32531-19-4Relevant academic research and scientific papers
Overcoming chloroquine resistance in malaria: Design, synthesis and structure-activity relationships of novel chemoreversal agents
Boudhar, Aicha,Ng, Xiao Wei,Loh, Chiew Yee,Chia, Wan Ni,Tan, Zhi Ming,Nosten, Francois,Dymock, Brian W.,Tan, Kevin S.W.
, p. 231 - 249 (2016/05/24)
Malaria remains a significant infectious disease with even artemisinin-based therapies now facing resistance in the field. Development of new therapies is urgently needed, either by finding new compounds with unique modes of action, or by reversing resistance towards known drugs with 'chemosensitizers' or 'chemoreversal' agents (CRA). Concerning the latter, we have focused on the resistance mechanisms developed against chloroquine (CQ). We have synthesized a series of compounds related to previously identified CRAs, and found promising novel compounds. These compounds show encouraging results in a coumarin labeled chloroquine uptake assay, exhibiting a dose response in resensitising parasites to the antimalarial effects of chloroquine. Selected compounds show consistent potency across a panel of chloroquine and artemisinin sensitive and resistant parasites, and a wide therapeutic window. This data supports further study of CRAs in the treatment of malaria and, ultimately, their use in chloroquine-based combination therapies.
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.
The Discovery of (2S,3S)-cis-2-(diphenylmethyl)-N--1-azabicyclooctan-3-amine as a Novel, Nonpeptide Substance P Antagonist
Lowe, John A.,Drozda, Suzan E.,Snider, R. Michael,Longo, Kelly P.,Zorn, Stevin H.,et al.
, p. 2591 - 2600 (2007/10/02)
We describe the structure-activity relationship development of a series of quinuclidines which culminated in the first potent, selective, nonpeptide substance P (SP) antagonist, (2S,3S)-cis-2-(diphenylmethyl)-N--1-azabicyclo2.2.2
