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H, 3.83; N, 9.98. Found: C, 48.46; H, 3.83; N, 9.96. HRMS calcd for m/z: a sealed vial. The reaction was allowed to proceed for 30 min at room tem-
442.0367. Found: 442.0368. perature, after which it was terminated by the addition of sodium bisulfite
1-[4-(4-Iodobenzyloxy)benzoyl]-2-(2-cyanoethyl)hydrazine (4c): Yield (0.1 ml, 100 mg/ml in water). [125I]2-IBPO was isolated by HPLC using
53.7%, mp 156—157 °C. IR (KBr): 3261, 3208, 2251, 1598, 1365 cmϪ1. 1H- water–methanol (2 : 8, v/v) as an eluent at a flow rate of 3.0 ml/min. The
NMR (DMSO) d: 2.59 (2H, t, Jϭ6.4 Hz, CH2CN), 3.04 (2H, q, Jϭ6.4 Hz, product fractions were collected and the solvent was removed in vacuo. The
CH2CH2), 5.21 (2H, s, CH2O), 5.39 (1H, q, Jϭ4.0 Hz, NHCH2), 7.05 (2H, d, final product, [125I]2-IBPO, was taken up in an isotonic saline solution and
Jϭ6.9 Hz, aromatics), 7.18 (2H, d, Jϭ6.7 Hz, aromatics), 7.57 (2H, d, Jϭ passed through a 0.22 mm filter. The radiochemical yield was 90—95%. The
6.7 Hz, aromatics), 7.76 (2H, d, Jϭ6.9 Hz, aromatics), 9.98 (1H, d, Jϭ4.0 radiochemical purity and specific activity were higher than 99% and
Hz, NHNH). Anal. Calcd for C17H16IN3O2: C, 48.45; H, 3.83; N, 9.98. 7.4 TBq/mmol, respectively, as determined by HPLC.
Found: C, 48.43; H, 3.85; N, 9.98. HRMS calcd for m/z: 442.0367. Found:
In Vivo Tissue Biodistribution Studies in Mice Groups of four male
442.0370.
ddY mice (20—25 g) were injected intravenously through a lateral tail vein
1-[4-(Benzyloxy)-3-iodobenzoyl]-2-(2-cyanoethyl)hydrazine (4d): Yield with [125I]2-IBPO in 0.1 ml of saline solution. At the desired time interval
80.7%, mp 143—145 °C. IR (KBr): 3264, 3212, 2248, 1603, 1367 cmϪ1. 1H- after administration, the animals were sacrificed. Samples of blood and or-
NMR (DMSO) d: 2.50 (2H, t, Jϭ6.4 Hz, CH2CN), 2.88 (2H, q, Jϭ6.4 Hz, gans of interest were excised and weighed. The radioactivity was measured
CH2CH2), 5.14 (2H, s, CH2O), 5.35 (1H, q, Jϭ4.0 Hz, NHCH2), 7.03—7.74
using a well-type NaI(Tl) gamma scintillation counter. The results were ex-
(8H, m, aromatics), 9.90 (1H, d, Jϭ4.0 Hz, NHNH). Anal. Calcd for pressed in terms of the percentage of the injected dose per gram of blood or
C17H16IN3O2: C, 48.45; H, 3.83; N, 9.98. Found: C, 48.48; H, 3.81; N, 9.97.
HRMS calcd for m/z: 442.0367. Found: 442.0365.
organs.
Effect of Various MAO Inhibitors on Tissue Distribution of [125I]2-
Substituted 5-[4-(Benzyloxy)phenyl]-3-(2-cyanoethyl)-1,3,4-oxadiazol- IBPO For our pretreatment experiment, mice were given an i.v. injection
2(3H)-one (5a—d) Compounds 4a—d were dissolved in dry THF, then
of l-depreny, Ro16-6491, clorgyline or Ro-41-1049 (10 mg/kg, respectively)
triphosgene in dry THF was added dropwise. The reaction mixture was 1 h before administration of [125I]2-IBPO. At the desirable time after the in-
stirred for 3 h at room temperature. The solvent was removed in vacuo. The jection of [125I]2-IBPO, these mice were killed by decapitation. Samples of
obtained solid was recrystallized from MeOH.
5-[4-(2-Iodobenzyloxy)phenyl]-3-(2-cyanoethyl)-1,3,4-oxadiazol-2(3H)-
blood and organs of interest were excised, weighed, and the radioactivity of
these samples measured. These results were expressed as a percentage of the
one (5a): Yield 82.0%, mp 167—168 °C. IR (MeOH): 2244, 1788, 1614, injected dose per gram of blood or organs compared with the non-treated
1257, 985 cmϪ1 1H-NMR (DMSO) d: 3.01 (2H, t, Jϭ6.3 Hz, CH2CH2), control mice, referred to as 100%.
.
4.02 (2H, t, Jϭ6.3 Hz, CH2CN), 5.13 (2H, s, CH2O), 7.21 (2H, d, Jϭ6.9 Hz,
aromatics), 7.41—7.95 (4H, m, aromatics), 7.79 (2H, d, Jϭ6.9 Hz, aromat-
ics). Anal. Calcd for C18H14IN3O3: C, 48.34; H, 3.16; N, 9.40. Found: C,
48.34; H, 3.20; N, 9.38. HRMS calcd for m/z: 447.0082. Found: 447.0074.
5-[4-(3-Iodobenzyloxy)phenyl]-3-(2-cyanoethyl)-1,3,4-oxadiazol-2(3H)-
one (5b): Yield 62.7%, mp 150—151 °C. IR (KBr): 2247, 1771, 1612, 1255,
983 cmϪ1. 1H-NMR (DMSO) d: 3.05 (2H, t, Jϭ6.3 Hz, CH2CH2), 4.00 (2H,
t, Jϭ6.3 Hz, CH2CN), 5.11 (2H, s, CH2O), 7.24 (2H, d, Jϭ6.9 Hz, aromat-
ics), 7.32—7.68 (4H, m, aromatics), 7.75 (2H, d, Jϭ6.9 Hz, aromatics).
Anal. Calcd for C18H14IN3O3: C, 48.34; H, 3.16; N, 9.40. Found: C, 48.36;
H, 3.14; N, 9.37. HRMS calcd for m/z: 447.0082. Found: 447.0070.
5-[4-(4-Iodobenzyloxy)phenyl]-3-(2-cyanoethyl)-1,3,4-oxadiazol-2(3H)-
one (5c): Yield 69.3%, mp 169—170 °C. IR (KBr): 2249, 1779, 1613, 1248,
986 cmϪ1. 1H-NMR (DMSO) d: 2.80 (2H, t, Jϭ6.3 Hz, CH2CH2), 4.01 (2H,
t, Jϭ6.3 Hz, CH2CN), 5.01 (2H, s, CH2O), 6.93 (2H, d, Jϭ6.9 Hz, aromat-
ics), 7.18 (2H, d, Jϭ6.7 Hz, aromatics), 7.65 (2H, d, Jϭ6.7 Hz, aromatics),
7.69 (2H, d, Jϭ6.9 Hz, aromatics). Anal. Calcd for C18H14IN3O3: C, 48.34;
H, 3.16; N, 9.40. Found: C, 48.30; H, 3.18; N, 9.43. HRMS calcd for m/z:
447.0082. Found: 447.0079.
Acknowledgements This research was partially supported by the Min-
sitry of Education, Science, Sports and Culture, Grant-in-Aid for Encour-
agement of Young Scientists (A), No1838284.
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1
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