Category: 166883-20-1

Lin, Shu-Yu published the artcilePhenyl Benzenesulfonylhydrazides Exhibit Selective Indoleamine 2,3-Dioxygenase Inhibition with Potent in Vivo Pharmacodynamic Activity and Antitumor Efficacy, Product Details of C9H8ClNO3S, the publication is Journal of Medicinal Chemistry (2016), 59(1), 419-430, database is CAplus and MEDLINE.

Tryptophan metabolism has been recognized as an important mechanism in immune tolerance. Indoleamine 2,3-dioxygenase plays a key role in local tryptophan metabolism via the kynurenine pathway and has emerged as a therapeutic target for cancer immunotherapy. The prior study identified Ph benzenesulfonyl hydrazide as a potent in vitro (though not in vivo) inhibitor of indoleamine 2,3-dioxygenase. Further lead optimization to improve in vitro potencies and pharmacokinetic profiles resulted in N’-(4-bromophenyl)-2-oxo-2,3-dihydro-1H-indole-5-sulfonyl hydrazide (I), which demonstrated 59% oral bioavailability and 73% of tumor growth delay without apparent body weight loss in the murine CT26 syngeneic model, after oral administration of 400 mg/kg. Accordingly, I is proposed as a potential drug lead worthy of advanced preclin. evaluation.

Journal of Medicinal Chemistry published new progress about 166883-20-1. 166883-20-1 belongs to indole-building-block, auxiliary class Indoline,Chloride,Sulfonyl chlorides,Amide, name is 1-Methyl-2-oxoindoline-5-sulfonyl chloride, and the molecular formula is C9H8ClNO3S, Product Details of C9H8ClNO3S.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Zhang, Chufeng published the artcileDiscovery of 3-(4-(2-((1H-Indol-5-yl)amino)-5-fluoropyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile Derivatives as Selective TYK2 Inhibitors for the Treatment of Inflammatory Bowel Disease, Synthetic Route of 166883-20-1, the publication is Journal of Medicinal Chemistry (2021), 64(4), 1966-1988, database is CAplus and MEDLINE.

The design, synthesis, and structure-activity relationships (SARs) of 3-(4-(2-((1H-indol-5-yl)amino)-5-fluoropyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile I [R⁵= 2-cyanoethyl; R⁶ = Me, fluoro; R⁷ = indolin-5-yl, 1-oxoisoindolin-5-yl, 1-tert-butoxycarbonylindol-5-yl, etc.] as selective TYK2 inhibitors was reported. Among them, compound I [R⁵ = 2-cyanoethyl; R⁶ = fluoro; R⁷ = 1-tert-butoxycarbonylindol-5-yl] exhibited acceptable TYK2 inhibition with an IC₅₀ value of 9 nM, showed satisfactory selectivity characteristics over the other three homologous JAK kinases, and performed good functional potency in the JAK/STAT signaling pathway on lymphocyte lines and human whole blood. In liver microsomal assay studied that the clearance rate and half-life of I [R⁵ = 2-cyanoethyl; R⁶ = fluoro; R⁷ = 1-tert-butoxycarbonylindol-5-yl] were 11.4 mL/min/g and 121.6 min, resp. Furthermore, in a dextran sulfate sodium colitis model, I [R⁵ = 2-cyanoethyl; R⁶ = fluoro; R⁷ = 1-tert-butoxycarbonylindol-5-yl] reduced the production of pro-inflammatory cytokines IL-6 and TNF-α and improved the inflammation symptoms of mucosal infiltration, thickening, and edema. Compound I [R⁵ = 2-cyanoethyl; R⁶ = fluoro; R⁷ = 1-tert-butoxycarbonylindol-5-yl] was aselective TYK2 inhibitor and was used to treat immune diseases and deserved further investigation.

Journal of Medicinal Chemistry published new progress about 166883-20-1. 166883-20-1 belongs to indole-building-block, auxiliary class Indoline,Chloride,Sulfonyl chlorides,Amide, name is 1-Methyl-2-oxoindoline-5-sulfonyl chloride, and the molecular formula is C10H11NO4, Synthetic Route of 166883-20-1.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Zhang, Chufeng published the artcileDiscovery of 3-(4-(2-((1H-Indol-5-yl)amino)-5-fluoropyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile Derivatives as Selective TYK2 Inhibitors for the Treatment of Inflammatory Bowel Disease, Synthetic Route of 166883-20-1, the publication is Journal of Medicinal Chemistry (2021), 64(4), 1966-1988, database is CAplus and MEDLINE.

The design, synthesis, and structure-activity relationships (SARs) of 3-(4-(2-((1H-indol-5-yl)amino)-5-fluoropyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile I [R⁵= 2-cyanoethyl; R⁶ = Me, fluoro; R⁷ = indolin-5-yl, 1-oxoisoindolin-5-yl, 1-tert-butoxycarbonylindol-5-yl, etc.] as selective TYK2 inhibitors was reported. Among them, compound I [R⁵ = 2-cyanoethyl; R⁶ = fluoro; R⁷ = 1-tert-butoxycarbonylindol-5-yl] exhibited acceptable TYK2 inhibition with an IC₅₀ value of 9 nM, showed satisfactory selectivity characteristics over the other three homologous JAK kinases, and performed good functional potency in the JAK/STAT signaling pathway on lymphocyte lines and human whole blood. In liver microsomal assay studied that the clearance rate and half-life of I [R⁵ = 2-cyanoethyl; R⁶ = fluoro; R⁷ = 1-tert-butoxycarbonylindol-5-yl] were 11.4 mL/min/g and 121.6 min, resp. Furthermore, in a dextran sulfate sodium colitis model, I [R⁵ = 2-cyanoethyl; R⁶ = fluoro; R⁷ = 1-tert-butoxycarbonylindol-5-yl] reduced the production of pro-inflammatory cytokines IL-6 and TNF-α and improved the inflammation symptoms of mucosal infiltration, thickening, and edema. Compound I [R⁵ = 2-cyanoethyl; R⁶ = fluoro; R⁷ = 1-tert-butoxycarbonylindol-5-yl] was aselective TYK2 inhibitor and was used to treat immune diseases and deserved further investigation.

Journal of Medicinal Chemistry published new progress about 166883-20-1. 166883-20-1 belongs to indole-building-block, auxiliary class Indoline,Chloride,Sulfonyl chlorides,Amide, name is 1-Methyl-2-oxoindoline-5-sulfonyl chloride, and the molecular formula is C10H11NO4, Synthetic Route of 166883-20-1.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles