Category: 25999-04-6

Safina, Brian S.; McKerrall, Steven J.; Sun, Shaoyi; Chen, Chien-An; Chowdhury, Sultan; Jia, Qi; Li, Jun; Zenova, Alla Y.; Andrez, Jean-Christophe; Bankar, Girish; Bergeron, Philippe; Chang, Jae H.; Chang, Elaine; Chen, Jun; Dean, Richard; Decker, Shannon M.; DiPasquale, Antonio; Focken, Thilo; Hemeon, Ivan; Khakh, Kuldip; Kim, Amy; Kwan, Rainbow; Lindgren, Andrea; Lin, Sophia; Maher, Jonathan; Mezeyova, Janette; Misner, Dinah; Nelkenbrecher, Karen; Pang, Jodie; Reese, Rebecca; Shields, Shannon D.; Sojo, Luis; Sheng, Tao; Verschoof, Henry; Waldbrook, Matthew; Wilson, Michael S.; Xie, Zhiwei; Young, Clint; Zabka, Tanja S.; Hackos, David H.; Ortwine, Daniel F.; White, Andrew D.; Johnson, J. P. Jr.; Robinette, C. Lee; Dehnhardt, Christoph M.; Cohen, Charles J.; Sutherlin, Daniel P. published the artcile< Discovery of Acyl-sulfonamide Nav1.7 Inhibitors GDC-0276 and GDC-0310>, Quality Control of 25999-04-6, the main research area is acyl sulfonamide sodiumv17 inhibitor GDC0276 GDC0310 pain.

Nav1.7 is an extensively investigated target for pain with a strong genetic link in humans, yet in spite of this effort, it remains challenging to identify efficacious, selective, and safe inhibitors. Here, we disclose the discovery and preclin. profile of GDC-0276 (1) and GDC-0310 (2), selective Nav1.7 inhibitors that have completed Phase 1 trials. Our initial search focused on close-in analogs to early compound 3. This resulted in the discovery of GDC-0276 (1), which possessed improved metabolic stability and an acceptable overall pharmacokinetics profile. To further derisk the predicted human pharmacokinetics and enable QD dosing, addnl. optimization of the scaffold was conducted, resulting in the discovery of a novel series of N-benzyl piperidine Nav1.7 inhibitors. Improvement of the metabolic stability by blocking the labile benzylic position led to the discovery of GDC-0310 (2), which possesses improved Nav selectivity and pharmacokinetic profile over 1.

Journal of Medicinal Chemistry published new progress about Analgesics. 25999-04-6 belongs to class amides-buliding-blocks, and the molecular formula is C4H10N2O3S, Quality Control of 25999-04-6.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Bolli, Martin H.; Boss, Christoph; Binkert, Christoph; Buchmann, Stephan; Bur, Daniel; Hess, Patrick; Iglarz, Marc; Meyer, Solange; Rein, Josiane; Rey, Markus; Treiber, Alexander; Clozel, Martine; Fischli, Walter; Weller, Thomas published the artcile< The Discovery of N-[5-(4-Bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-propylsulfamide (Macitentan), an Orally Active, Potent Dual Endothelin Receptor Antagonist>, SDS of cas: 25999-04-6, the main research area is alkyl sulfamide pyrimidine preparation oral endothelin receptor antagonist antihypertensive.

Starting from the structure of bosentan (1), we embarked on a medicinal chem. program aiming at the identification of novel potent dual endothelin receptor antagonists with high oral efficacy. This led to the discovery of a novel series of alkyl sulfamide substituted pyrimidines. Among these, compound 17 (macitentan, ACT-064992) emerged as particularly interesting as it is a potent inhibitor of ETA with significant affinity for the ETB receptor and shows excellent pharmacokinetic properties and high in vivo efficacy in hypertensive Dahl salt-sensitive rats. Compound 17 successfully completed a long-term phase III clin. trial for pulmonary arterial hypertension.

Journal of Medicinal Chemistry published new progress about Antihypertensives. 25999-04-6 belongs to class amides-buliding-blocks, and the molecular formula is C4H10N2O3S, SDS of cas: 25999-04-6.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Simons, R. Thomas; Scott, Georgia E.; Kanegusuku, Anastasia Gant; Roizen, Jennifer L. published the artcile< Photochemically Mediated Nickel-Catalyzed Synthesis of N-(Hetero)aryl Sulfamides>, Name: Morpholine-4-sulfonamide, the main research area is photocatalyst nickel heteroaryl sulfamide arylbromide arylation.

A general method for the N-arylation of sulfamides with aryl bromides is described. The protocol leverages a dual-catalytic system, with [Ir(ppy)2(dtbbpy)]PF6 as a photosensitizer, NiBr2•glyme as a precatalyst, and DBU as a base, and proceeds at room temperature under visible light irradiation Using these tactics, aryl boronic esters and aryl chlorides can be carried through the reaction untouched. The developed reactions efficiently engage simple bromoarenes and primary sulfamides in between 66% and quant. yields. For more challenging substrates, such as secondary sulfamides, reaction efficiency is documented. Thereby, these methods complement known Buchwald-Hartwig coupling methods for N-arylation of sulfamides. A general method for the N-arylation of sulfamides with aryl bromides is described. The protocol leverages a dual-catalytic system of Ni and a photoexcitable Ir complex and proceeds at room temperature under visible light irradiation Using these tactics, aryl boronic esters and aryl chlorides can be carried through the reaction untouched. Thereby, this method complements known Buchwald-Hartwig coupling methods for N-arylation of sulfamides.

Journal of Organic Chemistry published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 25999-04-6 belongs to class amides-buliding-blocks, and the molecular formula is C4H10N2O3S, Name: Morpholine-4-sulfonamide.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics