172035-65-3Relevant articles and documents
Identification of a series of 3-(benzyloxy)-1-azabicyclo[2.2.2]octane human NK1 antagonists
Swain,Seward,Cascieri,Fong,Herbert,MacIntyre,Merchant,Owen,Owens,Sabin,Teall,VanNiel,Williams,Sadowski,Strader,Ball,Baker
, p. 4793 - 4805 (2007/10/03)
The synthesis and in vitro and in vivo evaluation of a series of 3- (benzyloxy)-1-azabicyclo-[2.2.2]octane NK1 antagonists are described. While a number of 3,5-disubstituted benzyl ethers afford high affinity, the 3,5- bis(trifluoromethyl)benzyl was found to combine high in vitro affinity with good oral activity. Detailed structure-activity relationship studies in conjunction with data from molecular modeling and mutagenesis work have allowed the construction of a model of the pharmacophore. Specific interactions that have been identified include an interaction between His- 197 and one of the rings of the benzhydryl, a lipophilic pocket containing His-265 that the benzyl ether occupies, and a possible hydrogen bond between Gln-165 and the oxygen of the benzyl ether.
Azabicyclic compounds, pharmaceutical compositions containing them and their use in therapy
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, (2008/06/13)
Compounds of formula (I), and salts and prodrugs thereof: STR1 wherein Q is the residue of an optionally substituted azabicyclic ring system; X represents oxa or thia; Y represents H or hydroxy; R1 represents phenyl or thienyl, either of which groups may be optionally substituted by halo, trifluoromethyl or C1-3 alkoxy, or C5-7 cycloalkyl; R2 represents benzyl which may be substituted in the benzyl ring by halo, trifluoromethyl or C1-3 alkoxy, or C5-7 cycloalkyl; and R3, R4 and R5 independently represent H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halo, cyano, nitro, trifluoromethyl, trimethylsilyl, --ORa, SCH3, SOCH3, S02 CH3, --NRa Rb, --NRa CORb, --NRa C02 Rb, --C02 Ra or --CONRa Rb ; and Ra and Rb independently represent H, C1-6 alkyl, phenyl or trifluoromethyl, are tachykinin receptor antagonists. They and compositions thereof are useful in therapy.
