- Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation of 1,4-Diazepan-5-ones
-
We report the palladium-catalyzed asymmetric allylic alkylation of 1,4-diazepan-5-ones. This reaction proceeds smoothly to give gem-disubstituted diazepanone heterocycles bearing various functional groups in up to >99% yield and up to 95% ee. An electron-
- Sercel, Zachary P.,Sun, Alexander W.,Stoltz, Brian M.
-
-
Read Online
- Discovery of ORN0829, a potent dual orexin 1/2 receptor antagonist for the treatment of insomnia
-
Here, we present the design, synthesis, and SAR of dual orexin 1 and 2 receptor antagonists, which were optimized by balancing the antagonistic activity for orexin receptors and lipophilicity. Based on the prototype compound 1, ring construction and the i
- Aoki, Takeshi,Futamura, Aya,Hino, Noriko,Hiyoshi, Tetsuaki,Kambe, Daiji,Kawamoto, Hiroshi,Kirinuki, Sora,Nozawa, Dai,Ohmichi, Mari,Suzuki, Ryo,Tamura, Yunoshin,Tokumaru, Yuichi
-
-
Read Online
- METHOD FOR PRODUCING (2S)-2-[(1H-PYRAZOL-1-YL)METHYL]-1,3-OXAZINANE DERIVATIVE
-
Provided is a novel process for producing a (2S)-2-[(1H-pyrazol-1-yl)methyl]-1,3-oxazinane derivative. More specifically, provided is a process for producing a (2S)-2-[(1H-pyrazol-1-yl)methyl]-1,3-oxazinane derivative represented by formula (1): the process comprising reacting 3-aminopropan-1-ol with glyoxylic acid.
- -
-
Paragraph 0270-0274
(2021/05/21)
-
- The Quest for the Best Dual Orexin Receptor Antagonist (Daridorexant) for the Treatment of Insomnia Disorders
-
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.
- Boss, Christoph,Gatfield, John,Brotschi, Christine,Heidmann, Bibia,Sifferlen, Thierry,von Raumer, Markus,Schmidt, Gunther,Williams, Jodi T.,Treiber, Alexander,Roch, Catherine
-
supporting information
p. 2286 - 2305
(2020/10/30)
-
- Octahydropyrrolo[3,4-c]pyrrole derivative and application method and application thereof
-
The invention relates to an octahydropyrrolo[3,4-c]pyrrole derivative and an application method and application thereof. The compound and a pharmaceutical composition containing the compound are usedfor antagonizing orexin receptors. The invention also re
- -
-
-
- Octahydropyrrolo[3,4-c]pyrrole derivatives and use thereof
-
The invention relates to octahydropyrrolo[3,4-c]pyrrole derivatives and a use thereof. The above compounds and a medicinal composition containing the compounds are used for suppressing an orexin receptor. The invention also relates to a method for preparing the compounds and the medicinal composition, and the use of the compounds and the medicinal composition in the treatment or prevention of orexin receptor related diseases.
- -
-
-
- SUBSTITUTED QUINAZOLINE COMPOUNDS AND PREPARATION AND USES THEREOF
-
The present invention relates quinazolinone compounds of Formula (I), as well as their preparation and uses, and further relates pharmaceutical compositions comprising these compounds and their uses; wherein the compounds or pharmaceutical compositions disclosed herein can be used for antagonizing the orexin receptor. The present invention also relates to uses of the compounds or pharmaceutical compositions in treating or preventing neurological and psychiatric disorders and diseases of the central nervous system in mammals, especially in humans.
- -
-
-
- OCTAHYDROPYRROLO [3, 4-c] PYRROLE DERIVATIVES AND USES THEREOF
-
The invention relates to octahydropyrrolo [3, 4-c] pyrrole derivatives and uses thereof. Compounds and pharmaceutical compositions comprising the compounds provided herein are used for antagonizing orexin receptors. The invention also relates to processes for preparing the compounds and pharmaceutical compositions, and uses thereof in treating or preventing a disease related to orexin receptors.
- -
-
-
- Indole derivative and uses thereof
-
The present invention relates to an indole derivative and uses thereof, wherein the compound and the pharmaceutical composition comprising the compound can be used for antagonizing orexin receptors. The present invention further relates to a method for preparing the compound and the pharmaceutical composition, and uses of the compound and the pharmaceutical composition in treatment or prevention of diseases associated with orexin receptors.
- -
-
-
- Method for preparing N-heterocyclic compound
-
The invention provides a method for preparing an N-heterocyclic compound and belongs to the technical field of pharmacy. The method for preparing the N-heterocyclic compound comprises the steps of carrying out condensation reaction on an N-heterocyclic intermediate compound and 2-ethoxy-5-chlorobenzoxazole under an acid condition, and carrying out aftertreatment to prepare the compound (1). The method is simple and convenient, and can be applied to industrial production.
- -
-
Paragraph 0052; 0054
(2017/11/18)
-
- Substituted heterocyclic compound, and use method and use thereof
-
The invention relates to a substituted heterocyclic compound, and a use method and a use thereof. The substituted heterocyclic compound and a medicinal composition including the compound can be used to depress orexin receptors, especially an orexin-1 rece
- -
-
-
- Substituted heterocyclic compound, preparation method and uses thereof
-
The present invention relates to a substituted heterocyclic compound, a preparation method and uses thereof, further to a pharmaceutical composition containing the heterocyclic compound and uses thereof, wherein the compound or pharmaceutical composition
- -
-
-
- Octahydropyrrole[3, 4-c]pyrrole derivative and using method and application thereof
-
The invention relates to an ctahydropyrrole[3, 4-c]pyrrole derivative and a using method and application thereof. A compound and a drug composition containing the same are used for resisting orexin receptors. The invention further relates to methods of pr
- -
-
-
- PROCESS FOR THE RESOLUTION OF (R,S)-DIAZEPANE AND DIAZEPANONE DERIVATIVES
-
The present invention relates to a process for the preparation of an acid salt (T) of a compound of formula (A) (A) as well as to the acid salt (T) and the compound (A) as such,wherein R1 is selected from the group consisting of H, PG1 and RA, with RA being or and wherein PG1 is a suitable protecting group, and wherein n is 0 or 1, wherein the acid salt (T) is the salt of one stereoisomer of a chiral acid, preferably wherein the chiral acid salt is a tartaric acid derivative salt, preferably wherein the tartaric acid derivative salt is selected from the group consisting of 2,3-ditoluoyl tartaric acid salt, 2,3-dibenzoyl tartaric acid salt, 2,3-dianisoyl tartaric acid salt, 2,3-dibenzoyl tartaric acid mono(dimethylamide) salt and a mixture of two or more thereof. Further the present invention relates to use of (T) and/or (A) for the preparation of suvorexant.
- -
-
Page/Page column 75
(2016/04/05)
-
- NOVEL ROUTES OF SYNTHESIS FOR THE PREPARATION OF SUVOREXANT
-
The present invention relates to a process for the preparation of a compound of formula (A), Further, the present invention relates to the respective compound (A) as such and to its use in the preparation of antifungal agent.
- -
-
Paragraph 128
(2016/04/26)
-
- PROCESS FOR THE PREPARATION OF SUVOREXANT AND INTERMEDIATES USEFUL IN THE SYNTHESIS OF SUVOREXANT
-
A novel processes for the preparation of suvorexant (formula I), its related compounds and its intermediates that are simple, economical and commercially viable. (I)
- -
-
Paragraph 0130-0131
(2016/07/05)
-
- Preparation method of chiral high piperazine ring compound
-
The present invention relates to a preparation method of a chiral high piperazine ring compound shown in (R)-I, and the method includes reduction of a compound shown in a formula Int to obtain the compound shown in the formula (R)-I. The invention also relates to a novel intermediate compound shown in the formula Int. The chiral high piperazine ring compound shown in (R)-I is an important intermediate in the synthesis of a medicament Suvorexant for the treatment of sleep disorders. The preparation method introduces a chiral center from the starting material, does not employ reagent or reaction affecting the chiral center in the whole reaction process, and avoids the chiral resolution or chiral catalyst method, which has high cost but low yield; no reaction of chiral participation exists in the process, so as to ensure the purity of the chiral product; and the method uses only the conventional methods and equipment, has the advantages of simple operation, mild condition, short route and high yield, and is applicable to industrialized production.
- -
-
Paragraph 0170
(2016/10/08)
-
- Method for preparing 5-chlorine-2[5-(R)-methyl-1,4-diazacycloheptyl-1-] benzoxazole
-
The invention relates to a method for preparing 5-chlorine-2[5-(R)-methyl-1,4-diazacycloheptyl-1-] benzoxazole. The method includes the step of reducing a compound in the formula I (please see the formula in the specification). The invention further relates to a new midbody compound shown in the formula I. 5-chlorine-2[5-(R)-methyl-1,4-diazacycloheptyl-1-] benzoxazole is an important midbody for synthesizing medicine Suvorexant treating sleep disorders. According to the preparation method, initial materials are introduced into a chiral center, in the whole reaction process, reactions and reagents influencing the chiral center are not adopted, the chiral separation or chiral catalystic method which is high in cost and low in yield is avoided, chiral interference reactions do not exist in the technological process, chiral purity of products is guaranteed, only conventional methods and equipment are used, operation is easy, conditions are moderate, lines are short, the yield is high, and the method is suitable for industrial production.
- -
-
Paragraph 0164; 0165; 0166; 0167
(2016/10/09)
-
- Discovery and in vitro and in vivo profiles of N-ethyl-N-[2-[3-(5-fluoro-2-pyridinyl)-1H-pyrazol-1-yl]ethyl]-2-(2H-1,2,3-triazol-2-yl)-benzamide as a novel class of dual orexin receptor antagonist
-
Orexins play an important role in sleep/wake regulation, and orexin receptor antagonists are a focus of novel therapy for the treatment of insomnia. We identified 27e (TASP0428980) as a potent dual orexin receptor antagonist through the systematic modification of our original designed lead A. We demonstrated the potent sleep-promoting effects of 27e at ip dose of 3 mg/kg in a rat polysomnogram study. 27e exhibited relatively short half-life profiles in rats and dogs. Furthermore, accumulating evidence regarding ADME profiles indicates that the predicted human half-life of 27e should be 1.2-1.4 h. These data indicated that 27e has a short-acting hypnotic property, suggesting that 27e might be useful for treating primary insomnia while exhibiting a low risk of next-day residual somnolence. Thus, 27e and its related compounds should be further evaluated to enable advancement to clinical trials.
- Suzuki, Ryo,Nozawa, Dai,Futamura, Aya,Nishikawa-Shimono, Rie,Abe, Masahito,Hattori, Nobutaka,Ohta, Hiroshi,Araki, Yuko,Kambe, Daiji,Ohmichi, Mari,Tokura, Seiken,Aoki, Takeshi,Ohtake, Norikazu,Kawamoto, Hiroshi
-
p. 1260 - 1275
(2015/03/04)
-
- 2,5-DISUBSTITUTED THIOMORPHOLINE OREXIN RECEPTOR ANTAGONISTS
-
The present invention is directed to 2,5-disubstituted thiomorpholine amide compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the 2,5-disubstituted thiomorpholine amide compounds described herein in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
- -
-
-
- PIPERIDINYL ALKYNE OREXIN RECEPTOR ANTAGONISTS
-
The present invention is directed to piperidinyl alkyne compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the piperidinyl alkyne compounds described herein in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
- -
-
Page/Page column 43
(2013/05/21)
-
- Enantioselective synthesis of a dual orexin receptor antagonist
-
A concise, enantioselective synthesis of the potent dual orexin inhibitor suvorexant (1) is reported. Key features of the synthesis include a mild copper-catalyzed amination, a highly chemoselective conjugate addition, and a tandem enantioselective transamination/seven-membered ring annulation. The synthesis requires inexpensive starting materials and only four linear steps for completion.
- Mangion, Ian K.,Sherry, Benjamin D.,Yin, Jingjun,Fleitz, Fred J.
-
p. 3458 - 3461
(2012/08/08)
-
- 2,5-DISUBSTITUTED PIPERIDINE OREXIN RECEPTOR ANTAGONISTS
-
The present invention is directed to 2,5-disubstituted piperidine amide compounds which are antagonists of orexin receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
- -
-
Page/Page column 38
(2010/05/13)
-
- 2,3-DISUBSTITUTED PIPERIDINE OREXIN RECEPTOR ANTAGONISTS
-
The present invention is directed to 2,3-disubstituted piperidine amide compounds which are antagonists of orexin receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin recepto
- -
-
Page/Page column 33
(2010/05/13)
-
- AMIDOETHYL ALKYLAMINO OREXIN RECEPTOR ANTAGONISTS
-
The present invention is directed to amidoethylamine compounds which are antagonists of orexin receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
- -
-
-
- PYRIDYL PIPERIDINE OREXIN RECEPTOR ANTAGONISTS
-
The present invention is. directed to pyridyl piperidine compounds of formula (I) which are antagonists of orexin receptors, and which are useful' in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
- -
-
-