219317-52-9Relevant academic research and scientific papers
Iridium complexes with new 1,2-dithioether chiral ligands containing a rigid cyclic backbone. Application in homogeneous catalytic asymmetric hydrogenation
Dieguez, Montserrat,Ruiz, Aurora,Claver, Carmen,Pereira, Maria M.,Rocha Gonsalves, Antonio M. D'A.
, p. 3517 - 3522 (1998)
New chiral dithioether compounds (-)-1-benzyl-3,4-bis(methylsulfanyl)pyrrolidine (-)-degusme, (-)-1-benzyl-3,4-bis(isopropylsulfanyl)pyrrolidine (-)-deguspri and (+)-1-benzyl-3,4-bis(phenylsulfanyl)pyrrolidine (+)-degusph were prepared from (+)-L-tartaric acid. The addition of the dithioether compounds to a dichloromethane solution of [Ir(cod)2]BF4 afforded the chiral cationic complexes [Ir(cod){(-)-degusme}]BF4 1 [Ir(cod){(-)-deguspri}]BF4·CH2Cl 2 2 and [Ir(cod){(+)-degusph}]BF4 3. The dithioether ligands were replaced by PPh3 in complexes 1, 2 and 3 providing the [Ir(cod)(PPh3)2]BF4 complex. The addition of H2 to 1, 2 and 3 at -70°C gave cis-dihydridoiridium(III) complexes [IrH2(cod)L]BF4 [L = (-)-degusme 4, (-)-deguspri 5 or (+)-degusph 6]. The relative stability of possible isomers for complexes 1-6 was studied by molecular mechanics calculations. Complexes 1-3 were active precursors in the asymmetric hydrogenation of different prochiral dehydroamino acid derivatives and itaconic acid, at room temperature under atmospheric pressure of H2, and the highest enantiomeric excess obtained was 68%.
Urea Derivatives of 2-Aryl-benzothiazol-5-amines: A New Class of Potential Drugs for Human African Trypanosomiasis
Patrick, Donald A.,Gillespie, J. Robert,McQueen, Joshua,Hulverson, Matthew A.,Ranade, Ranae M.,Creason, Sharon A.,Herbst, Zackary M.,Gelb, Michael H.,Buckner, Frederick S.,Tidwell, Richard R.
supporting information, p. 957 - 971 (2017/02/19)
A previous publication from this lab (Patrick, et al. Bioorg. Med. Chem. 2016, 24, 2451-2465) explored the antitrypanosomal activities of novel derivatives of 2-(2-benzamido)ethyl-4-phenylthiazole (1), which had been identified as a hit against Trypanosoma brucei, the causative agent of human African trypanosomiasis. While a number of these compounds, particularly the urea analogues, were quite potent, these molecules as a whole exhibited poor metabolic stability. The present work describes the synthesis of 65 new analogues arising from medicinal chemistry optimization at different sites on the molecule. The most promising compounds were the urea derivatives of 2-aryl-benzothiazol-5-amines. One such analogue, (S)-2-(3,4-difluorophenyl)-5-(3-fluoro-N-pyrrolidylamido)benzothiazole (57) was chosen for in vivo efficacy studies based upon in vitro activity, metabolic stability, and brain penetration. This compound attained 5/5 cures in murine models of both early and late stage human African trypanosomiasis, representing a new lead for the development of drugs to combat this neglected disease.
New fluorinated pyrrolidine and azetidine amides as dipeptidyl peptidase IV inhibitors
Hulin, Bernard,Cabral, Shawn,Lopaze, Michael G.,Van Volkenburg, Maria A.,Andrews, Kim M.,Parker, Janice C.
, p. 4770 - 4773 (2007/10/03)
Cyclohexylglycine amides of various fluorinated pyrrolidines and azetidines were prepared and tested for activity against dipeptidyl peptidase IV and in vivo in the KK mouse model of type 2 diabetes. The tetrafluoropyrrolidide, cis-3,4-difluoropyrrolidide and the fluorinated azetidides displayed unexpectedly strong activity.
