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. Author manuscript; available in PMC: 2011 Feb 11.
Published in final edited form as: J Med Chem. 2010 Feb 11;53(3):1288. doi: 10.1021/jm901563p

Table 3.

Effect of C(2) (S)-Stereochemistry on the Anticonvulsant Activities of (4-Substituted)benzyl Analogs of (N)-Benzyl 2-Acetamido-3-methoxypropionamide Derivativesa

graphic file with name nihms168020u7.jpg
Mice (ip)b
 Rat (po)c
no. R4 mp (°C) MES,d ED50 Tox,e TD50 PI f MES,d ED50 Tox,g TD50 PI f
(S)-3h H 143–144 >100, <300 >300 >30 >30
(S)-11 CH2CH3 132–133 >100, <300 [0.5] >100, <300 [0.5] >30 [0.25 to 4] >30 [0.25 to 4]
(S)-21 CH=CH2 140–142 >100, <300 [0.5] >300
(S)-23i C≡CH 159–160 >300 >300
(S)-26 C≡C- Si(CH3)3 126–127 >30, <100 [0.5] >100, <300 [0.5] >30 >30
(S)-28 CN 168–169 >100, <300 [0.5] >300 [0.5] >30 >30
(S)-29 C(H)O 132–133 >300 >300
(S)-34 N3 149–150 >100, <300 >300 >30 >30
(S)-38 I 159–160 >100, <300 [0.5] >300 >30 >30
phenytoin j 9.5 [2] (8.1 – 10) 66 [2] (53 – 72) 6.9 30 [4] (22 – 39) k >100
phenobarbital j 22 [1] (15 – 23) 69 [0.5] (63 – 73) 3.2 9.1 [5] (7.6 – 12) 61 [0.5] (44 – 96) 6.7
valproate j 270 [0.25] (250 – 340) 430 [0.25] (370 – 450) 1.6 490 [0.5] (350 – 730) 280 [0.5] (190 – 350) 0.6
a

The compounds were tested through the auspices of the NINDS ASP.

b

The compounds were administered intraperitoneally. ED50 and TD50 values are in milligrams per kilogram.

c

The compounds were administered orally. ED50 and TD50 values are in mg/kg.

d

MES = maximal electroshock seizure test.

e

TD50 value determined from the rotorod test.

f

PI = protective index (TD50/ED50).

g

Tox = behavioral toxicity.

h

ref 18.

i

ref 24

j

Porter, R. J.; Cereghino, J J.; Gladding, G. D.; Hessie, B. J.: Kupferberg, H. J.; Scoville, B.; White, B. G.; Cleveland Clin. Q. 1984, 51, 293–305.

k

No ataxia observed up to 3000 mg/kg.