76653-16-2

Upstream product

• 102879-16-3 2-phenylpropanesulfonyl chloride 
• 54664-53-8 2-phenylpropanesulfonyl azide 

Relevant academic research and scientific papers

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.

The Decomposition of β-Phenethylsulfonyl Azides. Solution Chemistry and Flash Vacuum Pyrolysis

The intramolecular cyclization of the parent title compound and a number of para-substituted derivatives (1) in solution was found to take place in low yield and to be accompanied by products of intermolecular reactions, namely, C-H insertion (4) and hydrogen abstraction (3).The use of an excess of a relatively inert solvent Freon 113 led to a better yield of the desired 3,4-dihydro-2,1-benzothiazine 2,2-dioxides (2).Flash vacuum pyrolysis (FVP) of 1 at 250-300 deg C also gave some 2, but the use of higher temperatures led to the formation of styrenes (8), indolines (9), indoles (10), sulfur dioxide, and the remarkable transformation products, the 4-substituted 6,7-dihydro-5H-1-pyrindines (7), in good yield.The styrenes result from the elimination of HN3 and SO2 from the azides, and indolines are formed in good yield by FVP of 2 at 650 deg C.The dihydropyrindines are not obtained from 2, and β-phenethynitrene is not a source of any of the above observed products.A mechanism is proposed for the formation of 7 from β-arylethylsulfonylnitrenes.Consistent with the mechanism is the observation that both 1- and 2-phenylpropanesulfonyl azide give a mixture of 6- and 7-methyl-6,7-dihydro-5H-1-pyrindines in the same ratio on FVP at 650 deg C.Thermolysis of 1a in benzene at 100 deg C gives an N-sulfonylazepine derivative.The FVP of 1 and 2 at 650 deg C are preparative routes to 7 and 9, respectively.