16993-47-8

Upstream product

• 629-59-4 tetradecane 
• 54664-50-5 β-phenethylsulfonyl azide 
• 110-82-7 cyclohexane 
• 622-46-8 carbamic acid phenyl ester 
• 4025-71-2 2-phenylethylsulfonyl chloride 
• 29768-32-9 carbamate de 2,6-dimethylphenyle 
• 66499-24-9 2-phenyl-ethanesulfinic acid 
• 3277-89-2 phenethylmagnesium bromide 
• 103-63-9 1-phenyl-2-bromoethane 
• 71-43-2 benzene 

Downstream Products

• 93808-43-6 3-Phenethylsulfonyl-1-pentyl-harnstoff 
• 89981-94-2 C₈H₉Cl₃NO₂PS 
• 91905-19-0 N-Butyl-N'-(2-phenyl-ethansulfonyl)-harnstoff 
• 143769-71-5 C₁₁H₁₅NO₄S 
• 143769-97-5 N-acetyl-2-(phenyl)ethanesulfonamide 
• 143769-98-6 2-Phenyl-ethanesulfonic acid benzoylamide 
• 117290-23-0 [2-Oxo-2-(2-phenyl-ethanesulfonylamino)-ethyl]-carbamic acid benzyl ester 
• 143769-75-9 C₁₅H₁₇NO₄S₂ 
• 218601-21-9 N-[6-chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethanesulfonamide 
• 875105-71-8 tert-butyl (1S)-(1-{[(2-phenylethanesulfonyl)amino]carbonyl}butyl)carbamate 
• 143769-80-6 N-benzyl-1,2,4,5-tetrahydro-3,2-benzothiazepine 3,3-dioxide 
• 143769-95-3 (7,7-Dioxo-5,7,8,9-tetrahydro-7λ⁶-thia-6-aza-benzocyclohepten-6-yl)-phenyl-methanone 
• 143769-99-7 6-Phenethyl-5,6,8,9-tetrahydro-7-thia-6-aza-benzocycloheptene 7,7-dioxide 
• 143769-91-9 2-(7,7-Dioxo-5,7,8,9-tetrahydro-7λ⁶-thia-6-aza-benzocyclohepten-6-yl)-1-phenyl-ethanone 

Relevant academic research and scientific papers

Sulfinates from Amines: A Radical Approach to Alkyl Sulfonyl Derivatives via Donor-Acceptor Activation of Pyridinium Salts

Synthetically versatile alkyl sulfinates can be prepared from readily available amines, using Katritzky pyridinium salt intermediates. In a catalyst-free procedure, primary, secondary, and benzylic alkyl radicals are generated by photoinduced or thermally induced single-electron transfer (SET) from an electron donor-acceptor (EDA) complex, and trapped by SO2 to generate sulfonyl radicals. Hydrogen atom transfer (HAT) from Hantzsch ester gives alkyl sulfinate products, which are used to prepare a selection of medicinal chemistry relevant sulfonyl-containing motifs.

Structure property relationships of N-acylsulfonamides and related bioisosteres

The N-acylsulfonamide functional group is a feature of the pharmacophore of several biologically active molecules, including marketed drugs. Although this acidic moiety presents multiple points of attachments that could be exploited to introduce structural diversification, depending on the circumstances, the replacement of the functional group itself with a suitable surrogate, or bioisostere, may be desirable. A number of N-acylsulfonamide bioisosteres have been developed over the years that provide opportunities to modulate both structure and physicochemical properties of this important structural motif. To enable an assessment of the relative impact on physicochemical properties that these replacements may have compared to the N-acylsulfonamide group, we conducted a structure-property relationship study based on matched molecular pairs, in which the N-acylsulfonamide moiety of common template reference structures is replaced with a series of bioisosteres. The data presented, which include an assessment of relative changes in acidity, permeability, lipophilicity and intrinsic solubility, provides a basis for informed decisions when deploying N-acylsulfonamides, or surrogates thereof, in analog design.

Primary Sulfonamide Synthesis Using the Sulfinylamine Reagent N-Sulfinyl- O-(tert-butyl)hydroxylamine, t-BuONSO

Sulfonamides have played a defining role in the history of drug development and continue to be prevalent today. In particular, primary sulfonamides are common in marketed drugs. Here we describe the direct synthesis of these valuable compounds from organometallic reagents and a novel sulfinylamine reagent, t-BuONSO. A variety of (hetero)aryl and alkyl Grignard and organolithium reagents perform well in the reaction, providing primary sulfonamides in good to excellent yields in a convenient one-step process.

COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH APJ RECEPTOR ACTIVITY

This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt and/or hydrate and/or prodrug of the compound) that modulate (e.g., agonize) the apelin receptor (also referred to herein as the APJ receptor; gene symbol "APLNR"). This disclosure also features compositions containing the same as well as other methods of using and making the same. The chemical entities are useful, e.g., for treating a subject (e.g., a human) having a disease, disorder, or condition in which a decrease in APJ receptor activity (e.g., repressed or impaired APJ receptor signaling; e.g., repressed or impaired apelin-APJ receptor signaling) or downregulation of endogenous apelin contributes to the pathology and/or symptoms and/or progression of the disease, disorder, or condition. Non-limiting examples of such diseases, disorders, or conditions include: (i) cardiovascular disease; (ii) metabolic disorders; (iii) diseases, disorders, and conditions associated with vascular pathology; and (iv) organ failure; (v) diseases, disorders, and conditions associated with infections (e.g., microbial infections); and (vi) diseases, disorders, or conditions that are sequela or comorbid with any of the foregoing or any disclosed herein. More particular non-limiting examples of such diseases, disorders, or conditions include pulmonary hypertension (e.g., PAH); heart failure; type II diabetes; renal failure; sepsis; and systemic hypertension.

NRF2 REGULATORS

The present invention relates to bis aryl analogs, pharmaceutical compositions containing them and their use as Nrf2 regulators.

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

Starting from the structure of bosentan (1), we embarked on a medicinal chemistry 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 ET B 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 clinical trial for pulmonary arterial hypertension.

Unprecedented observation of sulfonamides in the transesterification of N-unsubstituted carbamates with sulfonyl chlorides

Sulfonamides have been identified as by-products in the base-mediated transesterification of N-unsubstituted carbamates with sulfonyl chlorides to give the corresponding sulfonates. A proposed mechanism and the synthesis of hindered 2,6-disubstituted arylsulfonates via this method are also reported.

Arylalkane-sulfonamides having endothelin-antagonist activity

The invention relates to novel aryl-alkane-sulfonamides and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as endothelin receptor antagonists.

A mild, convenient synthesis of sulfinic acid salts and sulfonamides from alkyl and aryl halides

A general, mild, and convenient method has been developed for the synthesis of various alkyl and aryl sulfinic acid salts and sulfonamides from the corresponding halides. Key to the success of this methodology is the design and facile synthesis of sodium 3-methoxy-3-oxopropane-1-sulfinate (SMOPS), a reagent that serves to introduce the protected sulfinate moiety directly to the substrate, thus avoiding the use of oxidizing and other harsh reaction conditions such as organolithium or Grignard reagents. Many functional groups, as well as heterocycles, are tolerated in the sequence.

Oxidatively sonochemical dealkylation of various N-alkylsulfonamides to free sulfonamides and aldehydes

Various N-alkylsulfonamides were easily dealkylated to give the corresponding free sulfonamides in moderate to good yields in the presence of (diacetoxyiodo)benzene and iodine under ultrasonic irradiation. Application of this methodology to various N-prot