- MONOACYLGLYCEROL LIPASE INHIBITORS
-
Provided are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof: Also provided are compositions comprising compounds of formula (I). The compounds and compositions are also provided for use as medicaments, for example as medicaments useful in the treatment of a condition modulated by monoacylglycerol lipase (MAGL). Also provided are the use of compounds and compositions for the inhibition of monoacylglycerol lipase (MAGL).
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Paragraph 0109-0110; 0141; 0151-0152; 0179-0180
(2021/09/09)
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- COMPOUND SIMULTANEOUSLY INHIBITING LSD1 AND HDAC TARGETS AND APPLICATION THEREOF
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A compound having a general structural formula as shown in Formula I: X-AB-Y (Formula I); in the above Formula I, X is selected from any one of -CO2H, -CONHZ, -CH=CH-CO2H, -CH=CH-CONHZ, wherein Z is selected from any one of substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted aryl, and hydroxyl; Y = -NR1R2, wherein NR1R2 is a substituted or unsubstituted 3- to 9-membered nitrogen-containing heterocycloalkyl; A and B are each independently selected from substituted or unsubstituted phenylene, substituted or unsubstituted azaphenylene. The compound or corresponding pharmaceutical salt thereof can inhibit LSD1 and HDAC target proteins at the same time, thus inhibit the proliferation of many kinds of tumor cells and have good antitumor effect.
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Paragraph 0041-0042; 0044
(2020/11/26)
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- POLYCYCLIC COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF RAPIDLY ACCELERATED FIBROSARCOMA POLYPEPTIDES
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The present disclosure relates to bifunctional compounds, ULM— L—PTM, which find utility as modulators of Rapidly Accelerated Fibrosarcoma (RAF, such as c-RAF, A- RAF and/or B-RAF; the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein RAF, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein, or the constitutive activation of the target protein, are treated or prevented with compounds and compositions of the present disclosure.
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Paragraph 0544; 0545
(2020/03/29)
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- RET INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
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Provided herein are a RET inhibitor, a pharmaceutical composition thereof and uses thereof. In particular, provided is a compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Provided is a pharmaceutical composition comprising the compound, and uses of the compound and pharmaceutical composition thereof for the preparation of a medicament, in particular for treatment and prevention of RET-related diseases and conditions, including cancer, irritable bowel syndrome, and/or pain associated with irritable bowel syndrome.
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Paragraph 00497; 00499
(2020/07/06)
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- RET INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
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Provided herein are a RET inhibitor, a pharmaceutical composition thereof and uses thereof. In particular, provided is a compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Provided is a pharmaceutical composition comprising the compound, and uses of the compound and pharmaceutical composition thereof for the preparation of a medicament, in particular for treatment and prevention of RET-related diseases and conditions, including cancer, irritable bowel syndrome, and/or pain associated with irritable bowel syndrome.
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Paragraph 00230; 00538
(2020/07/05)
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- ANTI-PAIN COMPOUND AND PREPARATION METHOD THEREFOR
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Disclosed are a compound represented by the general Formula (I), or a stereisomer, tautomer, derivative, prodrug or pharmaceutically acceptable salt thereof, and a method for preparing the compound and use of the compound in manufacture of a medicament for treating a neuropathic pain and/or neuropathic pain syndrome or a medicament for combating an inflammation: wherein R1 is selected from hydrogen, halogen, alkyl, cyano and haloalkyl, R2 and R3 are independently selected from hydrogen, halogen, alkyl, haloalkyl and nitro, and R1, R2 and R3 are not hydrogen at the same time; furthermore, when either R2 or R3 is nitro or halogen, the other two of R1, R2 and R3 are not hydrogen at the same time. The compound has good effects in treating a neuropathic pain and/or neuropathic pain syndrome and good effects in combating an inflammation, and has not side effects such as addiction.
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Paragraph 0095; 0100
(2020/11/23)
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- Substituted piperazine compounds and method and use thereof
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The invention relates to a new piperazine compound and a drug composition comprising the compound, which are used for inhibiting 5-hydroxytryptamine reuptake and/or agonizing 5-HT1A receptors. The invention also relates to methods for preparing the compou
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Paragraph 0346; 0348; 0349
(2019/03/21)
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- METHODS FOR TREATING PATIENTS WITH CANCER HAVING DEFECTS IN CYCLIN D REGULATION
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The present disclosure relates to methods of treating cancer comprising administering Parkin ligase activator or a pharmaceutically acceptable salt thereof to a subject who has a mutant form of a protein in the Rb checkpoint pathway. The Parkin ligase activator includes triazole compounds, such as compounds of formula (I), and pharmaceutically acceptable salts thereof as disclosed herein. R1, R2, R3, M1, M2, M3, L1, L2, and L3 are as defined herein.
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Paragraph 718; 720
(2019/11/12)
-
- COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF RAPIDLY ACCELERATED FIBROSARCOMA POLYPEPTIDES
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The present disclosure relates to bifunctional compounds, which find utility as modulators of Rapidly Accelerated Fibrosarcoma (RAF, such as c-RAF, A-RAF and/or B-RAF; the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein RAF, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein, or the constitutive activation of the target protein, are treated or prevented with compounds and compositions of the present disclosure.
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Paragraph 1272
(2018/07/15)
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- METALLOENZYME INHIBITOR COMPOUNDS
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The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.
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Page/Page column 112
(2017/07/31)
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- COMPOUNDS FOR TREATMENT OF INFLAMMATORY DISEASES
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The present invention relates to a compound for treating inflammatory diseases, wherein the compound is represented by chemical formula I, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof. According to the present invent
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Paragraph 0131-0134
(2016/10/07)
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- HETEROCYCLIC COMPOUND
-
The present invention provides a compound having a superior JAK inhibitory action, which is useful as an agent for the prophylaxis or treatment of autoimmune diseases (rheumatoid arthritis, psoriasis, inflammatory bowel disease, Sjogren's syndrome, Behcet's disease, multiple sclerosis, systemic lupus erythematosus, etc.), cancer (leukemia, uterine leiomyosarcoma, prostate cancer, multiple myeloma, cachexia, myelofibrosis, etc.) and the like, or a salt thereof. The present invention relates to a compound represented by the formula wherein each symbol is as defined in the specification, or a salt thereof.
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Paragraph 1050
(2015/04/15)
-
- Novel inhibitors of bacterial biofilms and related methods
-
Multi-cyclic compounds of chemical structure represented by formula given below and compositions thereof are useful for reducing or inhibiting the growth of bacterial biofilms and for controlling bacterial biofilm infections. Such compounds and compositions are also useful in methods for reducing or inhibiting the growth of biofilms and for controlling bacterial biofilm infections involving biofilms.
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Paragraph 0405; 0406
(2014/05/06)
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- Palladium-mediated conversion of para-aminoarylboronic esters into para-aminoaryl-11C-methanes
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Cross-couplings are an alternative to conventional 11C- methylations which are generally employed in PET tracer synthesis. Therefore, we set out to develop a general procedure for the synthesis of para- 11CH3 labeled aromatic amines from the corresponding para-aminoarylboronic esters in the presence of free amines. Aryl boronic esters containing primary, secondary, and tertiary amines were successfully converted into corresponding labeled methyl derivatives in sufficient radiochemical yield to apply this method for tracer development. This procedure was applied to the labeling of CIMBI-712, a promising candidate for the in vivo imaging of the 5-HT7 receptor in the CNS.
- Andersen, Valdemar L.,Herth, Matthias M.,Lehel, Szabolcs,Knudsen, Gitte M.,Kristensen, Jesper L.
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supporting information
p. 213 - 216
(2013/02/22)
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- SOLUBLE GUANYLATE CYCLASE ACTIVATORS
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This inventions relates to compounds having the structure Formula I and pharmaceutically acceptable salts thereof which are soluble guanylate cyclase activators. The compounds are useful for treatment or prevention of cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, pulmonary hypertension, angina pectoris, thromboses, restenosis, myocardial infarction, strokes, cardiac insufficiency, pulmonary hypertonia, erectile dysfunction, asthma bronchiale, chronic kidney insufficiency, diabetes, or cirrhosis of the liver.
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Paragraph 0224; 0225
(2013/08/28)
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- Inhibitors of bacterial biofilms and related methods
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Certain multi-cyclic compounds and compositions thereof are useful for reducing or inhibiting the growth of bacterial biofilms and for controlling bacterial biofilm infections. Such compounds and compositions are also useful in methods for reducing or inhibiting the growth of biofilms and for controlling bacterial biofilm infections involving biofilms.
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Page/Page column 173
(2012/12/13)
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- Copper-catalyzed amination of arylboronates with N,N-dialkylhydroxylamines
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A tolerant coupling: The title reaction has been developed to deliver arylamines (see scheme; Bz=benzoyl, dppbz=1,2-bis(diphenylphosphino)benzene). The catalysis is based on electrophilic, umpolung amination and enables the use of secondary acyclic amines. Various functional groups are tolerated, thus opening up a new substrate class for the Chan-Lam-type coupling.
- Matsuda, Naoki,Hirano, Koji,Satoh, Tetsuya,Miura, Masahiro
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p. 3642 - 3645
(2012/05/20)
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- UREA DERIVATIVES AS ANTIBACTERIAL AGENTS
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This invention relates to compounds of the Formula (I):or a pharmaceutically acceptable salt, solvate, ester or isomer thereof, which is useful for the treatment of diseases or conditions mediated by LpxC.
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Page/Page column 32
(2010/04/03)
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- NOVEL INDOLE DERIVATIVE HAVING INHIBITORY ACTIVITY ON I B KINASE
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Disclosed is a compound represented by the general formula (1) or a salt thereof. The compound or a salt thereof has an inhibitory activity on IKKβ and is therefore useful as preventive and/or therapeutic agent for a disease associated with IKKβ. In the formula, R1 represents a hydrogen atom, a lower alkyl group, an aryl group, a hydroxy group, or the like; R2 represents a halogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, or the like; and m represents 0, 1, 2, or the like.
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Page/Page column 38
(2009/12/05)
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- SYNTHESIS AND USE OF HETEROCYCLIC ANTIBACTERIAL AGENTS
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This invention relates to compounds of the following Formula (I); or a pharmaceutically acceptable salt, solvate, ester or isomer thereof, which is useful for the treatment of diseases or conditions mediated by LpxC.
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Page/Page column 51
(2010/01/30)
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- Identification of small molecule agonists of the motilin receptor
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High-throughput screening resulted in the identification of a series of novel motilin receptor agonists with relatively low molecular weights. The series originated from an array of biphenyl derivatives designed to target 7-transmembrane (7-TM) receptors. Further investigation of the structure-activity relationship within the series resulted in the identification of compound (22) as a potent and selective agonist at the motilin receptor.
- Heightman, Tom D.,Conway, Elizabeth,Corbett, David F.,Macdonald, Gregor J.,Stemp, Geoffrey,Westaway, Susan M.,Celestini, Paolo,Gagliardi, Stefania,Riccaboni, Mauro,Ronzoni, Silvano,Vaidya, Kalindi,Butler, Sharon,McKay, Fiona,Muir, Alison,Powney, Ben,Winborn, Kim,Wise, Alan,Jarvie, Emma M.,Sanger, Gareth J.
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scheme or table
p. 6423 - 6428
(2009/10/01)
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- HETEROCYCLIC COMPOUNDS AND USE THEREOF AS ERK INHIBITORS
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Disclosed are the ERK inhibitors of formula 1.0: [Formula (1.0)] and the pharmaceutically acceptable salts, esters and solvates thereof. Q is a piperidine or piperazine ring that can have a bridge or a fused ring. The piperidine ring can have a double bond in the ring. All other substitutents are as defined herein. Also disclosed are methods of treating cancer using the compounds of formula 1.0.
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Page/Page column 195
(2009/01/23)
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- POLYCYCLIC INDAZOLE DERIVATIVES THAT ARE ERK INHIBITORS
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Disclosed are the ERK inhibitors of formula 1.0 and the pharmaceutically acceptable salts and solvates thereof. Q is a piperidine or piperazine ring that can have a bridge or a fused ring. The piperidine ring can have a double bond in the ring. All other substitutents are as defined herein. Also disclosed are methods of treating cancer using the compounds of formula 1.0.
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Page/Page column 189-190
(2008/06/13)
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- PYRROLIDINE DERIVATIVES AS ERK INHIBITORS
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Disclosed are the ERK inhibitors of Formula (1.0): and the pharmaceutically acceptable salts and solvates thereof. Q is a piperidine or piperazine ring that can have a bridge or a fused ring. The piperidine ring can have a double bond in the ring. All other substitutents are as defined herein. Also disclosed are methods of treating cancer using the compounds of Formula (1.0).
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Page/Page column 178
(2010/11/28)
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- SELECTED CGRP ANTAGONISTS, METHOD FOR PRODUCTION AND USE THEREOF AS MEDICAMENT
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The invention relates to CGRP antagonists of general formula (I), in which A, U, V, W, X and R1 to R 3 are as defined in claim 1, the tautomers, diastereomers, enantiomers, hydrates, mixtures, salts, hydrates of the salts, in particular the physiologically-acceptable salts thereof with inorganic or organic acids, medicaments containing said compounds and the use and methods for production thereof.
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Page/Page column 167
(2008/06/13)
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- METHOD OF PREPARING INHIBITORS OF PHOSPHODIESTERASE-4
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In one aspect, the present invention is directed to a one pot method of preparing intermediates of Formula V, which are useful in making inhibitors of phosphodiesterase-4: The present invention is also directed to a method of preparing phosphodiesterase inhibitors comprising the Formula
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- Practical asymmetric synthesis of a potent Cathepsin K inhibitor. Efficient palladium removal following Suzuki coupling
-
A large-scale, chromatography-free synthesis of a potent and selective Cathepsin K inhibitor 1 is reported. The key asymmetric center was installed by addition of (R)-pantolactone to the in situ-generated ketene 4a. The final step of the convergent synthe
- Chen, Cheng-yi,Dagneau, Philippe,Grabowski, Edward J.J.,Oballa, Renata,O'Shea, Paul,Prasit, Peppi,Robichaud, Joel,Tillyer, Rich,Wang, Xin
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p. 2633 - 2638
(2007/10/03)
-
- A novel class of nonpeptidic biaryl inhibitors of human cathepsin K
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A novel series of nonpeptidic biaryl compounds was identified as potent and reversible inhibitors of cathepsin K. The P2-P3 amide bond of a known amino acetonitrile dipeptide 1 was replaced with a phenyl ring, thereby giving rise to this biaryl series that retained potency vs cathepsin K and showed an improved selectivity profile against other cathepsins. Structural modification within this series resulted in the identification of compound (R)-2, a potent human cathepsin K inhibitor (IC50 = 3 nM) that is selective versus cathepsins B (IC50 = 3950 nM), L (IC50 = 3725 nM), and S (IC50 = 2010 nM). In an in vitro assay involving rabbit osteoclasts and bovine bone, compound (R)-2 inhibited bone resorption with an IC 50 of 95 nM. It was shown that, unlike some peptidic nitrile inhibitors of cysteine proteases, the nitrile moiety of (R)-2 is not converted to the corresponding amide 3 by cathepsin K. This indicates that this class of nonpeptidic nitrile inhibitors is unlikely to be hydrolyzed by cysteine proteases. Furthermore, the inhibition of cathepsin K by compound (R)-2 was shown to be fully reversible and not observably time-dependent. To demonstrate the efficacy of compound (R)-2 in vivo, it was administered to ovariectomized (OVX) rhesus monkeys at 20 mg/kg, po once daily for 8 days, and a urinary marker of bone turnover, N-telopeptide of type I collagen (uNTx), was measured. During the eight-day dosing period, the mean reduction by compound (R)-2 in uNTx was 80% (p 0.001). This demonstrates that inhibition of cathepsin K leads to an inhibition of this bone resorption marker in OVX rhesus monkeys and strongly suggests that inhibition of cathepsin K is a viable therapeutic approach for the treatment of osteoporosis.
- Robichaud, Jo?l,Oballa, Renata,Prasit, Peppi,Falgueyret, Jean-Pierre,Percival, M. David,Wesolowski, Gregg,Rodan, Sevgi B.,Kimmel, Donald,Johnson, Colena,Bryant, Cliff,Venkatraman, Shankar,Setti, Eduardo,Mendonca, Rohan,Palmer, James T.
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p. 3709 - 3727
(2007/10/03)
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