- AN UNEXPECTED β-ELIMINATION FROM 3,3-DIFLUOROCYCLOBUTANECARBONITRILE
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3,3-Difluorocyclobutanecarbonitrile (2) reacts with bases to give β rather than γ-elimination, the latter being the prevailing reaction mode in similar systems.
- Hoz, S.,Aurbach, D.,Avivi, C.
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- Discovery of Reldesemtiv, a Fast Skeletal Muscle Troponin Activator for the Treatment of Impaired Muscle Function
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The discovery of reldesemtiv, a second-generation fast skeletal muscle troponin activator (FSTA) that increases force production at submaximal stimulation frequencies, is reported. Property-based optimization of high throughput screening hit 1 led to compounds with improved free exposure and in vivo muscle activation potency compared to the first-generation FSTA, tirasemtiv. Reldesemtiv demonstrated increased muscle force generation in a phase 1 clinical trial and is currently being evaluated in clinical trials for the treatment of amyotrophic lateral sclerosis.
- Ashcraft, Luke,Bergnes, Gustave,Chuang, Chihyuan,Collibee, Scott E.,Durham, Nickie,Garard, Marc,Gardina, Jeffrey,Hartman, James,Hinken, Aaron,Hwee, Darren T.,Jamison, Chris R.,Lu, Kevin,Lu, Pu-Ping,Malik, Fady I.,Marquez, Anna,Morgan, Bradley P.,Morgans, David,Muci, Alexander,Romero, Antonio,Schaletzky, Julia,Valkevich, Ellen,Wang, Wenyue,Warrington, Jeffrey,Xu, Donghong,Yao, Bing
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supporting information
p. 14930 - 14941
(2021/11/01)
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- IMIDAZO[1,2-A]PYRIDINES AS SOLUBLE GUANYLATE CYCLASE STIMULATORS FOR THE TREATMENT OF CARDIOVASCULAR DISEASES
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The present application relates to novel substituted imidazo[1,2-a]pyridine-3-carboxamides, to processes for preparation thereof, to the use thereof, alone or in combinations, for treatment and/or prophylaxis of diseases, and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially for treatment and/or prophylaxis of cardiovascular disorders.
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- FUSED IMIDAZOLE COMPOUNDS
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The present invention provides compounds represented by formula (I), pharmaceutically acceptable salts thereof, N-oxides thereof, solvates thereof or prodrugs thereof (wherein the characters are as defined in the description). The compounds represented by formula (I) have affinity and selectivity for the gamma-aminobutyric acid A receptor subunit alpha 5 (GABAA α5) and act as GABAA α5 negative allosteric modulators (GABAA α5 NAM), so that they are useful in the prevention and/or treatment of diseases which are related to the GABAA α5 such as Alzheimer's disease.
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- 9-AMINOMETHYL SUBSTITUTED TETRACYCLINE COMPOUNDS
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The present invention relates to 9-aminomethyl substituted tetracycline compounds represented by formula (I), or pharmaceutically acceptable salt, prodrug, solvate or isomer thereof, as well as a method for preparing these compounds and a pharmaceutical composition comprising the same. The present invention relates also to a use of these compounds in the preparation of a medicament for the treatment and/or prophylaxis of tetracycline drug-sensitive disease. wherein, R2a, R2b, R3, R4a, R4b, R5, R6a, R6b, R7, R8, R9a, R9b, R10, R11, R12, R13a and R13b are each independently as defined in the description.
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Page/Page column
(2014/07/08)
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- 9-AMINOMETHYL SUBSTITUTED TETRACYCLINE COMPOUND
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The present invention relates to 9-aminomethyl substituted tetracycline compounds represented by formula (I), or pharmaceutically acceptable salt, prodrug, solvate or isomer thereof, as well as a method for preparing these compounds and a pharmaceutical composition comprising the same. The present invention relates also to a use of these compounds in the preparation of a medicament for the treatment and/or prophylaxis of tetracycline drug-sensitive disease. wherein, R2a, R2b, R3, R4a, R4b, R5, R6a, R6b, R7, R8, R9a, R9b, R10, R11, R12, R13a and R13b are each independently as defined in the description.
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- NOVEL TRPV3 MODULATORS
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Disclosed herein are modulators of TRPV3 of Formula (I) wherein p is 1, 2, 3, or 4, and G1, X1, X2, X3, X4, X5, G2, Z1, Ra, Rb, and u are as defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also presented.
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- NOVEL TRPV3 MODULATORS
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Disclosed herein are modulators of TRPV3 of Formula (I) (I) wherein p is 1, 2, 3, or 4, and G1, X1, X2, X3, X 4, X5, G2, Z1, Ra, Rb, and u are as defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also presented.
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- Discovery of novel HCV inhibitors: Synthesis and biological activity of 6-(indol-2-yl)pyridine-3-sulfonamides targeting hepatitis C virus NS4B
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A novel series of 6-(indol-2-yl)pyridine-3-sulfonamides was prepared and evaluated for their ability to inhibit HCV RNA replication in the HCV replicon cell culture assay. Preliminary optimization of this series furnished compounds with low nanomolar potency against the HCV genotype 1b replicon. Among these, compound 8c has identified as a potent HCV replicon inhibitor (EC50 = 4 nM) with a selectivity index with respect to cellular GAPDH of more than 2500. Further, compound 8c had a good pharmacokinetic profile in rats with an IV half-life of 6 h and oral bioavailability (F) of 62%. Selection of HCV replicon resistance identified an amino acid substitution in HCV NS4B that confers resistance to these compounds. These compounds hold promise as a new chemotype with anti-HCV activity mediated through an underexploited viral target.
- Zhang, Xiaoyan,Zhang, Nanjing,Chen, Guangming,Turpoff, Anthony,Ren, Hongyu,Takasugi, James,Morrill, Christie,Zhu, Jin,Li, Chunshi,Lennox, William,Paget, Steven,Liu, Yalei,Almstead, Neil,George Njoroge,Gu, Zhengxian,Komatsu, Takashi,Clausen, Valerie,Espiritu, Christine,Graci, Jason,Colacino, Joseph,Lahser, Fred,Risher, Nicole,Weetall, Marla,Nomeir, Amin,Karp, Gary M.
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p. 3947 - 3953
(2013/07/27)
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- Compounds and Their Use for Treatment of Amyloid Beta-Related Diseases
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The present invention relates to novel compounds of formula (I) and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising said compounds, processes for making said compounds, and their use as medicaments for treatment and/or prevention of Aβ-related diseases.
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- A practical synthesis of 3,3-difluorocyclobutane carboxylic acid
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We reported a straightforward, three step synthesis of 3,3- difluorocyclobutane carboxylic acid.
- Elend, Dirk,Fengas, David,Fray, M. Jonathan
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p. 657 - 662
(2007/10/03)
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