1293284-55-5Relevant articles and documents
The Quest for the Best Dual Orexin Receptor Antagonist (Daridorexant) for the Treatment of Insomnia Disorders
Boss, Christoph,Gatfield, John,Brotschi, Christine,Heidmann, Bibia,Sifferlen, Thierry,von Raumer, Markus,Schmidt, Gunther,Williams, Jodi T.,Treiber, Alexander,Roch, Catherine
, p. 2286 - 2305 (2020/10/30)
Since its discovery in 1998, the orexin system has been of interest to the research community as a potential therapeutic target for the treatment of sleep/wake disorders, stress and anxiety disorders, addiction or eating disorders. It consists of two G protein-coupled receptors, the orexin 1 and orexin 2 receptors, and two neuropeptides with agonistic effects, the orexin A and orexin B peptides. Herein we describe our efforts leading to the identification of a promising set of dual orexin receptor antagonists (DORAs) which subsequently went through physiology-based pharmacokinetic and pharmacodynamic modelling>[1] and finally led to the selection of daridorexant, currently in phase 3 clinical trials for the treatment of insomnia disorders.
Monoacylglycerol Lipase Modulators
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Paragraph 0410; 0539-0540; 0543-0544, (2020/04/24)
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.
Monoacylglycerol Lipase Modulators
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Paragraph 0371; 0486; 0550, (2020/04/24)
Fused 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 R1, R2, R2a, R3, R3a, R4, and R4a are defined herein.
Highly Selective Synthesis of 2-(2 H-1,2,3-Triazol-2-yl)benzoic Acids
Roth, Remo,Schmidt, Gunther,Prud'homme, Alice,Abele, Stefan
, p. 234 - 243 (2019/02/01)
A selective and scalable synthesis of 2-(2H-1,2,3-triazol-2-yl)benzoic acid starting from 1-fluoro-2-nitrobenzene derivatives is presented. The four-step synthesis introduces the triazole at the start via N2-arylation of 4,5-dibromo-2H-1,2,3-triazole. A sequence of consecutive functional group transformations, namely hydrogenation, Sandmeyer iodination, and Grignard carboxylation, provides the target molecules in a reliable and scalable manner. The usefulness of this method is demonstrated by the synthesis of di-or tri(2H-1,2,3-triazol-2-yl)benzene derivatives, which are difficult to produce by other methods.
Highly selective synthesis of 2-(2H-1,2,3-Triazol-2-yl)benzoic acids
Roth, Remo,Schmidt, Gunther,Prudhomme, Alice,Abele, Stefan
, p. 234 - 243 (2019/08/26)
A selective and scalable synthesis of 2-(2H-1,2,3-triazol-2-yl)benzoic acid starting from 1-fluoro-2-nitrobenzene derivatives is presented. The four-step synthesis introduces the triazole at the start via N2-arylation of 4,5-dibromo-2H-1,2,3- triazole. A sequence of consecutive functional group transformations, namely hydrogenation, Sandmeyer iodination, and Grignard carboxylation, provides the target molecules in a reliable and scalable manner. The usefulness of this method is demonstrated by the synthesis of di- or tri(2H-1,2,3-triazol-2-yl)benzene derivatives, which are difficult to produce by other methods.
PREPARATION OF 2-([1,2,3]TRIAZOL-2-YL)-BENZOIC ACID DERIVATIVES
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, (2018/11/26)
The present invention relates to a process for the preparation of particular 2-(2H-[1,2,3]triazol-2-yl)-benzoic acid derivatives of formula (I), to certain crystalline forms of potassium salts of said 2-(2H-[1,2,3]triazol-2-yl)-benzoic acid derivatives of formula (IK), to certain crystalline forms of said 2-(2H-[1,2,3]triazol-2-yl)-benzoic acid derivatives of formula (I), and to their use in the preparation of pharmaceuticals such as (S)-(2-(5-chloro-4-methyl-1H-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl)-(5-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone.
USE OF BENZIMIDAZOLE-PROLINE DERIVATIVES
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Page/Page column 16; 17, (2015/06/18)
The present invention relates to compounds of the formula (I), wherein Ar1 and Ar2 are as described in the description and to their use as pharmaceuticals for the treatment of sundown syndrome. The invention also relates to the preparation of such compounds and of pharmaceutically acceptable salts thereof.
CRYSTALLINE SALT FORM OF (S)-(2-(6-CHLORO-7-METHYL-1 H-BENZO[D]IMIDAZOL-2-YL)-2-METHYLPYRROLIDIN-1 -YL)(5-METHOXY-2-(2H-1,2,3-TRIAZOL-2-YL)PHENYL)METHANONE AS OREXIN RECEPTOR ANTAGONIST
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Page/Page column 19; 20, (2015/06/18)
The invention relates to a crystalline form of (S)-(2-(6-chloro-7-methyl-1 H-benzo[d]imidazol- 2-yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone hydrochloride, processes for the preparation thereof, pharmaceutical compositions containing said crystalline form, and its use as medicament, especially as orexin receptor antagonist.
Novel Octahydropyrrolo[3,4- c ]pyrroles Are Selective Orexin-2 Antagonists: SAR Leading to a Clinical Candidate
Letavic, Michael A.,Bonaventure, Pascal,Carruthers, Nicholas I.,Dugovic, Christine,Koudriakova, Tatiana,Lord, Brian,Lovenberg, Timothy W.,Ly, Kiev S.,Mani, Neelakandha S.,Nepomuceno, Diane,Pippel, Daniel J.,Rizzolio, Michele,Shelton, Jonathan E.,Shah, Chandra R.,Shireman, Brock T.,Young, Lana K.,Yun, Sujin
, p. 5620 - 5636 (2015/08/03)
The preclinical characterization of novel octahydropyrrolo[3,4-c]pyrroles that are potent and selective orexin-2 antagonists is described. Optimization of physicochemical and DMPK properties led to the discovery of compounds with tissue distribution and d
CRYSTALLINE FORM OF (S)-(2-(6-CHLORO-7-METHYL-1H-BENZO[D]IMIDAZOL-2-YL)-2-METHYLPYRROLIDIN-1 -YL)(5-METHOXY-2-(2H-1,2,3-TRIAZOL-2-YL)PHENYL)METHANONE AND ITS USE AS OREXIN RECEPTOR ANTAGONISTS
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Page/Page column 23, (2015/06/18)
The invention relates to crystalline forms of (S)-(2-(6-chloro-7-methyl-1H-benzo[d]imidazol-2- yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone, processes for the preparation thereof, pharmaceutical compositions containing such crystalline forms, pharmaceutical compositions prepared from such crystalline forms, and their use as a medicament, especially as orexin receptor antagonists.
