- COMPOUNDS AND USES THEREOF
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The present disclosure features compounds useful for the treatment of BAF complex-related disorders.
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Page/Page column 71; 114
(2021/08/06)
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- 5-MEMBERED HETEROARYLAMINOSULFONAMIDES FOR TREATING CONDITIONS MEDIATED BY DEFICIENT CFTR ACTIVITY
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The invention relates to heteroaryl compounds, pharmaceutically acceptable salts thereof, and pharmaceutical preparations thereof. Also described herein are compositions and the use of such compounds in methods of treating diseases and conditions mediated by deficient CFTR activity, in particular cystic fibrosis.
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Page/Page column 420
(2021/05/21)
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- 6-MEMBERED HETEROARYLAMINOSULFONAMIDES FOR TREATING DISEASES AND CONDITIONS MEDIATED BY DEFICIENT CFTR ACTIVITY
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The invention relates to heteroaryl compounds, pharmaceutically acceptable salts thereof, and pharmaceutical preparations thereof. Also described herein are compositions and the use of such compounds in methods of treating diseases and conditions mediated by deficient CFTR activity, in particular cystic fibrosis.
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Page/Page column 59-60
(2021/05/21)
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- MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR
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This disclosure provides modulators of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), pharmaceutical compositions containing at least one such modulator, methods of treatment of cystic fibrosis using such modulators and pharmaceutical compositions, and processes for making such modulators.
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Paragraph 00681
(2021/02/19)
-
- SULFONIMIDAMIDE COMPOUNDS AS INHIBITORS OF INTERLEUKIN-1 ACTIVITY
-
The present disclosure relates to novel sulfonimidamide compounds and related compounds and their use in treating a disorder responsive to modulation of cytokines such as IL-1β and IL-18, modulation of NLRP3 or inhibition of the activation of NLRP3 or related components of the inflammatory process. (I)
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Paragraph 0407
(2020/02/14)
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- ENDOPARASITIC DEPSIPEPTIDES
-
The present invention provides cyclic depsipeptides of Formula (1), stereoisomers thereof, and veterinary acceptable salts thereof (1) wherein each of R1, R2, R3, R4, L1, and L2, are as defined herein. The present invention also contemplates compositions and methods of treatment as an endoparasiticide with a Formula (1) compound.
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Page/Page column 74
(2019/06/17)
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- COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH APJ RECEPTOR ACTIVITY
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This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt and/or hydrate and/or prodrug of the compound) that modulate (e.g., agonize) the apelin receptor (also referred to herein as the APJ receptor; gene symbol "APLNR"). This disclosure also features compositions containing the same as well as other methods of using and making the same. The chemical entities are useful, e.g., for treating a subject (e.g., a human) having a disease, disorder, or condition in which a decrease in APJ receptor activity (e.g., repressed or impaired APJ receptor signaling; e.g., repressed or impaired apelin-APJ receptor signaling) or downregulation of endogenous apelin contributes to the pathology and/or symptoms and/or progression of the disease, disorder, or condition. Non-limiting examples of such diseases, disorders, or conditions include: (i) cardiovascular disease; (ii) metabolic disorders; (iii) diseases, disorders, and conditions associated with vascular pathology; and (iv) organ failure; (v) diseases, disorders, and conditions associated with infections (e.g., microbial infections); and (vi) diseases, disorders, or conditions that are sequela or comorbid with any of the foregoing or any disclosed herein. More particular non-limiting examples of such diseases, disorders, or conditions include pulmonary hypertension (e.g., PAH); heart failure; type II diabetes; renal failure; sepsis; and systemic hypertension.
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Page/Page column 102-104
(2019/09/18)
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- SULPHONAMIDES AND COMPOSITIONS THEREOF FOR TREATING CONDITIONS ASSOCIATED WITH NLRP ACTIVITY
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In one aspect, compounds of Formula AA, or a pharmaceutically acceptable salt thereof, are featured: wherein the variables shown in Formula AA can be as defined anywhere herein. Compounds AA are modulators of NLRP1 and/or NLRP3
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Page/Page column 530; 531
(2019/05/10)
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- MODULATOR OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR, PHARMACEUTICAL COMPOSITIONS, METHODS OF TREATMENT, AND PROCESS FOR MAKING THE MODULATOR
-
Compounds of Formula (I), pharmaceutically acceptable salts thereof, deuterated derivatives of any of the foregoing, and metabolites of any of the foregoing are disclosed. Pharmaceutical compositions comprising the same, methods of treating cystic fibrosis using the same, and methods for making the same are also disclosed.
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Paragraph 00650; 00651
(2018/04/17)
-
- CHEMICAL COMPOUNDS AS INHIBITORS OF INTERLEUKIN-1 ACTIVITY
-
The present disclosure relates to novel sulfonylurea and sulfonyl thiourea compounds and related compounds and their use in treating a disease or condition responsive to modulation of cytokines such as IL-1β and IL-18, modulation of NLRP3 or inhibition of the activation of NLRP3 or related components of the inflammatory process.
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Paragraph 00667; 00668
(2018/08/12)
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- HETEROCYCLIC DEGRONIMERS FOR TARGET PROTEIN DEGRADATION
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This invention provides heterocyclic compounds that bind to E3 Ubiquitin Ligase (typically through cereblon) ("Degrons"), which can be used as is or linked to a Targeting Ligand for a selected Target Protein for therapeutic purposes and methods of use and compositions thereof as well as methods for their preparation.
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Page/Page column 226
(2017/12/02)
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- BROMODOMAIN TARGETING DEGRONIMERS FOR TARGET PROTEIN DEGRADATION
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This invention provides a Degronimer that has an E3 Ubiquitin Ligase targeting moiety (Degron) that can be linked to a Targeting Ligand for a bromodomain protein selected for in vivo degradation to achieve a therapeutic effect, and methods of use and compositions thereof as well as methods for their preparation.
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Page/Page column 252
(2017/12/05)
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- Novel Compounds as Autotaxin Inhibitors and Pharmaceutical Compositions Comprising the Same
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The present invention relates to a novel autotaxin inhibitor compound for preventing and treating disease or symptoms due to an increase in concentration of lysophosphatidic acid or activation of autotaxin. The present invention further relates to a pharmaceutical composition containing the same. The novel compound of the present invention is an autotaxin inhibitor which inhibits production of lysophosphatidic acid, and thus is useful for treating or preventing cardiovascular disease, cancer, metabolic disease, kidney disease, liver disease, inflammatory diseases, nervous disease, respiratory disease, desmoid disease, eye disease, cholestatic symptoms, other types of chronic pruritus or acute, or chronic rejection of transplanted organs.COPYRIGHT KIPO 2017
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Paragraph 0382-0383; 0388-0389
(2018/05/17)
-
- MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR
-
The present invention features a compound of formula I: or a pharmaceutically acceptable salt thereof, where R1, R2, R3, W, X, Y, Z, n, o, p, and q are defined herein, for the treatment of CFTR mediated diseases, such as cystic fibrosis. The present invention also features pharmaceutical compositions, method of treating, and kits thereof.
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Page/Page column 1087-1088
(2021/02/10)
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- TETRAZOLINONE COMPOUND AND USE THEREOF
-
A tetrazolinone compound represented by formula (1): wherein Q represents a divalent 5-membred aromatic heterocyclic group optionally having one or more atoms or groups selected from Group P2; A represents a 5- to 10-membered monocyclic or fused ring heterocyclic group optionally having one or more atoms or groups selected from Group P1; R1 and R2 each represents a hydrogen atom, etc.; R3 represents a C1-C6 alkyl group optionally having one or more halogen atoms, etc.; R4, R5, and R6 each represents a hydrogen atom, etc.; and X represents an oxygen atom or a sulfur atom, has excellent control activity against pests.
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-
Paragraph 0551; 0552; 0553; 0554
(2016/07/27)
-
- Pyrazole-Based Acid Ceramidase Inhibitors: Design, Synthesis, and Structure-Activity Relationships
-
Acid ceramidase (AC) is a lysosomal cysteine amidase responsible for the cleavage of ceramide into sphingosine, which is then phosphorylated to sphingosine 1-phosphate. AC regulates the intracellular levels of ceramide and sphingosine, and AC inhibition may be useful in the treatment of disorders, such as cancer, in which ceramide-mediated signaling may be dysfunctional. Despite their potential experimental and therapeutic value, the number of available small-molecule inhibitors of AC activity remains limited. In the present study is described the discovery of a class of potent pyrazole carboxamide-based AC inhibitors, which were identified using the atomic property field (APF) approach and developed through systematic SAR investigations and in vitro pharmacological characterization. The best compound of this series inhibits AC with nanomolar potency and causes ceramide accumulation and sphingosine depletion in intact G361 proliferative melanoma cells. By expanding the current armamentarium of AC inhibitors, these results should facilitate future efforts to unravel the biology of AC and the therapeutic potential of its inhibition.
- Diamanti, Eleonora,Bottegoni, Giovanni,Goldoni, Luca,Realini, Natalia,Pagliuca, Chiara,Bertozzi, Fabio,Piomelli, Daniele,Pizzirani, Daniela
-
supporting information
p. 2739 - 2756
(2016/08/31)
-
- Tetrazolinone compound and use thereof
-
A tetrazolinone compound represented by formula (1) [wherein Q represents a bivalent 5-membered aromatic heterocyclic group which may have at least one atom or group selected from the group P2; A represents a 5- to 10-membered monocyclic or condensed-cyclic heterocyclic group which may have at least one atom or group selected from the group P1; R1 and R2 independently represent a hydrogen atom or the like; R3 represents a C1-C6 alkyl group which may have at least one halogen atom or the like; R4, R5 and R6 independently represent a hydrogen atom or the like; and X represents an oxygen atom or a sulfur atom] has an excellent controlling effect on harmful organisms.
- -
-
Paragraph 0937; 0938; 0939; 0940; 0941
(2016/10/08)
-
- Modulators of Cystic Fibrosis Transmembrane Conductance Regulator
-
The present invention features a compound of formula I: or a pharmaceutically acceptable salt thereof, where R1, R2, R3, W, X, Y, Z, n, o, p, and q are defined herein, for the treatment of CFTR mediated diseases, such as cystic fibrosis. The present invention also features pharmaceutical compositions, method of treating, and kits thereof.
- -
-
Paragraph 5266; 5267
(2016/05/02)
-
- Design, Synthesis, and Biological Evaluation of Novel Nonsteroidal Farnesoid X Receptor (FXR) Antagonists: Molecular Basis of FXR Antagonism
-
Farnesoid X receptor (FXR) plays an important role in the regulation of cholesterol, lipid, and glucose metabolism. Recently, several studies on the molecular basis of FXR antagonism have been reported. However, none of these studies employs an FXR antagonist with nonsteroidal scaffold. On the basis of our previously reported FXR antagonist with a trisubstituted isoxazole scaffold, a novel nonsteroidal FXR ligand was designed and used as a lead for structural modification. In total, 39 new trisubstituted isoxazole derivatives were designed and synthesized, which led to pharmacological profiles ranging from agonist to antagonist toward FXR. Notably, compound 5s (4′-[(3-{[3-(2-chlorophenyl)-5-(2-thienyl)isoxazol-4-yl]methoxy}-1H-pyrazol-1-yl)methyl]biphenyl-2-carboxylic acid), containing a thienyl-substituted isoxazole ring, displayed the best antagonistic activity against FXR with good cellular potency (IC50=12.2±0.2μM). Eventually, this compound was used as a probe in a molecular dynamics simulation assay. Our results allowed us to propose an essential molecular basis for FXR antagonism, which is consistent with a previously reported antagonistic mechanism; furthermore, E467 on H12 was found to be a hot-spot residue and may be important for the future design of nonsteroidal antagonists of FXR. X marks the spot: 39 trisubstituted isoxazoles were designed and synthesized, leading to compounds with pharmacological profiles ranging from agonist to antagonist at the farnesoid X receptor (FXR). By using the most potent antagonist as a probe, the essential molecular basis of FXR antagonism is proposed, and E467 on H12 can be regarded as a hot-spot residue for the future design of nonsteroidal antagonists of FXR.
- Huang, Huang,Si, Pei,Wang, Lei,Xu, Yong,Xu, Xin,Zhu, Jin,Jiang, Hualiang,Li, Weihua,Chen, Lili,Li, Jian
-
p. 1184 - 1199
(2015/07/07)
-
- 2-ACYLAMIDOMETHYL AND SULFONYLAMIDOMETHYL BENZOXAZINE CARBAMATES FOR INHIBITION OF RORgamma ACTIVITY AND THE TREATMENT OF DISEASE
-
The invention provides certain benzoxazine compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, Ra, Rb, Rc, Rd, Rg, and Cy are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds of the Formula (I) or pharmaceutically acceptable salts thereof, and methods of using the compounds of the Formula (I) or pharmaceutically acceptable salts thereof or pharmaceutical compositions comprising the same for treating diseases or conditions mediated by RORgammaT.
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Paragraph 0227
(2015/07/07)
-
- CARBAMATE BENZOXAXINE PROPIONIC ACIDS AND ACID DERIVATIVES FOR MODULATION OF RORGAMMA ACTIVITY AND THE TREATMENT OF DISEASE
-
The invention provides certain benzoxazine compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, Ra1, Ra2, Rb1, Rb2, Rc, Rd, and C
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-
Paragraph 0224
(2015/07/07)
-
- TETRAZOLINONE COMPOUNDS AND ITS USE AS PESTICIDES
-
The present invention provides a compound having an excellent efficacy for controlling pests. A tetrazolinone compound of a formula (1): [wherein R1 represents an C6-C16 aryl group, an C1-C12 alkyl group, or a C3-C12 cycloalkyl group, etc., which each optionally be substituted; R2, R3, R4 and R5 represent independently of each other a hydrogen atom, a halogen atom or an C1-C3 alkyl group, etc.; R6 represents an C1-C6 alkyl group, a C3-C6 cycloalkyl group, a halogen atom, a C1-C6 haloalkyl group, an C2-C6 alkenyl group, an C1-C6 alkoxy group, or a C1-C6 haloalkoxy group, etc.; R7, R8 and R9 represent independently of each other a hydrogen atom, a halogen atom, or an C1-C4 alkyl group, etc.; X represents an oxygen atom or a sulfur atom; and R10 represents an C1-C6 alkyl group, etc.] shows an excellent controlling efficacy on pests.
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Page/Page column 960
(2013/11/18)
-
- PROCESS FOR PREPARING 1-PHENYLPYRAZOLES
-
The present invention to a process for preparing 1-phenylpyrazoles of the formula I in which each R1 is independently selected from chlorine, fluorine, alkyl, haloalkyl, alkoxy and haloalkoxy;n is 1, 2 or 3;each R2 is independently selected from cyano, nitro, halogen, alkyl, haloalkyl,alkoxy, haloalkoxy,alkylthio and alkoxycarbonyl; mis 0, 1 or 2;A is alkyl, aryl or aryl-C1-C4-alkyl, where A optionally bears 1, 2, 3 or 4 substituents comprising reacting a phenyl halide of the formula (II) with apyrazole derivative of the formula (III) in which X is chlorine, iodine or bromine; and R1, n, R2, m and A are each as defined above, in the presence of a base and a catalytic system comprising a ligand and a metal compound selected from palladium compounds, iron compounds and copper compounds.
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Page/Page column 26
(2011/04/14)
-
- Fused Bicyclic Kinase Inhibitors
-
Compounds of Formula I, as shown below and defined herein: pharmaceutically acceptable salts thereof, synthesis, intermediates, formulations, and methods of disease treatment therewith, including treatment of cancers, such as tumors driven at least in part by at least one of RON, MET or ALK. This Abstract is not limiting of the invention.
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Page/Page column 69
(2011/11/30)
-
- Pyrazolyl derivatives, preparation process and intermediates of this process as medicinal products and pharmaceutical compositions containing them
-
The present invention relates to the novel derivatives of formula (I) in which A is, if it is present, a (C1-C6) alkyl, a (C3-C6) alkenyl, a (C3-C6) alkynyl, a (C3-C7) cycloalkyl or a (C5-C7) cycloalkenyl, R1 is an NR6R7, (C4-C7) azacycloalkyl, (C5-C7) azacycloalkenyl, (C5-C9) azabicycloalkyl or (C5-C9) azabicycloalkenyl group; A-R1 is such that the nitrogen of R1 and the nitrogen in the 1-position of the pyrazole are necessarily separated by at least two carbon atoms, R3 is an H, halogen, OH, SH, NH2, ORc, SRc, SORa, SO2Ra, NHCHO, NRaRb, NHC(O)Ra, NHC(S)Ra or NHSO2Ra, R4 is an aryl or heteroaryl; and R5 is an H, halogen, CF3, CHF2, CH2F, linear or branched (C1-C6) alkyl or (C3-C7) cycloalkyl to their racemates, enantiomers and diastereoisomers and to their mixtures, their tautomers and to their pharmaceutically acceptable salts.
- -
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Page/Page column 44
(2008/06/13)
-