Synthesis, Molecular Structure, Anticancer Activity, and QSAR Study of N-(aryl/heteroaryl)-4-(1H-pyrrol-1-yl)Benzenesulfonamide Derivatives - Publikacja - MOST Wiedzy

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Synthesis, Molecular Structure, Anticancer Activity, and QSAR Study of N-(aryl/heteroaryl)-4-(1H-pyrrol-1-yl)Benzenesulfonamide Derivatives

Abstrakt

A series of N-(aryl/heteroaryl)-4-(1H-pyrrol-1-yl)benzenesulfonamides were synthesized from 4-amino-N-(aryl/heteroaryl)benzenesulfonamides and 2,5-dimethoxytetrahydrofuran. All the synthesized compounds were evaluated for their anticancer activity on HeLa, HCT-116, and MCF-7 human tumor cell lines. Compound 28, bearing 8-quinolinyl moiety, exhibited the most potent anticancer activity against the HCT-116, MCF-7, and HeLa cell lines, with IC50 values of 3, 5, and 7 M, respectively. The apoptotic potential of the most active compound (28) was analyzed through various assays: phosphatidylserine translocation, cell cycle distribution, and caspase activation. Compound 28 promoted cell cycle arrest in G2/M phase in cancer cells, induced caspase activity, and increased the population of apoptotic cells. Relationships between structure and biological activity were determined by the QSAR (quantitative structure activity relationships) method. Analysis of quantitative structure activity relationships allowed us to generate OPLS (Orthogonal Projections to Latent Structure) models with verified predictive ability that point out key molecular descriptors influencing benzenosulfonamide’s activity

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Autorzy (8)

Informacje szczegółowe

Kategoria:
Publikacja w czasopiśmie
Typ:
artykuł w czasopiśmie wyróżnionym w JCR
Opublikowano w:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES nr 19, wydanie 5, strony 1482 - 1505,
ISSN: 1422-0067
Język:
angielski
Rok wydania:
2018
Opis bibliograficzny:
Żołnowska B., Sławiński J., Brzozowski Z., Kawiak A., Belka M., Zielińska J., Bączek T., Chojnacki J.: Synthesis, Molecular Structure, Anticancer Activity, and QSAR Study of N-(aryl/heteroaryl)-4-(1H-pyrrol-1-yl)Benzenesulfonamide Derivatives// INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. -Vol. 19, iss. 5 (2018), s.1482-1505
DOI:
Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.3390/ijms19051482
Bibliografia: test
  1. (C=N, C=C), 1342 (SO 2 asym ), 1158 (SO 2 sym ) cm −1 ; anal. C 47.04, H 3.29, N 18.29% calcd. for C 12 H 10 N 4 O 2 S 2 , C 46.77, H 2.96, N 17.91%.
  2. General Procedures for the Synthesis of N-(aryl/heteroaryl)-4-(1-H-pyrrol-1-yl) otwiera się w nowej karcie
  3. Benzenesulfonamides (23-40)
  4. Method A. A mixture of 2,5-dimethoxytetrahydrofuran (198 mg, 1.5 mmol), p-dioxane (1.5 mL), glacial acetic acid (0.75 mL), and the corresponding 4-amino-N-(aryl/heteroaryl)benzenesulfonamide (13-19, I, II) (1.45 mmol) was stirred at reflux for 24 h. After cooling to room temperature, the mixture was evaporated in vacuum to dryness, and a residue was dissolved in boiling ethanol. After standing overnight, the precipitate was collected by filtration, washed with ethanol (2 × 2 mL), and dried at 105 • C. Method B. A mixture of 2,5-dimethoxytetrahydrofuran (198 mg, 1.5 mmol), p-dioxane (1 mL), glacial acetic acid (2 mL), and the corresponding 4-amino-N-(heteroaryl)benzenesulfonamide (20, 21, VII) (1.4 mmol) was stirred at reflux for 24 h. After cooling to room temperature and standing overnight, the precipitate was collected by filtration, washed successively with p-dioxane (3 × 1.5 mL), water (4 × 2 mL) and ethanol (3 × 1.5 mL), and dried at temperatures gradually increasing to 105 • C. Method C. A mixture of 2,5-dimethoxytetrahydrofuran (203 mg, 1.54 mmol), p-dioxane (2 mL), glacial acetic acid (1 mL), and the corresponding 4-amino-N-(heteroaryl)benzenesulfonamide (22, III-VI) (1.45 mmol) was stirred at reflux for 26 h. After cooling to room temperature and standing overnight, the precipitate was collected by filtration, washed successively with p-dioxane (2 × 2 mL), water (4 × 2 mL), and ethanol (3 × 3 mL), and dried at temperatures gradually increasing to 110 • C. otwiera się w nowej karcie
  5. N-(4-Chlorophenyl)-4-(1H-pyrrol-1-yl)benzenesulfonamide (23). A mixture of 2,5-dimethoxytetrahydrofuran (198 mg, 1.5 mmol), p-dioxane (1 mL), glacial acetic acid (2 mL), and 4-amino-N-(4-chlorophenyl)benzenesulfonamide 12 (410 mg, 1.4 mmol) was stirred at reflux for 24 h. After cooling to room temperature and standing overnight, the small amount (8 mg) of insoluble side products was filtered out, and the filtrate was concentrated in vacuum. To the residue water, 5 mL was added and stirred at room temperature for 6 h. The precipitate was collected by filtration, washed successively with water (6 × 1 mL) and ethanol (3 × 1 mL), and dried at temperatures gradually increasing to 105 • C. Yield for 23 (434 mg, 90%): m.p. 141-142 • C; IR (KBr) 3255 (NH), 1596 (NH def ), 1507, 1489, 1436 (C=N, C=C), 1333 (SO 2 asym ), 1157 (SO 2 sym ) cm −1 ; 1 H NMR (500 MHz, DMSO-d 6 ) δ 6.30 (t, 2H, H-3 and H-4, pyrrole), 7.11 (d, J = 8.8 Hz, 2H, H-3 and H-5, 4-ClPh), 7.30 (d, J = 8.8 Hz, 2H, H-2 and H-6, 4-ClPh), 7.47 (t, 2H, H-2 and H-5, pyrrole), 7.77 (s, 4H, PhSO 2 ), 10.43 (s, 1H, SO 2 NH) ppm; 13 C NMR (125 MHz, DMSO-d 6 ) δ 112.4, 119.7, 119.8, 122.4, 129.0, 129.2, 129.9, 135.6, 137.4, 143.6 ppm; anal. C 57.74, H 3.93, N 8.41% calcd. for C 16 H 13 ClN 2 O 2 S, C 57.80, H 4.02, N 8.43%. otwiera się w nowej karcie
  6. N-(2-(Phenylthio)phenyl)-4-(1H-pyrrol-1-yl)benzenesulfonamide (24). Method A. Starting from 4-amino- N-[2-(phenylthio)phenyl]benzenesulfonamide 13 (517 mg), the title compound 24 was obtained (413 mg, 70%): m.p. 121.8-125.0 • C; IR (KBr) 3231 (NH), 1596 (NH def ), 1509, 1475, 1440 (C=N, C=C), 1337 (SO 2 asym ), 1168 (SO 2 sym ) cm −1 ; 1 H NMR (500 MHz, DMSO-d 6 ) δ 6.32 (t, 2H, H-3 and H-4, pyrrole), 7.02-7.07 (m, 3H, arom.), 7.15-7.18 (m, 2H, arom.), 7.21-7.25 (m, 4H, arom.), 7.48 (t, 2H, H-2 and H-5, pyrrole), 7.73 (s, 4H, PhSO 2 ), 9.86 (s, 1H, SO 2 NH) ppm; anal. C 65.00, H 4.46, N 6.89% calcd. otwiera się w nowej karcie
  7. N-(2-Phenoxyphenyl)-4-(1H-pyrrol-1-yl)benzenesulfonamide (25). Method A. Starting from 4-amino- N-(2-phenoxyphenyl)benzenesulfonamide 14 (554 mg), the title compound 25 was obtained (396 mg, 70%): m.p. 146 • C; IR (KBr) 3309 (NH), 1598 (NH def ), 1510, 1491, 1421 (C=N, C=C), 1338 (SO 2 asym ), 1168 (SO 2 sym ) cm −1 ; 1 H NMR (500 MHz, DMSO-d 6 ) δ 6.31 (t, 2H, H-3 and H-4, pyrrole), 6.63 (d, J = 7.8 Hz, 2H, arom.), 6.70 (d, J = 7.3 Hz, 1H, arom.), 7.00 (t, 1H, arom.), 7.06-7.13 (m, 2H, arom.), 7.19 (t, 2H, arom.), 7.40 (d, J = 7.3 Hz, 1H, arom.), 7.44 (t, 2H, H-2 and H-5, pyrrole), 7.66 (d, J = 8.8 Hz, 2H, PhSO 2 ), 7.72 (d, J = 8.8 Hz, 2H, PhSO 2 ), 9.96 (s, 1H, SO 2 NH); 13 C NMR (125 MHz, DMSO-d 6 ) otwiera się w nowej karcie
  8. N-[2-(Phenylthio)pyridin-3-y]-4-(1H-pyrrol-1-yl)benzenesulfonamide (26). Method A. Starting from 4-amino-N-[2-(phenylthio)pyridin-3-y]benzenesulfonamide 15 (518 mg), the title compound 26 was obtained (236 mg, 40%): m.p. 113.4-113.8 • C; IR (KBr) 3253 (NH), 1598 (NH def ), 1510, 1475, 1439 (C=N, C=C), 1337 (SO 2 asym ), 1160 (SO 2 sym ) cm −1 ; 1 H NMR (500 MHz, DMSO-d 6 ) δ 6.33 (t, 2H, H-3 and H-4, pyrrole), 7.15 (dd, J = 8.1, 4.7 Hz, 1H, arom.), 7.20 (d, J = 7.8 Hz, 2H, arom.), 7.27-7.32 (m, 3H, arom.), 7.39 (d, J = 8.3 Hz, 1H, arom.), 7.51 (t, 2H, H-2 and H-5, pyrrole), 7.76 (d, J = 8.8 Hz, 2H, PhSO 2 ), 7.81 (d, J = 8.8 Hz, 2H, PhSO 2 ), 8.17 (d, J = 4.9 Hz, 1H, arom.), 10.19 (s, 1H, SO 2 NH) ppm; anal. C 61.89, H 4.20, N 10.31% calcd. for C 21 H 17 N 3 O 2 S 2 , C 61.71, H 4.13, N 10.23%. otwiera się w nowej karcie
  9. N-(2-Phenoxypyridin-3-yl)-4-(1H-pyrrol-1-yl)benzenesulfonamide (27). otwiera się w nowej karcie
  10. Method A. Starting from 4-amino-N-(2-phenoxypyridin-3-yl)benzenesulfonamide 16 (495 mg), the title compound 27 was obtained (369 mg, 65%): m.p. 163.7-165.8 • C; IR (KBr) 3295 (NH), 1598 (NH def ), 1512, 1489, 1451 (C=N, C=C), 1336 (SO 2 asym ), 1167 (SO 2 sym ) cm −1 ; 1 H NMR (500 MHz, DMSO-d 6 ) δ 6.33 (t, 2H, H-3 and H-4, pyrrole), 6.72 (d, J = 7.8 Hz, 2H, arom.), 7.07-7.13 (m, 2H, arom.), 7.23 (t, 2H, arom.), 7.46 (t, 2H, H-2 and H-5, pyrrole), 7.73-7.80 (m, 5H, arom.), 7.86 (dd, J = 4.9, 1.5 Hz, 1H, arom.), 10.23 (s, 1H, SO 2 NH);
  11. C NMR (125 MHz, DMSO-d 6 ) δ 112.1, 119.5, 119.6, 119.7, 121.6, 121.6, 124.9, 129.0, 129.7, 135.4, 136.4, 143.4, 144.2, 153.7, 156.7 ppm; anal. C 64.43, H 4.38, N 10.73% calcd. for C 21 H 17 N 3 O 3 S, C 64.09, H 4.41, N 10.66%. otwiera się w nowej karcie
  12. -(1H-Pyrrol-1-yl)-N-(quinolin-8-yl)benzenesulfonamide (28). otwiera się w nowej karcie
  13. Method A. Starting from 4-amino- N-(quinolin-8-yl)benzenesulfonamide 17 (434 mg), the title compound 28 was obtained (258 mg, 51%): m.p. 151.9-153.0 • C dec.; IR (KBr) 3254 (NH), 1597 (NH def ), 1505, 1471 (C=N, C=C), 1335 (SO 2 asym ), 1163 (SO 2 sym ) cm −1 ; 1 H NMR (500 MHz, DMSO-d 6 ) δ 6.26 (t, 2H, H-3 and H-4, pyrrole), 7.41 (t, 2H, H-2 and H-5, pyrrole), 7.53 (t, 1H, arom.), 7.56 (dd, J = 8.3, 3.9 Hz, 1H, arom.), 7.66 (d, J = 8.3 Hz, 1H, arom.), 7.69 (d, J = 8.8 Hz, 2H, PhSO 2 ), 7.72 (d, J = 7.9 Hz, 1H, arom.), 7.96 (d, J = 8.8 Hz, 2H, PhSO 2 ), 8.33 (dd, J = 8.3, 2 Hz, 1H, arom.), 8.86 (dd, J = 4.4, 1.9 Hz, 1H, arom.), 10.06 (s, 1H, SO 2 NH); 13 C NMR (125 MHz, DMSO-d 6 ) δ 112.9, 117.3, 119.3, 119.5, 122.8, 123.6, 127.2, 128.6, 129.3, 134.1, 135.7, 136.0, 139.3, 143.4, 149.9 ppm; anal. C 65.31, H 4.33, N 12.03% calcd. for C 19 H 15 N 3 O 2 S, C 65.07, H 4.20, N 12.00%. otwiera się w nowej karcie
  14. N-(2-Methylquinolin-8-yl)-4-(1H-pyrrol-1-yl)benzenesulfonamide (29). otwiera się w nowej karcie
  15. Method A. Starting from 4-amino-N-(2-methylquinolin-8-yl)benzenesulfonamide 18 (454 mg), the title compound 29 was obtained (316 mg, 60%): m.p. 167.6-168.7 • C; IR (KBr) 3225 (NH), 1596 (NH def ), 1506, 1472 (C=N, C=C), 1327 (SO 2 asym ), 1166 (SO 2 sym ) cm −1 ; 1 H NMR (500 MHz, DMSO-d 6 ) δ 2.66 (s, 3H, CH 3 ), 6.27 (t, 2H, H-3 and H-4, pyrrole), 7.40-7.46 (m, 4H, arom. and H-2 and H-5, pyrrole), 7.60 (d, J = 7.8 Hz, 1H, arom.), 7.64 (d, J = 7.3 Hz, 1H, arom.), 7.69 (d, J = 8.8 Hz, 2H, PhSO 2 ), 7.94 (d, J = 8.8 Hz, 2H, PhSO 2 ), 8.20 (d, J = 8.8 Hz, 1H, arom.), 9.83 (s, 1H, SO 2 NH) ppm; anal. C 66.10, H 4.71, N 11.56% calcd. for C 20 H 17 N 3 O 2 S, C 66.02, H 4.69, N 11.56%. otwiera się w nowej karcie
  16. N-(7-Methylquinolin-8-yl)-4-(1H-pyrrol-1-yl)benzenesulfonamide (30). otwiera się w nowej karcie
  17. Method A. Starting from 4-amino-N-(7-methylquinolin-8-yl)benzenesulfonamide 19 (454 mg), the title compound 30 was obtained (343 mg, 65%): m.p. 142-145 • C; IR (KBr) 3235 (NH), 1599 (NH def ), 1516, 1503, 1466 (C=N, C=C), 1335 (SO 2 asym ), 1167 (SO 2 sym ) cm −1 ; 1 H NMR (500 MHz, DMSO-d 6 ) δ 2.59 (s, 3H, CH 3 ), 6.29 (t, 2H, H-3 and H-4, pyrrole), 7.29 (dd, J = 8.3, 3.9 Hz, 1H, arom.), 7.41 (t, 2H, H-2 and H-5, pyrrole), 7.53 (d, J = 8.3 Hz, 1H, arom.), 7.56 (br. s, 4H, arom.), 7.78 (d, J = 8.3 Hz, 1H, arom.), 8.21 (d, J = 8.3 Hz, 1H, arom.), 8.39 (d, J = 3.9 Hz, 1H, arom.), 9.74 (s, 1H, SO 2 NH); 13 C NMR (125 MHz, DMSO-d 6 ) δ 19.9, 111.9, 118.5, 119.5, 121.1, 127.0, 127.1, 129.3, 130.3, 131.5, 136.2, 137.3, 138.9, 142.5, 144.5, 149.7 ppm; anal. C 66.10, H 4.71, N 11.56% calcd. for C 20 H 17 N 3 O 2 S, C 65.82, H 4.68, N 11.51%. otwiera się w nowej karcie
  18. N-(2-Methylquinolin-6-yl)-4-(1H-pyrrol-1-yl)benzenesulfonamide (31). otwiera się w nowej karcie
  19. Method B. Starting from 4-amino-N-(2-methylquinolin-6-yl)benzenesulfonamide 20 (439 mg), the title compound 31 was obtained (280 mg, 55%): m.p. 286-288 • C; IR (KBr) 3265, 3140 (SO 2 NH), 1596 (NH def ), 1510, 1475 (C=N, C=C), 1340 (SO 2 asym ), 1160 (SO 2 sym ) cm −1 ; 1 H NMR (500 MHz, DMSO-d 6 ) δ 2.57 (s, 3H, CH 3 ), 6.26 (br. s, 2H, H-3 and H-4, pyrrole), 7.33 (d, J = 6.8 Hz, 1H, H-3, quinoline), 7.42-7.46 (m, 3H, arom.), 7.59 (s, 1H, H-5, quinoline), 7.73-7.96 (m, 5H, arom.), 8.14 (d, J = 6.4 Hz, 1H, H-8, quinoline), 10.58 (s, 1H, SO 2 NH) ppm; 13 C NMR (125 MHz, DMSO-d 6 ) δ 24.7, 111,9, 116.3, 119.3, 122.9, 124.0, 126.7, 128.8, 129.6, 135.4, 143.1, 144.7, 158.0 ppm; anal. C 66.09, H 4.71, N 11.56% calcd. for C 20 H 17 N 3 O 2 S, C 66.12, H 4.81, N 11.55%. otwiera się w nowej karcie
  20. -(1H-pyrrol-1-yl)-N-(4H-1,2,4-triazol-4-yl)benzenesulfonamide (32). otwiera się w nowej karcie
  21. Method B. Starting from 4-amino-N-(4H-1,2,4-triazol-4-yl)benzenesulfonamide 21 (335 mg), the title compound 32 was obtained (219 mg, 54%): m.p. 251-252 • C dec.; IR (KBr) 3150 (NH), 1595 (NH def ), 1515, 1475, 1425 (C=N, C=C), 1340 (SO 2 asym ), 1165 (SO 2 sym ) cm −1 ; 1 H NMR (500 MHz, DMSO-d 6 ) δ 6.35 (br. s, 2H, H-3 and H-4, pyrrole), 7.57 (br. s, 2H, H-2 and H-5, pyrrole), 7.70 (d, J = 8.3 Hz, 2H, H-3 and H-5, PhSO 2 ), 7.88 (d, J = 8.3 Hz, 2H, H-2 and H-6, PhSO 2 ), 8.37 (s, 2H, H-3 and H-5, 1,2,4-triazole), 11.90 (br. s, 1H, SO 2 NH) ppm; 13 C NMR (DMSO-d 6 ) δ 112.7, 119.9, 120.0, 130.4, 143.5, 144.7 ppm; anal. C 49.82, H 3.83, N 24.20% calcd. for C 12 H 11 N 5 O 2 S, C 49.80, H 3.93, N 24.19%.
  22. N-(Benzo-2,1,3-thiadiazol-4-yl)-4-(1H-pyrrol-1-yl)benzenesulfonamide (33). Method C. Starting from 4-amino-N-(benzo-2,1,3-thiadiazol-4-yl)benzenesulfonamide 22 (444 mg), the title compound 33 was obtained (336 mg, 65%): m.p. 325-327 • C dec.; IR (KBr) 3320, 3225 (NH), 1595 (NH def ), 1540, 1510, 1495 (C=N, C=C), 1340 (SO 2 asym ), 1170 (SO 2 sym ) cm −1 ; 1 H NMR (220 MHz, DMSO-d 6 ) δ 6.30 (br. s, 2H, H-3 and H-4, pyrrole), 7.46 (br. s, 2H, H-2 and H-5, pyrrole), 7.64 (t, J = 7.8 Hz, 1H, H-6, benzothiadizole), 7.68-7.80 (m, 4H, H-3 and H-5, PhSO 2 and H-5 and H-7 benzothiadiazole), 7.90 (d, J = 8.0 Hz, 2H, H-2 and H-6 PhSO 2 ), 11.0 (br. s, 1H, SO 2 NH) ppm; 13 C NMR (DMSO-d 6 ) δ 111.9, 117.2, 118.1, 119.2, 119.4, 129.0, 129.7, 130.7, 136.0, 143.2, 149.0, 155.1 ppm; anal. C 53.91, H 3.39, N 15.72% calcd. for C 16 H 12 N 4 O 2 S 2 , C 54.02, H 3.48, N 15.81%. otwiera się w nowej karcie
  23. N-(5-Methylisoxazol-3-yl)-4-(1H-pyrrol-1-yl)-benzenesulfonamide (34). otwiera się w nowej karcie
  24. Method A. Starting from 4-amino-N-(5-methylisoxazol-3-yl)benzenesulfonamide I (367 mg), the title compound 34 was obtained (387 mg, 88%): m.p. 203-204.8 • C; IR (KBr) 3235 (NH), 1599 (NH def ), 1516, 1503, 1466 (C=N, C=C), 1337 (SO 2 asym ), 1168 (SO 2 sym ) cm −1 ; 1 H NMR (500 MHz, DMSO-d 6 ) δ 2.29 (s, 3H, CH 3 ), 6.17 (s, 1H, arom.), 6.32 (s, 2H, H-3 and H-4, pyrrole), 7.49 (s, 2H, H-2 and H-5, pyrrole), 7.82 (d, J = 8.8 Hz, 2H, H-2 and H-6 PhSO 2 ), 7.89 (d, J = 8.8 Hz, 2H, H-2 and H-6 PhSO 2 .), 11.46 (s, 1H, SO 2 NH); 13 C NMR
  25. MHz, DMSO-d 6 ) δ 12.7, 96.1, 112.4, 119.8, 119.9, 129.3, 135.9, 143.9, 158.2, 171.2 ppm; anal. C 55.43, H 4.32, N 13.85% calcd. for C 14 H 13 N 3 O 3 S, C 54.96, H 4.24, N 13.75%.
  26. N-(Pyridin-2-yl)-4-(1H-pyrrol-1-yl)benzenesulfonamide (35). Method A. Starting from 4-amino-N- (pyridin-2-yl)benzenesulfonamide II (361 mg), the title compound 35 was obtained (391 mg, 90%): m.p. 244-246.4 • C; IR (KBr) 3138 (NH), 1634 (NH def ), 1535, 1512, 1466 (C=N, C=C), 1359 (SO 2 asym ), 1142 (SO 2 sym ) cm −1 ; 1 H NMR (500 MHz, DMSO-d 6 ) δ 6.29 (s, 2H, H-3 and H-4, pyrrole), 6.86 (t, 1H, arom.), 7.17 (d, 1H, arom.), 7.45 (s, 2H, H-2 and H-5, pyrrole), 7.71 (d, 1H, arom.), 7.74 (d, J = 8.8 Hz, 2H, H-2 and H-6 PhSO 2 ), 7.90 (d, J = 8.8 Hz, 2H, H-2 and H-6 PhSO 2 .), 8.00 (d, 1H, arom.), 12.06 (s, 1H, SO 2 NH); 13 C NMR (125 MHz, DMSO-d 6 ) δ 112.2, 114.6, 116.1, 119.6, 119.8, 129.0, 138.8, 141.4, 143.0, 153.9 ppm; anal. C 60.18, H 4.38, N 14.04% calcd. for C 15 H 13 N 3 O 2 S, C 60.00, H 4.19, N 13.88%. N-(Pyrimidin-2-yl)-4-(1H-pyrrol-1-yl)benzenesulfonamide (36). Method C. Starting from 4-amino-N -(pyrimidin-2-yl)benzenesulfonamide III (363 mg), the title compound 36 was obtained (379 mg, 87%): m.p. 260-261 • C dec.; IR (KBr) 3150 (NH), 1600 (NH def ), 1585, 1510, 1445 (C=N, C=C), 1345 otwiera się w nowej karcie
  27. (SO 2 asym ), 1160 (SO 2 sym ) cm −1 ; 1 H NMR (200 MHz, DMSO-d 6 ) δ 6.30 (br. s, 2H, H-3 and H-4, pyrrole), 7.04 (t, J = 4.9 Hz, 1H, H-5, pyrimidine), 7.48 (br. s, 2H, H-2 and H-5, pyrrole), 7.85 (d, J = 8.8 Hz, 2H, H-3 and H-5, PhSO 2 ), 8.01 (d, J = 8.8 Hz, 2H, H-2 and H-6, PhSO 2 ), 8.50 (d, J = 4.9 Hz, 2H, H-4 and H-6, (pyrimidine), 11.88 (br. s, 1H, SO 2 NH) ppm; 13 C NMR (50 MHz, DMSO-d 6 ) δ 112.3, 119.4, 119.8, 130.1, 136.9, 143.5, 157.5, 159.0 ppm; anal. C 55.99, H 4.02, N 18.65% calcd. for C 14 H 12 N 4 O 2 S, C 56.20, H 4.22, N 18.72%. otwiera się w nowej karcie
  28. N-(4-Methylpyrimidin-2-yl)-4-(1H-pyrrol-1-yl)benzenesulfonamide (37). otwiera się w nowej karcie
  29. Method C. Starting from 4-amino-N-(4-methylpyrimidin-2-yl)benzenesulfonamide IV (383 mg) the title compound 37 was obtained (392 mg, 86%): m.p. 256-257 • C dec.; IR (KBr) 3235 (NH), 1600 (NH def ), 1565, 1510, 1405 (C=N, C=C), 1345 (SO 2 asym ), 1150 (SO 2 sym ) cm −1 ; 1 H NMR (200 MHz, DMSO-d 6 ) δ 2.31 (s, 3H CH 3 ), 6.30 (br. s, 2H, H-3 and H-4, pyrrole), 6.90 (d, J = 4.9 Hz, 1H, H-5, pyrimidine), 7.47 (br. s, 2H, H-2 and H-5, pyrrole), 7.77 (d, J = 8.3 Hz, 2H, H-3 and H-5, PhSO 2 ), 8.01 (d, J = 8.3 Hz, 2H, H-2 and H-6, PhSO 2 ), 8.32 (d, J = 4.9 Hz, 1H, H-6, pyrimidine), 11.82 (br. s, 1H, SO 2 NH) ppm; 13 C NMR (50 MHz, DMSO-d 6 ) δ 23.9, 112.3, 119.2, 119.8, 130.3, 137.2, 143.4, 157.2 ppm; anal. C 57.31, H 4.49, N 17.82% otwiera się w nowej karcie
  30. N-(4,6-Dimethylpyrimidin-2-yl)-4-(1H-pyrrol-1-yl)benzenesulfonamide (38). Method C. Starting from 4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide V (404 mg), the title compound 38 was obtained (376 mg, 79%): m.p. 224-227 • C dec.; IR (KBr) 3245 (NH), 1600 (NH def ), 1585, 1510, 1475 (C=N, C=C), 1335 (SO 2 asym ), 1160 (SO 2 sym ) cm −1 ; 1 H NMR (200 MHz, DMSO-d 6 ) δ 2.24 (s, 6H, 2 × CH 3 ), 6.29 (br. s, 2H, H-3 and H-4, pyrrole), 6.74 (s, 1H, H-5, pyrimidine), 7.46 (br. s, 2H, H-2 and H-5, pyrrole), 7.76 (d, J = 8.3 Hz, 2H, H-3 and H-5, PhSO 2 ), 8.02 (d, J = 8.3 Hz, 2H, H-2 and H-6, PhSO 2 ), 11.86 (br. s, 1H, SO 2 NH) ppm; 13 C NMR (50 MHz, DMSO-d 6 ) δ 23.5, 112.2, 119.0, 119.8, 130.5, 143.2, 156.8 ppm; anal. C 58.51, H 4.91, N 17.06% calcd. for C 16 H 16 N 4 O 2 S, C 58.85, H 5.30, N 17.52%. N-(2,6-Dimethoxypirimidin-4-yl)-4-(1H-pyrrol-1-yl)benzenesulfonamide (39). Method C. Starting from 4-amino-N-(2,6-dimethoxypirimidin-4-yl)benzenesulfonamide VI (450 mg) the title compound 39 was obtained (423 mg, 81%): m.p. 162-163 • C dec.; IR (KBr) 3240, 3150 (NH), 1595 (NH def ), 1510, 1490, 1455 (C=N, C=C), 1335 (SO 2 asym ), 1160 (SO 2 sym ) cm −1 ; 1 H NMR (200 MHz, DMSO-d 6 ) δ 3.78 (s, 3H CH 3 O, pyrimidine), 3.81 (s, 3H, CH 3 O-2, pyrimidine), 5.99 (s, 1H, H-5, pyrimidine), 6.34 (br. s, 2H, H-3 and H-4, pyrrole), 7.51 (br. s, 2H, H-2 and H-5, pyrrole), 7.84 (d, J = 8.4 Hz, 2H, H-3 and H-5, PhSO 2 ), 8.00 (d, J = 8.4 Hz, 2H, H-2 and H-6, PhSO 2 ), 11.86 (br. s, 1H, SO 2 NH) ppm; 13 C NMR otwiera się w nowej karcie
  31. MHz, DMSO-d 6 ) δ 54.1, 54.8, 85.0, 112.0, 119.3, 119.5, 129.3, 136.0, 143.4, 160.1, 164.2, 171.9 ppm; anal. C 53.32, H 4.47, N 15.54% calcd. for C 16 H 16 N 4 O 4 S, C 53.48, H 4.60, N 15.70%. otwiera się w nowej karcie
  32. N-(6-Methoxypyridazin-3-yl)-4-(1H-pyrrol-1-yl)benzenesulfonamide (40). otwiera się w nowej karcie
  33. Method B. Starting from 4-amino-N-(6-methoxypyridazin-3-yl)benzenesulfonamide VII (392 mg), the title compound 40 was obtained (241 mg, 52%): 191-192 • C; IR (KBr) 3215 (NH), 1645 (NH def ), 1525, 1510, 1470 (C=N, C=C), 1335 (SO 2 asym ), 1145 (SO 2 sym ) cm −1 ; 1 H NMR (200 MHz, DMSO-d 6 ) δ 3.83 (s, 3H, CH 3 O), 6.30 (br. s, 2H, H-3 and H-4, pyrrole), 7.37 (d, J = 7.9 Hz, 1H, H-5, pyridazine), 7.48 (br. s, 2H, H-2 and H-5, pyrrole), 7.72-7.81 (m, 3H, H-3 and H-5, PhSO 2 , and H-4, pyridazine), 7.87 (d, J = 8.6 Hz, 2H, H-2 and H-6, PhSO 2 ), 13.00 (br. s, 1H, SO 2 NH) ppm; 13 C NMR (50 MHz, DMSO-d 6 ) δ 53.54, 110.9, 117.8, 118.5, 119.2, 125.0, 128.2, 140.5, 144.3, 158.7, 159.9 ppm; anal. C 54.53, H 4.27, N 16.96% calcd. for C 15 H 14 N 4 O 3 S, C 54.52, H 4.30, N 16.95%. otwiera się w nowej karcie
  34. X-ray Structure Determination X-Ray diffraction data were collected on the IPDS 2T dual-beam diffractometer (STOE & Cie GmbH, Darmstadt, Germany) at 120.0(2) K with Cu-Kα radiation of a microfocus X-ray source (GeniX 3D Cu High Flux, Xenocs, Sassenage, France, 50 kV, 0.6 mA, λ = 154.186 pm). During the experiment, the crystal was kept in nitrogen stream at 120 K using CryoStream-800 device (Oxford CryoSystem, Oxford, UK). Control of data collection and data reduction was performed by X-Area 1.75 otwiera się w nowej karcie
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