- SUBSTITUTED BENZAZINONES AS ANTIBACTERIAL COMPOUNDS
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The present invention relates to LpxC antibacterial compounds of Formula (1A), corresponding pharmaceutically acceptable salts thereof, corresponding pharmaceutical compositions:, compound preparation, treatment methods and uses for bacterial infections, especially those caused by gram-negative bacteria.
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Page/Page column 184
(2017/07/14)
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- ANTIDIABETIC TRICYCLIC COMPOUNDS
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Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR 40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds may be useful in the treatment of Type 2 diabetes mellitus and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.
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Page/Page column 133
(2015/12/08)
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- INHIBITORS OF FATTY ACID AMIDE HYDROLASE
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The present invention provides compounds, and pharmaceutically acceptable compositions thereof, encompassed by any of formulae (I), (II), (III), (IV), (V), or (VI), or subgenera thereof. The present invention also provides methods for treating an FAAH mediated disease, disorder or condition by administering a therapeutically effective amount of a compound or composition comprising a compound of any of formulae (I), (II), (III), (IV), (V), or (VI), or subgenera thereof, to a patient in need thereof. Additionally, the present invention provides methods for inhibiting FAAH by administering a therapeutically effective amount of a compound or composition comprising a compound of any of formulae (I), (II), (III), (IV), (V), or (VI), or subgenera thereof, to a patient in need thereof.
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Paragraph 1263
(2016/01/15)
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- NOVEL COMPOUNDS AS REARRANGED DURING TRANSFECTION (RET) INHIBITORS
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This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.
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Paragraph 0347; 0348
(2014/09/30)
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- PYRIDINE DERIVATIVES AS REARRANGED DURING TRANSFECTION (RET) KINASE INHIBITORS
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This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.
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Page/Page column 76
(2014/09/29)
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- TETRAHYDROTHIAZEPINE DERIVATIVE
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The present invention relates to a compound represented by the following general formula (I) or a pharmacologically acceptable salt thereof having an excellent effect of inhibiting 11β-hydroxysteroid dehydrogenase type 1: General formula (I) wherein R1 represents a phenyl group that may be substituted with 1 to 5 group(s) independently selected from substituent group A or a heterocyclic group that may be substituted with 1 to 4 group(s) independently selected from substituent group A; R2 independently represents a halogen atom or a C1-C6 alkyl group; n represents an integer of 0 to 2; and substituent group A represents the group consisting of halogen atoms, C1-C6 alkyl groups, and so forth.
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Paragraph 0235
(2014/03/24)
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- Inhibition of amyloidogenesis by nonsteroidal anti-inflammatory drugs and their hybrid nitrates
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Poor blood-brain barrier penetration of nonsteroidal anti-inflammatory drugs (NSAIDs) has been blamed for the failure of the selective amyloid lowering agent (SALA) R-flurbiprofen in phase 3 clinical trials for Alzheimer's disease (AD). NO-donor NSAIDs (NO-NSAIDs) provide an alternative, gastric-sparing approach to NSAID SALAs, which may improve bioavailability. NSAID analogues were studied for anti-inflammatory activity and for SALA activity in N2a neuronal cells transfected with human amyloid precursor protein (APP). Flurbiprofen (1) analogues were obtained with enhanced anti-inflammatory and antiamyloidogenic properties compared to 1, however, esterification led to elevated A 1-42 levels. Hybrid nitrate prodrugs possessed superior anti-inflammatory activity and reduced toxicity relative to the parent NSAIDs, including clinical candidate CHF5074. Although hybrid nitrates elevated A 1-42 at higher concentration, SALA activity was observed at low concentrations (1 μM): both A1-42 and the ratio of A 42/A1-40 were lowered. This biphasic SALA activity was attributed to the intact nitrate drug. For several compounds, the selective modulation of amyloidogenesis was tested using an immunoprecipitation MALDI-TOF approach. These data support the development of NO-NSAIDs as an alternative approach toward a clinically useful SALA.
- Schiefer, Isaac T.,Abdul-Hay, Samer,Wang, Huali,Vanni, Michael,Qin, Zhihui,Thatcher, Gregory R. J.
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experimental part
p. 2293 - 2306
(2011/06/20)
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- PROCESS FOR THE PREPARATION OF DERIVATIVES OF 1-(2-HALOBIPHENYL-4-YL)-CYCLOPROPANECARBOXYLIC ACID
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The invention relates to a process for the preparation of a compound of formula (IA).
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Page/Page column 13; 14
(2011/02/24)
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- PROCESS FOR THE PREPARATION OF DERIVATIVES OF 1-(2- HALOBIPHENYL-4-YL)-CYCLOPROPANECARBOXYLIC ACID
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Compounds according to formula (IA): may be efficiently prepared by the disclosed process.
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Page/Page column 5
(2011/04/13)
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- SUBSTITUTED IMIDAZOLES AS BOMBESIN RECEPTOR SUBTYPE-3 MODULATORS
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Certain novel substituted imidazoles are ligands of the human bombesin receptor and, in particular, are selective ligands of the human bombesin receptor subtype-3 (BRS-3). They are therefore useful for the treatment, control, or prevention of diseases and disorders responsive to the modulation of BRS-3, such as obesity, and diabetes.
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Page/Page column 67
(2008/12/05)
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- NEW OXABISPIDINE COMPOUNDS FOR THE TREATMENT OF CARDIAC ARRHYTHMIAS
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There is provided compounds of formula I, [Chemical formula should be inserted here. Please see paper copy] wherein R1 to R4 , R41 to R46 and Z have meanings given in the description, which are useful in the prophylaxis and in the treatment of arrhythmias, in particular atrial and ventricular arrhythmias
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Page/Page column 92
(2010/11/27)
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- REVERSIBLE INHIBITORS OF MONOAMINE OXIDASE A AND B
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The instant invention relates to compounds of formula I, diagrammed below, wherein R3, E, D and Y are defined in the application, which are useful as reversible inhibitors of monoamine oxidase-B and/or monoamine oxidase-A, and therefore useful to treat or prevent neurological diseases or conditions in mammals, preferably humans.
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Page/Page column 30
(2008/06/13)
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- BENZENE COMPOUND HAVING 2 OR MORE SUBSTITUENTS
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Disclosed is an excellent LXR modulator. Specifically disclosed is a compound represented by the general formula (I) below or the like. (I) [In the formula, R1 represents a -COR9 (wherein R9 represents an alkyl, optionally substituted alkoxy or optionally substituted amino); R2 represents an H, OH, alkoxy, optionally substituted amino or the like; R3 represents an H, optionally substituted alkyl, cycloalkyl, optionally substituted alkoxy, optionally substituted amino, halogeno or the like; R4 and R5 respectively represent an H, optionally substituted alkyl, halogeno or the like; R6 and R7 respectively represent an H or alkyl; R8 represents a -X2R10 [wherein R10 represents a -COR11 (wherein R11 represents an OH, optionally substituted alkoxy, optionally substituted amino or the like), -SO2R12 (wherein R12 represents an optionally substituted alkyl, optionally substituted amino or the like), tetrazole-5-yl or the like; and X2 represents a single bond, optionally substituted alkylene or the like]; X1 represents an -NH-, -O-, -S- or the like; Y1 represents an optionally substituted phenyl or optionally substituted 5-membered or 6-membered aromatic heterocyclyl; and Y2 represents an optionally substituted aryl, substituted heterocyclyl or the like.]
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Page/Page column 192
(2010/11/08)
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- SUBSTITUTED INDOLE COMPOUND
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Disclosed is an excellent LXR modulator. A compound represented by the general formula (I): (I) wherein R1, R2, R3 and R4: H, an alkyl which may be substituted, OH, an alkoxy which may be substituted, an amino which may be substituted, a halogeno, a phenyl or the like; R5: H or an alkyl; R6: -COR8 (wherein R8: an alkoxy which may be substituted, a phenyloxy which may be substituted, an amino which may be substituted, or the like), -SO2R9 (wherein R9: an alkyl which may be substituted, a phenyl which may be substituted or a heterocyclyl which may be substituted), or an alkyl which may be substituted; R7: -X2R10 [wherein R10: -COR11 (where R11: OH, an alkoxy which may be substituted or an amino which may be substituted), -SO2R12 (where R12: an alkyl which may be substituted or amino which may be substituted), -N(R13)COR14 (where R13: H or an alkyl which may be substituted; R14: H or an alkyl which may be substituted), -N(R13)SO2R15 (where R13: as defined above; R15: an alkyl which may be substituted) or tetrazol-5-yl; and X2: a single bond or an alkylene which may be substituted]; X1: a methylene which may be substituted; Y1: a phenyl which may be substituted or a heterocyclyl which may be substituted; and Y2: an aryl which may be substituted, a heterocyclyl which may be substituted or the like], or the like.
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Page/Page column 159
(2010/11/24)
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- CATHEPSIN CYSTEINE PROTEASE INHIBITORS
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This invention relates to a novel class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.
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Page/Page column 37
(2010/02/12)
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- Synthesis and biological activity of flurbiprofen analogues as selective inhibitors of β-amyloid1-42 secretion
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Flurbiprofen, a nonsteroidal antiinflammatory drug (NSAID), has been recently described to selectively inhibit β-amyloid1-42 (Aβ42) secretion, the most toxic component of the senile plaques present in the brain of Alzheimer patients. The use of this NSAID in Alzheimer's disease (AD) is hampered by a significant gastrointestinal toxicity associated with cyclooxygenase (COX) inhibition. New flurbiprofen analogues were synthesized, with the aim of increasing Aβ42 inhibitory potency while removing anti-COX activity. In vitro ADME developability parameters were taken into account in order to identify optimized compounds at an early stage of the project. Appropriate substitution patterns at the alpha position of flurbiprofen allowed for the complete removal of anti-COX activity, while modifications at the terminal phenyl ring resulted in increased inhibitory potency on Aβ42 secretion. In rats, some of the compounds appeared to be well absorbed after oral administration and to penetrate into the central nervous system. Studies in a transgenic mice model of AD showed that selected compounds significantly decreased plasma Aβ42 concentrations. These new flurbiprofen analogues represent potential drug candidates to be developed for the treatment of AD.
- Peretto, Ilaria,Radaelli, Stefano,Parini, Carlo,Zandi, Michele,Raveglia, Luca F.,Dondio, Giulio,Fontanella, Laura,Misiano, Paola,Bigogno, Chiara,Rizzi, Andrea,Riccardi, Benedetta,Biscaioli, Marcello,Marchetti, Silvia,Puccini, Paola,Catinella, Silvia,Rondelli, Ivano,Cenacchi, Valentina,Bolzoni, Pier Tonino,Caruso, Paola,Villetti, Gino,Facchinetti, Fabrizio,Del Giudice, Elda,Moretto, Nadia,Imbimbo, Bruno P.
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p. 5705 - 5720
(2007/10/03)
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- 1-PHENYLALKANECARBOXYLIC ACID DERIVATIVES FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
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1-Phenylalkanecarboxylic acid derivatives, the processes for the preparation thereof and the use thereof in the treatment and/or prevention of neurodegenerative diseases such as Alzheimer's disease.
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