- Monoacylglycerol Lipase Modulators
-
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.
- -
-
Paragraph 0410; 0539-0540; 0613-0614
(2020/04/24)
-
- From Oxadiazole to Triazole Analogues: Optimization toward a Dual Orexin Receptor Antagonist with Improved in vivo Efficacy in Dogs
-
The orexin system is responsible for regulating the sleep-wake cycle. Suvorexant, a dual orexin receptor antagonist (DORA) is approved by the FDA for the treatment of insomnia disorders. Herein, we report the optimization efforts toward a DORA, where our starting point was (5-methoxy-4-methyl-2-[1,2,3]triazol-2-yl-phenyl)-{(S)-2-[5-(2-trifluoromethoxy-phenyl)-[1,2,4]oxadiazol-3-yl]-pyrrolidin-1-yl}methanone (6), a compound which emerged from our in-house research program. Compound 6 was shown to be a potent, brain-penetrating DORA with in vivo efficacy similar to suvorexant in rats. However, shortcomings from low metabolic stability, high plasma protein binding (PPB), low brain free fraction (fu brain), and low aqueous solubility, were identified and hence, compound 6 was not an ideal candidate for further development. Our optimization efforts addressing the above-mentioned shortcomings resulted in the identification of (4-chloro-2-[1,2,3]triazol-2-yl-phenyl)-{(S)-2-methyl-2-[5-(2-trifluoromethoxy-phenyl)-4H-[1,2,4]triazol-3-yl]-pyrrolidin-1-yl}l-methanone (42), a DORA with improved in vivo efficacy compared to 6.
- Bolli, Martin H.,Boss, Christoph,Brotschi, Christine,Gatfield, John,Heidmann, Bibia,Jenck, Francois,Roch, Catherine,Sifferlen, Thierry,Treiber, Alexander,Williams, Jodi T.
-
supporting information
(2020/01/25)
-
- SUBSTITUTED 2-AZABICYCLO[3.1.1]HEPTANE AND 2-AZABICYCLO[3.2.1]OCTANE DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS
-
There is provided a compound of formula (I), wherein L1 to L3, R1 to R4, X, A and B have meanings given in the description, and pharmaceutically acceptable salts, solvates and prodrugs thereof, which compounds are useful as antagonists of the orexin-1 and orexin-2 receptors or as selective antagonists of the orexin-1 receptor, and thus, in particular, in the treatment or prevention of inter alia substance dependence, addiction, anxiety disorders, panic disorders, binge eating, compulsive disorders, impulse control disorders, cognitive impairment and Alzheimer's disease.
- -
-
Page/Page column 90-91
(2019/03/17)
-
- Highly Selective Synthesis of 2-(2 H-1,2,3-Triazol-2-yl)benzoic Acids
-
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.
- Roth, Remo,Schmidt, Gunther,Prud'homme, Alice,Abele, Stefan
-
p. 234 - 243
(2019/02/01)
-
- Highly selective synthesis of 2-(2H-1,2,3-Triazol-2-yl)benzoic acids
-
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.
- Roth, Remo,Schmidt, Gunther,Prudhomme, Alice,Abele, Stefan
-
p. 234 - 243
(2019/08/26)
-
- A method of preparing intermediates of su wolei lives (by machine translation)
-
The invention discloses a method for the preparation of su wolei lives, comprises the following steps: to trace cuprous iodide as a catalyst, in order to water-free potassium carbonate as the alkali and three types of solvent acetone as solvent, 2 - iodo - 5 methyl benzoic acid and 1, 2, 3 - triazole generating Ullman reaction, after an ethanol and water mixed solvent can be refined to obtain high-purity of intermediates su wolei lives. Preparation method of the invention, make full use of the atom economic theory, easy operation, low cost, pollution-free. For large scale industrial production; and by only one refining, chromatographic purity can be up to 99.8% or more, isomer is less than 0.1%, the yield is 90% or more. (by machine translation)
- -
-
Paragraph 0027-0041
(2019/06/08)
-
- Oxadiazole Derivatives as Dual Orexin Receptor Antagonists: Synthesis, Structure–Activity Relationships, and Sleep-Promoting Properties in Rats
-
The orexin system plays an important role in the regulation of wakefulness. Suvorexant, a dual orexin receptor antagonist (DORA) is approved for the treatment of primary insomnia. Herein, we outline our optimization efforts toward a novel DORA. We started our investigation with rac-[3-(5-chloro-benzooxazol-2-ylamino)piperidin-1-yl]-(5-methyl-2-[1,2,3]triazol-2-ylphenyl)methanone (3), a structural hybrid of suvorexant and a piperidine-containing DORA. During the optimization, we resolved liabilities such as chemical instability, CYP3A4 inhibition, and low brain penetration potential. Furthermore, structural modification of the piperidine scaffold was essential to improve potency at the orexin 2 receptor. This work led to the identification of (5-methoxy-4-methyl-2-[1,2,3]triazol-2-ylphenyl)-{(S)-2-[5-(2-trifluoromethoxyphenyl)-[1,2,4]oxadiazol-3-yl]pyrrolidin-1-yl}methanone (51), a potent, brain-penetrating DORA with in vivo efficacy similar to that of suvorexant in rats.
- Brotschi, Christine,Roch, Catherine,Gatfield, John,Treiber, Alexander,Williams, Jodi T.,Sifferlen, Thierry,Heidmann, Bibia,Jenck, Francois,Bolli, Martin H.,Boss, Christoph
-
supporting information
p. 1257 - 1270
(2019/06/17)
-
- PREPARATION OF 2-([1,2,3]TRIAZOL-2-YL)-BENZOIC ACID DERIVATIVES
-
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.
- -
-
Page/Page column 31-32
(2018/11/26)
-
- Synthesis method of 5-methyl-2-(2H-1,2,3-triazole-2-yl) benzoic acid
-
The invention relates to a synthesis method of 5-methyl-2-(2H-1,2,3-triazole-2-yl) benzoic acid. Specifically, the method comprises the following steps: (1) performing a reaction on a raw material 2-(4-methylphenyl)-2H-[1,2,3]-triazole and azodicarboxylate for 5-20 hours in an organic solvent with a palladium catalyst, an antioxidant copper salt and an acid additive in a 80-120 DEG C sealed tube,separating to prepare a compound I; and (2) adding the compound I into a mixed solution of alkali and a polar organic solvent to react, adjusting pH of the mixed solution to 1, extracting, drying, andthen performing chromatography and separation by using a silica column so as to obtain the 5-methyl-2-(2H-1,2,3-triazole-2-yl) benzoic acid. Compared with the prior art, the synthesis method is easyto operate, has mild conditions, uses non-expensive, low-toxic raw materials, and has high yield. An ester base is introduced to the 2 site of 2-(4-methylphenyl)-2H-[1,2,3]-triazole benzene ring in one step through a C-H activation method, and the target product is obtained through simple hydrolyzation, so that the reaction process is shortened greatly, the prepared product has high purity, has noisomer, and has great application prospect.
- -
-
Paragraph 0040
(2018/03/26)
-
- Rhodium-Catalyzed ortho-Cyanation of 2-Aryl-1,2,3-triazole: An Alternative Approach to Suvorexant
-
A rhodium-catalyzed ortho-cyanation protocol for 2-aryl-1,2,3-triazole has been developed by using N-cyano-N-phenyl-p-toluensulfonamide (NCTS) as an environmentally friendly cyanide source. This simple cyanation reaction provides a new protocol for the diversification of benzonitriles in moderate to good yields and tolerates useful functional groups. In addition, the method was used to synthesize 5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid, which is the key intermediate of suvorexant.
- Zhang, Hailong,Jing, Li,Zheng, Yang,Sang, Rui,Zhao, Yi,Wang, Qiantao,Wu, Yong
-
supporting information
p. 723 - 729
(2018/02/21)
-
- Method for synthesizing 5-methyl-2-(2H-1,2,3-triazole) benzoic acid
-
The invention relates to synthesis of 5-methyl-2-(2H-1,2,3-triazole) benzoic acid and belongs to the field of organic chemistry. 2-(4-methyl phenyl)-2H-[1,2,3]-triazole serves as a raw material and undergoes tube sealing reaction at 150 DEG C for 48 h with N-cyano-N phenyl para toluene sulfonamide (NCTS) in an organic solvent in which a rhodium catalyst, a silver salt oxidizing agent and an acetate additive are added, and separation is performed, to obtain a compound I; the compound I undergoes heating reflux for 12 h in an alkaline solution, reaction liquid cools to room temperature and the pH is adjusted to 4-5, and a target compound II is obtained after extraction, drying and spin-drying. Compared with the prior art, a method for synthesis of 5-methyl-2-(2H-1,2,3-triazole) benzoic acidis simple to operate, the raw materials are economical, low in toxicity and high in yield; through one step in a C-H activation method, cyano groups are introduced at the second position of 2-(4-methyl phenyl)-2H-[1,2,3]-triazole benzene ring, and 5-methyl-2-(2H-1,2,3-triazole) benzoic acid is obtained by hydrolytic acidification. A reaction path is shortened, and the prepared product is high in purity, has no isomer and has a great application prospect.
- -
-
Paragraph 0021; 0023; 0025; 0027; 0029; 0031; 0033
(2018/03/26)
-
- Rhodium-Catalyzed Direct C-H Bond Cyanation in Ionic Liquids
-
A Cp?Rh(III)/IL-based direct C-H bond cyanation system was developed for the first time. The system is a mild, efficient, and recyclable method for the synthesis of aryl nitriles. Many different directing groups can be used in this cyanation, and the reaction tolerates a variety of functional groups.
- Lv, Songyang,Li, Yaling,Yao, Tian,Yu, Xinling,Zhang, Chen,Hai, Li,Wu, Yong
-
supporting information
p. 4994 - 4997
(2018/08/24)
-
- 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
- -
-
Paragraph 0183-0187
(2018/03/24)
-
- 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.
- -
-
Paragraph 0193-0198
(2020/02/06)
-
- One of the acid of preparation method
-
The invention relates to an acid preparation method, belonging to the technical field of pharmacy. The preparation method comprises the following steps: a crude product reacts with an alkali in a ketone solvent and then reacts with an acid to obtain an ac
- -
-
Paragraph 0037; 0038
(2018/02/22)
-
- Identification of ortho-Substituted Benzoic Acid/Ester Derivatives via the Gas-Phase Neighboring Group Participation Effect in (+)-ESI High Resolution Mass Spectrometry
-
Benzoic acid/ester/amide derivatives are common moieties in pharmaceutical compounds and present a challenge in positional isomer identification by traditional tandem mass spectrometric analysis. A method is presented for exploiting the gas-phase neighbor
- Blincoe, William D.,Rodriguez-Granillo, Agustina,Saurí, Josep,Pierson, Nicholas A.,Joyce, Leo A.,Mangion, Ian,Sheng, Huaming
-
p. 694 - 703
(2018/04/14)
-
- Substituted aryl heteroaryl compound and application thereof
-
The invention relates to a substituted aryl heteroaryl compound and application thereof, and further relates to a pharmaceutical composition containing the substituted aryl heteroaryl compound and application thereof. The compound or the pharmaceutical co
- -
-
Paragraph 0236-0239
(2017/08/18)
-
- 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.
- -
-
Paragraph 00182
(2017/07/04)
-
- A triazole compound of preparation method
-
The invention provides a preparation method of a triazoie compound and belongs to the technical field of pharmaceutical manufacturing. The preparation method comprises the following steps: a raw material reacts in a ketone reaction solvent at a solvent re
- -
-
Paragraph 0011; 0032-0037; 0038; 0039; 0040-0041
(2017/08/25)
-
- 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.
- -
-
Page/Page column 53
(2017/03/08)
-
- 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.
- -
-
Paragraph 0185; 0186
(2017/09/01)
-
- METHYL OXAZOLE OREXIN RECEPTOR ANTAGONISTS
-
The present invention is directed to methyl oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.
- -
-
-
- PREPARATION OF A BENZOIC ACID DERIVATIVE AND ITS USE FOR THE PREPARATION OF SUVOREXANT
-
The present invention relates to a process for the preparation of a compound of formula (1) wherein the process is based on the use of an organolithium reagent and wherein Ra, Rb, Rc and Rd are, independently of each other, selected from the group consisting of H, alkyl, aryl, cycloalkyl, heteroalkyl, heteroaryl, heterocycloalkyl, halogen, carbonyl, alkoxy, hydroxyl, -NR6R7, -SR and -NO2, wherein R6 and R7 are, independently of each other, selected from the group consisting of H, alkyl, aryl, cycloalkyl, heteroalkyl, heteroaryl and heterocycloalkyl, and wherein E is an electrophilic group. The present invention further relates as to a compound obtained or obtainable by said method and to a compound of formula (1) as such. Further, the present invention relates to use of the compound of formula (1) for the preparation of Suvorexant.
- -
-
Page/Page column 91
(2016/04/04)
-
- 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
- -
-
Paragraph 0238; 0239; 0240; 0241; 0242
(2017/04/19)
-
- 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
- -
-
Paragraph 0239; 0240; 0241; 0242
(2016/10/08)
-
- 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
- -
-
Paragraph 0179; 0193; 0194
(2018/02/04)
-
- Process for the preparation of an intermediate for an orexin receptor antagonist
-
The present invention is directed to processes for preparing an intermediate for a diazepane compound which is an antagonist of orexin receptors, and which is useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved.
- -
-
Page/Page column 13; 14
(2017/02/02)
-
- 2,5-DISUBSTITUTED MORPHOLINE OREXIN RECEPTOR ANTAGONISTS
-
The present invention is directed to 2,5-disubstituted morpholine 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
- -
-
Paragraph 0061; 0067
(2015/11/09)
-
- 2-(1,2,3-TRIAZOL-2-YL)BENZAMIDE AND 3-(1,2,3-TRIAZOL-2-YL)PICOLINAMIDE DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS
-
The present invention relates to 2-(1,2,3-triazol-2-yl)benzamide and 3-(1,2,3-triazol-2-yl)picolinamide derivatives of formula (I) wherein Ar1, Q, and R1 to R5 are as described in the description, to their preparation, to
- -
-
Paragraph 0434; 0435
(2015/06/17)
-
- NOVEL COMPOUNDS
-
The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein L, X, Ra, Rb, R1, R2 and R3 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.
- -
-
Paragraph 0441-0444
(2015/09/22)
-
- Facile synthesis of suvorexant, an orexin receptor antagonist, via a chiral diazepane intermediate
-
A facile synthesis of suvorexant, an orexin receptor antagonist, is described. The key intermediate 6 was prepared from R-3-aminobutyric acid through protection, condensation, deprotection, cyclization, and hydrogenation steps. The title product was obtained with a total yield of 31% (>99% ee) after eight linear steps using commercially available raw materials.
- Chen, Yin,Zhou, Yan,Li, Jun-Hong,Sun, Jia-Quan,Zhang, Gui-Sen
-
p. 103 - 107
(2015/01/30)
-
- Novel Octahydropyrrolo[3,4- c ]pyrroles Are Selective Orexin-2 Antagonists: SAR Leading to a Clinical Candidate
-
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
- 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)
-
- CYCLOPENTYLBENZAMIDE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF PSYCHOTIC AND COGNITIVE DISORDERS
-
The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein n, L, X, Ra, Rb, R1, R2 and R3 their preparation, pharmaceutical compositions containing them and their use in therapy.
- -
-
Page/Page column 59
(2015/05/05)
-
- OREXIN RECEPTOR ANTAGONISTS WHICH ARE [ORTHO BI (HETERO )ARYL]-[2-(META BI (HETERO )ARYL)-PYRROLIDIN-1-YL]-METHANONE DERIVATIVES
-
The present invention relates to [ortho bi-(hetero-)aryl]-[2-(meta bi-(hetero-)aryl)-pyrrolidin-1-yl]- methanone derivatives of formula (I) wherein R, and the rings A1 A2 and A3 are as described in the description, to pharmaceutically acceptable salts thereof, to their preparation, to pharmaceutical compositions containing one or more compounds of formula (I), and to their use as pharmaceuticals, especially to their use as orexin receptor antagonists.
- -
-
Page/Page column 92
(2014/05/07)
-
- AZETIDINE AMIDE DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS
-
The present invention relates to azetidine amide derivatives derivatives of formula (I) wherein rings A1 A2 and A3 are as described in the description, to pharmaceutically acceptable salts thereof, to their preparation, to
- -
-
Page/Page column 40; 41
(2014/09/29)
-
- Regioselective halogenation of 2-substituted-1,2,3-triazoles via sp 2 C-H activation
-
A highly regioselective halogenation of 2-substituted-1,2,3-triazoles was developed via sp2 C-H activation. This method is compatible with halogen atoms, as well as electron-donating and electron-withdrawing groups. Meanwhile, the strategy is a
- Tian, Qingshan,Chen, Xianmin,Liu, Wei,Wang, Zechao,Shi, Suping,Kuang, Chunxiang
-
p. 7830 - 7833
(2013/11/19)
-
- SUBSTITUTED PROLINES / PIPERIDINES AS OREXIN RECEPTOR ANTAGONISTS
-
The present invention is directed to compounds that can modulate the bioactivity of an orexin receptor such as OX1 or OX2, or both; to pharmaceutical compositions and combinations comprising a compound of the invention; to methods of treatment of malconditions in patients wherein modulation of an orexin receptor is medically indicated; and to methods of preparation of compounds of the invention.
- -
-
Page/Page column 153; 154
(2013/08/28)
-
- 3,7-DIAZABICYCLO[3.3.1]NONANE AND 9-OXA-3,7-DIAZABICYCLO[3.3.1]NONANE DERIVATIVES
-
The present invention relates to 3,7-diazabicyclo[3.3.1]nonane and 9-oxa-3,7- diazabicyclo[3.3.1 ]nonane derivatives of formula (I) wherein Ar1 and Ar2 are as described in the description, to their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of formula (I), and especially to their use as orexin receptor antagonists.
- -
-
Page/Page column 59; 61
(2013/04/24)
-
- 2-(1,2,3-TRIAZOL-2-YL)BENZAMIDE AND 3-(1,2,3-TRIAZOL-2-YL)PICOLINAMIDE DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS
-
The present invention relates to 2-(1,2,3-triazol-2-yl)benzamide and 3-(1,2,3-triazol-2- yl)picolinamide derivatives of formula (I) Formula (I) wherein Ar1, Q, and R1 to R5 are as described in the description, to their pre
- -
-
Page/Page column 56; 57
(2013/05/23)
-
- 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.
- -
-
Page/Page column 37-38
(2013/05/09)
-
- DISUBSTITUTED OCTAHY-DROPYRROLO [3,4-C] PYRROLES AS OREXIN RECEPTOR MODULATORS
-
Disubstituted octahydropyrrolo[3,4-c]pyrrole compounds are described, which are useful as orexin receptor modulators. Such compounds may be useful in pharmaceutical compositions and methods for the treatment of diseased states, disorders, and conditions mediated by orexin activity, such as insomnia.
- -
-
Page/Page column 48
(2012/11/07)
-
- AZABICYCLO [4.1.0] HEPT - 4 - YL DERIVATIVES AS HUMAN OREXIN RECEPTOR ANTAGONISTS
-
This invention relates to azabicyclo[4.1.0]hept-4-yl derivatives and their use as pharmaceuticals.
- -
-
Page/Page column 46
(2012/07/14)
-
- PROCESS FOR THE PREPARATION OF AN OREXIN RECEPTOR ANTAGONIST
-
The present invention is directed to processes for preparing a diazepane compound which is an antagonist of orexin receptors, and which is useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is further directed to crystalline forms of this diazepane compound and pharmaceutical compositions thereof.
- -
-
Page/Page column 48-49
(2012/11/13)
-
- 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.
-
supporting information; experimental part
p. 3458 - 3461
(2012/08/08)
-
- SPIRO AMINO COMPOUNDS SUITABLE FOR THE TREATMENT OF INTER ALIA SLEEP DISORDERS AND DRUG ADDICTION
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The invention concerns a spiro-amino compound of Formula (Vl) wherein m is 1 or 2 or 3, n is 1 or 2, R is selected from a 5- or 6-membered aromatic ring and a 5- or 6-membered heteroaromatic ring comprising 1 to 3 heteroatoms selected from S, O e N, such ring being substituted with one or two substituents selected from the group consisting of (C1-C3)alkyl, halogen, (C3-C5)cycloalkyloxy, (C1-C3)alkylcarbonyl, phenyl optionally substituted with one or more halogen atoms, a 5- or 6-membered heterocycle comprising at least one nitrogen atom; P is a substituent Q or COQ, wherein Q is selected from the group consisting of phenyl, pyridil, pyrimidil, quinolyl, isoquinolyl, quinoxalyl, benzofuranyl, imidazotriazolyl, being such Q optionally substituted with one or more substituents selected from the group consisting of (C1-C3)alkyl, halogen, trifluoromethyl, carbammido, methylcarbammido, carboxy, methylcarboxy or a pharmaceutically acceptable salt thereof.
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Page/Page column 69
(2011/02/24)
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- FUSED HETEROCYCLIC COMPOUNDS AS OREXIN RECEPTOR MODULATORS
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Disubstituted 3,8-diaza-bicyclo[4.2.0]octane and 3,6-diazabicyclo [3.2.0]heptane compounds are described, which are useful as orexin receptor modulators. Such compounds may be useful in pharmaceutical compositions and methods for the treatment of diseased states, disorders, and conditions mediated by orexin activity, such as insomnia.
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Page/Page column 81-82
(2011/05/06)
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- DISUBSTITUTED OCTAHY - DROPYRROLO [3,4-C] PYRROLES AS OREXIN RECEPTOR MODULATORS
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Disubstituted octahydropyrrolo[3,4-c]pyrrole compounds are described, which are useful as orexin receptor modulators. Such compounds may be useful in pharmaceutical compositions and methods for the treatment of diseased states, disorders, and conditions mediated by orexin activity, such as insomnia.
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Page/Page column 48
(2011/05/06)
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- FUSED HETEROCYCLIC COMPOUNDS AS OREXIN RECEPTOR MODULATORS
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Certain disubstituted 3,8-diaza-bicyclo[4.2.0]octane and 3,6-diazabicyclo [3.2.0]heptane are described, which are useful as orexin inhibitors. Such compounds may be useful in pharmaceutical compositions and methods for the treatment of diseased states, disorders, and conditions mediated by orexin activity, such as insomnia.
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Page/Page column 83-84
(2011/05/06)
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- The first large-scale synthesis of MK-4305: A dual orexin receptor antagonist for the treatment of sleep disorder
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A new synthetic route to drug candidate 1, a potent and selective dual orexin antagonist for the treatment of sleep disorders, has been developed. The key acyclic precursor 10 was prepared in a one-step process in 75% isolated yield from commercially available starting materials using novel chemistry to synthesize 2-substituted benzoxazoles. A reductive amination was followed by a classical resolution to afford chiral diazepane (R)-11. Finally, coupling of (R)-11 with acid 5 furnished the desired drug candidate 1.
- Baxter, Carl A.,Cleator, Ed,Brands, Karel M. J.,Edwards, John S.,Reamer, Robert A.,Sheen, Faye J.,Stewart, Gavin W.,Strotman, Neil A.,Wallace, Debra J.
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experimental part
p. 367 - 375
(2012/05/19)
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