54221-37-3Relevant academic research and scientific papers
Synthesis and Structure-Activity Relationship of Di-(3,8-diazabicyclo[3.2.1]octane) Diquaternary Ammonium Salts as Unique Analgesics
Liu, Hong,Cheng, Tie-Ming,Zhang, Hong-Mei,Li, Run-Tao
, p. 510 - 513 (2007/10/03)
Based on the structure characteristics of the lead compounds, 1,1′2-octanedioyl-4,4′-dimethyl-4,4′-dibenzyl dipiperazinium dibromide (2) and 3,8-disubstituted-3,8-diazabicyclo[3.2.1]octanes (DBO), di-(3,8-diazabicyclo[3.2.1]octane) diquaternary ammonium salts 3 a-c were designed and synthesized through a highly practical procedure. Target compounds 3 a-c and the hydrochloride salts of their precursors 10 a-c were evaluated for their in vivo analgesic and sedative activities. Interestingly, the introduction of an endoethylenic bridge in the piperazine of lead compound 2 causes loss of the analgesic activity and increases the toxicity dramatically. This result shows that the flexible conformation of piperazine in compound 2 is favorable for interaction with the receptor, and the quaternization of compounds 10 a-c is the main reason for the toxicity increase.
Restricted stereochemistry of solvation of allylic lithium compounds: Structural and dynamic consequences
Fraenkel, Gideon,Duncan, Joseph H.,Wang, Jinhai
, p. 432 - 443 (2007/10/03)
Several 1-sila allylic lithium compounds have been prepared with potential ligands for Li substituted at the 2-position. They are [2-[[cis-2,5-bis(methoxymethyl)-1-pyrrolidinyl]methyl]-1-(trimethylsilyl)allyl] lithium (22), [2-[[cis-2,5-bis(methoxymethyl)-1-pyrrolidinyl]methyl]-1-(dimethylethylsilyl) allyl]lithium(23), [2-[[bis-(2-methoxyethyl)amino]methyl]-1-(dimethylethylsilyl)allyl]lithium (24), [2-[[bis(2-methoxyethyl)amino]methyl]-1-(tert-butyldimethylsilyl)allyl]lithium (25), and [2-[2-[bis(2-methoxyethyl)amino]-1,1-dimethylethyl](ethyl-dimethylsilyl)] allyllithium (26). Using diethyl ether or THF solutions all these compounds exhibited one bond 13C, 7Li spin coupling of ～8 Hz, a 1:1:1:1 13C NMR pattern indicating monomeric structures; all show ligand resonances to be magnetically nonequivalent and reveal C1, C3 13C NMR shifts of about 40 and 75 δ which lie between those for model delocalized 1 and localized species 2. These compounds are concluded to be examples of the heretofore missing folded, internally tridentately coordinated partially delocalized structures with small detectable C, Li covalence. The exception is 25 which, in diethyl ether, consists of a rapidly interconverting equilibrium mixture of localized and delocalized more solvated forms, the former prevailing at 300 K and progressively converting mainly to the latter by 180 K. NMR line shape analysis of the diastereotopic gem methylsilyl 13C resonances as well as that due to the ligand carbons shows that all these line shape changes are due to the dynamics of inversion at lithium-bound carbon and that other ligand reorientation processes are slower than carbanide inversion; for inversion, ΔH? is found to be 6-9 kcal?mol-1, respectively. Averaging with increasing temperature of the 13C, 7Li spin coupling in 24 provides the dynamics of bimolecular carbon lithium bond exchange with ΔH? of 12 kcal?mol-1. Mechanisms are proposed on the basis of the data. We ascribe restricted stereochemistry of ligand lithium coordination to be responsible for these unusual internally coordinated structures.
