81311-66-2Relevant articles and documents
Crystallographic characterization of N-oxide tripod amphiphiles
Chae, Pil Seok,Guzei, Ilia A.,Gellman, Samuel H.
supporting information; experimental part, p. 1953 - 1959 (2010/05/11)
Tripod amphiphiles are designed to promote the solubilization and stabilization of intrinsic membrane proteins in aqueous solution; facilitation of crystallization is a long-range goal. Membrane proteins are subjects of extensive interest because of their critical biological roles, but proteins of this type can be difficult to study because of their low solubility in water. The nonionic detergents that are typically used to achieve solubility can have the unintended effect of causing protein denaturation. Tripod amphiphiles differ from conventional detergents in that the lipophilic segment contains a branchpoint, and previous work has shown that this unusual amphiphilic architecture can be advantageous relative to traditional detergent structures. Here, we report the crystal structures of several tripod amphiphiles that contain an N-oxide hydrophilic group. The data suggest that tripods can adapt themselves to a nonpolar surface by altering the hydrophobic appendage that projects toward that surface and their overall orientation relative to that surface. Although it is not possible to draw firm conclusions regarding amphiphile association in solution from crystallographic data, trends observed among the packing patterns reported here suggest design strategies to be implemented in future studies.
Synthesis and Cardiovascular Activity of a New Series of Cyclohexylaralkylamine Derivatives Related to Perhexiline
Leclerc, Gerard,Decker, Nicole,Schwartz, Jean
, p. 709 - 714 (2007/10/02)
A series of 24 cyclohexylaralkylamine derivatives related to perhexilene has been synthesized and screened for cardiovascular activity.All the compounds contained an exocyclic amine which was substituted either by an alkyl, cycloalkyl, or aralkyl group.In the hope of further reducing toxicity, the synthesis of p-tolyl- and p-hydroxyphenyl derivatives 23 and 24 was undertaken.The effect of separating the cyclohexylamine moiety with respect to the aromatic nucleus has been systematically examined.The pharmacological investigations were directed to a search for compounds having an activity better than perhexiline according to the following order of criteria: (1) α-adrenolytic activity; (2) increase of coronary blood flow; (3) calcium antagonism.Several compounds were more potent and exhibited lower toxicity than perhexiline.Further detailed pharmacological investigations (tension time index and decreased cardiac work) have led to the selection of N,2-dicyclohexyl-2-phenethylamine (3) for clinical trials, which are now under way.