- 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; 00427
(2020/07/05)
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- SELECTIVE FLUORESCENT PROBE FOR ALDEHYDE DEHYDROGENASE
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High aldehyde dehydrogenase 1A1 (ALDH1A1) activity has emerged as a reliable marker for the identification of both normal and cancer stem cells. Herein, is presented AlDeSense, a turn-on green fluorescent probe for aldehyde dehydrogenase 1A1 (ALDH1A1) and Ctrl-AlDeSense, a matching non-responsive reagent. AlDeSense exhibits a 20-fold fluorescent enhancement when treated with ALDH1A1. Through the application of surface marker antibody staining, tumorsphere assays, and assessment of tumorigenicity, the disclosed results show that cells exhibiting high AlDeSense signal intensity have properties of cancer stem cells. Herein, is also reported the development of a red congener, red-AlDeSense. Importantly, red-AlDeSense represents one of only a few examples of a turn-on sensor in the red region using the d-PeT quenching mechanism.
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Paragraph 0259
(2020/07/14)
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- COMPOUNDS
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A compound for use in the treatment of a disease ameliorated by the inhibition of Notum of formula (I): (I)
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Page/Page column 44
(2020/03/23)
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- HORMONE RECEPTOR MODULATORS FOR TREATING METABOLIC CONDITIONS AND DISORDERS
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The invention relates to activators of FXR useful in the treatment of autoimmune disorders, liver disease, intestinal disease, kidney disease, cancer, and other diseases in which FXR plays a role, having the Formula (I): (I), wherein L1, A, X1, X2, R1, R2, and R3 are described herein.
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Page/Page column 236; 237
(2018/03/25)
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- Visible-Light photoredox decarboxylation of perfluoroarene iodine(III) Trifluoroacetates for C-H trifluoromethylation of (Hetero)arenes
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A scalable and operationally simple decarboxylative trifluoromethylation of (hetero)arenes with easily accessible C6F5I(OCOCF3)2 under photoredox catalysis has been developed. This method is tolerant of various (hetero)arenes and functional groups. Notably, C6F5I is recycled from the decarboxylation reaction and further used for the preparation of C6F5I(OCOCF3)2. The combination of photoredox catalysis and hypervalent iodine reagent provides a practical approach for the application of trifluoroacetic acid in trifluoromethylation reactions.
- Yang, Bin,Yu, Donghai,Xu, Xiu-Hua,Qing, Feng-Ling
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p. 2839 - 2843
(2018/04/14)
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- Silver-Catalyzed C-H Trifluoromethylation of Arenes Using Trifluoroacetic Acid as the Trifluoromethylating Reagent
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Direct trifluoromethylation of arenes using TFA as the trifluoromethylating reagent was achieved with Ag as the catalyst. This reaction not only provides a new protocol for aryl C-H trifluoromethylation, but the generation of CF3· from TFA may prove useful in other contexts and could potentially be extended to other trifluoromethylation reactions. (Chemical Equation Presented).
- Shi, Guangfa,Shao, Changdong,Pan, Shulei,Yu, Jingxun,Zhang, Yanghui
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supporting information
p. 38 - 41
(2015/07/28)
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- Identification of a potent sodium hydrogen exchanger isoform 1 (NHE1) inhibitor with a suitable profile for chronic dosing and demonstrated cardioprotective effects in a preclinical model of myocardial infarction in the rat
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Sodium-hydrogen exchanger isoform 1 (NHE1) is a ubiquitously expressed transmembrane ion channel responsible for intracellular pH regulation. During myocardial ischemia, low pH activates NHE1 and causes increased intracellular calcium levels and aberrant cellular processes, leading to myocardial stunning, arrhythmias, and ultimately cell damage and death. The role of NHE1 in cardiac injury has prompted interest in the development of NHE1 inhibitors for the treatment of heart failure. This report outlines our efforts to identify a compound suitable for once daily, oral administration with low drug-drug interaction potential starting from NHE1 inhibitor sabiporide. Substitution of a piperidine for the piperazine of sabiporide followed by replacement of the pyrrole moiety and subsequent optimization to improve potency and eliminate off-target activities resulted in the identification of N-[4-(1-acetyl- piperidin-4-yl)-3-trifluoromethyl-benzoyl]-guanidine (60). Pharmacological evaluation of 60 revealed a remarkable ability to prevent ischemic damage in an ex vivo model of ischemia reperfusion injury in isolated rat hearts.
- Huber, John D.,Bentzien, J?rg,Boyer, Stephen J.,Burke, Jennifer,De Lombaert, Stéphane,Eickmeier, Christian,Guo, Xin,Haist, James V.,Hickey, Eugene R.,Kaplita, Paul,Karmazyn, Morris,Kemper, Raymond,Kennedy, Charles A.,Kirrane, Thomas,Madwed, Jeffrey B.,Mainolfi, Elizabeth,Nagaraja, Nelamangara,Soleymanzadeh, Fariba,Swinamer, Alan,Eldrup, Anne B.
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p. 7114 - 7140
(2012/11/07)
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- 5-(BIPHENYL-4-YL)-3-PHENYL-1,2,4-OXADIAZOLYL DERIVATIVES AS LIGANDS ON THE SPHINGOSINE 1-PHOSPHATE (S1P) RECEPTORS
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The present invention provides compounds of Formula (I), as selective S1 P1 inhibitors, as well as their use for treating multiple sclerosis and other diseases.
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Page/Page column 64-65
(2012/02/01)
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- OXAZOLE PYRIDINE DERIVATIVES USEFUL AS S1P1 RECEPTOR AGONISTS
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The present invention provides oxadiazole pyridine derivatives of Formula (I), their use as medicaments and their use for treating multiple sclerosis and other diseases
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- PYRROLIDINYL AND PIPERIDINYL COMPOUNDS USEFUL AS NHE-1 INHIBITORS
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Disclosed are compounds of formula (I) and compositions of the present invention which are inhibitors of the sodium proton exchanger isoform-1 (NHE-I). Also disclosed are methods of using and making the same.
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Page/Page column 109
(2010/04/03)
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- OXADIAZOLE FUSED HETEROCYCLIC DERIVATIVES USEFUL FOR THE TREATMENT OF MULTIPLE SCLEROSIS
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The invention provides compounds of Formula (I) for the treatment of multiple sclerosis and other diseases.
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Page/Page column 72
(2010/08/05)
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- OXADIAZOLE DERIVATIVES
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The invention relates to compounds of formula (I); wherein R1, R2, Ra, Rb, W, Q and S have the meanings given in claim 1. The compounds are useful e.g. in the treatment of autoimmune disorders, such as multiple
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Page/Page column 65; 66
(2010/11/03)
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- OXADIAZOLE DIARYL COMPOUNDS
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The invention relates to compounds of formula (I): wherein R1, R2, Ra , Rb,Rc and W, have the meanings given in claim 1. The compounds are useful e.g. in the treatment of autoimmune disorders, such as multiple sclerosis.
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Page/Page column 70
(2009/05/29)
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- HETEROARYLAMIDE LOWER CARBOXYLIC ACID DERIVATIVE
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To provide a novel compound which has S1P receptor agonistic activity, exhibits excellent immunosuppressing effect, gives less adverse side effects, and can be orally administered. The invention provides a compound represented by general formula (I) (wherein A is a single bond, -O-, or - CH2-; R1 represents a hydrogen atom or a C1-C6 alkyl group, and V represents any one group selected from among the following groups (1) to (3) : (1) -G1-, (2) -G2-N(R2) -G3-, and (3) a group represented by formula 2, wherein each of Z1 and Z2 represents a hydrogen atom or a C1-C6 alkyl group, Z3 represents a hydrogen or the like, Q represents -CH2-O- or the like, and Y represents a group represented by foumula 3, a salt thereof, or a solvate thereof.
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Page/Page column 248-249
(2009/02/10)
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