Fluorinated isatin derivatives. Part 1: Synthesis of new N-substituted (S)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatins as potent caspase-3 and -7 inhibitors

Bioorganic and Medicinal Chemistry

Volumn 17, Issue 7, 2009, Pages 2680-2688

  Podichetty, Anil Kumar ^a   Faust, Andreas ^a,b   Kopka, Klaus ^a,b   Wagner, Stefan ^a,b   Schober, Otmar ^b   Schäfers, Michael ^a   Haufe, Günter ^a  

^a UNIVERSITY OF MÜNSTER   (Germany)

^b UNIVERSITY HOSPITAL MÜNSTER   (Germany)

Author keywords

Apoptosis; Caspase inhibitors; Fluorine; Isatin derivatives; Substitution; Synthesis

Indexed keywords

1 (2 FLUOROALLYL) 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL]ISATIN; 1 (2 FLUOROETHYL) 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL]ISATIN; 1 (3 CHLORO 2 HYDROXYPROPYL) 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL]ISATIN; 1 (3 CHLOROPROPYL) 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL]ISATIN; 1 (3 FLUOROBUTYL) 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL]ISATIN; 1 (3 FLUOROPROPYL) 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL]ISATIN; 1 (3 HYDROXYPROPYL) 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL]ISATIN; 1 (4 FLUOROBUTYL) 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL]ISATIN; 1 (4 HYDROXYBUTYL) 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL]ISATIN; 1 [3 (3 FLUOROPROPOXY)PROPYL] 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL]ISATIN; 1 [3 (3 HYDROXYPROPOXY)PROPYL] 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL]ISATIN; 1 [3 [3 (2 FLUOROETHOXY)PROPOXY]PROPYL] 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL]ISATIN; 1 BUTYL 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL]ISATIN; 1 ETHYL 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL]ISATIN; 3 [3 [5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL]2,3 DIOXOINDOLIN 1 YL]PROPOXY]PROPYLMETHANESULFONATE; 3 [5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL] 2,3 DIOXOINDOLIN 1 YL]PROPANOIC ACID; 3 [5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL] 2,3 DIOXOINDOLIN 1 YL]PROPYLMETHANESULFONATE; 3,3 DIFLUORO 1 (3 FLUOROPROPYL) 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL]INDOLIN 2 ONE; 3,3 DIFLUORO 1 PROPYL 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL]INDOLIN 2 ONE; 3,5 BISTRIFLUOROMETHYLBENZYL 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL]ISATIN; 4 [5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL] 2,3 DIOXOINDOLIN 1 YL]BUTYL 4 METHYLBENZENESULFONATE; 4 FLUOROBENZYL 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL]ISATIN; 4 TRIFLUOROMETHYLBENZYL 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL]ISATIN; 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL] 1 (3,4,4 TRIFLUOROBUT 3 ENYL)ISATIN; 5 [1 (2 METHOXYMETHYLPYRROLIDINYL)SULFONYL] 1 PROPYLISATIN; CASPASE 3 INHIBITOR; CASPASE 7 INHIBITOR; CASPASE INHIBITOR; ISATIN DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

APOPTOSIS; ARTICLE; DRUG POTENCY; DRUG SYNTHESIS; ENZYME INHIBITION; FLUORINATION; IC 50; STEREOISOMERISM; STRUCTURE ACTIVITY RELATION;

ALKYLATION; APOPTOSIS; CASPASE 3; CASPASE 7; HALOGENATION; ISATIN; PROTEASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 62949137154     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmc.2009.02.048     Document Type: Article

References (20)

1. Hengartner M.O. Nature 407 (2000) 770
2. Kumar S. Clin. Exp. Pharmacol. Physiol. 26 (1999) 295
3. Riedl S.J., and Shi Y. Nat. Rev., Mol. Cell. Biol. 5 (2004) 897
4. Alam J.J. Trends Biotechnol. 21 (2003) 479
5. Lee D., Long S.A., Adams J.L., Chan G., Vaidya K.S., Francis T.A., Kikly K., Winkler J.D., Sung C.-M., Debouck C., Richardson S., Levy M.A., DeWolf Jr. W.E., Keller P.M., Tomaszek T., Head M.S., Ryan M.D., Haltiwanger R.C., Liang P.-H., Janson C.A., McDevitt P.J., Johanson K., Concha N.O., Chan W., Suva L.J., Gowen M., and Nuttall M.E. J. Biol. Chem. 275 (2000) 16007
6. Calvo M.G., Peterson E.P., Leiting B., Ruel R., Nicholson D.W., and Thornberry N.A. J. Biol. Chem. 273 (1998) 32608
7. Lahorte C.M., Vanderheyden J.L., Steinmetz N., van de Wiele C., Dierckx R.A., and Slegers G. Eur. J. Nucl. Med. Mol. Imaging 31 (2004) 887
8. Thimister P.W., Hofstra L., Liem I.H., Boersma H.H., Kemerink G., Reutelingsperger C.P., and Heinendal G.A. J. Nucl. Med. 44 (2003) 391
9. Lee D., Long S.A., Murray J.H., Adams J.L., Nuttall M.E., Nadeau D.P., Kikly K., Winkler J.D., Sung C.-M., Ryan M.D., Levy M.A., Keller P.M., and DeWolf Jr. W.E. J. Med. Chem. 44 (2001) 2015
10. Chu W.C., Zhang J., Zeng C.B., Rothfuss J., Tu Z.D., Chu Y.X., Reichert D.E., Welch M.J., and Mach R.H. J. Med. Chem. 48 (2005) 7637
11. Chapman J.G., Magee W.P., Stukenbrok H.A., Beckius G.E., Milici A.J., and Tracey W.R. Eur. J. Pharmacol. 456 (2002) 59
12. Kopka K., Faust A., Keul P., Wagner S., Breyholz H.-J., Höltke C., Schober O., Schäfers M., and Levkau B. J. Med. Chem. 49 (2006) 6704
13. Zhou D., Chu W.H., Rothfuss J., Zeng C.D., Xu J.B., Jones L., Welch M.J., and Mach R.H. Bioorg. Med. Chem. Lett. 16 (2006) 5041
14. Faust A., Wagner S., Keul P., Law M.P., Hermann S., Schnöckel U., Schober O., Schäfers M., Levkau B B., and Kopka K. Quart. J. Nucl. Med. Mol. Imaging 51 (2007) 67
15. Smith G., Glaser M., Perumal M., Nguyen Q.D., Shan B., Årstad E., and Aboagye E.O. J. Med. Chem. 51 (2008) 8057
16. Laue K.W., and Haufe G. Synthesis (1998) 1453
17. Shendage D.M., Fröhlich R., Bergander K., and Haufe G. Eur. J. Org. Chem. (2005) 719
18. Hugenberg V., and Haufe G. Synlett (2009) 106
19. Chi D.Y., Kilbourn M.R., Katzenellenbogen J.A., and Welch M.J. J. Org. Chem. 52 (1987) 658
20. Bosse K., Marineau J., Nason D.M., Fliri A.J., Segelstein B.E., Desai K., and Volkmann R.A. Tetrahedron Lett. 47 (2006) 7285