304-53-0Relevant articles and documents
Spirotetrahydro β-carbolines (spiroindolones): A new class of potent and orally efficacious compounds for the treatment of malaria
Yeung, Bryan K. S.,Zou, Bin,Rottmann, Matthias,Lakshminarayana, Suresh B.,Ang, Shi Hua,Leong, Seh Yong,Tan, Jocelyn,Wong, Josephine,Keller-Maerki, Sonja,Fischli, Christoph,Goh, Anne,Schmitt, Esther K.,Krastel, Philipp,Francotte, Eric,Kuhen, Kelli,Plouffe, David,Henson, Kerstin,Wagner, Trixie,Winzeler, Elizabeth A.,Petersen, Frank,Brun, Reto,Dartois, Veronique,Diagana, Thierry T.,Keller, Thomas H.
experimental part, p. 5155 - 5164 (2010/09/05)
The antiplasmodial activity of a series of spirotetrahydro β-carbolines is described. Racemic spiroazepineindole (1) was identified from a phenotypic screen on wild type Plasmodium falciparum with an in vitro IC50 of 90 nM. Structure-activity relationships for the optimization of 1 to compound 20a (IC50 = 0.2 nM) including the identification of the active 1R,3S enantiomer and elimination of metabolic liabilities is presented. Improvement of the pharmacokinetic profile of the series translated to exceptional oral efficacy in the P. berghei infected malaria mouse model where full cure was achieved in four of five mice with three daily doses of 30 mg/kg.
Antihypertensive indole derivatives of phenoxypropanolamines with β-adrenergic receptor antagonist and vasodilating activity
Kreighbaum,Matier,Dennis,Minielli,Deitchman,Perhach Jr.,Comer
, p. 285 - 289 (2007/10/02)
A series of 25 aryloxypropanolamines containing the 3-indolyl-tert-butyl[i.e., 1,1-dimethyl-2-(1H-indol-3-yl)ethyl] or substituted 3-indolyl-tert-butyl moiety as the N substituent is reported. These compounds have been tested for antihypertensive activity in spontaneously hypertensive rats (SHR), β-adrenergic receptor antagonist action in conscious normotensive rats, vasodilating activity in ganglion-blocked rats with blood pressure maintained by angiotensin II infusion, and for intrinsic sympathomimetic action (ISA) in reserpinized rats. Some of the compounds exhibit antihypertensive activity in combination with β-adrenergic receptor antagonist and vasodilating action. The structure-activity relationships in these tests are discussed.