- COMPOUND AS ACC INHIBITOR AND USE THEREOF
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Disclosed are a class of compounds which are inhibitors of acetyl-CoA carboxylase (ACC) and the use thereof. In particular, provided are compounds as shown in formula I or isomers, pharmaceutically acceptable salts, solvates, crystals or prodrugs thereof, and methods for preparing the same, and pharmaceutical compositions comprising the compounds and the use of the compounds or compositions for treating and/or preventing diseases associated with ACC expression, such as fibrotic diseases, metabolic diseases, cancers or tissue hyperplasia diseases. The compound has a good inhibitory activity against ACC and shows good promise to be a therapeutic drug for fibrotic diseases, metabolic diseases, cancers or tissue hyperplasia diseases.
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Paragraph 0117; 0118
(2020/06/15)
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- SUBSTITUTED 2-AZABICYCLO[3.1.1]HEPTANE AND 2-AZABICYCLO[3.2.1]OCTANE DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS
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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.
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Page/Page column 60
(2019/03/17)
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- Multigram Synthesis of C 4/C5 3,3-Difluorocyclobutyl-Substituted Building Blocks
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An approach for the multigram synthesis of 3,3-difluorocyclobutyl-substituted building blocks (including carboxylic acid, amines, alcohols, azide, trifluoroborate ketone) is described. It is shown that, in most cases, ethyl 3,3-difluorocyclobutanecarboxylate is a convenient common synthetic intermediate to obtain the target derivatives. For preparation of 3,3-difluorocyclobutanol or -cyclobutanone, an alternative pathway via reaction of dichloroketene and tert -butyl or benzyl vinyl ether should be applied.
- Melnykov, Kostiantyn P.,Granat, Dmitriy S.,Volochnyuk, Dmitriy M.,Ryabukhin, Sergey V.,Grygorenko, Oleksandr O.
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p. 4949 - 4957
(2018/12/13)
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- Copper-Catalyzed Coupling Reactions of Cyclobutanone Oxime Esters with Sulfur Nucleophiles at Room Temperature
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A copper-catalyzed iminyl radical-mediated C-C bond cleavage/cross-coupling tandem reaction of cyclobutanone oxime esters with aryl thiols in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) at room temperature was developed, and aryl cyanopropyl sulfides were smoothly synthesized in 20-88% yields. By altering the copper reagent and the molar ratio of cyclobutanone oxime ester/aryl thiol/DBU, substitutional product N-arylthio cyclobutanone imines were selectively generated in 50-91% yields. Using this protocol, C-S bond and N-S bond formations using aryl thiols as sulfur sources were realized under very mild conditions without the use of photocatalysis and electrocatalysis techniques.
- He, Mingchuang,Yan, Zhaohua,Zhu, Fuyuan,Lin, Sen
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p. 15438 - 15448
(2019/01/04)
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- ISOXAZOLE DERIVATIVES FOR USE IN THE TREATMENT OF PULMONARY DISEASES AND DISORDERS
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The present disclosure features disclosed method of treating disorders such as COPD, bronchitis and/or asthma using disclosed compounds, optionally together with one or more additional active agents. Contemplated methods include administrating orally or by inhalation to a patient one or more disclosed compounds.
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Paragraph 0227
(2017/03/21)
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- DERIVATIVES OF 3-HETEROARYLISOXAZOL-5-CARBOXYLIC AMIDE USEFUL FOR THE TREATMENT OF INTER ALIA CYSTIC FIBROSIS
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The present disclosure is based, in part, on the discovery that disclosed compounds can increase cystic fibrosis transmembrane conductance regulator (CFTR) activity as measured in human bronchial epithelial (hBE) cells.
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Paragraph 0171
(2016/07/27)
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- COMPOUNDS, COMPOSITIONS AND METHODS FOR INCREASING CFTR ACTIVITY
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The present disclosure features compounds such as those having the Formulae (Ila), (lIb), (lIc), (Ild), (IlIa), and (Illb), which can increase cystic fibrosis transmembrane conductance regulator (CFTR) activity as measured in human bronchial epithelial (hBE) cells. The present disclosure also features methods of treating a condition associated with decreased CFTR activity or a condition associated with a dysfunction of proteostasis comprising administering to a subject an effective amount of a disclosed compound, such as a compound of Formula (Ila), (lIb), (lIc), (lId), (IlIa), or (Illb).
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Paragraph 0268
(2016/11/07)
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- DERIVATIVES OF 5-PHENYL- OR 5-HETEROARYLTHIAZOL-2-CARBOXYLIC AMIDE USEFUL FOR THE TREATMENT OF INTER ALIA CYSTIC FIBROSIS
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The present disclosure is based, in part, on the discovery that disclosed compounds such as those having Formula (IlIa), (III), or (IV) can increase cystic fibrosis transmembrane conductance regulator (CFTR) activity as measured in human bronchial epithel
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Page/Page column 0139
(2016/07/27)
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- PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES USEFUL FOR INHIBITING JANUS KINASE
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Described herein are pyrrolo{2,3-d}pyrimidine derivatives, their use as Janus Kinase (JAK) inhibitors, pharmaceutical compositions containing them, and therapeutic uses thereof.
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Page/Page column 126; 127
(2016/02/29)
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- Baeyer–Villiger monooxygenase-catalyzed desymmetrizations of cyclobutanones. Application to the synthesis of valuable spirolactones
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A series of γ-butyrolactone derivatives, including some spiranic ones, was obtained through desymmetrization of the corresponding prochiral 3-substituted cyclobutanones via Baeyer–Villiger monooxygenase (BVMO)-catalyzed oxidation. After reaction optimization using several commercial enzymes, both antipodes of various lactones were synthesized in most cases with >90% conversion and >80% enantiomeric excess under mild reaction conditions. In some cases alcohol formation was also observed (up to 40% conversion) as an undesired side reaction due to the presence of alcohol dehydrogenases in these preparations. Selected transformations were achieved on a 100 mg scale showing the possibilities of these oxidative biocatalysts as a new source of highly interesting compounds.
- Rodríguez-Mata, María,Lavandera, Iván,Gotor-Fernández, Vicente,Gotor, Vicente,García-Cerrada, Susana,Mendiola, Javier,de Frutos, óscar,Collado, Iván
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supporting information
p. 7268 - 7275
(2016/10/26)
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- CYCLOBUTANE CONTAINING CARBOXYLIC ACID GPR120 MODULATORS
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The present invention provides compounds of Formula (I): or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are GPR120 G protein-coupled receptor modulators which may be used as medicaments.
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Paragraph 00217
(2016/06/01)
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- COMPOUNDS, COMPOSITIONS AND METHODS OF INCREASING CFTR ACTIVITY
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The present disclosure features disclosed compounds which can increase cystic fibrosis transmembrane conductance regulator (CFTR) activity as measured in human bronchial epithelial (hBE) cells. The present disclosure also features methods of treating a condition associated with decreased CFTR activity or a condition associated with a dysfunction of proteostasis comprising administering to a subject an effective amount of a disclosed compound.
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Paragraph 0274
(2016/02/24)
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- Lactonization reactions through hydrolase-catalyzed peracid formation. Use of lipases for chemoenzymatic Baeyer-Villiger oxidations of cyclobutanones
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A one-pot chemoenzymatic method has been described for the synthesis of γ-butyrolactones starting from the corresponding ketones through a Baeyer-Villiger reaction. The approach is based on a lipase-catalyzed perhydrolysis for the formation of peracetic acid, which is the responsible for the ketone oxidation. Optimization studies have been performed in the oxidation of cyclobutanone, finding Candida antarctica lipase type B, ethyl acetate and urea-hydrogen peroxide complex as the best system. The relative ratio of these reagents has also been analyzed in depth. This synthetic approach has been successfully extended to a family of 3-substituted cyclobutanones in high substrate concentration, yielding the corresponding lactones with excellent isolated yields and purities, under mild reaction conditions and after a simple extraction protocol.
- González-Martínez, Daniel,Rodríguez-Mata, María,Méndez-Sánchez, Daniel,Gotor, Vicente,Gotor-Fernández, Vicente
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- Boc-protected 1-(3-oxocycloalkyl)ureas via a one-step Curtius rearrangement: Mechanism and scope
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1-(3-Oxocyclobutyl) carboxylic acid (4a) was converted into N-Boc-protected 1-(3-oxocyclobutyl) urea (5a), a key intermediate for the preparation of agonists of metabotropic glutamate receptor 5, in one-step when treated with diphenyl phosphoryl azide and triethylamine in tert-butanol. The mechanism of the reaction involves a nucleophilic addition of the in situ generated tert-butyl carbamate to the isocyanate intermediate. This reaction is applicable to other 1-(3-oxocycloalkyl) carboxylic acids but not to linear γ-keto carboxylic acids.
- Sun, Xianyu,Rai, Rachita,Deschamps, Jeffrey R.,Mackerell Jr., Alexander D.,Faden, Alan I.,Xue, Fengtian
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p. 842 - 844
(2014/02/14)
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- NEW THIADIAZOLE DERIVATIVES
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The present invention relates to thiadiazole derivatives of formula (I), to processes for their preparation and to pharmaceutical compositions containing them. These compounds are potent agonists of S1P1 receptors and thus, they are useful In the treatment, prevention or suppression of diseases and disorders known to be susceptible to improvement by sphingosine-1-phosphate receptors agonists (S1P1), such as autoimmune diseases, chronic immune and inflammatory diseases, transplant rejection, malignant neoplastic diseases, angiogenic-related disorders, pain, neurological diseases, viral and infectious diseases.
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Page/Page column 105
(2011/04/24)
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- AZETIDINE AND CYCLOBUTANE DERIVATIVES AS JAK INHIBITORS
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The present invention relates to azetidine and cyclobutane derivatives, as well as their compositions, methods of use, and processes for preparation, which are JAK inhibitors useful in the treatment of JAK-associated diseases including, for example, inflammatory and autoimmune disorders, as well as cancer.
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Page/Page column 43
(2009/09/28)
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- CYCLOBUTYL CARBOXYLIC ACID DERIVATIVES
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The invention relates to compounds of formula (I) and to pharmaceutically acceptable salts, prodrugs, solvates or hydrates thereof. This invention also relates to a method of using such compounds in the treatment of hyperproliferative diseases and autoimm
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Page/Page column 46
(2009/06/27)
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- CYCLOALKYLAMINO ACID DERIVATIVES
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The invention relates to compounds of formula I and to pharmaceutically acceptable salts, prodrugs, solvates or hydrates thereof; wherein B, D, E, R1, R2, R3, R4, R5, R8, m, n, p, q, r, s, t and u are as defined herein. This invention also relates to a method of using such compounds in the treatment of hyperproliferative diseases and autoimmune diseases in mammals, especially humans, and to pharmaceutical compositions containing such compounds.
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Page/Page column 32
(2008/06/13)
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