17126-75-9Relevant articles and documents
Synthesis and structure-analgesic activity relationships of a novel series of monospirocyclopiperazinium salts (MSPZ)
Lin, Song-Wen,Sun, Qi,Ge, Ze-Mei,Wang, Xin,Ye, Jia,Li, Run-Tao
supporting information; experimental part, p. 940 - 943 (2011/03/21)
A series of monospirocyclopiperazinium salts were designed and synthesized to search for a peripherally-acting analgesic drug with low side effects. Extensive SAR studies revealed that a suitable NR2R3 was critical for the analgesic activity, which might be beneficial to expose the cationic nitrogen to bind to the receptor, and possibly interact with the receptor via π-π interaction. Introduction of substituting group on the N4-phenyl ring could improve the activity, and the best position was the 4-position. Compound 14n showed more potent analgesic activity (63%, 20 μM/kg, sc) and holds promise for development as a mechanically new analgesic drug.
Hypoxia-Selective Antitumor Agents. 3. Relationships between Structure and Cytotoxicity against Cultured Tumor Cells for Substituted N,N-Bis(2-chloroethyl)anilines
Palmer, Brian D.,Wilson, William R.,Pullen, Susan M.,Denny, William A.
, p. 112 - 121 (2007/10/02)
A series of aniline mustards with a wide range of electron-donating and -withdrawing substituents in the 3- and 4-positions has been synthesized and evaluated for cytotoxicity in cell culture to examine the potential of using nitro group deactivated nitrogen mustards for the design of novel hypoxia-selective anticancer drugs (Denny, W.A.; Wilson, W.R.J.Med Chem. 1986, 29, 879).Hydrolytic half-lives in tissue culture media, determined by bioassay against a cell line (UV4) defective in the repair of DNA interstrand cross-links showed the expected dependence on the Hammett electronic parameter, ?, varying from 0.13 h for the 4-amino analogue to >100 h for analogues with strongly electron-withdrawing substituents.Cytotoxic potencies in aerobic UV4 cultures showed a similar dependence on ?.This dependence predicted that the 4-nitroaniline mustard would be 7200-fold less potent than its potential six-electron reduction product, the 4-amino compound, in growth inhibition assays using a 1-h drug exposure.The measured differential was much lower (225-fold) because of the instability of the latter compound, but a differential of 17500-fold was observed in the initial rate of killing by using a clonogenic assay.The potential for formation of reactive mustards by reduction to the amine or hydroxylamine was demonstrated by the 4-nitroso compound, which had an aerobic toxicity similar to that of the amine.Although these features confirmed the original rationale, the 3-nitro- and 4-nitroaniline mustards had only minimal hypoxic selectivity against UV cells.Toxicity to hypoxic cells appears to be limited by the low reduction potentials of these compounds and consequent lack of enzymatic nitroreduction.However, this study has demonstrated that nitro groups can be used to latentiate aromatic nitrogen mustards and indicates that examples with higher reduction potentials could provide useful hypoxia-selective therapeutic agents.
A NEW APPROACH TO THE SYNTHESIS OF ARYLDIFLUOROPHOSHINES. FORMATION OF CIS-DICHLORO-BIS(ARYLDIFLUOROPHOSPHINE)PLATINUM(II) COMPLEXES
Heuer, Lutz,Schmutzler, Reinhard
, p. 197 - 216 (2007/10/02)
Reaction of chlorodifluorophosphine with aryllithium compounds has been found to furnish aryldifluorophosphines.This type of reaction is applicable to any aromatic system for which a regioselective lithiation is possible.The most stable products are those
