- HETEROCYCLIC COMPOUNDS AS PAD INHIBITORS
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Heterocyclic compounds of Formula (I), (II), and (III) are described herein along with their polymorphs, stereoisomers, prodrugs, solvates, co-crystals, intermediates, pharmaceutically acceptable salts, and metabolites thereof. The compounds described herein, their polymorphs, stereoisomers, prodrugs, solvates, co-crystals, intermediates, pharmaceutically acceptable salts, and metabolites thereof are PAD4 inhibitors and may be useful in the treatment of various disorders, for example rheumatoid arthritis, vasculitis, systemic lupus erythematosis, cutaneous lupus erythematosis, ulcerative colitis, cancer, cystic fibrosis, asthma, multiple sclerosis and psoriasis.
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Paragraph 000367
(2019/04/16)
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- IMIDAZO-PYRIDINE COMPOUNDS AS PAD INHIBITORS
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Heterocyclic compounds of Formula (I), (II), and (III) are described herein along with their polymorphs, stereoisomers, prodrugs, solvates, co-crystals, intermediates, pharmaceutically acceptable salts, and metabolites thereof. The compounds described herein, their polymorphs, stereoisomers, prodrugs, solvates, co-crystals, intermediates, pharmaceutically acceptable salts, and metabolites thereof are PAD4 inhibitors and may be useful in the treatment of various disorders, for example rheumatoid arthritis, vasculitis, systemic lupus erythematosis, cutaneous lupus erythematosis, ulcerative colitis, cancer, cystic fibrosis, asthma, multiple sclerosis and psoriasis. The process of preparation of the compounds of Formula (I), (II), and (III), their polymorphs, stereoisomers, prodrugs, solvates, co-crystals, intermediates, pharmaceutically acceptable salts, and metabolites thereof, along with a pharmaceutical composition comprising a compound of Formula (I), Formula (II), Formula (III), or a pharmaceutically acceptable salt thereof have also been described.
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Paragraph 000133; 000330
(2019/05/10)
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- Design, synthesis, and pharmacological evaluation of 4-azolyl-benzamide derivatives as novel GPR52 agonists
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G protein-coupled receptor 52 (GPR52) agonists are expected to improve the symptoms of psychiatric disorders. During exploration for a novel class of GPR52 agonists with good pharmacokinetic profiles, we synthesized 4-(3-(3-fluoro-5-(trifluoromethyl)benzyl)-5-methyl-1H-1,2,4-triazol-1-yl)-2-methylbenzamide (4u; half maximal effective concentration (EC50)?=?75?nM, maximal response (Emax)?=?122%) starting from a high-throughput screening hit 3 (EC50?=?470?nM, Emax?=?56%). The structural features of a reported GPR52 agonist were applied to 3, led to design 4-azolylbenzamides as novel GPR52 agonists. A structure–activity relationship study of 4-azolylbenzamide resulted in the design of the 1,2,4-triazole derivative 4u, which demonstrated excellent bioavailability in rats (F?=?53.8%). Oral administration of 4u (10?mg/kg) significantly suppressed methamphetamine-induced hyperlocomotion in mice. Thus, 4u is a promising lead compound for drug discovery research of GPR52 agonists.
- Tokumaru, Kazuyuki,Ito, Yoshiteru,Nomura, Izumi,Nakahata, Takashi,Shimizu, Yuji,Kurimoto, Emi,Aoyama, Kazunobu,Aso, Kazuyoshi
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p. 3098 - 3115
(2017/05/24)
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- ALKYNE COMPOUNDS AS S-NITROSOGLUTATHIONE REDUCTASE INHIBITORS
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Provided are compounds of formula (Ia) and pharmaceutically acceptable salts thereof, wherein A, B, R 1, R 2, m and n are as defined herein, which are active as inhibitors of S-Nitrosoglutathione reductase (GSNOR). These compounds prevent, inhibit, or suppress the action of GSNOR and are therefore useful in the treatment of GSNOR mediated diseases, disorders, syndromes or conditions such as, e.g., pulmonary hypertension, acute respiratory distress syndrome (ARDS), asthma, bronchospasm, cough, pneumonia, pulmonary fibrosis, interstitial lung diseases, cystic fibrosis and chronic obstructive pulmonary disease (COPD).
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Page/Page column 71; 126; 127
(2016/05/02)
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- FUSED PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY ON FMS KINASES
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Disclosed are a fused pyrimidine derivative of formula (I), and a pharmaceutically acceptable salt, stereoisomer, hydrate and solvate thereof, which have an excellent inhibitory activity on FMS kinases, and a pharmaceutical composition comprising the same is effective in preventing or treating diseases caused by abnormal activation of FMS kinases such as immunologic diseases, metabolic diseases, inflammatory diseases, cancers and tumors.
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Page/Page column 46
(2014/01/17)
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- SUBSTITUTED XANTHINES AND METHODS OF USE THEREOF
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Compounds, compositions and methods are described for inhibiting the TRPC5 ion channel and disorders related to TRPC5.
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Page/Page column 412; 413
(2014/09/29)
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- SUBSTITUTED XANTHINES AND METHODS OF USE THEREOF
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Compounds, compositions and methods are described for inhibiting the TRPC5 ion channel and disorders related to TRPC5.
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Paragraph 0355; 0356
(2014/09/30)
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- ANTIMICROBIAL AGENTS
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The invention provides compounds of formual (I): wherein R1-R7 and W have any of the values defined in the specification, and salts thereof. The compounds have good solubility and are useful for treating bacterial infections.
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Page/Page column 49
(2013/10/08)
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- 1-(DIHYDRONAPHTHALENYL)PYRIDONES AS MELANIN-CONCENTRATING HORMONE RECEPTOR 1 ANTAGONISTS
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Provided are 1-(dihydronaphthalenyl)pyridones which are antagonists at the melanin-concentrating hormone receptor 1 (MCHR1), pharmaceutical compositions containing them, processes for their preparation, and their use in therapy for the treatment of obesity and diabetes.
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Page/Page column 34
(2013/10/22)
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- OXADIAZOLE COMPOUNDS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF
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The invention provides novel beta-secretase inhibitors and methods for their including methods of treating Alzheimer's disease.
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Page/Page column 82
(2012/05/05)
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- FAAH INHIBITORS
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The present disclosure relates to compounds useful as inhibitors of the enzyme Fatty Acid Amide Hydrolase (FAAH). The disclosure also provides pharmaceutically acceptable compositions comprising the compounds of the disclosure and methods of using the com
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Page/Page column 108
(2012/07/13)
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- COMPOUNDS CONTAINING FUSED RINGS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF
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The invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating Alzheimer's disease.
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Page/Page column 80
(2011/11/01)
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- HETEROCYCLIC DERIVATIVES FOR THE TREATMENT OF DISEASES
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The invention relates to compounds of Formula (1) and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such derivatives. The compounds according to the present invention are useful in numerous diseases in which ALK protein is involved or in which inhibition of ALK activity may induce benefit, especially for the treatment of cancer mediated by a mutated EML4-ALK fusion protein.
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Page/Page column 119-120
(2011/11/30)
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- (3-HYDROXY-4-AMINO-BUTAN-2-YL) -3- (2-THIAZOL-2-YL-PYRROLIDINE-1-CARBONYL) BENZAMIDE DERIVATIVES AND RELATED COMPOUNDS AS BETA-SECRETASE INHIBITORS FOR TREATING
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The present invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating of Alzheimer's disease. (Formula)
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Page/Page column 65
(2009/05/29)
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- Compounds
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Compounds of Formula (I), compositions containing them, their use in therapy, including their use as antibacterials, for example in the treatment of tuberculosis, and methods for the preparation of such compounds, are provided.
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Page/Page column 37-38
(2009/08/14)
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- COMPOUNDS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF
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The present invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating of Alzheimer's disease.
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Page/Page column 75
(2009/03/07)
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- Amino-Containing Compounds Which Inhibit Memapsin 2 Beta-Secretase Activity and Methods of Use Thereof
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The present invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating of Alzheimer's disease.
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Page/Page column 19
(2008/12/05)
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- TETRAHYDROCARBAZOLE DERIVATIVES USEFUL AS ANDROGEN RECEPTOR MODULATORS
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The present invention provides a compound of the formula: Formula I or a pharmaceutically acceptable salt thereof; pharmaceutical compositions comprising an effective amount of a compound of Formula I in combination with a suitable carrier, diluent, or ex
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Page/Page column 134
(2010/11/25)
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- BICYCLIC COMPOUNDS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF
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The present invention provides bicyclic beta-secretase inhibitors and methods for their use, including methods of treating of Alzheimer’s disease.
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Page/Page column 59
(2010/10/20)
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- COMPOUNDS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF
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The present invention provides novel beta-secretase inhibitors of the general formula (I), where the variables A1, A2, L1, L2, L3, R1, R2, R3, R4, R5, R6 and R7 are as defined in the claims, a method for their use in treating Alzheimer's disease, and methods for their use in reducing memapsin 2 catalytic activity.
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Page/Page column 49
(2008/06/13)
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- Discovery of functionally selective 7,8,9,10-tetrahydro-7,10-ethano-1,2,4- triazolo[3,4-a]phthalazines as GABAA receptor agonists at the α3 subunit
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We have previously identified the 7,8,9,10-tetrahydro-7,10-ethano-1,2,4- triazolo[3,4-a]phthalazine (1) as a potent partial agonist for the 0.3 receptor subtype with 5-fold selectivity in binding affinity over α1. This paper describes a detailed investigation of the substituents on this core structure at both the 3- and 6-positions. Despite evaluating a wide range of groups, the maximum selectivity that could be achieved in terms of affinity for the α3 subtype over the α1 subtype was 12-fold (for 57). Although most analogues showed no selectivity in terms of efficacy, some did show partial agonism at α1 and antagonism at α3 (e.g., 25 and 75). However, two analogues tested (93 and 96), both with triazole substituents in the 6-position, showed significantly higher efficacy for the α3 subtype over the α1 subtype. This was the first indication that selectivity in efficacy in the required direction could be achieved in this series.
- Russell, Michael G. N.,Carling, Robert W.,Atack, John R.,Bromidge, Frances A.,Cook, Susan M.,Hunt, Peter,Isted, Catherine,Lucas, Matt,McKernan, Ruth M.,Mitchinson, Andrew,Moore, Kevin W.,Narquizian, Robert,Macaulay, Alison J.,Thomas, David,Thompson, Sally-Anne,Wafford, Keith A.,Castro, José L.
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p. 1367 - 1383
(2007/10/03)
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- Diastereoselective synthesis of 2-oxiranyl and 2-aziridinyl thiazoles
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2-Chloroalkylthiazolyllithiums, prepared by deprotonating the 2-chloroalkylthiazoles with n-BuLi at -78°C in THF, add to ketones or imines affording in 'one-pot' oxiranes and aziridines in a Z stereoselective manner.
- Bona, Fabio,De Vitis, Luisella,Florio, Saverio,Ronzini, Ludovico,Troisi, Luigino
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p. 1381 - 1387
(2007/10/03)
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- Inhibitors of protein isoprenyl transferases
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The present invention relates to novel compounds of Formula I which are useful in inhibiting protein isoprenyl transferases and the farnesylation or geranylgeranylation of the oncogene protein Ras and other related small g-proteins, and compositions containing such compounds and methods of using such compounds.
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- TOCOLYTIC OXYTOCIN RECEPTOR ANTAGONISTS
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This invention relates to certain novel benzoxazinone compounds and derivatives thereof, their synthesis, and their use as oxytocin receptor antagonists. One application of these compounds is in the treatment of preterm labor. The ability of the compounds to relax uterine contractions in mammals also makes them useful for treating dysmenorrhea and stopping labor prior to cesarean delivery. A typical compound is as follows: STR1
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- PHARMACEUTICAL COMPOSITIONS AND METHODS OF INHIBITING H-1 AND H-2 HISTAMINE RECEPTORS
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Pharmaceutical compositions and methods of inhibiting H-1 and H-2 histamine receptors by administering an antihistamine and an H-2 histamine receptor inhibitor. Exemplary of the antihistamine in the compositions and methods of this invention is mepyramine and exemplary of the H-2 histamine receptor inhibitor is N-cyano-N'-methyl-N"-2-((4-methyl-5-imidazolyl)-methylthio)ethyl!guanidine. "
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- PHARMACOLOGICALLY ACTIVE GUANIDINE COMPOUNDS
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The compounds are substituted thioalkyl-, aminoalkyl-and oxyalkyl-guanidines which are inhibitors of histamine activity.
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