.J.,Didelot, Myriam,Germain, Hervé,Harris, Craig S.,Brempt, Christine Lambert-Van Der,Lebraud, Honorine,Ouvry, Gilles
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supporting information
p. 6078 - 6082
(2012/11/07)
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- NOVEL THERAPEUTIC COMPOUNDS
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Disclosed herein are novel compounds of Formula (I), wherein the variables are defined as herein. The compounds of Formula (I) are useful as kinase inhibitors and as such would be useful in treating certain conditions and diseases, especially inflammatory conditions and diseases as well as proliferative disorders such as cancer.
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Page/Page column 57
(2009/03/07)
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- Diheteroarylmethanes. 8.1 Mapping charge and electron-withdrawing power of the 1,2,4-triazol-5-yl substituent
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Three new triazolyl derivatives, bis(1H-1-phenyl-1,2,4-triazol-5- yl)methane (11), 1H-1-phenyl-5-(β-styryl)-1,2,4-triazole (12), and 1H-5- benzyl-1-phenyl-1,2,4-triazole (13) have been synthesized and the carbanions 11- and 13- investigated in DMSO by multinuclear NMR spectroscopy. By applying previously proposed and widely used π-charge/13C shift relationships on the spectra of the anions, it is possible to rank the π electron-withdrawing power of the 1,2,4-triazol-5-yl group in terms of charge demand c(X), a quantity that represents the fraction of π negative charge delocalized by the heterocyclic ring. Our results indicate that the charge demand c(X) of this heterocycle is considerably greater than that of other 1,3-azoles (2-imidazolyl, 2-oxazolyl, 2-benzoimidazolyl), being close to that of some mono- and diazinyl substituents. A single set of resonances is presented by both carbanions 11- and 13-, thus showing that they exist either as a single geometric isomer species or as a mixture of isomers in a rapid (on the NMR time scale) equilibrium, 13C and 15N shift/π-charge relationships allow accurate π-charge mapping of carbanionic systems. Our results clearly show that, in the case of benzyl carbanion 13-, all of the three nitrogen atoms are almost equally involved in delocalizing the negative charge. Also, the N-phenyl group contributes to charge delocalization. Anion 11- is the first of the bis(heteroaryl)methyl carbanions that we have studied, in which all of the negative charge originated by deprotonation of the carbon acid 11 is hosted on the nitrogen atoms without any appreciable involvement of the heteroaromatic carbon frame.
- Abbotto, Alessandro,Bradamante, Silvia,Facchetti, Antonio,Pagani, Giorgio A.
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p. 6756 - 6763
(2007/10/03)
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- sym-TRIAZINE DERIVATIVES. 8. STRUCTURE AND FURTHER REACTIONS OF PRODUCTS FORMED IN THE REACTION OF 2,4,6-TRIETHOXYCARBONYL-sym-TRIAZINE WITH ARYLHYDRAZINES
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It has been demonstrated, based on detailed spectral analysis and chemical reaction studies, that the products of the reactions of arylhydrazines or semicarbazide with 2,4,6-triethoxycarbonyl-sym-triazine are 1,2,4-triazine derivatives.
- Alekseeva, N. V.,Turchin, K. F.,Anisimova, O. S.,Sheinker, Yu. N.,Yakhontov, L. N.
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p. 1280 - 1288
(2007/10/02)
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