34274-10-7Relevant academic research and scientific papers
Selective intramolecular cleavage of the carbon-silicon bond by palladium salts
Valk, Jean-Marc,Boersma, Jaap,Koten, Gerard van
, p. 213 - 216 (1994)
Several (aryl)trimethylsilane derivatives containing a potentially intramolecularly coordinating dimethylaminomethyl group were prepared and treated with Li2PdCl4 or Pd(OAc)2.Highly selective cleavage of the aryl-C-Si bond took place to give the correspon
Tropylium ion mediated α-cyanation of amines
Allen, Julia M.,Lambert, Tristan H.
supporting information; experimental part, p. 1260 - 1262 (2011/04/15)
Tropylium ion mediated α-cyanation of amines is described. Even in the presence of KCN, tropylium ion is capable of oxidizing various amine substrates, and the resulting iminium ions undergo salt metathesis with cyanide ion to produce aminonitriles. The byproducts of this transformation are simply cycloheptatriene, a volatile hydrocarbon, and water-soluble potassium tetrafluoroborate. Thirteen total substrates are shown for the α-cyanation procedure, including a gram scale synthesis of 17β-cyanosparteine. In addition, a tropylium ion mediated oxidative aza-Cope rearrangement is demonstrated.
Endothelin antagonists: Substituted mesitylcarboxamides with high potency and selectivity for ET(A) receptors
Wu, Chengde,Decker, E. Radford,Blok, Natalie,Bui, Huong,Chen, Qi,Raju,Bourgoyne, Andree R.,Knowles, Vippra,Biediger, Ronald J.,Market, Robert V.,Lin, Shuqun,Dupré, Brian,Kogan, Timothy P.,Holland, George W.,Brock, Tommy A.,Dixon, Richard A. F.
, p. 4485 - 4499 (2007/10/03)
We have previously disclosed the discovery of 2,4-disubstituted anilinothiophenesulfonamides with potent ET(A)-selective endothelin receptor antagonism and the subsequent identification of sitaxsentan (TBC11251, 1) as a clinical development compound (Wu et al. J. Med. Chem. 1997, 40, 1682 and 1690). The orally active 1 has demonstrated efficacy in a phase II clinical trial of congestive heart failure (Givertz et al. Circulation 1998, 98, Abstr. 3044) and was active in rat models of myocardial infarction (Podesser et al. Circulation 1998, 98, Abstr. 2896) and acute hypoxia-induced pulmonary hypertension (Chen et al. FASEB J. 1996, 10 (3), A104). We now report that an additional substituent at the 6-position of the anilino ring further increases the potency of this series of compounds. It was also found that a wide range of functionalities at the 3-position of the 2,4,6-trisubstituted ring increased ETA selectivity by ~10-fold while maintaining in vitro potency, therefore rendering the compounds amenable to fine-tuning of pharmacological and toxicological profiles with enhanced selectivity. The optimal compound in this series was found to be TBC2576 (7u), which has ~10- fold higher ETA binding affinity than 1, high ET(A)/ET(B) selectivity, and a serum half-life of 7.3 h in rats, as well as in vivo activity.
