Synthesis and muscarinic acetylcholine receptor (mAChR) antagonist activity of substituted…
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128.1 (CH), 128.8 (CH), 128.9 (CN), 129.2 (CH), 129.2 (C),
130.3 (C), 134.5 (CH), 134.9 (C), 136.5 (C), 136.7 (C); ESI–
MS: m/z=396.32 (MH+).
(4h, 2 mmol) to obtain 0.55 g of 5h (70%). H NMR
(400 MHz, CDCl3): δ = 2.327 (s, 3H), 2.463–2.523 (m,
8H), 3.454 (s, 2H), 3.641 (s, 2H), 3.772 (s, 3H), 5.425 (s,
2H), 6.773–7.386 (m, 8H), 7.386 (s, 1H) ppm; 13C NMR
(100 MHz, DMSO-d6): δ=21.4 (CH3), 52.6 (OCH3), 52.9
(CH2), 53.0 (CH2), 55.5 (CH2), 62.5 (CH2), 113.9 (CH),
114.5(CH), 120.3 (CH), 126.3 (CH), 128.0 (CH), 128.4
(CH), 129.9 (C), 133.3 (CH), 137.6 (C), 138.1(C), 138.5(C),
159.9 (C) ppm; ESI–MS: m/z=392.41 (MH+).
1‑[1‑(2‑Fluorobenzyl)‑1H‑[1,2,3]triazol‑4‑ylmethyl]‑4‑(4‑meth‑
ylbenzyl)piperazine (5e, C22H26FN5) Synthesized by above
method from 0.45 g of 2a (2 mmol) and 0.3 g of 1-azido-
methyl-2-fuorobenzene (4e, 2 mmol) to obtain 0.57 g of
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5e (75%). H NMR (400 MHz, CDCl3): δ=2.322 (s, 3H),
2.453–2.517 (m, 8H), 3.453 (s, 2H), 3.652 (s, 2H), 5.559 (s,
2H), 7.092–7.183 (m, 8H), 7.461 (s, 1H) ppm; 13C NMR
(100 MHz, DMSO-d6): δ = 21.3 (CH3), 22.5 (CH2), 29.4
(CH2), 29.9 (CH2), 31.7 (CH2), 32.0 (CH2), 34.8 (CH2) 47.5
(CH2), 115.9 (CH), 116.1 (CH), 122.9 (CH), 123.0 (CH),
123.1 (CH), 123.6 (CH), 125.4 (CH), 127.9 (CH), 129.8 (C),
131.2 (CH), 131.8 (C), 139.5 (C), 159.7 (C), 161.3 (C) ppm;
ESI–MS: m/z=380.32 (MH+).
4‑[4‑(1‑Benzyl‑1H‑[1,2,3]triazol‑4‑ylmethyl)‑3,5‑dimethyl‑
piperazin‑1‑yl]‑3‑chlorobenzonitrile (5i, C23H25ClN6) Syn-
thesized by above method from 0.6 g of 2c (2 mmol) and
0.27 g of azidomethylbenzene (4i, 2 mmol) to obtain 0.59 g
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of 5i (71%). H NMR (400 MHz, CDCl3): δ = 1.276 (s,
3H), 1.291 (s, 3H), 2.677–2.705 (m, 2H), 2.755–2.761 (m,
2H), 3.317–3.344 (m, 2H), 4.190 (s, 2H), 5.559 (s, 2H),
6.977–6.999 (m, 1H), 7.242–7.270 (m, 2H), 7.372–7.382
(m, 4H), 7.460–7.577 (m, 1H), 7.582 (s, 1H) ppm; 13C NMR
(100 MHz, CDCl3): δ=17.5 (CH3), 41.7 (CH), 53.2 (CH2),
54.05 (CH2), 57.41 (CH2), 105.8 (CCN), 120.2 (CCl), 122.6
(CN), 127.7 (CH), 128.0 (CH), 128.7 (CH), 129.1 (CH),
131.7 (C), 134.1 (CH), 134.7 (C), 152.4 (C) ppm; ESI–MS:
m/z=421.32 (MH+).
1‑(3‑Methylbenzyl)‑4‑[1‑(3‑methylbenzyl)‑1H‑[1,2,3]tria‑
zol‑4‑ylmethyl]piperazine (5f, C23H29N5) Synthesized by
above method from 0.45 g of 2b (2 mmol) and 0.3 g of
1-azidomethyl-3-methylbenzene (4f, 2 mmol) to obtain
0.59 g of 5f (80%). 1H NMR (400 MHz, CDCl3): δ=2.326
(s, 3H), 2.364 (s, 3H), 2.428–2.541 (m, 8H), 3.461 (s, 2H),
3.663 (s, 2H), 5.445 (s, 2H), 7.040–7.260 (m, 8H), 7.378 (s,
1H), ppm; 13C NMR (100 MHz, CDCl3): δ = 21.1 (CH3),
22.1 (CH3), 51.4 (CH2), 51.5 (CH2), 54.1 (CH2), 62.0 (CH2),
125.0 (CH), 126.5 (CH), 128.1 (CH), 128.3 (CH), 128.6
(CH), 128.8 (CH), 129.3 (CH), 130.2 (CH), 134.1 (CH),
135.2 (C), 137.9 (C), 138.7 (C) ppm; IR (KBr): v= 2886,
2215, 1594, 1480, 1322, 1600, 1508, 1458, 1266 cm−1; ESI–
MS: m/z=376.35 (MH+).
4‑[4‑(1‑Benzyl‑1H‑[1,2,3]triazol‑4‑ylmethyl)‑3,5‑dimethyl‑
piperazin‑1‑yl]‑2‑chlorobenzonitrile (5j, C23H25ClN6) Syn-
thesized by above method from 0.6 g of 2c (2 mmol) and
0.27 g of azidomethylbenzene (4i, 2 mmol) to obtain 0.6 g
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of 5i (72%). H NMR (400 MHz, CDCl3): δ = 1.277 (s,
3H), 1.292 (s, 3H), 2.628 (m, 2H), 2.800–2.858 (m, 2H),
3.541–3.571 (m, 2H), 4.112–4.147 (m, 2H), 5.528 (s, 2H),
6.654–6.677 (m, 1H), 6.779–6.785 (m, 1H), 7.237–7.255
(m, 2H), 7.272–7.414 (m, 5H) ppm; 13C NMR (100 MHz,
CDCl3): δ=17.8 (CH3), 42.3 (CH2), 53.1 (CH2), 53.5 (CH2),
54.1 (CH2), 100.1 (CCN), 111.8 (CH), 113.9 (CH), 117.3
(CN), 127.8 (CH), 128.7 (CH), 129.1 (C), 134.4 (CH), 134.5
(CCl), 152.9 (C) ppm; ESI–MS: m/z=421.35 (MH+).
1‑[1‑(3‑Fluorobenzyl)‑1H‑[1,2,3]triazol‑4‑ylmethyl]‑4‑(3‑meth‑
ylbenzyl)piperazine (5 g, C22H26FN5) Synthesized by above
method from 0.45 g of 2b (2 mmol) and 0.3 g of 1-azido-
methyl-3-fuorobenzene (4g, 2 mmol) to obtain 0.59 g of
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5g (78%). H NMR (400 MHz, CDCl3): δ=3.248 (s, 3H),
2.473–2.533 (m, 8H), 3.459 (s, 2H), 3.672 (s, 2H), 5.496 (s,
2H), 6.936–6.959 (m, 1H), 7.027–7.108 (m, 5H), 7.165–7.203
(m, 1H), 7.312–7.367 (m, 1H), 7.409 (m, 1H) ppm; 13C NMR
(100 MHz, CDCl3): δ=21.3 (CH3), 52.7 (CH2), 53.1 (CH2),
53.4 (CH2), 62.8 (CH2), 114.8 (CH), 115.0 (CH), 115.5 (CH),
115.8 (CH), 123.5 (CH), 126.2 (CH), 127.7 (CH), 128.0 (CH),
129.9 (CH), 130.6 (CH), 130.7 (CH), 133.1 (CH), 137.0 (C),
137.5 (C), 137.7 (C), 161.6 (C), 164.1 (C) ppm; IR (KBr):
v = 2839, 2227, 1597, 1443, 1341, 1230 cm−1; ESI–MS:
m/z=380.35 (MH+).
Antimuscarinic evaluation
In a typical experimental protocol [23] male rats were sac-
rifced by decapitation. Two-centimeter long of terminal
ileum was dissected out proximal to 5 cm from the ileum-
cecum junction and mounted in an organ bath containing
Krebs–Ringer solution (KRS) at 35 °C and aerated with 95%
oxygen and 5% carbon dioxide in an automatic organ bath
(Panlab, Harvad). Composition of 1 dm3 KRS was: NaCl
(6.9 g, 118 mM), NaHCO3 (2.1 g, 2.5 mM), 10% KCl (3.6
cm3, 4.8 mM), 10% MgSO4‧7H2O (2.9 cm3, 1.2 mM), 10%
KH2PO4 (3.6 cm3, 1.2 mM), 10% CaCl2 (3.7 cm3, 2.5 mM),
glucose (2 g, 11 mM) in 1 dm3 water. Stock solution of
all the compounds was prepared in KRS and kept at room
1 ‑ [ 4 ‑ ( 3 ‑ M e t h o x y b e n z y l ) ‑ 1 H ‑ [ 1 , 2 , 3 ] t r i a ‑
zol‑1‑ylmethyl]‑4‑(3‑methylbenzyl)piperazine (5 h,
C23H29N5O) Synthesized by above method from 0.45g of 2b
(2 mmol) and 0.33 g of 1-azidomethyl-3-methoxybenzene
1 3