1.Synthesis and structure-activity relationships of naphthamides as dopamine D3 receptor ligands.
Huang Y1, Luedtke RR, Freeman RA, Wu L, Mach RH. J Med Chem. 2001 May 24;44(11):1815-26.
A series of naphthamides were synthesized, and the affinities of these compounds were determined for dopamine D2 and D3 receptors using radioligand binding techniques. The naphthamide compounds that were prepared include N-(1-alkylpiperidin-4-yl)-4-bromo-1-methoxy-2-naphthamides (1-6), (S)-N-(1-alkylpyrrolidin-3-yl)-4-bromo-1-methoxy-2-naphthamides (7-12), (R)-N-(1-alkylpyrrolidin-3-yl)-4-bromo-1-methoxy-2-naphthamides (13-18), (S)-N-(1-alkyl-2-pyrrolidinylmethyl)-4-bromo-1-methoxy-2-naphthamides (19-25), (R)-N-(1-alkyl-2-pyrrolidinylmethyl)-4-bromo-1-methoxy-2-naphthamides (26-31), and N-(9-alkyl-9-azabicyclo[3.3.1]nonan-3beta-yl)-4-bromo-1-methoxy-2-naphthamides (32, 33). The results of in vitro radioligand binding studies indicated that the majority of the naphthamide analogues bound with high affinity at both the D2 and D3 dopamine receptor subtypes and most of the compounds demonstrated some selectivity for the dopamine D3 dopamine receptor subtype.
2.Synthesis and binding properties of the fluorinated substituted benzamide [3H]NCQ 115, a new selective dopamine D2 receptor ligand.
Hall H1, Högberg T, Halldin C, Bengtsson S, Wedel I. Eur J Pharmacol. 1991 Aug 16;201(1):1-10.
[3H]NCQ 115 [R)-5-bromo-2,3-dimethoxy-N-[1-([2,5-3H]-4- fluorobenzyl)-2-pyrrolidinyl)methyl)benzamide) was prepared by acylation of (R)-(2-aminomethyl)-1- ([2,5-3H]-4-fluorobenzyl)pyrrolidine, which was obtained in a stereo-conservative synthesis from (R)-prolinamide. Purification by reversed phase high performance liquid chromatography (HPLC) gave [3H]NCQ 115 with a radiochemical purity of greater than 99% and a specific activity of 0.97 GBq/mumol (36 Ci/mmol). Saturation analyses, association and dissociation kinetics as well as binding competition with several compounds of various classes were performed with [3H]NCQ 115 in rat striatal homogenates. Saturation analyses in vitro showed that [3H]NCQ 115 bound to a single binding site with a Kd = 214 pM and Bmax = 35.4 fmol/mg. The binding of [3H]NCQ 115 was dependent upon sodium ions, since the number of binding sites was altered when sodium ions were excluded from the incubation medium.
3.Chiral amines as reagents for HPLC-MS enantioseparation of chiral carboxylic acids.
Tsutsui H1, Fujii S, Sakamoto T, Min JZ, Todoroki K, Toyo'oka T. J Sep Sci. 2012 Jul;35(13):1551-9. doi: 10.1002/jssc.201200091.
Mass spectrometry (MS) has become a popular analytical technique because of its high sensitivity and specificity. Therefore, the use of a chiral derivatization reagent for the MS detection seems to be efficient for the enantiomeric separation of racemates. However, the number of chiral reagents for the liquid chromatography (LC)-tandem mass spectrometry (MS/MS) analysis is very limited. The applicability of commercially available chiral amines as the derivatization reagents for the enantiomeric separation of chiral carboxylic acids is reported in this paper by using non-steroidal anti-inflammatory drugs (NSAIDs), i.e. ibuprofen, flurbiprofen, and loxoprofen. The efficiency of the chiral reagents was evaluated in terms of tagging easiness, separation by reversed-phase chromatography, and detection sensitivity by electrospray ionization (ESI)-MS/MS. Among the tested eight chiral amines, i.e. (R)-(+)-4-(3-aminopyrrolidin-1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole (DBD-APy), (S)-(+)-1-(2-pyrrolidinylmethyl)-pyrrolidine (PMP), L-prolinamide, (3R)-(-)-1-benzyl-3-aminopyrrolidine, (S)-(+)-1-cyclohexyl-ethylamine, (3R)-(+)-3-(trifluoroacetamido)-pyrrolidine (TFAP), (R)-(-)-1-aminoindan (AI), and (S)-(+)-tetrahydrofurfuryl-amine, DBD-APy, PMP, AI, and TFAP could be used as the chiral reagents for the enantiomeric separation of the NSAIDs.
