Discovery of 4-amino-3-arylsulfoquinolines, a novel non-acetylenic chemotype of metabotropic glutamate 5 (mGlu5) receptor negative allosteric modulators

European Journal of Medicinal Chemistry

Volumn 133, Issue , 2017, Pages 240-254

  Galambos, János ^a   Bielik, Attila ^a   Wágner, Gábor ^b   Domány, György ^a   Kóti, János ^a   Béni, Zoltán ^a   Szigetvári, Áron ^a   Sánta, Zsuzsanna ^a   Orgován, Zoltán ^c   Bobok, Amrita ^a   Kiss, Béla ^a   Mikó Bakk, Mónika L ^a   Vastag, Mónika ^a   Sághy, Katalin ^a   Krasavin, Mikhail ^d   Gál, Krisztina ^a   Greiner, István ^a   Szombathelyi, Zsolt ^a   Keserű, György M ^c  

^a GEDEON RICHTER LTD   (Hungary)

^b AMSTERDAM INSTITUTE FOR MOLECULES   (Netherlands)

^c INSTITUTE OF EXPERIMENTAL MEDICINE   (Hungary)

^d ST PETERSBURG STATE UNIVERSITY   (Russian Federation)

Author keywords

4 amino 3 arylsulfonyl quinolines; mGlu5 receptor; Negative allosteric modulator; Optimization; Parallel synthesis

Indexed keywords

3 (PHENYLSULFONYL) 4 (PIPERIDIN 1 YL)QUINOLINE; 3 [(3 FLUOROPHENYL)SULFONYL] 6 METHYL 4 (4 METHYLPIPERIDIN 1 YL)QUINOLINE; 3 [(3,4 DICHLOROPHENYL)SULFONYL] 6 FLUORO 4 (4 METHYLPIPERIDIN 1 YL)QUINOLINE; 3 [(3,4 DIMETHYLPHENYL)SULFONYL] 4 (MORPHOLIN 4 YL)QUINOLINE; 3 [[7 CHLORO 4 [4 (HYDROXYMETHYL)PIPERIDIN 1 YL]QUINOLIN 3YL]SULFONYL] 5 FLUOROBENZONITRILE; 4 (4 METHYLPIPERIDIN 1 YL) 3 (PHENYLSULFONYL)QUINOLINE; 4 (AZEPAN 1 YL) 3 (PHENYLSULFONYL)QUINOLINE; 4 AMINO 3 ARYLSULFOQUINOLINE DERIVATIVE; 6 CHLORO 3 [(3 CHLOROPHENYL)SULFONYL] 4 (4 METHYLPIPERIDIN 1 YL) QUINOLINE; 6 CHLORO 3 [(3,4 DICHLOROPHENYL)SULFONYL] 4 (4 METHYLPIPERIDIN 1 YL)QUINOLINE; 7 CHLORO 3 [(3 FLUOROPHENYL)SULFONYL] 4 (4 METHYLPIPERIDIN 1 YL)QUINOLINE; 7 CHLORO 3 [(3 FLUOROPHENYL)SULFONYL] 4 (MORPHOLIN 4 YL) QUINOLINE; 7 CHLORO 3 [(3,5 DIFLUOROPHENYL)SULFONYL] 4 (4 METHYLPIPERIDIN 1 YL)QUINOLINE; 7 CHLORO 3 [(4 FLUOROPHENYL)SULFONYL] 4 (MORPHOLIN 4 YL)QUINOLINE; ANXIOLYTIC AGENT; METABOTROPIC RECEPTOR 5; N BENZYL 3 [(4 METHYLPHENYL)SULFONYL]QUINOLIN 4 AMINE; N,N DIETHYL 3 [(4 METHYLPHENYL)SULFONYL]QUINOLIN 4 AMINE; QUINOLINE DERIVATIVE; UNCLASSIFIED DRUG; [1 [7 CHLORO 3 [(3 CHLOROPHENYL)SULFONYL]QUINOLIN 4 YL]PIPERIDIN 4 YL]METHANOL; [1 [7 CHLORO 3 [(3 FLUOROPHENYL)SULFONYL]QUINOLIN 4 YL]PIPERIDIN 4 YL]METHANOL; [1 [7 CHLORO 3 [(4 FLUOROPHENYL)SULFONYL]QUINOLIN 4 YL]PIPERIDIN 4 YL]METHANOL; PIPERAZINE DERIVATIVE;

ALLOSTERISM; ANIMAL TISSUE; ANXIETY DISORDER; ARTICLE; BINDING SITE; DEPRESSION; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG SCREENING; DRUG SOLUBILITY; ELECTROSPRAY MASS SPECTROMETRY; ENZYME MECHANISM; HEPATIC EXTRACTION RATIO; HUMAN; HUMAN TISSUE; IN VITRO STUDY; IN VIVO STUDY; LIVER MICROSOME; MAXIMUM REACTION VELOCITY; METABOLIC STABILITY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; PHYSICAL CHEMISTRY; PROTON NUCLEAR MAGNETIC RESONANCE; RAT; STRUCTURE ACTIVITY RELATION; SUBSTRATE CONCENTRATION; TRANQUILIZING ACTIVITY; AMINATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DRUG EFFECTS; METABOLISM; WISTAR RAT;

ALLOSTERIC REGULATION; AMINATION; ANIMALS; HUMANS; PIPERAZINES; QUINOLINES; RATS, WISTAR; RECEPTOR, METABOTROPIC GLUTAMATE 5;

EID: 85017010704     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2017.03.071     Document Type: Article

References (21)

1. [1] Nakanishi, S., Science 258 (1992), 597–603.
2. [2] Niswender, C.M., Conn, P.J., Annu. Rev. Pharmacol. Toxicol. 50 (2010), 295–322.
3. [3] Berry-Kravis, E., Des Portes, V., Hagerman, R., Jacquemont, S., Charles, P., Visootsak, J., Brinkman, M., Rerat, K., Koumaras, B., Zhu, L., Barth, G.M., Jaecklin, T., Apostol, G., von Raison, F., Sci. Transl. Med., 8, 2016 321ra5.
4. [4] Petrov, D., Pedros, I., de Lemos, M.L., Pallàs, M., Canudas, A.M., Lazarowski, A., Beas-Zarate, C., Auladell, C., Folch, J., Camins, A., Expert Opin. Investig. Drugs 23 (2014), 1165–1179.
5. [5] Pecknold, J.C., McClure, D.J., Appeltauer, L., Wrzesinski, L., Allan, T., J. Clin. Psychopharmacol. 2 (1982), 129–133.
6. [6] Zerbib, F., Bruley des Varannes, S., Roman, S., Tutuian, R., Galmiche, J.P., Mion, F., Tack, J., Malfertheiner, P., Keywood, C., Aliment. Pharmacol. Ther. 33 (2011), 911–921.
7. [7] Quiroz, J.A., Tamburri, P., Deptula, D., Banken, L., Beyer, U., Fontoura, P., Santarelli, L., Eur. Neuropsychopharmacol., 2014, 24 S468.
8. [8] Terbeck, S., Akkus, F., Chesterman, L.P., Hasler, G., Front. Neurosci., 9, 2015, 86.
9. [9] Varney, M.A., Cosford, N.D., Jachec, C., Rao, S.P., Sacaan, A., Lin, F.F., Bleicher, L., Santori, E.M., Flor, P.J., Allgeier, H., Gasparini, F., Kuhn, R., Hess, S.D., Veliçelebi, G., Johnson, E.C., J. Pharm. Exp. Ther. 290 (1999), 170–181.
10. [10] O'Leary, D.M., Movsesyan, V., Vicini, S., Faden, A.I., Br. J. Pharmac 131 (2000), 1429–1437.
11. [11] Gasparini, F., Andres, H., Flor, P.J., Heinrich, M., Inderbitzin, W., Lingenhöhl, K., Müller, H., Munk, V.C., Omilusik, K., Stierlin, C., Stoehr, N., Vranesic, I., Kuhn, R., Bioorg. Med. Chem. Lett. 12 (2002), 407–409.
12. [12] Cosford, N.D., Tehrani, L., Roppe, J., Schweiger, E., Smith, N.D., Anderson, J., Bristow, L., Brodkin, J., Jiang, X., McDonald, I., Rao, S., Washburn, M., Varney, M.A., J. Med. Chem. 46 (2003), 204–206.
13. [13] Dore, A.S., Okrasa, K., Patel, J.C., Serrano-Vega, M., Bennett, K., Cooke, R.M., Errey, J.C., Jazayeri, A., Khan, S., Tehan, B., Weir, M., Wiggin, G.R., Marshall, F.H., Nature 511 (2014), 557–562.
14. [14] Emmitte, K.A., mGlu5 negative allosteric modulators: a patent review (2010–2012). Expert Opin. Ther. Pat. 23 (2013), 393–408.
15. [15] Emmitte, K.A., mGlu5 negative allosteric modulators: a patent review (2013–2016). Expert Opin. Ther. Pat. 27 (2017), 1–16.
16. [16] Raboisson, P., Breitholtz-Emanuelsson, A., Dahllöf, H., Edwards, L., Heaton, W.L., Isaac, M., Jarvie, K., Kers, A., Minidis, A.B., Nordmark, A., Sheehan, S.M., Slassi, A., Ström, P., Terelius, Y., Wensbo, D., Wilson, J.M., Xin, T., McLeod, D.A., Bioorg. Med. Chem. Lett. 22 (2012), 6974–6979.
17. [17] Christopher, J.A., Aves, S.J., Bennett, K.A., Doré, A.S., Errey, J.C., Jazayeri, A., Marshall, F.H., Okrasa, K., Serrano-Vega, M.J., Tehan, B.G., Wiggin, G.R., Congreve, M., J. Med. Chem. 58 (2015), 6653–6664.
18. [18] Ballesteros, J.A., Weinstein, H., Methods Neurosci. 25 (1995), 366–428.
19. [19] Keserű, G. M., Wéber Cs, Bielik, A., Bobok, A. Á., Gál, K., Sípos-Meszlényi, M., Molnár, L., Vastag, M. U.S. Patent 2009/0270371 A1, October 29, 2009.
20. [20] Rane, A., Wilkinson, G.R., Shand, D.G., J. Pharmacol. Exp. Ther. 200 (1977), 420–424.
21. [21] Vogel, J.R., Beer, B., Clody, D.E., Psychopharmacology 100 (1971), 138–140.