- COMPOUNDS AND USES THEREOF
-
The present disclosure features compounds useful for the treatment of BAF complex-related disorders.
- -
-
Page/Page column 115
(2021/08/06)
-
- COMPOUNDS AND USES THEREOF
-
The present disclosure features compounds and methods useful for the treatment of BAF complex-related disorders.
- -
-
Page/Page column 231; 232
(2021/08/06)
-
- Structure-Based Discovery of Potent CARM1 Inhibitors for Solid Tumor and Cancer Immunology Therapy
-
CARM1 is a protein arginine methyltransferase and acts as a transcriptional coactivator regulating multiple biological processes. Aberrant expression of CARM1 has been related to the progression of multiple types of cancers, and therefore CARM1 was consid
- Zhang, Zhuqing,Guo, Zuhao,Xu, Xiaowei,Cao, Danyan,Yang, Hong,Li, Yanlian,Shi, Qiongyu,Du, Zhiyan,Guo, Xiaobin,Wang, Xin,Chen, Danqi,Zhang, Ying,Chen, Lin,Zhou, Kaixin,Li, Jian,Geng, Meiyu,Huang, Xun,Xiong, Bing
-
p. 16650 - 16674
(2021/12/02)
-
- COMPOUNDS AND USES THEREOF
-
The present disclosure features compounds useful for the treatment of BAF complex-related disorders.
- -
-
Page/Page column 162
(2020/08/22)
-
- COUMARIN-LIKE CYCLIC COMPOUND AS MEK INHIBITOR AND USE THEREOF
-
Disclosed are a class of coumarin-like cyclic compounds as MEK inhibitors and pharmaceutical compositions comprising the compounds, and the use of same in the preparation of a drug for treating MEK-related diseases. Particularly disclosed are compounds as shown in formula (I) and pharmaceutically acceptable salts thereof or tautomers thereof.
- -
-
Paragraph 0137-0139
(2020/05/30)
-
- First Contact: 7-Phenyl-2-Aminoquinolines, Potent and Selective Neuronal Nitric Oxide Synthase Inhibitors That Target an Isoform-Specific Aspartate
-
Inhibition of neuronal nitric oxide synthase (nNOS), an enzyme implicated in neurodegenerative disorders, is an attractive strategy for treating or preventing these diseases. We previously developed several classes of 2-aminoquinoline-based nNOS inhibitor
- Cinelli, Maris A.,Reidl, Cory T.,Li, Huiying,Chreifi, Georges,Poulos, Thomas L.,Silverman, Richard B.
-
p. 4528 - 4554
(2020/05/05)
-
- CHEMICAL COMPOUNDS
-
The invention is directed to substituted salicylamide derivatives. Specifically, the invention is directed to compounds according to FormμLa (I): wherein R, R1,P, X, Y, and Z are as defined herein; or a pharmaceutically acceptable salt thereof. The compounds of the invention are inhibitors of CD73 and can be usefμL in the treatment of cancer, pre-cancerous syndromes and diseases associated with CD73 inhibition, such as AIDS, the treatment of HIV, autoimmune diseases, infections, atherosclerosis, and ischemia–reperfusion injury. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting CD73 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
- -
-
Page/Page column 106; 107
(2019/04/11)
-
- Arginine methyltransferase inhibitor and pharmaceutical composition and application thereof
-
The invention relates to an arginine methyltransferase inhibitor and a pharmaceutical composition and application thereof, in particular to a compound represented by a formula (I), a pharmaceuticallyacceptable salt, isomer, racemate, prodrug, co-crystal c
- -
-
Paragraph 0345; 0347-0350
(2019/10/29)
-
- K-RAS MODULATORS WITH A VINYL SULFONAMIDE MOIETY
-
Provided herein are compounds comprising a vinyl sulfonamide moiety. Also provided herein are pharmaceutical compositions comprising such compounds, and methods of using such compounds and pharmaceutical compositions for inhibiting the post-translational
- -
-
Paragraph 0414
(2019/11/12)
-
- Reevaluating the Substrate Specificity of the L-Type Amino Acid Transporter (LAT1)
-
The L-type amino acid transporter 1 (LAT1, SLC7A5) transports essential amino acids across the blood-brain barrier (BBB) and into cancer cells. To utilize LAT1 for drug delivery, potent amino acid promoieties are desired, as prodrugs must compete with millimolar concentrations of endogenous amino acids. To better understand ligand-transporter interactions that could improve potency, we developed structural LAT1 models to guide the design of substituted analogues of phenylalanine and histidine. Furthermore, we evaluated the structure-activity relationship (SAR) for both enantiomers of naturally occurring LAT1 substrates. Analogues were tested in cis-inhibition and trans-stimulation cell assays to determine potency and uptake rate. Surprisingly, LAT1 can transport amino acid-like substrates with wide-ranging polarities including those containing ionizable substituents. Additionally, the rate of LAT1 transport was generally nonstereoselective even though enantiomers likely exhibit different binding modes. Our findings have broad implications to the development of new treatments for brain disorders and cancer.
- Chien, Huan-Chieh,Colas, Claire,Finke, Karissa,Springer, Seth,Stoner, Laura,Zur, Arik A.,Venteicher, Brooklynn,Campbell, Jerome,Hall, Colton,Flint, Andrew,Augustyn, Evan,Hernandez, Christopher,Heeren, Nathan,Hansen, Logan,Anthony, Abby,Bauer, Justine,Fotiadis, Dimitrios,Schlessinger, Avner,Giacomini, Kathleen M.,Thomas, Allen A.
-
supporting information
p. 7358 - 7373
(2018/08/06)
-
- NOVEL NON-SYSTEMIC TGR5 AGONISTS
-
The present invention relates to tricyclic compounds of formula (I) and formula (II), or a pharmaceutically acceptable salt thereof. The present tricyclic compounds are useful non-sytemic TGR5 agonists that can be used to treat diabetic diseases in human. The present invention provides a pharmaceutical composition containing tricyclic compounds of formula (I) and formula (II) and a method of making as well as a method of using same in treating patients inflicted with metabolic disorders by administering same. The compounds of the present invention may be used in combination with additional anti-diabetic drugs.
- -
-
Page/Page column 94
(2018/02/28)
-
- Trisubstituted Imidazoles with a Rigidized Hinge Binding Motif Act As Single Digit nM Inhibitors of Clinically Relevant EGFR L858R/T790M and L858R/T790M/C797S Mutants: An Example of Target Hopping
-
The high genomic instability of non-small cell lung cancer tumors leads to the rapid development of resistance against promising EGFR tyrosine kinase inhibitors (TKIs). A recently detected triple mutation compromises the activity of the gold standard third-generation EGFR inhibitors. We have prepared a set of trisubstituted imidazoles with a rigidized 7-azaindole hinge binding motif as a new structural class of EGFR inhibitors by a target hopping approach from p38α MAPK inhibitor templates. On the basis of an iterative approach of docking, compound preparation, biological testing, and SAR interpretation, robust and flexible synthetic routes were established. As a result, we report two reversible inhibitors 11d and 11e of the clinically challenging triple mutant L858R/T790M/C797S with IC50 values in the low nanomolar range. Furthermore, we developed a kinome selective irreversible inhibitor 45a with an IC50 value of 1 nM against the EGFR L858R/T790M double mutant. Target binding kinetics and metabolic stability data are included. These potent mutant EGFR inhibitors may serve as a basis for the development of structurally novel EGFR probes, tools, or candidates.
- Juchum, Michael,Günther, Marcel,D?ring, Eva,Sievers-Engler, Adrian,L?mmerhofer, Michael,Laufer, Stefan
-
supporting information
p. 4636 - 4656
(2017/06/13)
-
- ADENINE DERIVATIVES AS PROTEIN KINASE INHIBITORS
-
The present invention relates to a compound suitable for use as a kinase inhibitor according to general formula (I) [compound (C), herein after], or the N- oxide, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or stereoisomer thereof, formula (I) wherein A, R1, R2, R3, R3', R4, R4', X, Y, Z, T are as defined in the claims. The invention further relates to an in vitro method of inhibiting protein kinase activity which comprises contacting a protein kinase with a compound of formula (I), or the N-oxide, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or stereoisomer thereof. The invention further relates to the compounds of formula (I) per se, as well as to their use as a medicament, and for use or in a method of treatment of a disease mediated by a protein kinase selected from cancer, inflammatory disorders, cardiovascular diseases, viral induced diseases, circulatory diseases, fibro-proliferative diseases and pain sensitization disorders.
- -
-
Page/Page column 130
(2017/12/14)
-
- HETEROCYCLIC SULFONAMIDE DERIVATIVE AND MEDICINE COMPRISING SAME
-
The present invention provides a compound represented by the formula (I): wherein each symbol is as defined in the DESCRIPTION, or a pharmaceutically acceptable salt thereof. The compound has a superior TRPA1 antagonist activity, and can provide a medicament useful for the prophylaxis or treatment of diseases involving TRPA1 antagonist and TRPA1.
- -
-
Paragraph 0420; 0421
(2016/12/01)
-
- CINNAMIC ACID AMIDE DERIVATIVE
-
The present invention provides a cinnamic acid amide derivative having an excellent analgesic action. The cinnamic acid amide derivative of the present invention is a compound showing excellent analgesic actions to not only a nociceptive pain model animal but also a neuropathic pain model animal, which is very useful as an agent for treating various pain diseases showing acute or chronic pains or neuropathic pains.
- -
-
Paragraph 0132
(2015/11/24)
-
- Design and synthesis of novel and highly-active pan-histone deacetylase (pan-HDAC) inhibitors
-
Histone deacetylase (HDAC) inhibitions are known to elicit anticancer effects. We designed and synthesized several HDAC inhibitors. Among these compounds, compound 40 exhibited a more than 10-fold stronger inhibitory activity compared with that of suberoylanilide hydroxamic acid (SAHA) against each human HDAC isozyme in vitro (IC50 values of 40: HDAC1, 0.0038 μM; HDAC2, 0.0082 μM; HDAC3, 0.015 μM; HDAC8, 0.0060 μM; HDAC4, 0.058 μM; HDAC9, 0.0052 μM; HDAC6, 0.058 μM). The dose of the administered HDAC inhibitors that contain hydroxamic acid as the zinc-binding group may be reduced by 40. Because the carbostyril subunit is a time-tested structural component of drugs and biologically active compounds, 40 most likely exhibits good absorption, distribution, metabolism, excretion, and toxicity (ADMET). Thus, compound 40 is expected to be a promising therapeutic agent or chemical tool for the investigation of life process.
- Tashima, Toshihiko,Murata, Hiroaki,Kodama, Hidehiko
-
p. 3720 - 3731
(2014/07/07)
-
- CaMKII INHIBITORS AND USES THEREOF
-
The present invention provides compounds useful as inhibitors of Ca2+/calmodulindependent protein kinase (CaMKII), compositions thereof, and methods of using the same. Cardiovascular disease remains the number one cause of death in developed countries. Furthermore, incidence of cardiovascular disease has increased dramatically in developing countries. Although cardiovascular disease usually affects older adults, the antecedents of cardiovascular disease, notably atherosclerosis, begin in early life, making primary prevention efforts necessary from childhood.
- -
-
Paragraph 00191-00192; 00203-00204
(2014/09/29)
-
- Cyclopentane-1,3-dione: A novel isostere for the carboxylic acid functional group. Application to the design of potent thromboxane (A2) receptor antagonists
-
Cyclopentane-1,3-diones are known to exhibit pKa values typically in the range of carboxylic acids. To explore the potential of the cyclopentane-1,3-dione unit as a carboxylic acid isostere, the physical-chemical properties of representative co
- Ballatore, Carlo,Soper, James H.,Piscitelli, Francesco,James, Michael,Huang, Longchuan,Atasoylu, Onur,Huryn, Donna M.,Trojanowski, John Q.,Lee, Virginia M.-Y.,Brunden, Kurt R.,Smith, Amos B.
-
supporting information; experimental part
p. 6969 - 6983
(2011/12/02)
-
- Development of an enabling route to PF-00610355: A novel inhaled β2-adrenoreceptor agonist
-
The initial route used to prepare PF-00610355 (8) for early clinical development is described. Through careful choice of solvent, an efficient, telescoped route to carboxylic acid 23 was developed, affording this late-stage intermediate in 80% yield over 4 steps. Deprotection of 23 to give sodium salt 24a and coupling with amine 6·HCl afforded the desired API. Effective synthetic routes to two of the starting materials, chiral bromide 1 and amine 6, are also described.
- De Koning, Pieter D.,Gladwell, Iain R.,Moses, Ian B.,Panesar, Maninder S.,Pettman, Alan J.,Thomson, Nicholas M.
-
experimental part
p. 1247 - 1255
(2012/01/19)
-
- Synthesis and application of a new fluorous-tagged ammonia equivalent
-
A novel fluorous-tagged ammonia equivalent has been developed. It is based on a nitrogen-oxygen bond, which can be cleaved in a traceless manner by a molybdenum complex or samarium diiodide. The application in the synthesis of ureas, amides, sulfonamides, and carbamates is described. The scope of the fluo-rous N-O linker is exemplified by the synthesis of itopride, a drug used for the treatment of functional dyspepsia. Itopride was synthesized with the aid of fluorous purification methods and the product was isolated in good overall yield, with high purity.
- Nielsen, Simon D.,Smith, Garrick,Begtrup, Mikael,Kristensen, Jesper L.
-
supporting information; experimental part
p. 4557 - 4566
(2010/08/20)
-
- ASPARTYL PROTEASE INHIBITORS
-
A compound of formula (I): N-oxides, addition salts, quaternary amines metal complexes stereochemically isomeric forms and metabolites thereof, wherein A is CR1 or N; D is H, C1-C6alkyl, C2-C6alkenyl,
- -
-
Page/Page column 62
(2010/04/28)
-
- NOVEL INDOLE DERIVATIVE HAVING INHIBITORY ACTIVITY ON I B KINASE
-
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.
- -
-
Page/Page column 38
(2009/12/05)
-
- Dual Pharmacophores - PDE4-Muscarinic Antagonistics
-
The present invention is directed to novel compounds of Formula (I) and pharmaceutically acceptable salts thereof, pharmaceutical compositions and their use as dual chromaphores having inhibitory activity against PDE4 and muscarinic acetylcholine receptors (mAChRs), and thus being useful for treating respiratory diseases.
- -
-
Page/Page column 69
(2009/08/18)
-
- Dual Pharmacophores - PDE4-Muscarinic Antagonistics
-
The present invention is directed to novel compounds of Formula (I), pharmaceutical compositions and their use in therapy, for example as inhibitors of phosphodiesterase type IV (PDE4) and as antagonists of muscarinic acetylcholine receptors (mAChRs), in the treatment of/and or prophylaxis of respiratory diseases, including antiinflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rhinitis (e.g. allergic rhinitis), atopic dermatitis or psoriasis.
- -
-
Page/Page column 103
(2009/08/16)
-
- DUAL PHARMACOPHORES - PDE4-MUSCARINIC ANTAGONISTICS
-
The present invention is directed to novel compounds of Formula's (I) - (VI), and pharmaceutically acceptable salts thereof, pharmaceutical compositions and their use in therapy, for example as inhibitors of phosphodiesterase type IV (PDE4) and as antagonists of muscarinic acetylcholine receptors (mAChRs), in the treatment of and/or prophylaxis of respiratory diseases, including inflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rhinitis (e.g. allergic rhinitis), atopic dermatitis or psoriasis.
- -
-
Page/Page column 159
(2009/10/09)
-
- NOVEL BIAROMATIC COMPOUNDS THAT MODULATE PPAR-RECEPTORS
-
Novel biaromatic compounds that modulate peroxisome proliferator-activator receptors, known as PPAR, having the formula (I): are formulated into pharmaceutical compositions useful in human or veterinary medicine, or alternatively, in cosmetic compositions.
- -
-
Page/Page column 21
(2009/01/23)
-
- (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
-
The present invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating of Alzheimer's disease. (Formula)
- -
-
Page/Page column 117
(2009/05/29)
-
- PYRIDINONYL PDK1 INHIBITORS
-
The present invention provides pyridinonyl PDKl inhibitors and methods of treating cancer using the same.
- -
-
Page/Page column 178
(2008/06/13)
-
- PROCESS FOR THE PREPARATION OF SULFONAMIDE DERIVATIVES
-
The invention relates to a process for the preparation of compounds of formula (I) wherein Q1 is a group selected from formulae (II and (III) and a group *-NR6 -Q2-A or, if appropriate, their pharmaceutically acceptable sa
- -
-
Page/Page column 32
(2010/11/25)
-
- Multicyclic bis-amide MMP inhibitors
-
The present invention relates generally to bis-amide group containing pharmaceutical agents, and in particular, to multicyclic bis-amide MMP-13 inhibitor compounds. More particularly, the present invention provides a new class of MMP-13 inhibiting compounds, containing a pyrimidinyl bis-amide group in combination with a heterocyclic moiety, that exhibit an increased potency and solubility in relation to currently known bis-amide group containing MMP-13 inhibitors.
- -
-
Page/Page column 83
(2008/06/13)
-
- NOVEL BIAROMATIC COMPOUNDS WHICH ACTIVATE RECEPTORS OF PPAR TYPE AND THEIR USE IN COSMETIC OR PHARMACEUTICAL COMPOSITIONS
-
The invention relates to novel biaromatic compounds which correspond to the following general formula (I) and to their method of preparation and to their use in pharmaceutical compositions intended for use in human or veterinary medicine (in dermatology a
- -
-
Page/Page column 28 - 29
(2010/10/20)
-
- Biaromatic compound activators of PPARy-type receptors
-
The invention relates to novel biaromatic compounds which correspond to the general formula (I) below: and also to the method for preparing them and their use in pharmaceutical compositions intended for use in human or veterinary medicine (in dermatology, and also in the field of cardiovascular diseases, immune diseases and/or diseases associated with lipid metabolism), or alternatively in cosmetic compositions.
- -
-
-
- CARBOXYLIC ACID DERIVATIVE AND SALT THEREOF
-
The present invention provides a novel carboxylic acid compound, a salt thereof or a hydrate of them useful as an insulin sensitizer, and a medicament comprising the compound as an active ingredient. That is, the present invention provides a carboxylic acid compound represented by the following formula, a salt thereof, an ester thereof or a hydrate of them. Wherein R1 represents a hydrogen atom, hydroxyl group, halogen, carboxyl group, or a C1-6 alkyl group etc., each of which may have one or more substituents; L represents a single bond, or a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group, each of which may have one or more substituents; M represents a single bond, or a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group, each of which may have one or more substituents; T represents a single bond, or a C1-3 alkylene group, a C2-3 alkenylene group or a C2-3 alkynylene group, each of which may have one or more substituents; W represents a carboxyl group;- - - represents a single bond etc. ; X represents a single bond, oxygen atom, a group represented by -NRX1CQ1O- (wherein Q1 represents an oxygen atom or sulfur atom; and RX1 represents a hydrogen atom, formyl group, or a C1-6 alkyl group etc., each of which may have one or more substituents), -OCQ1NRX1- (wherein Q1 and RX1 are as defined above), -CQ1NRx1O- (wherein Q1 and RX1 are as def ined above), ONRX1CQ1- (wherein Q1 and RX1 are as defined above), - Q2SO2- (wherein Q2 is an oxygen atom or -NRX10- (wherein RX10 represents a hydrogen atom, formyl group, or a C1-6 alkyl group etc., each of which may have one or more substituents)) or -SO2Q2- (wherein Q2 is as defined above), (wherein, provided that RX2 and RX3, and/or RX4 and RX5 may together form a ring, Q3 and Q4 are the same as or different from each other and each represents an oxygen atom, (O)S(O) or NRX10 (wherein NRX10 is as defined above)); Y represents a 5- to 14-membered aromatic group etc., which may have one or more substituents and one or more hetero atoms; and the ring Z represents a 5-to 14-membered aromatic group which may have 0 to 4 substituents and one or more hetero atoms, and wherein part of the ring may be saturated.
- -
-
-
- 2-'5-(5-CARBAMIMIDOYL-1H-HETEROARYL)-6-HYDROXYBIPHENYL-3-YL!- CARBOXYLIC ACID DERIVATIVES AS FACTOR VIIA INHIBITORS
-
The present invention relates to novel inhibitors of Factors VIIa, IXa, Xa, XIa, in particular Factor VIIa, pharmaceutical compositions comprising these inhibitors, and methods for using these inhibitors for treating or preventing thromboembolic disorders. Processes for preparing these inhibitors are also disclosed.
- -
-
Page/Page column 24
(2010/02/07)
-
- 2-(2-HYDROXYBIPHENYL-3-YL)-1H-BENZOIMIDAZOLE-5-CARBOXAMIDINE DERIVATIVES AS FACTOR VIIA INHIBITORS
-
The present invention relates to novel inhibitors of Factors VIIa, IXa, Xa, XIa, in particular Factor VIIa, pharmaceutical compositions comprising these inhibitors, and methods for using these inhibitors for treating or preventing thromboembolic disorders, cancer or rheumatoid arthritis. Processes for preparing these inhibitors are also disclosed.
- -
-
-
- NOVEL BIAROMATIC COMPOUNDS WHICH ACTIVATE PPAR? TYPE RECEPTORS, AND USE THEREOF IN COSMETIC OR PHARMACEUTICAL COMPOSITIONS
-
The invention relates to novel biaromatic compounds that correspond to the general formula (I) below: and to a method for preparing them, and to their use in pharmaceutical compositions intended for use in human or veterinary medicine (in dermatology, and
- -
-
-
- COMPOUNDS WHICH MODULATE PPARγ TYPE RECEPTORS, AND USE THEREOF IN COSMETIC OR PHARMACEUTICAL COMPOSITIONS
-
The invention relates to novel compounds that correspond to the general formula (I) below and to a method for preparing them, and to their use in pharmaceutical compositions intended for use in human or veterinary medicine (in dermatology, and also in the field of cardiovascular diseases, immune diseases and/or diseases associated with lipid metabolism), or alternatively in cosmetic compositions.
- -
-
-
- Biaromatic ligand activators of PPARgamma receptors
-
Novel pharmaceutical/cosmetic compositions contain at least one biaromatic ligand activator of a PPARγ receptor, such biaromatic ligand having the structural formula (I): and are well suited, inter alia, for regulating and/or restoring skin lipid metabolism, for treating a wide variety of dermatological afflictions, and for preventing and/or treating the signs of aging and/or dry skin.
- -
-
-