199589-50-9Relevant academic research and scientific papers
Generation of gold carbenes in water: Efficient intermolecular trapping of the α-oxo gold carbenoids by indoles and anilines
Li, Long,Shu, Chao,Zhou, Bo,Yu, Yong-Fei,Xiao, Xin-Yu,Ye, Long-Wu
, p. 4057 - 4064 (2014/10/15)
The efficient intermolecular reaction of gold carbene intermediates, generated via gold-catalyzed alkyne oxidation, with indoles and anilines has been realized in aqueous media. Importantly, it was revealed for the first time that water could dramatically suppress the undesired over-oxidation, providing a general and practical solution to the problem of over-oxidation in gold-catalyzed intermolecular alkyne oxidation with external nucleophiles. This strategy was successfully applied to the formal synthesis of the Pfizer's chiral endothelin antagonist UK-350,926.
An efficient and scalable synthesis of the endothelin antagonists UK-350,926 and UK-349,862 using a dynamic resolution process
Ashcroft, Christopher P.,Challenger, Stephen,Clifford, David,Derrick, Andrew M.,Hajikarimian, Yousef,Slucock, Keith,Silk, Terry V.,Thomson, Nicholas M.,Williams, John R.
, p. 663 - 669 (2012/12/25)
The development and scale-up of a potential manufacturing route to the endothelin antagonists UK-350,926 1 and UK-349,862 2 are described. A key synthetic challenge in designing an efficient route to these molecules was the optical lability of the stereogenic centre during the construction of the acylsulfonamide functionality. In the discovery synthesis of UK-350,926 the chiral centre was introduced by classical resolution and the acylsulfonamide functionality synthesized by construction of the N-sulfonyl bond. An alternative more efficient process route was developed involving the preparation of racemic UK-350,926 and final step dynamic resolution with (S)-(-)-1-phenylethylamine as the key step. The process route prepared the acylsulfonamide by construction of the N-carbonyl bond, eliminates a cryogenic reaction and a hazardous intermediate from the synthesis, improves the overall process yield, and allows access to both endothelin antagonists from common intermediates without the need for purification by chromatography. Full experimental details of the new five-step process to prepare UK-349,862 from commercially available starting materials are given for the first time.
The design and synthesis of a novel series of indole derived selective ETA antagonists
Rawson, David J.,Dack, Kevin N.,Dickinson, Roger P.,James, Kim
, p. 125 - 128 (2007/10/03)
Conformational constraint has been used as the key design element in the identification of a series of potent and selective ETA antagonists. The most potent antagonist, 32, (ETA IC50 = 0.55 nM) is 722-fold selective over t
Indole derivatives useful in therapy
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, (2008/06/13)
The invention provides S-(+)-3-{1-(1,3-benzodioxol-5-yl)-2-[(2-methoxy-4-methylphenyl)sulfonylamino]-2-oxoethyl}-1-methyl-1H-indole-6-carboxylic acid, which is substantially free from its (R)-(?)-enantiomer, and pharmaceutically acceptable derivatives the
