39810-52-1Relevant academic research and scientific papers
Discovery and development of a new class of potent, selective, orally active oxytocin receptor antagonists
Quattropani, Anna,Dorbais, Jér?me,Covini, David,Pittet, Pierre-André,Colovray, Véronique,Thomas, Russell J.,Coxhead, Richard,Halazy, Serge,Scheer, Alexander,Missotten, Marc,Ayala, Guidon,Bradshaw, Charles,De Raemy-Schenk, Anne-Marie,Nichols, Anthony,Cirillo, Rocco,Tos, Enrico Gillio,Giachetti, Claudio,Golzio, Lucia,Marinelli, Paolo,Church, Dennis J.,Barberis, Claude,Chollet, André,Schwarz, Matthias K.
, p. 7882 - 7905 (2007/10/03)
We report a novel chemical class of potent oxytocin receptor antagonists showing a high degree of selectivity against the closely related vasopressin receptors (Via, V1b, V2). An initial compound, 7, was shown to be active in an animal model of preterm labor when administered by the intravenous but not by the oral route. Stepwise SAR investigations around the different structural elements revealed one position, the arenesulfonyl moiety, to be amenable to structural changes. Consequently, this position was used to introduce a variety of substituents to improve the physicochemical properties. Some of the resulting analogues were found to be superior to 7 both in terms of potency in vitro and aqueous solubility, which translated into significantly improved efficacy in the animal model after intravenous and oral administration. The best compound, 73, potently inhibited oxytocin-induced uterine contractions in nonpregnant rats and reduced spontaneous uterine contractions in late-term pregnant rats.
THE REACTIONS OF SOME THIOPHENE SULFONYL DERIVATVES
Cremlyn, Richard J.,Goulding, Kenneth H.,Swinbourne, Frederick J.,Yung, Kin-Man
, p. 111 - 120 (2007/10/02)
Thiophene-2-sulfonyl chloride has been allowed to react with 7 amines, hydrazine and sodium azide.The hydrazide was converted into 21 hydrazones.The azide reacts with cyclohexene, norbornene and triphenylphosphine.The sulfonyl chloride with chlorosulfonic acid gave a mixture of the 2,4- and 2,5-bis-sulfonyl chlorides (2:1).These were not separated by conversion to amides, azides, hydrazides, or hydrazones. 2-Carboxythiophene with chlorosulfonic acid gave a mixture of the 4- and 5-sulfonyl chlorides (9:1), conversion to amides and recrystallization gave the 4-sulfonamides.Chlorosulfonation of 2-carboxamido- and 2-N,N-dimethylcarboxamidothiophene gave the 4-sulfonyl chlorides, characterized as amides, hydrazides and 18 hydrazones.Some N-arylthiophenesulfonamides were condensed with trichloromethylsulfonyl chloride.The i.r., n.m.r. and mass spectra of the various thiophenesulphonyl derivatives are discussed.
