- Highly regiocontrolled and stereocontrolled syntheses of polysubstituted aminocyclohexanes: mild inverse-electron-demand Diels–Alder cycloadditions of electrophilic 2-pyridones
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Strongly electrophilic N-arenesulfonyl-2-pyridone-3-carboxylate methyl esters complex with zinc dibromide and then react with nucleophilic benzyl vinyl ether or benzyloxyallene to achieve inverse-electron-demand Diels–Alder (IEDDA) cycloadditions. These cycloadducts are produced on gram scale and in 77–89% yields, importantly without the use of high pressure. These 4+2 cycloadditions strongly favor regioselective and stereoselective formation of endo bicyclic lactams as established by X-ray crystallography. These bicyclic lactams undergo useful reactions, including reductive cleavage of the N-sulfonyl group, exo-syn-dihydroxylations, and lactam ring-opening to produce a variety of aminocyclitols.
- Conyers, Ryan C.,Mazzone, Jennifer R.,Siegler, Maxime A.,Posner, Gary H.
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Read Online
- POLYCYCLIC AMIDES AS UBE2K MODULATORS FOR TREATING CANCER
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Provided are compounds of Formula (I) and pharmaceutically acceptable salts and compositions thereof, which are useful for treating conditions associated with modulation of UBE2K.
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Paragraph 00150-00152
(2021/07/10)
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- THROMBIN INHIBITORS, FORMULATIONS, AND USES THEREOF
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Thrombin-inhibiting acylated pyrazole-pyridone compounds of formula (II) are disclosed herein, as well as pharmaceutical compositions, including tablets, that contain acylated pyrazole- pyridone compounds. These compounds are useful for the treatment and prevention of thrombin-related related diseases and disorders. Processes for making tablets containing acylated pyrazole-pyridones are also included.
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Paragraph 00189
(2020/02/06)
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- MODIFIED COMPOUND OF ANDROGRAPHOLIDE
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The present disclosure discloses a modified compound of andrographolide, and particularly discloses a compound shown in formula (I) and (II) or a pharmaceutically acceptable salt thereof.
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Paragraph 0244-0246
(2019/01/04)
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- Development of a Practical Synthesis of a Peripherally Selective Noradrenaline Reuptake Inhibitor Possessing a Chiral 6,7-trans-Disubstituted-1,4-oxazepane as a Scaffold
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A practical synthesis of a peripherally selective noradrenaline reuptake inhibitor that has a chiral 6,7-trans-disubstituted-1,4-oxazepane as a new class of scaffold is described. The amino alcohol possessing the desired stereochemistry was obtained with excellent dr and ee, starting from a commercially available aldehyde via a Morita-Baylis-Hillman reaction, Michael addition, isolation as maleic acid salt, reduction, and diastereomeric salt formation with (+)-10-camphorsulfonic acid. The desired single stereoisomer obtained at an early stage of the synthesis was used for seven-membered ring formation in fully telescoped processes, providing the chiral 6,7-trans-disubstituted-1,4-oxazepane efficiently. In addition to controls of dr and ee of the chiral 1,4-oxazepane, and control of N,O-selectivity in SN2 reaction of the intermediate mesylate with a pyridone derivative, finding appropriate intermediates that were amenable to isolation and upgrade of purity enabled a practical chiral HPLC separation-free, column chromatograph-free synthesis of the drug candidate with excellent chemical and optical purities in a higher overall yield.
- Ishimoto, Kazuhisa,Yamaguchi, Kotaro,Nishimoto, Atsushi,Murabayashi, Mika,Ikemoto, Tomomi
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p. 2001 - 2011
(2017/12/26)
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- Indole-based small molecular C-MET inhibitor
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The invention belongs to the technical field of medicines, and provides indole compounds for treating lung cancer, breast cancer, kidney cancer, pancreatic cancer, colorectal cancer, stomach cancer and other cancers.
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Paragraph 0039
(2017/11/18)
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- PYRAZOLYL-SUBSTITUTED PYRIDONE COMPOUNDS AS SERINE PROTEASE INHIBITORS
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There are provided inter alia pyrazolyl-substituted pyridone compounds, which exhibit biological activity, e.g., inhibitory action, against serine proteases, including thrombin and various kallikreins. There are additionally provided pharmaceutical compositions. There are additionally provided methods of treating and preventing certain diseases or disorders, which disease or disorder is amenable to treatment or prevention by the inhibition of serine proteases, including thrombin and various kallikreins.
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Paragraph 00203-00204
(2016/04/09)
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- COMPOUND HAVING ZNF143 INHIBITORY ACTIVITY AND USE THEREOF
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PROBLEM TO BE SOLVED: To provide a compound having a ZNF143 inhibitory activity as well as to provide a ZNF143 inhibitory agent and pharmaceutical composition containing the same. SOLUTION: Provided is a compound represented by formula (I) or a salt thereof as well as a ZNF143 inhibitory agent containing the same and a pharmaceutical composition having the same as an active ingredient. A-B-C-D (I)[A is H, a methyl group, a naphthyl group, a phenyl group or a nitrogen-containing heterocyclic ring; B is as shown below, and C is an amide bond or a heteroaromatic ring containing N and O; D is a substituted/unsubstituted phenyl group or a monocyclic heteroaromatic ring containing N or S; and C and D are both fused heterocyclic ring or the like optionally having a substituent group.]. SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2016,JPOandINPIT
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Paragraph 0331
(2016/10/27)
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- MULTISUBSTITUTED AROMATIC COMPOUNDS AS SERINE PROTEASE INHIBITORS
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There are provided inter alia multisubstituted aromatic compounds useful for the inhibition of kallikrein, which compounds include substituted pyrazolyl or substituted triazolyl. There are additionally provided pharmaceutical compositions. There are additionally provided methods of treating and preventing certain diseases or disorders, which disease or disorder is amenable to treatment or prevention by the inhibition of kallikrein.
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Paragraph 0191; 0192
(2014/09/29)
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- Inhibitors of the TAM subfamily of tyrosine kinases: Synthesis and biological evaluation
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The TAM subfamily of Receptor Tyrosine Kinases (RTKs) contains three human proteins of therapeutical interest, Axl, Mer, and Tyro3. Our goal was to design a type II inhibitor specific for this family, i.e. able to interact with the allosteric pocket and with the hinge region of the kinase. We report the synthesis of several series of purine analogues of BMS-777607. The structural diversity of the designed inhibitors was expected to modify the interactions formed in the binding site and consequently to modulate their selectivity profiles. The most potent inhibitor 6g exhibits Kds of 39, 42, 65 and 200 nM against Axl, Mer, Met and Tyro3 respectively. Analysis of the affinity of 6g for active and inactive forms of Abl1, an RTK protein that does not belong to the TAM subfamily, together with the binding modes of 6g predicted by docking studies, indicates that 6g displays some selectivity for the TAM family and may act as a type II inhibitor. Crown Copyright
- Suarez, Rosa M.,Chevot, Franciane,Cavagnino, Andrea,Saettel, Nicolas,Radvanyi, Francois,Piguel, Sandrine,Bernard-Pierrot, Isabelle,Stoven, Veronique,Legraverend, Michel
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- PHARMACEUTICAL COMPOSITION COMPRISING PYRIDONE DERIVATIVES
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A pyridone derivative compound and a pharmaceutically acceptable salt, isomer, solvate or hydrate thereof, and a preventive or therapeutic pharmaceutical composition for cognitive disorders that includes the pyridone derivative compound or a pharmaceutically acceptable salt, isomer, solvate or hydrate thereof.
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- PHARMACEUTICAL COMPOSITION COMPRISING PYRIDONE DERIVATIVES
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A pyridone derivative compound and a pharmaceutically acceptable salt, isomer, solvate or hydrate thereof, and a preventive or therapeutic pharmaceutical composition for cognitive disorders that includes the pyridone derivative compound or a pharmaceutically acceptable salt, isomer, solvate or hydrate thereof.
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- Rational design, synthesis and anti-proliferative properties of new CB2 selective cannabinoid receptor ligands: An investigation of the 1,8-naphthyridin-2(1H)-one scaffold
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CB2 receptor ligands are becoming increasingly attractive drugs due to the potential role of this receptor in several physiopathological processes. Using our previously described series of 1,8-naphthyridin-2(1H)-on-3-carboxamides as a lead class, several nitrogen heterocyclic derivatives, characterized by different central cores, were synthesized and tested for their affinity toward the human CB1 and CB2 cannabinoid receptors. The obtained results suggest that the new series of quinolin-2(1H)-on-3-carboxamides, 4-hydroxy-2-oxo-1,2-dihydro- 1,8-naphthyridine-3-carboxamides and 1,2-dihydro-2-oxopyridine-3-carboxamides represent novel scaffolds very suitable for the development of promising CB2 ligands. Furthermore, the newly synthesized CB2 ligands inhibit proliferation of several cancer cell lines. In particular, it was demonstrated that in DU-145 cell line these ligands exert a CB2-mediated anti-proliferative action and decrease the CB2 receptor expression levels.
- Manera, Clementina,Saccomanni, Giuseppe,Malfitano, Anna Maria,Bertini, Simone,Castelli, Francesca,Laezza, Chiara,Ligresti, Alessia,Lucchesi, Valentina,Tuccinardi, Tiziano,Rizzolio, Flavio,Bifulco, Maurizio,Di Marzo, Vincenzo,Giordano, Antonio,MacChia, Marco,Martinelli, Adriano
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experimental part
p. 284 - 294
(2012/08/08)
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- AMIDOPHENOXYINDAZOLES USEFUL AS INHIBITORS OF C-MET
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The present invention provides amidophenoxyindazole compounds useful in the treatment of cancer.
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Page/Page column 14
(2010/02/17)
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- NOVEL PHENYL-ISOXAZOL-3-OL DERIVATIVE
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The present invention relates to a compound represented by formula (I), which has a GPR120 agonist action and thus is useful for treatment of diabetes mellitus or hyperlipidemia, or a pharmaceutically acceptable salt thereof. In the formula, (AA) represents a phenyl or the like, which may be substituted with a lower alkoxy group or the like; (BB) represents a divalent group or the like, derived by removal of two hydrogen atoms from a benzene which may be substituted with a halogen atom or the like; X represents a spacer having a main chain composed of 1-8 carbon atoms wherein 1-3 carbon atoms in the main chain may be substituted with an oxygen atom or the like; and Y represents a hydrogen atom or the like.
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Page/Page column 28
(2009/09/26)
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- AZAQUINOLONE BASED COMPOUNDS EXHIBITING PROLYL HYDROXYLASE INHIBITORY ACTIVITY, COMPOSITIONS, AND USES THEREOF
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Compounds of Formula (I) are useful as inhibitors of HIF prolyl hydroxylases where the definitions of the variables are provided herein.
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Page/Page column 53-54
(2008/12/06)
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- QUINOLONES AND AZAQUINOLONES THAT INHIBIT PROLYL HYDROXYLASE
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Compounds of Formula I are useful inhibitors of HIF prolyl hydroxylases. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.
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Page/Page column 45
(2008/12/08)
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- NUCLEOSIDES WITH NON-NATURAL BASES AS ANTI-VIRAL AGENTS
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A method and composition for treating a host infected with flavivirus, pestivirus or hepacivirus comprising administering an effective fiavivirus, pestivirus or hepacivirus treatment amount of a described base- modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.
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Page/Page column 130-131
(2008/06/13)
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- ANTIPRURITICS
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It is intended to provide antipruritics (drugs to control itching, antiitch agents and drugs to stop itching). It is found out that a compound having an agonistic activity to the cannabinoid receptor shows an antipruritics effect.
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Page/Page column 41
(2008/06/13)
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- PYRIDONE DERIVATIVE HAVING AFFINITY FOR CANNABINOID 2-TYPE RECEPTOR
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It was found that the compound having a binding activity to the cannabinoid type 2 receptor represented by the formula (I): wherein R' is a group represented by the formula: -Y1-Y2-Y3Ra wherein Y1 is single bond or the like; Y2 is -C(=O)-NH- or the like; Y3 is optionally substituted aryl or the like; R2 is hydrogen or the like; R3 is alkyl or the like; R4 is alkyl or the like; R5 is optionally substituted alkyl or the like; or R3 and R4 taken together with the adjacent atom form cyclic group or the like.
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Page/Page column 59-60
(2008/06/13)
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- Angiotensin II receptor antagonists
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Compounds are disclosed having the formula: STR1 The compounds of the invention are angiotensin II receptor antagonists.
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- 2-(Alkylamino)nicotinic Acid and Analogs. Potent Angiotensin II Antagonists
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A series of pyridines and other six-membered ring heterocycles connected to a biphenyltetrazole with a-CH2-NR'-link (1) were discovered to be potent angiotensin II antagonists.In the pyrimidine carboxylic acid series (W = CR, X = N, Y = CH, Z = COOH), compounds with an alkyl group (R') on the exocyclic nitrogen were much more potent than compounds with an alkyl group (R) on the heterocyclic ring.The corresponding pyridine, pyridazine, pyrazine, and 1,2,4-triazine carboxylic acids also showed potent in vitro angiotensin II antagonism.The pyridine (W, X, Y = CH, Z = COOH, R' = n-C3H7) demonstrated potent in vitro activity (pA2 = 10.10, rabbit aorta, and Ki = 0.61 nM, receptor binding in rat liver) as well as exceptional oral antihypertensive activity and bioavailability.Any nonacidic replacement for the carboxylic acid was detrimental for activity.
- Winn, Martin,De, Biswanath,Zydowsky, Thomas M.,Altenbach, Robert J.,Basha, Fatima Z.,et al.
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p. 2676 - 2688
(2007/10/02)
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- Process for the preparation of fused pyridine compounds
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2-Amino-4-hydroxy-6-[2-(4-carboxyphenyl)alk-1-en-1-yl]pyrido[2,3,-d]pyrimidines and 2-amino-4-hydroxy-6-[2-(4-carboxyphenyl)alk-1-yn-1-yl]pyrido[2,3-d]pyrimidines are prepared through the reaction of a haloaromatic compound and an unsaturated compound in the presence of a palladium catalyst. The products are chemical intermediates for the preparation of antineoplastic agents. A typical embodiment is the reaction of a protected 2-amino-4-hydroxy-6-ethynylpyrido[2,3-d]pyrimidine and an ester of 4-iodobenzoic acid.
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- The Mechanism of the Reaction of Nicotinic Acid 1-Oxide with Acetic Anhydride
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In order to elucidate the mechanism of the 2-acetylation in the reaction of nicotinic acid 1-oxide (2a) with boiling acetic anhydride, thermal reactions and reactions with hot acetic anhydride have been explored with 3-X-pyridine 1-oxides (2).The former reactions of 2d (X = CONHAc), 2f (X = CONMeAc), 2h (X = CH2OAc) and 2j result in recovery or decomposition.The latter reactions of 2c (X = CONH2), 2d, 2e (X = CONHMe), 2h and 2j bring about mainly deoxygenative α-acetoxylation, no 2-acetylation being noticed.However, the reaction of 2f with acetic anhydride affords 6,7-dihydro-6-methyl-7-methylene-5H-pyrrolopyridin-5-one 1-oxide (7) as an initial product, which further undergoes deoxygenative β-acetoxylation to give 7-acetoxy-7-acetoxymethyl-6,7-dihydro-6-methyl-5H-pyrrolopyridin-5-one (8) and 7-acetoxymethylene-6,7-dihydro-6-methyl-5H-pyrrolopyridin-5-one (9).On the basis of the results we propose a new electrophilic pathway for the 2-acetylation of 2a and 2f.Keywords - pyridine 1-oxide 3-substituted; nicotinic acid 1-oxide; nicotinamide 1-oxide N-acetyl-N-methyl; pyrrolopyridine; 2-acetylation; pyridone formation
- Nagano, Hiroyuki,Nawata, Yoshiharu,Hamana, Masatomo
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p. 4068 - 4077
(2007/10/02)
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- Ring Transformation Reactions of 1-Substituted 2(1H)-Pyrimidinones and Related Compounds with Active Methylene Compounds
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1-Substituted 2(1H)-pyrimidinones (I) underwent ring transformation with malononitrile and ethyl acetoacetate in the presence of sodium ethoxide to give 2-amino-3-pyridinecarbonitriles (II-VII) and N-(substituted)amino-3-pyridinecarboxylic acids (XIV and XV), respectively.Further, I reacted with ethyl cyanoacetate, dialkyl malonate, or ethyl benzoylacetate to give pyridine derivatives (VIII-XIII) bearing various functional groups at the C-3 position.The reaction of 1-substituted 2(1H)-pyrimidinethiones and 4,6-dimethyl-1-phenyl-2-phenylimino-1,2-dihydropyrimidine with active methylene compounds is also discussed.Keywords - ring transformation; 1-substituted 2(1H)-pyrimidinone; 1-substituted 2(1H)-pyrimidinethione; active methylene compound; sodium alkoxide; pyridine derivative.
- Katoh, Akira,Omote, Yoshimori,Kashima, Choji
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p. 2942 - 2946
(2007/10/02)
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