ꢁꢀꢀꢀ
M. Mansha et al.: Synthesis of structural analogues of GGT1-DU40ꢂ
ꢂ343
2.97 (dd, J ꢀ=ꢀ 5.8, 14.0 Hz, 1 H, CH2CH), 3.20 (dd, Jꢀ=ꢀ 6.1, 14.0
Hz, 1 H, CH2CH), 3.45 (m, 2 H, NCH2), 3.97 (t, J ꢀ=ꢀ 5.8 Hz,
2 H, OCH2), 4.05 (m, 1 H, CH2CH), 5.36 (d, J ꢀ=ꢀ 5.8 Hz, 1 H,
NH), 6.60 (br. s, 1 H, NH), 7.29 (dd, J ꢀ=ꢀ 4.9, 7.9 Hz, 1 H, aro-
matic H), 7.38 (dd, J ꢀ=ꢀ 4.9, 7.8 Hz, 1 H, aromatic H), 7.55 (d,
J ꢀ=ꢀ 7.9 Hz, 1 H, aromatic H), 7.61 (m, 1 H, aromatic H), 7.65
(dd, J ꢀ=ꢀ 2.4, 8.8 Hz, 1 H, aromatic H), 7.92 (d, J ꢀ=ꢀ 2.4 Hz, 1 H
aromatic H), 8.00 (m, 1 H, aromatic H), 8.49 (d, J ꢀ=ꢀ 2.1 Hz,
1 H, aromatic H), 8.52 (dd, J ꢀ=ꢀ 2.1, 8.1 Hz, 1 H, aromatic
H), 8.63 (dd, J ꢀ=ꢀ 2.1, 8.0 Hz, 1 H, aromatic H), 8.90 (d, J ꢀ=ꢀ
2.1 Hz, 1 H, aromatic H) ppm. – 13C NMR (125.7 MHz, CDCl3):
δ ꢀ=ꢀ 15.69 (SCH3), 23.20 (Ar-CH2), 29.54 (CH2CH2CH2), 34.02
(SCH2), 36.06 (CH2CH), 36.62 (NCH2), 40.95 (SO2CH3), 58.45
(CH2CH), 72.96 (OCH2), 121.07, 123.60, 123.68, 123.75, 129.61,
130.78, 130.92, 132.15, 133.15, 134.94, 137.19, 137.66, 148.49,
148.77, 149.37, 150.57, 151.71 (all Carom), 170.21 (Cꢀ=ꢀO) ppm.
– C29H32Cl2N6O4S2 (663.64): calcd. C 52.48, H 4.86, N 12.66;
found C 52.42, H 4.90, N 12.60.
4.25 (S)-N-(3-((1-(3,4-dichlorophenyl)-4-
(2-(methylthio)ethyl)-3-(pyridin-3-
yl)-1H-pyrazol-5-yl)oxy)propyl)-2-
(methylsulfonamido)-3-(pyridin-4-yl)
propanamide (12)
Following the procedure adopted for the synthesis of
2, the reaction of 40 with 26 yielded compound 12 as a
colorless crystalline solid (yield 62 %). M.p. 136–137 °C.
– [α]D20 ꢀ=ꢀ –20.0 (c ꢀ=ꢀ 0.003, EtOH). – IR (neat): ν ꢀ=ꢀ 3373,
3281, 3062, 2919, 1675, 1592, 1482, 1415, 1319, 1183, 1150
1
cm−1. – H NMR (500 MHz, CDCl3): δ ꢀ=ꢀ 1.92 (pent, 2 H,
CH2CH2CH2), 2.08 (s, 3 H, SCH3), 2.59 (s, 3 H, SO2CH3), 2.65
(t, J ꢀ=ꢀ 7.7 Hz, 2 H, SCH2), 2.88 (t, J ꢀ=ꢀ 6.7 Hz, 2 H, ArCH2),
2.97 (dd, J ꢀ=ꢀ 5.2, 13.7 Hz, 1 H, CH2CH), 3.20 (dd, J ꢀ=ꢀ 6.2, 13.7
Hz, 1 H, CH2CH), 3.47 (m, 2 H, NCH2), 3.97 (t, J ꢀ=ꢀ 5.9 Hz,
2 H, OCH2), 4.08 (m, 1 H, CH2CH), 5.11 (m, 1 H, NH), 6.44
(br. s, 1 H, NH), 7.19 (d, J ꢀ=ꢀ 5.8 Hz, 1 H, aromatic H), 7.38
(d, J ꢀ=ꢀ 6.8 Hz, 2 H, aromatic H), 7.56 (d, J ꢀ=ꢀ 8.2 Hz, 1 H,
aromatic H), 7.64 (dd, J ꢀ=ꢀ 2.4, 8.2 Hz, 1 H, aromatic H), 7.92
(d, J ꢀ=ꢀ 2.4 Hz, 1 H, aromatic H), 8.00 (m, 1 H, aromatic H),
8.56 (d, J ꢀ=ꢀ 6.8 Hz, 2 H, aromatic H), 8.62 (m, 1 H, aromatic
4.24 (S)-2-acetamido-N-(3-((1-(3,4-
dichlorophenyl)-4-(2-(methylthio)
ethyl)-3-(pyridin-3-yl)-1H-pyrazol-
5-yl)oxy)propyl)-3-(pyridin-4-yl)-
propanamide (11)
13
H), 8.90 (d, J ꢀ=ꢀ 1.5 Hz, 1 H, aromatic H) ppm. – C NMR
(125.7 MHz, CDCl3): δ ꢀ=ꢀ 15.71 (SCH3), 23.23 (Ar-CH2), 29.71
(CH2CH2CH2), 34.02 (SCH2), 36.65 (CH2CH), 38.16 (NCH2),
40.95 (SO2CH3), 58.02 (CH2CH), 72.91 (OCH2), 105.77, 121.10,
123.60, 123.70, 124.68, 130.94, 133.17, 134.92, 137.66, 145.44,
148.52, 149.42, 150.35, 151.68 (all Carom), 169.98 (Cꢀ=ꢀO) ppm.
– C29H32Cl2N6O4S2 (663.64): calcd. C 52.48, H 4.86, N 12.66;
found C 52.44, H 4.92, N 12.60.
Following the procedure adopted for the synthesis of
2, the reaction of 40 with 25 yielded compound 11 as a
light brown gum (yield 59 %). – [α]D20 ꢀ=ꢀ –14.6 (c ꢀ=ꢀ 0.003,
EtOH). – IR (neat): ν ꢀ=ꢀ 3478, 3289, 3060, 2919, 1659, 1592,
1482, 1367, 1133 cm−1. – 1H NMR (500 MHz, CDCl3): δ ꢀ=ꢀ 1.85
(pent, 2 H, CH2CH2CH2), 1.96 (s, 3 H, COCH3), 2.08 (s, 3 H,
SCH3), 2.63 (t, J ꢀ=ꢀ 7.0 Hz, 2 H, SCH2), 2.86 (t, J ꢀ=ꢀ 7.3 Hz,
2 H, ArCH2), 3.02 (dd, J ꢀ=ꢀ 6.4, 12.7 Hz, 1 H, CH2CH), 3.06
(dd, J ꢀ=ꢀ 5.3, 12.7 Hz, 1 H, CH2CH), 3.36 (m, 2 H, NCH2),
3.90 (t, J ꢀ=ꢀ 7.0 Hz, 2 H, OCH2), 4.60 (m, 1 H, CH2CH), 6.06
(br. s, 1 H, NH), 6.15 (br. s, 1 H, NH), 7.14 (d, J ꢀ=ꢀ 6.1 Hz, 1 H,
aromatic H), 7.39 (d, J ꢀ=ꢀ 6.6 Hz, 2 H, aromatic H), 7.54 (d,
J ꢀ=ꢀ 8.8 Hz, 1 H, aromatic H), 7.64 (dd, J ꢀ=ꢀ 2.4, 8.8 Hz, 1 H,
aromatic H), 7.92 (d, J ꢀ=ꢀ 2.4 Hz, 1 H, aromatic H), 8.00
(m, 1 H, aromatic H), 8.51 (d, J ꢀ=ꢀ 6.6 Hz, 2 H, aromatic
H), 8.62 (m, 1 H, aromatic H), 8.89 (d, J ꢀ=ꢀ 2.1 Hz, 1 H, aro-
matic H) ppm. – 13C NMR (125.7 MHz, CDCl3): δ ꢀ=ꢀ 15.69
(SCH3), 23.14 (COCH3), 23.20 (Ar-CH2), 29.54 (CH2CH2CH2),
34.02 (SCH2), 36.40 (CH2CH), 37.38 (NCH2), 53.82 (CH2CH),
72.96 (OCH2), 121.07, 123.60, 123.68, 123.75, 129.61, 130.78,
130.92, 132.15, 133.15, 134.94, 137.19, 137.66, 148.49, 148.77,
149.37, 150.57, 151.71 (all Carom), 170.21 (Cꢀ=ꢀO), 170.71 (Cꢀ=ꢀO)
ppm. – C30H32Cl2N6O3S (627.58): calcd. C 57.41, H 5.14,
N 13.39; found C 57.35, H 5.19, N 13.32.
Acknowledgments: The financial support from National
Plan for Science, Technology, and Innovation (project
11-BIO2138-04) and facilities provided by King Fahd
University of Petroleum and Minerals are gratefully
acknowledged.
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