420
V. A. Anisimova et al.
TABLE 2. Parameters of the 1H NMR Spectra of the Synthesized Compounds
Compound
IIa*
Solvent
Proton chemical shift d, ppm
0.87 (1H, bs, OH), 1.16 (9H, s, C(CH3)3), 1.2 (1H, s, NH), 3.48 (2H, t, CH2), 3.74 (2H, t, CH2),
4.6 (2H, s, CH2CO), 6.66 – 6.75 (1H, m), 6.93 – 7.02 (2H, m), 7.2 – 7.38 (1H, m, Harom
CDCl3
)
IIc
DMCO-d6
CDCl3
3.55 (2H, t, CH2), 3.68 (2H, t, CH2), 6.07 (2H, s, CH2CO), 7.10 – 8.10 (8H, m, Harom), 9.10 (1H, t, NH)
1.33 (9H, s, C(CH3)3), 1.80 (2H, q, CH2), 3.0 – 3.6 (2H, bs, NH, OH), 3.70 (4H, k, NCH2, CH2O), 4.80
IIe*
(2H, s, CH2O), 6.90 (1H, d), 7.0 – 7.14 (2H, dt), 7.43 (1H, d, Harom
)
IIh
DMCO-d6
CDCl3
1.85 (2H, q, CH2), 3.6 (4H, k, NCH2, CH2O), 6.15 (2H, s, CH2CO), 7.1 – 8.2 (8H, m, Harom),
9.12 (1H, t, NH)
IIIa
1.36 (9H, s, C(CH3)3), 4.10 (2H, t, CH2), 4.25 (2H, t, CH2), 6.23 (1H, bs, OH), 6.82 (1H, s, 3-H),
)
6.96 – 7.56 (4H, m, Harom
IIIc
IIIe
CDCl3
CDCl3
4.08 (4H, s, 2CH2), 5.2 – 6.4 (1H, bs, OH), 7.08 – 7.64 (9H, m, Harom)
1.43 (9H, s, C(CH3)3), 2.04 (2H, q, CH2), 3.57 (2H, t, CH2O), 4.42 (2H, t, NCH2), 6.27 (1H, bs, OH),
6.96 (1H, s, 3-H), 7.06 – 7.28 (2H, m, 6,7-H), 7.48 – 7.64 (2H, dd, 5,8-H)
IIIh
CDCl3
CDCl3
1.94 (2H, q, CH2), 3.60 (2H, t, CH2), 4.26 (2H, t, CH2), 7.1 – 7.75 (9H, m, Harom
1.33 (9H, s, C(CH3)3), 2.47 (2H, q, CH2), 3.68 (2H, t, CH2), 4.23 (2H, t, CH2), 6.75 (1H, s, 3-H),
6.9 – 7.5 (4H, m, Harom
)
IVd*
)
IVh
Va
DMCO-d6 – CCl4
DMCO-d6
2.1 (2H, q, CH2), 3.63 (2H, t, CH2), 4.50 (2H, t, CH2), 7.37 – 8.26 (9H, m, Harom), 14.9 – 16.0 (1H, bs,
=N+H–)
1.33 (9H, s, C(CH3)3), 1.46 (9H, s, C(CH3)3), 3.6 (2H, t, CH2), 4.8 (2H, t, CH2), 7.4 – 8.05 (5H, m,
Harom), 9.7 (2H, bs, 2 N+H–)
Vb
DMCO-d6 – CCl4
1.35 (6H, d, 2CH3), 3.25 (2H, m, CH2), 3.35 (1H, m, CH), 4.78 (2H, t, CH2), 7.40 – 7.52 (2H, dt),
7.60 – 7.68 (5H, m), 7.71 – 7.75 (1H, d), 8.02 – 8.08 (1H, d, Harom), 8.35 (1H, s, 3-H), 7.09 (2H, bs, NH,
=N+H–)
Vc
Ve
Ve
Vg
DMCO-d6 – CCl4
DMCO-d6 – CCl4
DMCO-d6 – CCl4
DMCO-d6 – CCl4
1.17 (6H, t, 2CH3), 3.14 (4H, k, 2CH2), 3.40 (2H, t, CH2), 4.90 (2H, t, N – CH2), 7.35 – 8.35 (10H, m,
Harom), 10.00 – 12.50 (1H, broad signal, =N+H–)
3.15 (4H, t, O(CH2)2), 3.55 (2H, t, NCH2), 3.84 (4H, t, N(CH2)2), 4.68 (2H, t, NCH2), 7.37 – 7.66
(7H, m, Harom), 8.0 (1H, d, 5-H), 8.38 (1H, s, 3-H)
1.25 (6H, t, 2CH3), 1.46 (9H, s, C(CH3)3), 2.30 (2H, q, CH2), 3.10 (6H, m, CH2N(CH2)2),
4.45 (2H, t, NCH2), 7.40 – 8.00 (5H, m, Harom), 10.40 (2H, bs, 2 N+H)
1.21 – 1.70 (6H, m, (CH2)3), 1.43 (9H, s, C(CH3)3), 1.80 (2H, m, CH2), 2.0 (2H, m, CH2),
2.25 (2H, m, CH2), 2.92 (1H, m, CH), 3.2 (2H, m, CH2), 4.6 (2H, t, CH2), 7.4 – 8.0 (5H, m, Harom),
9.1 (2H, bs, 2 N+H)
Vh
Vi
DMCO-d6 – CCl4
DMCO-d6 – CCl4
DMCO-d6 – CCl4
DMCO-d6 – CCl4
1.23 (6H, m, 2CH3), 2.27 (2H, q, CH2), 3.13 (6H, m, CH2N(CH2)2), 4.40 (2H, t, NCH2), 7.40 – 8.35
(10H, m, Harom), 11.15 (1H, bs, =N+H–), 13.50 – 17.00 (1H, bs, =N+H–)
1.98 (4H, m, (CH2)2), 2.30 (2H, m, CH2), 3.22 (6H, m, N(CH2)3), 4.38 (2H, t, NCH2), 7.40 – 8.08
(9H, m, Harom), 8.34 (1H, s, 3-H), 11.50 (2H, bs, 2 N+H)
Vj
Vk
1.12 (6H, t, 2CH3), 2.19 (2H, q, CH2), 3.08 (6H, m, CH2N(CH2)2), 4.30 (2H, t, NCH2), 7.40 – 7.80 (7H,
m, Harom), 8.05 (1H, d, 5-H), 8.40 (1H, s, 3-H), 9.50 – 10.5 (2H, bs, 2 N+H)
1.11 (6H, t, 2CH3), 2.19 (2H, q, CH2), 3.0 (6H, m, CH2N(CH2)2), 4.15 (2H, t, NCH2), 7.08 – 7.70 (7H,
m, Harom), 7.80 (1H, d, 5-H), 8.02 (1H, s, 3-H), 10.20 (1H, bs, =N+H)
*
Compound studied in the base form.
TABLE 3. Local Anesthetic Activity (Renier Index) of Compounds Va, Vc, Vh, Vi, and Vk Tested on Rabbit Cornea
Solution concentration, %
Compound
0.0625
0.125
0.25
0.5
1
Va
–
–
120.5 ± 18.6
368.7 ± 34.8
236.2 ± 56.6
749.3 ± 19.2
1250.0 ± 44.3
–
534.0 ± 35.0
367.5 ± 67.2
1139.8 ± 28.7
1300.0 ± 0.0
205.0 ± 25.6
1038.0 ± 47.9
689.8 ± 44.3
565.2 ± 70.7
1280.5 ± 13.9
Vc
–
Vh
539.0 ± 29.3
742.5 ± 17.6
–
630.0 ± 30.9
852.3 ± 17.7
–
Vi
Vk
452.0 ± 51.4
Dicaine
174.4 ± 22.9
346.4 ± 19.5
821.0 ± 40.5
1149.5 ± 27.3 (+)
Notes: (+) hyperemia of the palpebral conjunctiva.