- Improved synthesis of sterically encumbered heteroaromatic biaryls from aromatic β-keto esters
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A protocol for the synthesis of hindered 4-aryl 2-aminopyrimidines from β–keto esters is described. The process employs trifluoroethanol as an essential additive to promote the guanidine condensation reaction, enabling the synthesis of 25 aryl- and heteroaryl substituted aminopyrimidines in good yields and high purities with no column chromatography. The conditions described herein are readily scalable and have been employed in the large-scale synthesis of the clinical A2a/A2bR antagonist AB928.
- Rosen, Brandon R.,Ul Sharif, Ehesan,Miles, Dillon H.,Chan, Nicholas S.,Leleti, Manmohan R.,Powers, Jay P.
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supporting information
(2020/03/25)
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- BICYCLIC HYDROXAMIC ACIDS USEFUL AS INHIBITORS OF MAMMALIAN HISTONE DEACETYLASE ACTIVITY
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A compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof. The compound is an inhibitor of a histone deacetylase, and as such is useful in terepy, e.g. in the treatment of autoimmune disorders, mental disorders, neurodegenerative disorders, and hyperproliferative disorders.
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Page/Page column 92
(2017/07/14)
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- Tetrazolinone compound and application for same
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Provided is a tetrazolinone compound given by formula (1) (wherein E represents the following group E16 or the like; Y represents -O-CH2- or the like; Q represents the following group Q46 or the like; R8 represents a C1-C6 alkyl group; R3, R30, and R31 may be the same or different, and represent hydrogen atoms or the like; A represents a C6-C16 aryl group or the like, optionally having one or more atoms or groups selected from the group P1; R5 represents a C1-C3 alkyl group; and X represents an oxygen or sulfur atom), and having exceptional efficacy in controlling harmful organisms.
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Paragraph 0628; 0629
(2016/10/08)
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- ANTI-FIBROTIC PYRIDINONES
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This application relates to polycyclic compounds with a pyridinone or pyridinone derivative core including, substituted pyridinones, 5,6- and 6,6- bicyclic heterocycles and substituted pyridine-thiones. This application also discloses methods of preparing these polycyclic compounds, pharmaceutical compositions and medicaments comprising said compounds and methods to treat, prevent or diagnose diseases, disorders or conditions associated with fibrosis.
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Paragraph 0366
(2015/11/02)
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- ANTI-FIBROTIC PYRIDINONES
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Disclosed are pyridinone compounds, method for preparing these compounds, and methods for treating fibrotic disorders.
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Paragraph 0619-0620
(2014/04/17)
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- Rh(III)-catalyzed cascade oxidative olefination/cyclization of picolinamides and alkenes via C-H activation
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Rh(III)-catalyzed cascade oxidative alkenylation/cyclization of picolinamides and alkenes to furnish pyrido pyrrolone derivatives is described, in which three C-H bonds and one N-H bond broke, while one C-C bond and one C-N bond formed. The reaction proceeded with high yield and high regioselectivity and stereoselectivity. Moreover, copper acetate can also be used in catalytic amounts with O2 serving as the terminal oxidant.
- Cai, Shangjun,Chen, Chao,Shao, Peng,Xi, Chanjuan
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supporting information
p. 3142 - 3145
(2014/06/23)
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- Copper-mediated hydroxylation of arenes and heteroarenes directed by a removable bidentate auxiliary
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A copper-mediated C-H hydroxylation of arenes and heteroarenes using our newly developed PIP directing group has been developed. This procedure is scalable and compatible with a wide range of functional groups and heteroarenes, providing an operationally simple protocol for the synthesis of o-hydroxybenzamides. The hydroxylation of nicotinamides gave 4-oxo-1,4-dihydropyridine-3-carboxamides selectively. Preliminary mechanistic studies implicate that a basic ligand-enabled, irreversible, rate-determining CMD step is most likely involved in this process.
- Li, Xin,Liu, Yan-Hua,Gu, Wen-Jia,Li, Bo,Chen, Fa-Jie,Shi, Bing-Feng
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supporting information
p. 3904 - 3907
(2014/08/18)
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- OXADIAZOLE INHIBITORS OF LEUKOTRIENE PRODUCTION
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The present invention relates to compound of formula (I) and pharmaceutically acceptable salt thereof, wherein R1-R5 are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.
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Page/Page column 127
(2012/03/26)
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- Pd0/PR3-catalyzed arylation of nicotinic and isonicotinic acid derivatives
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(Chemical Eqation Presented) Good for your health: Intermolecular C-H functionalization of pyridine rings at the 3- and 4-positions is described using a Pd0/PR3/ArBr catalytic system. This reaction provides a powerful method for the preparation of structurally diverse nicotinic and isonicotinic acids that are of great importance in drug discovery.
- Wasa, Masayuki,Worrell, Brady T.,Yu, Jin-Quan
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supporting information; experimental part
p. 1275 - 1277
(2010/05/02)
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- Novel Derivatives
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The present invention relates to novel piperazine derivatives; to processes for their preparation; to pharmaceutical compositions containing the derivatives; and to the use of the derivatives in therapy to treat diseases for which blocking the Cav2.2 calcium channels is beneficial.
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Page/Page column 19
(2010/02/17)
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- Discovery of inducible nitric oxide synthase (iNOS) inhibitor development candidate KD7332, part 1: Identification of a novel, potent, and selective series of quinolinone iNOS dimerization inhibitors that are orally active in rodent pain models
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There are three isoforms of dimeric nitric oxide synthases (NOS) that convert arginine to citrulline and nitric oxide. Inducible NOS is implicated in numerous inflammatory diseases and, more recently, in neuropathic pain states. The majority of existing NOS inhibitors are either based on the structure of arginine or are substrate competitive. We describe the identification from an ultra high-throughput screen of a novel series of quinolinone small molecule, nonarginine iNOS dimerization inhibitors. SAR studies on the screening hit, coupled with an in vivo lipopolysaccharide (LPS) challenge assay measuring plasma nitrates and drug levels, rapidly led to the identification of compounds 12 and 42 - potent inhibitors of the human and mouse iNOS enzyme that were highly selective over endothelial NOS (eNOS). Following oral dosing, compounds 12 and 42 gave a statistical reduction in pain behaviors in the mouse formalin model, while 12 also statistically reduced neuropathic pain behaviors in the chronic constriction injury (Bennett) model.
- Bonnefous, Céline,Payne, Joseph E.,Roppe, Jeffrey,Zhuang, Hui,Chen, Xiaohong,Symons, Kent T.,Nguyen, Phan M.,Sablad, Marciano,Rozenkrants, Natasha,Zhang, Yan,Wang, Li,Severance, Daniel,Walsh, John P.,Yazdani, Nahid,Shiau, Andrew K.,Noble, Stewart A.,Rix, Peter,Rao, Tadimeti S.,Hassig, Christian A.,Smith, Nicholas D.
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experimental part
p. 3047 - 3062
(2010/01/16)
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- COMPOUNDS FOR THE PREVENTION AND TREATMENT OF CARDIOVASCULAR DISEASES
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The present disclosure relates to compounds, which are useful for regulating the expression of apolipoprotein A-I (ApoA-I), and their use for treatment and prevention of cardiovascular disease and related disease states, including cholesterol- or lipid-related disorders, such as, for example, atherosclerosis.
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Page/Page column 24
(2008/12/07)
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- ALKYL SULFONAMIDE DERIVATIVES
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This invention is directed to alkyl sulfonamide derivatives which are ligands at the NPY Y5 receptor. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a pharmaceutical composition made by admixing a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a method of treating a subject suffering from depression which comprises administering to the subject an amount of a compound of the subject invention. This invention also provides a method of treating a subject suffering from anxiety which comprises administering to the subject an amount of a compound of the subject invention. This invention also provides a method of treating a subject suffering from obesity which comprises administering to the subject an amount of a compound of the subject invention.
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Page/Page column 29
(2010/11/25)
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- PHARMACEUTICAL COMPOSITIONS FOR THE PREVENTION AND TREATMENT OF COMPLEX DISEASES AND THEIR DELIVERY BY INSERTABLE MEDICAL DEVICES
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The present invention relates to polyphenol-like compounds that are useful for inhibiting VCAM-1 expression, MCP-1 expression and/or SMC proliferation in a mammal. The disclosed compounds are useful for regulating markers of inflammatory conditions, including vascular inflammation, and for treatment and prevention of inflammatory and cardiovascular diseases and related disease states.
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Page/Page column 64-65; 93-94
(2008/06/13)
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- Preparation, X-ray structure and propylaminolysis of 7,7-dichloro-5,7- dihydro-thieno[3,4-b]pyridin-5-one
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Refluxing 2-methylpyridine-3-carboxylic acid with thionyl chloride for 6-7 h gave (~50%) title compound dichlorothienolactone 2 as was confirmed by a X-ray structure analysis. The propylaminolysis of 2 provides a new and convenient access to highly functi
- Van Es, Theodorus,Staskun, Benjamin,Fernandes, Manuel A.
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p. 373 - 376
(2008/09/19)
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- Alkyl sulfonamide derivatives
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This invention is directed to alkyl sulfonamide derivatives which are ligands at the NPY Y5 receptor. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a pharmaceutical composition made by admixing a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a method of treating a subject suffering from depression which comprises administering to the subject an amount of a compound of the subject invention. This invention also provides a method of treating a subject suffering from anxiety which comprises administering to the subject an amount of a compound of the subject invention. This invention also provides a method of treating a subject suffering from obesity which comprises administering to the subject an amount of a compound of the subject invention.
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Page/Page column 12
(2010/11/25)
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- (+)-(2R,5S)-4-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dimethyl-N-[6- (trifluoromethyl)pyridin-3-yl]piperazine-1-carboxamide (YM580) as an orally potent and peripherally selective nonsteroidal androgen receptor antagonist
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A novel series of trans-N-aryl-2,5-dimethylpiperazine-1-carboxamide derivatives was synthesized and their androgen receptor (AR) antagonist activities and in vivo antiandrogenic effects were evaluated. Pharmacological assays indicated that compound 33 was a potent AR antagonist, and subsequent optical resolution provided (+)-(2R,5S)4-[4-cyano-3-(trifluoromethyl)phenyl]-2, 5-dimethyl-N-[6(triflouromethyl)pyridin-3-yl]piperazine-1-carboxamide (33a, YM580) which exhibited the most potent antiandrogenic activity. Unlike bicalutamide, compound 33a decreased the weight of rat ventral prostate in a dose-dependent manner (ED50 = 2.2 mg/kg/day), and induced the maximum antiandrogenic effect, comparable to that of surgical castration, without significantly affecting serum testosterone levels. Compound 33a is a promising clinical candidate for prostate cancer monotherapy.
- Kinoyama, Isao,Taniguchi, Nobuaki,Toyoshima, Akira,Nozawa, Eisuke,Kamikubo, Takashi,Imamura, Masakazu,Matsuhisa, Akira,Samizu, Kiyohiro,Kawanimani, Eiji,Niimi, Tatsuya,Hamada, Noritaka,Koutoku, Hiroshi,Furutani, Takashi,Kudoh, Masafumi,Okada, Minoru,Ohta, Mitsuaki,Tsukamoto, Shin-Ichi
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p. 716 - 726
(2007/10/03)
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- Ready access to 7,8-dihydro- and 1,2,3,4-tetrahydro-1,6-naphthyridine-5(6H) -ones from simple pyridine precursors
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Short pathways are described for the synthesis of a representative example of each of the 7,8-dihydro- and 1,2,3,4-tetrahydro-1,6-naphthyridine-5(6H)-one ring systems from simple pyridine precursors. An attempted synthesis of the related 4,6-dihydro-1,6-naphthyridin-5(1H)-one ring system from a common intermediate was unsuccessful.
- Showalter, H. D. Hollis
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p. 1311 - 1317
(2007/10/03)
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- Synthesis of Pyridocyclobuten-5-one and 1-Azafulvenallene by Flash Vacuum Pyrolysis of 3-Chloroformyl-2-methylpyridine
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The temperature and pressure dependence of products formed on pyrolysis of 3-chloroformyl-2-methylpyridine (6) have been studied.Pyrolysis of 6 at 575 deg C and ca. 1 x 10-4 torr gives pyridocyclobuten-5-one (5) in 20percent yield.Pyrolysis of 6 at 575 and 800 deg C and under the pressure of ca. 1 x 10-2 torr give 1-azafulvenallene (7, 46percent) and 1-cyanocyclopentadiene (8, 42percent), respectively.Irradiation of 5 (λ > 300 nm) in methanol affords 2-methoxy-3-acetylpyridine (9) quantitatively.
- Chou, Chin-Hsing,Wu, Cheng-Chang,Chen, Wey-Kao
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p. 5065 - 5068
(2007/10/02)
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