- ETHANEDIAMINE-HETEROCYCLE DERIVATIVES AS INHIBITORS OF PROTEIN ARGININE METHYLTRANSFERASES
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The present invention relates to ethanediamine-heterocycle compounds that are able to act as inhibitors of PRMTs (protein arginine methyltransferases) for treating cancer and other diseases mediated by PRMTs.
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- ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS
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Compounds, methods of use, and processes for making inhibitors of complement Factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R12 or R13 on the A group is an aryl, heteroaryl or heterocycle (R32) are provided. The inhibitors of Factor D described herein reduce the excessive activation of complement.
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Paragraph 0574
(2017/03/14)
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- As hepatitis c inhibitor spiro compound and its use in medicine
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The invention provides a spiro compound serving as a hepatitis c inhibitor and application thereof in a medicine. The compound is a compound as shown in a formula (I) or a stereisomer, a geometric isomer, a tautomer, nitric oxide, an aquo-complex, a solvate, a metabolite, pharmaceutically acceptable salt or prodrug of the compound as shown in the formula (I). The invention also provides a pharmaceutical composition containing the compound, application of the compound and the pharmaceutical composition in inhibition of HCV (Hepatitis C Virus) copy and HCV virus protein, as well as the application of the compound and the pharmaceutical composition in prevention, handling, treatment or relieving of HCV infection or hepatitis c disease for a patient. The formula I is as shown in the specification.
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- NOVEL COMPOUNDS USEFUL FOR THE TREATMENT OF BACTERIAL INFECTIOUS DISEASES
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Compounds are disclosed that have a formula represented by the following: wherein A, B, R1, R2 and R3 are as defined herein. Novel compounds of the invention may be prepared as a pharmaceutical composition, and may be useful in the treatment of infectious diseases, in particular bacterial infectious diseases. The compounds may be active against a specific enzyme in the bacterial DNA replicative process, DNA polymerase IIIE.
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Paragraph 0303
(2016/10/31)
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- Bridged Ring compounds As Hepatitis C Virus (HCV) Inhibitors And Pharmaceutical Applications Thereof
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Provided herein is a compound having Formula (I), or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating HCV infection or a HCV disorder. Also provided herein are pharmaceutical compositions comprising the compounds disclosed herein, which can be used for treating HCV infection or a HCV disorder.
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- BRANIMYCIN DERIVATIVES AND THEIR USE FOR THE TREATMENT OF BACTERIAL INFECTIOUS DISEASES
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Compounds are disclosed that have a formula represented by Formula (I) wherein A, B, R1, R2 and R3 are as defined herein. Novel compounds of the invention may be prepared as a pharmaceutical composition, and may be useful in the treatment of infectious diseases, in particular bacterial infectious diseases. The compounds may be active against a specific enzyme in the bacterial DNA replicative process, DNA polymerase IIIE.
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Paragraph 00222
(2015/03/16)
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- NOVEL FAP INHIBITORS
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The present invention relates to novel inhibitors having high selectivity and specificity for FAP (fibroblast activation protein). Said inhibitors are useful as a human and/or veterinary medicine, in particular for the treatment and/or prevention of FAP-related disorders such as but not limited to proliferative disorders.
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- BRIDGED RING COMPOUNDS AS HEPATITIS C VIRUS (HCV) INHIBITORS AND PHARMACEUTICAL APPLICATIONS THEREOF
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Provided herein is a compound having Formula (I), or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating HCV infection or a HCV disorder. Also provided herein are pharmaceutical compositions comprising the compounds disclosed herein, which can be used for treating HCV infection or a HCV disorder.
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- FUSED RING COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
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Provided are fused tricyclic compounds effective to inhibit the function of the NS5A protein of formula (I), wherein X, X', Y, Y', A, A',Q1, Q2, R1-R4, X4, R5a, f and W are defined as in the description. Also provided herein are pharmaceutical compositions thereof, and uses in the manufacture of a medicament for treating HCV infection or a HCV disorder thereof.
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- SPIRO RING COMPOUND AS HEPATITIS C VIRUS (HCV) INHIBITOR AND USES THEREOF FIELD OF THE INVENTION
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A compound of formula (I) or a stereoisomer, a geometric isomer. a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof is provided, which can be used for treating HCV infection or a HCV disorder. Also a pharmaceutical composition comprising the compound and the use of the compound and the pharmaceutical composition thereof are provided, which can also be used for treating HCV infection or a HCV disorder.
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- Extended structure-activity relationship and pharmacokinetic investigation of (4-quinolinoyl)glycyl-2-cyanopyrrolidine inhibitors of fibroblast activation protein (FAP)
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Fibroblast activation protein (FAP) is a serine protease related to dipeptidyl peptidase IV (DPPIV). It has been convincingly linked to multiple disease states involving remodeling of the extracellular matrix. FAP inhibition is investigated as a therapeutic option for several of these diseases, with most attention so far devoted to oncology applications. We previously discovered the N-4-quinolinoyl-Gly-(2S)-cyanoPro scaffold as a possible entry to highly potent and selective FAP inhibitors. In the present study, we explore in detail the structure-activity relationship around this core scaffold. We report extensively optimized compounds that display low nanomolar inhibitory potency and high selectivity against the related dipeptidyl peptidases (DPPs) DPPIV, DPP9, DPPII, and prolyl oligopeptidase (PREP) the log D values, plasma stabilities, and microsomal stabilities of selected compounds were found to be highly satisfactory. Pharmacokinetic evaluation in mice of selected inhibitors demonstrated high oral bioavailability, plasma half-life, and the potential to selectively and completely inhibit FAP in vivo.
- Jansen, Koen,Heirbaut, Leen,Verkerk, Robert,Cheng, Jonathan D.,Joossens, Jurgen,Cos, Paul,Maes, Louis,Lambeir, Anne-Marie,De Meester, Ingrid,Augustyns, Koen,Van Der Veken, Pieter
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p. 3053 - 3074
(2014/05/06)
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- BRIDGED RING COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
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Provided herein is a compound of formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating HCV infection or a HCV disorder. Also provided herein are a pharmaceutical composition comprising the compound and the use of the compound and the pharmaceutical composition thereof, which can also be used for treating HCV infection or a HCV disorder.
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- NOVEL FAP INHIBITORS
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The present invention relates to novel inhibitors having high selectivity and specificity for FAP (fibroblast activation protein). Said inhibitors are useful as a human and/or veterinary medicine, in particular for the treatment and/or prevention of FAP-related disorders such as but not limited to proliferative disorders.
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- METABOTROPIC GLUTAMATE RECEPTORS 5 MODULATORS AND METHODS OF USE THEREOF
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Compounds that modulate GluR5 activity and methods of using the same are disclosed.
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Page/Page column 152
(2012/12/13)
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- PYRROLOTRIAZINONE DERIVATIVES AS PI3K INHIBITORS
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New pyrrolotriazinone derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Phosphoinositide 3-Kinases (PI3Ks).
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Page/Page column 138-139
(2012/11/13)
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- 1,3-Dihydro-2H-Indole-2-One Compound and Pyrrolidine-2-One Compound Fused With Aromatic Heterocycle
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It is intended to provide a drug which is efficacious against pathological conditions relating to arginine-vasopressin V1b receptor. More particularly speaking, it is intended to provide a drug which has a therapeutic or preventive effect on depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorders, hypertension, digestive diseases, drug addiction, epilepsy, brain infarction, brain ischemia, brain edema, head injury, inflammation, immune diseases, alopecia and so on. As the results of intensive studies, a novel 1,3-dihydro-2H-indol-2-one compound and a pyrrolidin-2-one compound fused with a heteroaromatic ring, which are highly selective antagonists of arginine-vasopressin V1b receptor, have high metabolic stabilities and show favorable brain penetration and high plasma concentrations, are found, thereby achieving the above objective.
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Page/Page column 60
(2009/01/24)
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- Synthesis, biological evaluation, and pharmacokinetic study of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives as VLA-4 antagonists
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A series of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives were synthesized and evaluated for their activity as VLA-4 antagonists. Of 22 compounds synthesized, 19 compounds showed potent activity with low nanomolar IC50 values. In addition, the representative compounds 11o and 11p with a hydroxy group in the pyrrolidine ring showed moderate plasma clearance in rats (11o, 30 ml/min/kg and 11p, 21 ml/min/kg) and in dogs (11o, 12 ml/min/kg and 11p, 9 ml/min/kg).
- Chiba, Jun,Takayama, Gensuke,Takashi, Tohru,Yokoyama, Mika,Nakayama, Atsushi,Baldwin, John J.,McDonald, Edward,Moriarty, Kevin J.,Sarko, Christopher R.,Saionz, Kurt W.,Swanson, Robert,Hussain, Zahid,Wong, Angela,MacHinaga, Nobuo
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p. 2725 - 2746
(2007/10/03)
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- 1,3-DIHYDRO-2H-INDOL-2-ONE DERIVATIVE
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A 1,3-dihydro-2H-indol-2-one derivative expressed by Formula 1 (wherein R1 is a halogen atom, a C1 to C4 alkyl group, etc., and R2 is a hydrogen atom, a halogen atom, etc., or R2 is in the 6-position of the indol-2-one and R1 and R2 join together to form a C3 to C6 alkylene group, R3 is a halogen atom, a hydroxyl group, etc., and R4 is a hydrogen atom, a halogen atom, a C1 to C4 alkyl group, etc., or R4 is in the 3-position of the phenyl and R3 and R4 join together to form a methylenedioxy group, R5 is a hydrogen atom or a fluorine atom, R6 is an ethylamino group, a dimethylamino group, etc., R7 is a C1 to C4 alkoxy group, and R8 is a C1 to C4 alkoxy group), or a pharmaceutically acceptable salt of this derivative. This is a novel compound that has antagonistic activity against an aruginine-vasopressin V1b receptor.
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Page/Page column 19-20
(2008/06/13)
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- PYRROLIDINE-2-CARBONITRILE DERIVATIVES AND THEIR USE AS INHIBITORS OF DIPEPTIDYL PEPTIDASE-IV (DPP-IV)
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The present invention relates to compounds of formula (I), (I), which inhibit dipeptidyl peptidase IV (DPP-IV) and are useful for the prevention or treatment of diabetes, especially type II diabetes, as well as hyperglycemia, syndrome X, hyperinsulinemia, b-cell failure, obesity, satiety disorders, atherosclerosis, and various immunomodulatory diseases.
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Page/Page column 72
(2008/06/13)
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- Pharmaceutical compositions as inhibitors of dipeptidyl peptidase-IV (DPP-IV)
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The present invention relates to compounds of formula (I), which inhibit dipeptidyl peptidase IV (DPP-IV) and are useful for the prevention or treatment of diabetes, especially type II diabetes, as well as hyperglycemia, syndrome X, hyperinsulinemia, β-cell failure, obesity, satiety disorders, atherosclerosis, and various immunomodulatory diseases.
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Page/Page column 31; 34
(2010/02/12)
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- 2-CYANOPYRROLIDINE DERIVATIVES AND THEIR USE AS DPP-IV INHIBITORS
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A compound of the formula (I) or a pharmaceutically acceptable salt thereof: [wherein X is CFH, or CF?2#191, R?1? is the moiety represented by the formula: [wherein R?2? is (lower) alkyl, R?3? is phenyl-(lower)alkyl, and the like.], and the like.] Compounds of formula (I) inhibit DPP-IV activity. They are therefore useful in the treatment of conditions mediated by DPP-IV, such as NIDDM.
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- Practical synthesis of Boc and Fmoc protected 4-fluoro and 4-difluoroprolines from trans-4-hydroxyproline
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Boc-cis-4-fluoro-L-proline and 4-difluoro-L-proline, usable in classical peptide synthesis, were obtained in respectively 71% (3 steps) and 65% (4 steps) overall yields from the readily available trans-4-hydroxy-L-proline methyl ester. The corresponding fluorinated trans-isomer was isolated in 24% yield (5 steps). Transformation of Boc-protected compounds to their Fmoc-equivalents was performed in high yields.
- Demange, Luc,Menez, Andre,Dugave, Christophe
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p. 1169 - 1172
(2007/10/03)
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