- The discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine cannabinoid type 2 receptor agonist
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The development of selective CB2 receptor agonists is a promising therapeutic approach for the treatment of inflammatory diseases, without CB1 receptor mediated psychoactive side effects. Preliminary structure-activity relationship studies on pyrazoylidene benzamide agonists revealed the -ylidene benzamide moiety was crucial for functional activity at the CB2 receptor. A small library of compounds with varying linkage moieties between the pyrazole and substituted phenyl group has culminated in the discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine agonist 19 (CB2R EC50 = 19 nM, CB1R EC50 > 10 μM). Docking studies have revealed key structural features of the linkage group that are important for potent functional activity.
- Moir, Michael,Lane, Samuel,Montgomery, Andrew P.,Hibbs, David,Connor, Mark,Kassiou, Michael
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- 5-OXA-2-AZASPIRO[3.4]OCTANE DERIVATIVES AS M4 AGONISTS
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Provided herein are compounds according to Formula (I) or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R5, and R7 are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) as well as the use of such compounds as M4 receptor agonists.
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Page/Page column 136; 73
(2021/04/17)
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- 5-AMINO-8-(4-PYRIDYL)-[1,2,4]TRIAZOLO[4,3-C]PYRIMIDIN-3-ONE COMPOUNDS FOR USE AGAINST CANCER
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Described herein are triazalone compounds of Formula (I) and pharmaceutically acceptable salts thereof. Methods of making and using compounds of Formula (I) are also described. Compounds of Formula (I) and pharmaceutically acceptable salts thereof can be
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Page/Page column 65-66
(2021/10/02)
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- C-2 auxiliaries for stereoselective glycosylation based on common additive functional groups
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The stereoselective introduction of the glycosidic bond is one of the main challenges in chemical oligosaccharide synthesis. Stereoselective glycosylation can be achieved using neighbouring group participation of a C-2 auxiliary or using additives, for example. Both methods aim to generate a defined reactive intermediate that reacts in a stereoselective manner with alcohol nucleophiles. This inspired us to develop new C-2 auxiliaries based on commonly used additive functionalities such as ethers, phosphine oxides and tertiary amides. Good 1,2-trans-selectivity was observed for the phosphine oxide and amide-based auxiliaries expanding the toolbox with new auxiliaries for stereoselective glycosylation reactions.
- Boltje, Thomas J.,De Kleijne, Frank F. J.,Moons, Sam J.,White, Paul B.
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p. 1165 - 1184
(2020/02/22)
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- Anti-Selective Catalytic Asymmetric Nitroaldol Reaction of α-Keto Esters: Intriguing Solvent Effect, Flow Reaction, and Synthesis of Active Pharmaceutical Ingredients
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A rare-earth metal/alkali metal bimetallic catalyst proved particularly effective for enantioselectively coupling nitroalkanes and α-keto esters in an anti-selective manner to afford synthetically versatile, densely functionalized, and optically active α-nitro tertiary alcohols. A chiral diamide ligand captured two distinct metal cations, giving rise to a catalytically competent solid-phase heterobimetallic catalyst by simple mixing via self-assembly. The advantage of the solid-phase asymmetric catalyst was realized by successful application to the enantio- and diastereoselective reaction in a continuous-flow platform. The use of closely related solvents in terms of structures and polarity parameters, THF and its methylated congener 2-Me-THF, had an unexpectedly large solvent effect both on the reaction rate and the stereoselectivity. The nitroaldol products share a privileged unit for active pharmaceutical ingredients, as demonstrated by the streamlined enantioselective synthesis of the marketed antifungal agents efinaconazole and albaconazole.
- Karasawa, Tomoya,Oriez, Rapha?l,Kumagai, Naoya,Shibasaki, Masakatsu
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p. 12290 - 12295
(2018/09/27)
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- NOVEL DIHYDROPYRIDINONE AND DIHYDROPYRIMIDINONE COMPOUNDS AND THEIR USE
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The present invention is directed to novel compounds of Formula I; pharmaceutically acceptable salts or solvates thereof, and their use.
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- COMPOUNDS THAT INHIBIT MCL-1 PROTEIN
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Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.
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Page/Page column 1259; 1260
(2017/09/15)
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- 2-OXO-3,4-DIHYDROPYRIDINE-5-CARBOXYLATES AND THEIR USE
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The present invention is directed to novel compounds of Formula (I), pharmaceutically acceptable salts or solvates thereof, and their use.
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- 1,3-THIAZOL-2-YL SUBSTITUTED BENZAMIDES
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The present invention relates to 1,3-thiazol-2-yl substituted benzamide compounds of general formula (I) as described and defined herein, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neurogenic disorder, as a sole agent or in combination with other active ingredients.
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Page/Page column 256; 272
(2016/07/05)
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- Practical access to four stereoisomers of naftidrofuryl and their binding affinity towards 5-hydroxytryptamine 2A receptor
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Naftidrofuryl oxalate (Praxilene, 1) has been used for the treatment of intermittent claudication for more than 30 years. It selectively blocks vascular and platelet 5-hydroxytryptamine 2 (5-HT2) receptors. This drug is marketed as a mixture of four stereoisomers, and so far there is no individual biological evaluation on the single isomers. The purpose of this study is to provide an improved method for the preparation of all four stereoisomers of naftidrofuryl, and more importantly, to distinguish them in terms of their binding affinity to 5-hydroxytryptamine 2A (5-HT2A) receptor. The bioassay results revealed that the C-2S configuration of naftidrofuryl was crucial for the binding affinity with 5-HT2A receptor, and the C-2′ configuration was less important for binding. In conclusion, our study may pave the way to develop single naftidrofuryl isomers with C-2S configuration as inhibitors of 5-HT2A receptor that have clinical significance as vasodilators and CNS agents.
- Hao, Jia,Chen, Bo,Yao, Yiwu,Hossain, Murad,Nagatomo, Takafumi,Yao, Hequan,Kong, Lingyi,Sun, Hongbin
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supporting information; experimental part
p. 3441 - 3444
(2012/06/18)
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- Enantioselective haloetherification by asymmetric opening of meso -halonium ions
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A new approach to enantioselective haloetherification reactions via desymmetrization of in situ-generated meso-halonium ions is described. The combination of N-haloamides as a halogen source and sodium salts of chiral phosphoric acids as catalysts can be used for the cyclization of symmetrical ene-diol substrates, yielding the haloetherification products under practical conditions in enantioenriched form.(Figure Presented)
- Hennecke, Ulrich,Mueller, Christian H.,Froehlich, Roland
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supporting information; experimental part
p. 860 - 863
(2011/05/03)
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- NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS
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The present application relates to cannabinoid receptor ligands of formula (I) wherein X1, A1, Rx, R2, R3, R4, and z are as defined in the specification. The present application also relates to compositions comprising such compounds, and methods for treating conditions and disorders using such compounds and compositions.
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Page/Page column 36
(2010/04/23)
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- NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS
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Disclosed herein are cannabinoid receptor ligands of formula (I) wherein A1, A5, Rx, X4, and z are as defined in the specification. Compositions comprising such compounds, and methods for treating conditions and disorders using such compounds and compositions are also disclosed.
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Page/Page column 38
(2010/04/23)
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- COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS
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Disclosed herein are compounds of formula (I) wherein Ring A and R1 are as defined in the specification. Pharmaceutical compositions comprising such compounds, and methods for treating conditions and disorders using such compounds and pharmaceutical compositions are also disclosed.
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Page/Page column 30-31
(2010/10/19)
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- NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS
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The present invention relates compounds of formula (I) wherein A and R1 are as defined in the specification, pharmaceutical compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and pharmaceutical compositions.
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Page/Page column 24
(2009/05/29)
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- NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS AND USES THEREOF
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The present invention relates to compounds of formula (I), or pharmaceutical salts, prodrugs, salts of prodrugs, or combinations thereof, formula (I). wherein R1, R2, R3, R4, and L1 are defined in the specfication, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions. The present invention also relates to compounds of formula (II), or pharmaceutical salts, prodrugs, salts of prodrugs, or combinations thereof, formula (II). wherein R1a, R2a, Rx, and n are as defined in the specification, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions.
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Page/Page column 122; 142-143
(2009/06/27)
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- Pyrazole glucokinase activators
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Disclosed herein are pyrazole glucokinase activators of the formula (I) useful for the treatment of metabolic diseases and disorders, preferably diabetes mellitus.
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Page/Page column 75
(2008/06/13)
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- NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS AND USES THEREOF
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The present invention relates to compounds of formula (I), or pharmaceutical salts, prodrugs, salts of prodrugs, or combinations thereof, wherein R1, R2, R3, and L1 are defined in the specfication, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions. The present invention also relates to compounds of formula (II), or pharmaceutical salts, prodrugs, salts of prodrugs, or combinations thereof, wherein R1a, R2a and (Rx)n are as defined in the specification, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions.
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Page/Page column 48
(2008/06/13)
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- NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS
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The present application relates to thiazolylidene containing compounds of formula (I) wherein R1, R2, R3, R4, L2 and A are as defined in the specification. Compositions comprising such compounds, and methods for treating conditions and disorders using such compounds and compositions are also disclosed.
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Page/Page column 32
(2008/12/07)
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- NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS AND USES THEREOF
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The present invention relates to compounds of formula (I), or pharmaceutically acceptable salts, prodrugs, salts of prodrugs, or combinations thereof, wherein R1, R2, R3, R4, and L2, are defined in th
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Page/Page column 115
(2008/06/13)
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- Aspects of Control and Selectivity in Anion Mediated Cascade Reaction Sequences: Applications in Homochiral Synthesis.
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The transformation of the homochiral lactone 1 into the diols 3 and 6, the tetrahydrofurans 4 and 5 and a number of analogues thereof is described.
- Harrowven, David C.,Dennison, Shelagh T.,Hayward, Jonathan S.
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p. 7467 - 7468
(2007/10/02)
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