2386-58-5Relevant academic research and scientific papers
Synthesis and reactions of ω-CF3O-substituted aliphatic sulfonyl chlorides
Dobrydnev, Alexey V.,Grygorenko, Oleksandr O.,Kondratov, Ivan S.,Kozytskiy, Andriy V.,Logvinenko, Ivan G.
, (2021)
A two-step approach to the synthesis of ω-CF3O-substituted aliphatic sulfonyl chlorides is reported. The method is based on the reaction of alkylating agents bearing a ω-CF3O substituent with thiourea and subsequent oxidative chlorination of the obtained isothiuronium salt. In this way, β-(trifluoromethoxy)ethane and γ-(trifluoromethoxy)propane sulfonyl chlorides were obtained and assessed as the reagents in the sulfonylation reaction with amines. The former one participated the reaction affording the corresponding vinylsulfonamides because of β-elimination of trifluoromethanol, while the latter one allowed for the preparation of desired γ-(trifluoromethoxy)propane sulfonamides.
A small molecule inhibitor of PCSK9 that antagonizes LDL receptor binding via interaction with a cryptic PCSK9 binding groove
Bonnar, James,Dixon, Ian,Evison, Benny J.,Kelly, Graham E.,Kumar, Sanjay,Lambert, Gilles,Nativel, Brice,Palmer, James T.,Parmar, Jasneet,Rathi, Anuj Kumar,Suchowerska, Alexandra K.,Tang, Wei,Teng, Yanfen,Treutlein, Herbert,Wang, Jie,Xu, Yanfeng,Zeng, Jun,Zhu, Qing,Chemello, Kévin
supporting information, (2020/02/13)
Proprotein convertase (PC) subtilisin kexin type 9 (PCSK9) inhibits the clearance of low density lipoprotein (LDL) cholesterol from plasma by directly interacting with the LDL receptor (LDLR). As the interaction promotes elevated plasma LDL cholesterol levels and a predisposition to cardiovascular disease (CVD), it has attracted much interest as a therapeutic target. While anti-PCSK9 monoclonal antibodies have been successful in the treatment of hypercholesteremia by decreasing CVD risk, their high cost and a requirement for injection have prohibited widespread use. The advent of an orally bioavailable small molecule inhibitor of the PCSK9-LDLR interaction is an attractive alternative, however efforts have been tempered as the binding interface is unfavourable for binding by small organic molecules. Despite its challenging nature, we report herein the discovery of compound 3f as a small molecule inhibitor of PCSK9. The kinase inhibitor nilotinib emerged from a computational screen that was applied to identify compounds that may bind to a cryptic groove within PCSK9 and proximal to the LDLR-binding interface. A subsequent in vitro PCSK9-LDLR binding assay established that nilotinib was a bona fide but modest inhibitor of the interaction (IC50 = 9.8 μM). Through multiple rounds of medicinal chemistry, 3f emerged as a lead-like molecule by demonstrating disruption of the PCSK9-LDLR interaction at nanomolar levels in vitro (IC50 = 537 nM) with no inhibitory activity (IC50 > 10 μM) against a small panel of kinases. Compound 3f restored LDL uptake by liver cells at sub-micromolar levels and demonstrated excellent bioavailability when delivered subcutaneously in mice. Most significantly, compound 3f lowered total cholesterol levels in the plasma of wild-type mice, thereby providing proof-of-concept that the notion of a small molecule inhibitor against PCSK9 is therapeutically viable.
METHOD FOR PRODUCING PHOSPHORYL IMIDE SALT, METHOD FOR PRODUCING NONAQUEOUS ELECTROLYTE SOLUTION CONTAINING SAID SALT, AND METHOD FOR PRODUCING NONAQUEOUS SECONDARY BATTERY
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Paragraph 0269, (2020/05/02)
To provide a method for producing a phosphoryl imide salt represented by the following general formula (1) at a satisfactory yield by cation exchange. The method comprises the step of performing cation exchange by bringing a phosphoryl imide salt represented by the following general formula (2) into contact with a cation exchange resin having M1 n+ or a metal salt represented by the general formula (4) in an organic solvent having a water content of 0.3% by mass or less.
ISOXAZOLE CARBOXAMIDE COMPOUNDS AND USES THEREOF
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Page/Page column 66-67, (2020/04/25)
A compound of Formula (I) or or a pharmaceutically acceptable salt thereof, is provided that has been shown to be useful for treating hearing loss or balance disorder: Formula (I) wherein R1 and Y are as defined herein.
HETEROCYCLIC INHIBITORS OF PCSK9
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Page/Page column 76, (2018/10/24)
This application relates to chemical compounds which may act as inhibitors of, or which may otherwise modulate the activity of, PCSK9, or a pharmaceutically acceptable salt, solvate, prodrug or polymorph thereof, and to compositions and formulations comprising such compounds, and methods of using and making such compounds. Compounds include compounds of Formula (I): (I) wherein A, D and Q are described herein.
ARYLOXYACETYLINDOLES AND ANALOGS AS ANTIBIOTIC TOLERANCE INHIBITORS
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Paragraph 0738, (2016/08/10)
The disclosure provides compounds and pharmaceutical compositions of aryloxyacetylindoles compounds and analogs useful for treating chronic and acute bacterial infections. Certain of the compounds are compounds of general Formula (I) (I) or a pharmaceutically acceptable salt or prodrug thereof. Certain compounds of this disclosure are MvfR inhibitors. MvfR inhibitors reduce the formation of antibiotic tolerant bacterial strains and are useful for treating Gram-negative bacterial infections and reducing the virulence of Pseudomonas aeruginosa. Methods of treating bacterial infections in a subject, including Pseudomonas aeruginosa infections, are also provided by the disclosure.
PROCESSES FOR PREPARING OXATHIAZIN-LIKE COMPOUNDS
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Page/Page column 35; 36, (2016/07/05)
Oxathiazin-like compounds, processes for making new oxathiazin-like compounds, compounds useful for making oxathiazin-like compounds, and their uses are disclosed. Processes of treating patients suffering from cancers, bacterial infections, fungal infections and/or viral infections by administering oxathiazin-like compounds are also disclosed. These compounds were found to have significantly longer half-life compared to taurolidine and taurultam.
HETEROARYL (ALKYL) DITHIOCARBAMATE COMPOUNDS, PREPARATION METHODS AND USES THEREOF
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Paragraph 0053; 0054, (2013/03/26)
Heteroaryl (alkyl) dithiocarbamate compounds represented by general formula (I) or their pharmaceutically acceptable salts, their preparing methods, and their uses for preparing antitumor medicines are disclosed, wherein each said substituent is defined as in the description. The compounds are new tyrosine kinase inhibitors useful as an anti-tumor agents, preferably useful in the preparation of medicines for treating breast cancer, liver cancer, non-small cell lung cancer, gastric cancer, colon cancer, leukaemia or nasal cancer.
HETEROARYL (ALKYL) DITHIOCARBAMATE COMPOUNDS, PREPARATION METHODS AND USES THEREOF
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Paragraph 0112; 0113, (2013/06/05)
Heteroaryl(alkyl)dithiocarbamate compounds represented by general formula (I) or their pharmaceutically acceptable salts, their preparing methods, and their uses for preparing antitumor medicines are disclosed, wherein each said substituent is defined as in the description. The compounds are new tyrosine kinase inhibitors useful as an anti-tumor agents, preferably useful in the preparation of medicines for treating breast cancer, liver cancer, non-small cell lung cancer, gastric cancer, colon cancer, leukaemia or nasal cancer.
PROCESS FOR PREPARATION OF NARATRIPTAN HYDROCHLORIDE
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Page/Page column 32, (2009/10/22)
The present invention relates to an improved process for the preparation of N-methyl-3- (1-methyl-4-piperidinyl)-1H-indole-5-ethanesulfonamide hydrochloride of formula (I) having less than 0.15 % area by HPLC of 3-(1-methyl-4-piperidinyl)-1H-indole-5- ethanesulfonamide (1A) and intermediates thereof.
