- A 1, 3, 4 - thiadiazole compound and its preparation method (by machine translation)
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The invention discloses 2 - (5 - chloro - 2 - fluoro - 4 - (2 - (4 - pyridazinyl) - 4 - (trifluoromethyl) phenoxy) phenyl) sulfonamide - 1, 3, 4 - thiadiazole and its preparation method. 2 - (5 - chloro - 2 - fluoro - 4 - (2 - (4 - pyridazinyl) - 4 - (trifluoromethyl) phenoxy) phenyl) sulfonamide - 1, 3, 4 - thiadiazole of formula (I) structural formula shown, belonging to a new 1, 3, 4 - thiadiazole compounds, has not seen the literature reports, widens the 1, 3, 4 - thiadiazole compounds of the study area, its synthesis yield is high, simple process, and is applicable to industrial production. (by machine translation)
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- Discovery of Clinical Candidate 4-[2-(5-Amino-1H-pyrazol-4-yl)-4-chlorophenoxy]-5-chloro-2-fluoro-N-1,3-thiazol-4-ylbenzenesulfonamide (PF-05089771): Design and Optimization of Diaryl Ether Aryl Sulfonamides as Selective Inhibitors of NaV1.7
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A series of acidic diaryl ether heterocyclic sulfonamides that are potent and subtype selective NaV1.7 inhibitors is described. Optimization of early lead matter focused on removal of structural alerts, improving metabolic stability and reducing cytochrome P450 inhibition driven drug-drug interaction concerns to deliver the desired balance of preclinical in vitro properties. Concerns over nonmetabolic routes of clearance, variable clearance in preclinical species, and subsequent low confidence human pharmacokinetic predictions led to the decision to conduct a human microdose study to determine clinical pharmacokinetics. The design strategies and results from preclinical PK and clinical human microdose PK data are described leading to the discovery of the first subtype selective NaV1.7 inhibitor clinical candidate PF-05089771 (34) which binds to a site in the voltage sensing domain.
- Swain, Nigel. A.,Batchelor, Dave,Beaudoin, Serge,Bechle, Bruce M.,Bradley, Paul A.,Brown, Alan D.,Brown, Bruce,Butcher, Ken J.,Butt, Richard P.,Chapman, Mark L.,Denton, Stephen,Ellis, David,Galan, Sebastien R. G.,Gaulier, Steven M.,Greener, Ben S.,De Groot, Marcel J.,Glossop, Mel S.,Gurrell, Ian K.,Hannam, Jo,Johnson, Matthew S.,Lin, Zhixin,Markworth, Christopher J.,Marron, Brian E.,Millan, David S.,Nakagawa, Shoko,Pike, Andy,Printzenhoff, David,Rawson, David J.,Ransley, Sarah J.,Reister, Steven M.,Sasaki, Kosuke,Storer, R. Ian,Stupple, Paul A.,West, Christopher W.
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p. 7029 - 7042
(2017/09/07)
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- 1,3,4-thiadiazole compound and preparation method thereof
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The invention discloses 2-(2,4-dimethoxy benzyl)-(5-chloro-2-fluoro-4-(2-(4-pyridazinyl)-4-(trifluoromethyl)phenoxy) phenyl)sulfamide-1,3,4-thiadiazole and a preparation method thereof. The structure of the 2-(2,4-dimethoxy benzyl)-(5-chloro-2-fluoro-4-(2-(4-pyridazinyl)-4-(trifluoromethyl)phenoxy) phenyl)sulfamide-1,3,4-thiadiazole is as shown in the formula (I), and the 2-(2,4-dimethoxy benzyl)-(5-chloro-2-fluoro-4-(2-(4-pyridazinyl)-4-(trifluoromethyl)phenoxy) phenyl)sulfamide-1,3,4-thiadiazole belongs to a novel 1,3,4-thiadiazole compound and is not reported in literature. The research field of 1,3,4-thiadiazole compounds is widened, the synthesis yield is high, the process is simple, and the method is suitable for industrial production.
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Paragraph 0019; 0042; 0043
(2017/03/08)
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- PYRIMIDINE CARBOXAMIDES AS SODIUM CHANNEL BLOCKERS
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The present disclosure provides substituted pyrimidine carboxamides of Formula (I) and the pharmaceutically acceptable salts and solvates thereof, wherein A1, X, A2, W1, W2, W3, E, Z, and R4 are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present disclosure are especially useful for treating pain.
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Paragraph 0358
(2014/09/29)
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- PYRIMIDINES AS SODIUM CHANNEL BLOCKERS
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The present disclosure provides substituted pyrimidine compounds of Formula (I), and the pharmaceutically acceptable salts, prodrugs, and solvates thereof, wherein A1, X, A2, W1, W2, W3, E, Z, and R4 are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present disclosure are especially useful for treating pain.
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Page/Page column 136
(2013/03/28)
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- CHEMICAL COMPOUNDS
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The invention relates to sulfonamide derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. More particularly the invention relates to a new sulfonamide Nav1.7 inhibitors of formula (I): or a pharmaceutically acceptable salt thereof, wherein X, Ar1, R1, R2, R3, R4 and R5 are as defined in the description. Nav 1.7 inhibitors are potentially useful in the treatment of a wide range of disorders, particularly pain.
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Page/Page column 98
(2012/02/02)
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