Anticonvulsant Activity of Cinnamylpiperazine Derivatives
Letters in Drug Design & Discovery, 2010, Vol. 7, No. 9 663
Table 2. The Data of Flunarizine Dihydrochloride by Different Route of Administration
Administration
ED40 (mg/kg)
TD40 (mg/kg)
PI(TD40/ED40)
Intraperitoneal
Oral
38.1
46.8
164.3
446.3
4.3
8.0
chased from Alderich Chemical Corporation. All other
chemicals were of analytical grade.
(m, 8H, CH2-CH2 ). IR (KBr) cm-1: 3351, 1638, 912, 691.
MS m/z 389 (M+1).
(E)-1-benzhydryl-4-styrylpiperazine dihydrochloride (4a)
(E)-1-((4-chlorophenyl)(phenyl)methyl)-4-styrylpiperazine
dihydrochloride (4g)
1
Yield = 75%, mp 180-182 ꢀ. H-NMR (CDCl3 ppm):
1
13.63 (s, 1H, H-Cl) 13.30 (s, 1H, H-Cl ) 7.92-7.27 (m, 15H,
Ar-H) 6.79 (d, 1H, J = 15.6 Hz, CH) 6.42-6.32 (m, 1H, CH)
5.13 (s, 1H, CH) 4.36 (d, 2H, J = 7.4 Hz, CH2) 3.90-3.55 (m,
8H, CH2-CH2). IR (KBr) cm-1: 3421, 1638, 920, 700. MS
m/z 355 (M+1).
Yield = 64%, mp 178-182 ꢀ. H-NMR (CDCl3 ppm):
13.51 (s, 1H, H-Cl) 13.13 (s, 1H, H-Cl) 7.42-7.27 (m, 14H,
Ar-H) 6.80 (d, 1 H, J = 15.6 Hz, CH) 6.39-6.25 (m, 1H, CH)
5.21 (s, 1H, CH) 4.60 (d, 2 H, J = 7.5 Hz, CH2) 3.88-3.51
(m, 8H, CH2-CH2 ). IR (KBr) cm-1: 3421, 1625, 920, 692.
MS m/z 389 (M+1).
(E)-1-((3-fluorophenyl)(phenyl)methyl)-4-styrylpiperazine
dihydrochloride (4b)
(E)-1-((2-chlorophenyl)(4-fluorophenyl)methyl)-4-
styrylpiperazine dihydrochloride (4h)
1
Yield = 56%, mp 178-188 ꢀ. H-NMR (CDCl3 ppm):
1
13.38 (s, 1H, H-Cl) 12.87 (s, 1H, H-Cl) 7.45-7.36 (m, 14H,
Ar-H) 6.82 (d, 1H, J = 15.7 Hz, CH) 6.42-6.37 (m, 1H, CH)
5.35 (s, 1H, CH) 4.43 (d, 2H, J = 7.5 Hz, CH2 ) 4.01-3.9 (m,
4H, CH2-CH2 ) 3.58-3.38 (m, 4H, CH2 ). IR (KBr) cm-1:
3391, 1618, 911, 690. MS m/z 373 (M+1).
Yield = 49%, mp198-208 ꢀ. H-NMR (CDCl3 ppm):
13.24 (s, 1H, H-Cl) 12.86 (s, 1H, H-Cl) 7.87-7.28 (m, 13H,
Ar-H) 6.79 (d, 1 H, J = 15.8 Hz, CH) 6.41-6.22 (m, 1H, CH)
5.74 (s, 1H, CH) 4.21 (d, 2 H, J = 7.6 Hz, CH2) 3.90-3.57
(m, 8H, CH2-CH2). IR (KBr) cm-1: 3381, 1600, 951, 750. MS
m/z 407 (M+1).
(E)-1-((4-fluorophenyl)(phenyl)methyl)-4-styrylpiperazine
dihydrochloride (4c)
(E)-1-(bis(4-fluorophenyl)methyl)-4-styrylpiperazine dihy-
drochloride (4i)
1
Yield = 65%, mp 208-216 ꢀ. H-NMR (CDCl3 ppm):
1
13.38 (s, 1H, H-Cl) 12.87 (s, 1H, H-Cl) 7.39-7.28 (m, 14H,
Ar-H) 6.82 (d, 1 H, J = 15.6 Hz, CH) 6.42-6.37 (m, 1H, CH)
5.36 (s, 1 H, CH) 4.43 (d, 2 H, J = 7.5 Hz, CH2 ) 4.01-3.58
(m, 8 H, CH2-CH2 ). IR (KBr) cm-1: 3361, 1663, 920, 693.
MS m/z 373 (M+1).
Yield = 63%, mp201-208 ꢀ. H-NMR (CDCl3 ppm):
13.85 (s, 1H, H-Cl) 13.15 (s, 1H, H-Cl) 7.12-7.39 (m, 13H,
Ar-H) 6.82 (d, 1 H, J = 15.8 Hz, CH) 6.34-6.39 (m, 1H, CH)
5.35 (s, 1H, CH) 4.28 (d, 2 H, J = 7.5 Hz, CH2) 3.95-3.48
(m, 8H, CH2-CH2). IR (KBr) cm-1: 3401, 1608, 920, 690. MS
m/z 391 (M+1).
(E)-1-((4-bromophenyl)(phenyl)methyl)-4-styrylpiperazine
dihydrochloride (4d)
(E)-1-((2-chlorophenyl)(4-chlorophenyl)methyl)-4-
styrylpiperazine dihydrochloride (4j)
1
Yield = 59%, mp 220-224 ꢀ. H-NMR (CDCl3 ppm):
1
13.24 (s, 1H, H-Cl) 12.59 (s, 1H, H-Cl) 7.92-7.28 (m, 14H,
Ar-H) 6.87 (d, 1 H, J = 15.7 Hz, CH) 6.45 (m, 1H, CH) 5.89
(s, 1H, CH) 4.51 (d, 2 H, J = 7.5 Hz, CH2 ) 3.97-3.56 (m, 8H,
CH2-CH2). IR (KBr) cm-1: 3360, 1663, 916, 696. MS m/z
433 (M+1).
Yield = 52%, mp188-185 ꢀ. H-NMR (CDCl3 ppm):
13.44 (s, 1H, H-Cl) 13.01 (s, 1H, H-Cl) 8.71-8.69 (d, 1H, J =
7.83, H-Cl) 7.85-7.28 (m, 13H, Ar-H) 6.80 (d, 1 H, J = 15.8
Hz, CH) 6.44-6.36 (m, 1H, CH) 5.76 (s, 1H, CH) 4.18 (d, 2
H, J = 7.5 Hz, CH2) 3.49-3.97 (m, 8H, CH2-CH2 ). IR (KBr)
cm-1: 3381, 1661, 916, 696. MS m/z 423 (M+1).
(E)-1-((4-methoxyphenyl)(phenyl)methyl)-4-
styrylpiperazine dihydrochloride (4e)
(E)-1-(bis(4-chlorophenyl)methyl)-4-styrylpiperazine dihy-
drochloride (4k)
1
Yield = 46%, mp 128-136 ꢀ. H-NMR (CDCl3 ppm):
1
13.57 (s, 1H, H-Cl) 13.24 (s, 1H, H-Cl) 7.90-7.27 (m, 14H,
Ar-H) 6.80 (d, 1 H, J = 15.7 Hz, CH) 6.40-6.35 (m, 1H, CH)
4.95 (s, 1H, CH) 4.34 (d, 2 H, J = 7.5 Hz, CH2) 3.85-3.80 (m,
4H, CH2-CH2) 3.78 (s, 3H, OCH3) 3.55-3.51 (m, 4H, CH2-
CH2). IR (KBr) cm-1: 3321, 1629, 917, 701. MS m/z 385
(M+1).
Yield = 55%, mp202-208 ꢀ. H-NMR (CDCl3 ppm):
13.86 (s, 1H, H-Cl) 13.35 (s, 1H, H-Cl) 7.83-7.28 (m, 13H,
Ar-H) 6.78 (d, 1 H, J = 15.7 Hz, CH) 6.43-6.33 (m, 1H, CH)
5.10 (s, 1H, CH) 4.26 (d, 2 H, J = 7.5 Hz, CH2) 3.87-3.57
(m, 8H, CH2-CH2). IR (KBr) cm-1: 3389, 1645, 932, 692. MS
m/z 423 (M+1).
(E)-1-((2-chlorophenyl)(phenyl)methyl)-4-styrylpiperazine
dihydrochloride (4f)
(E)-1-(bis(4-methoxyphenyl)methyl)-4-styrylpiperazine
dihydrochloride (4l)
1
1
Yield = 58%, mp 178-186 ꢀ. H-NMR (CDCl3 ppm):
Yield = 48%, mp120-125 ꢀ. H-NMR (CDCl3 ppm):
13.44 (s, 1H, H-Cl) 13.01 (s, 1H, H-Cl) 7.95-7.31 (m, 14H,
Ar-H) 6.80 (d, 1 H, J = 15.8 Hz, CH) 6.24-6.10 (m, 1H, CH)
5.78 (s, 1H, CH) 4,38 (d, 2 H, J = 7.4 Hz, CH2) 3.93-3.64
13.47 (s, 1H, H-Cl) 13.02 (s, 1H, H-Cl) 7.78-6.85 (m, 13H,
Ar-H) 6.78 (d, 1 H, J = 15.7 Hz, CH) 6.40-6.34 (m, 1H, CH)
4.90 (s, 1H, CH) 4.30 (d, 2 H, J = 7.5 Hz, CH2) 4.89-3.51