- 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; 0040; 0041
(2017/03/08)
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- 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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Paragraph 0044; 0045; 0058; 0062
(2017/04/28)
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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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supporting information
p. 7029 - 7042
(2017/09/07)
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- Facile preparation of 2-iodophenyl trifluoromethanesulfonates: Superior aryne precursors
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A comparative study of 3-methoxyaryne precursors revealed 2-iodo-3-methoxyphenyl triflate as the most effective in nonpolar solvent. Use of Hoppe's N-isopropyl carbamate allows for the systematic preparation of a variety of 2-iodophenyl triflates via a directed ortho-lithiation-iodination- decarbamation sequence. These steps are possible without isolation of the intermediate iodophenyl carbamates. Georg Thieme Verlag Stuttgart.
- Ganta, Ashok,Snowden, Timothy S.
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p. 2227 - 2231
(2008/02/10)
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- BIPHENYLOXYACETIC ACID DERIVATIVES FOR THE TREATMENT OF RESPIRATORY DISEASE
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The invention relates to substituted phenoxyacetic acids of formula (I), where the variables are as defined in claim 1, as useful pharmaceutical compounds for treating respiratory disorders, pharmaceutical compositions containing them, and processes for their preparation.
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Page/Page column 27
(2008/06/13)
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- A novel series of non-carboxylic acid, non-hydantoin inhibitors of aldose reductase with potent oral activity in diabetic rat models: 6-(5-Chloro-3- methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one and congeners
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Discovery of a highly selective, potent, and safe non-carboxylic acid, non-hydantoin inhibitor of aldose reductase (AR) capable of potently blocking the excess glucose flux through the polyol pathway that prevails under diabetic conditions has been a long-standing challenge. In response, we did high-throughput screening of our internal libraries of compounds and identified 6-phenylsulfonylpyridazin-2H-3-one, 8, which showed modest inhibition of AR, both in vitro and in vivo. Initial structure-activity relationships concentrated on phenyl substituents and led to 6-(2,4-dichlorophenylsulfonyl)-2/f-pyridazin- 3-one, 81, which was more potent than 8, both in vitro and in vivo. Incorporation of extant literature findings with other aldose reductase inhibitors, including zopolrestat, resulted in the title inhibitor, 19m, which is one of the most potent and highly selective non-carboxylic acid, non-hydantoin inhibitors of AR yet described (IC50, 1 nM; ED 90 vs sciatic nerve sorbitol and fructose, respectively, 0.8 and 4.0 mg/kg). In rats, its oral bioavailability is 98% and it has a favorable plasma t1/2 (26 ± 3 h).
- Mylari, Banavara L.,Armento, Sandra J.,Beebe, David A.,Conn, Edward L.,Coutcher, James B.,Dina, Michael S.,O'Gorman, Melissa T.,Linhares, Michael C.,Martin, William H.,Oates, Peter J.,Tess, David A.,Withbroe, Gregory J.,Zembrowski, William J.
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p. 6326 - 6339
(2007/10/03)
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- NOVEL COMPOUNDS
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The invention relates to substituted phenoxyacetic acids (I) as useful pharmaceutical compounds for treating respiratory disorders, pharmaceutical compositions containing them, and processes for their preparation
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- Pharmaceutical compounds and methods of use thereof
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The present invention provides substituted benzofuran, indene, thianaphthene and oxidized thianaphthene compounds and methods of treatment and pharmaceutical compositions that comprise such compounds. Preferred compounds of the invention contain benzofuran, indene or thianaphthene group substituted with a tetrahydrofuran or other alicyclic group.
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- Pyridazinone aldose reductase inhibitors
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The present invention relates to novel pyridazinone compounds, pharmaceutical compositions comprising those compounds and to methods of using such compounds and compositions to inhibit aldose reductase, lower sorbitol levels and, thus, lower fructose levels, and/or treat or prevent diabetic complications such as diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic microangiopathy and diabetic macroangiopathy in mammals. This invention also relates to methods of affording cardioprotection to subjects not suffering from diabetes. This invention also relates to pharmaceutical compositions and kits comprising a combination of an aldose reductase inhibitor (ARI) of this invention and a sorbitol dehydrogenase inhibitor and to methods of using such compositions or kits to treat or prevent the above diabetic complications in mammals. This invention also relates to other combinations with the ARIs of this invention, including combinations with adendsine agonists; NHE-1 inhibitors; glycogen phosphorylase inhibitors; selective serotonin reuptake inhibitors; GABA agonists; antihypertensive agents; 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors; phosphodiesterase-5 inhibitors; and to glucose lowering agents.
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- Insect control compounds
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The invention is novel hydrocarbon ethers of aminophenol derivatives, and their use in preventing the proliferation of insects by interfering with their normal development and growth pattern.
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