3-Oxo-hexahydro-1H-isoindole-4-carboxylic Acid as a Drug Chiral Bicyclic Scaffold: Structure-Based Design and Preparation of Conformationally Constrained Covalent and Noncovalent Prolyl Oligopeptidase Inhibitors

Journal of Medicinal Chemistry

Volumn 59, Issue 9, 2016, Pages 4221-4234

  Mariaule, Gaëlle ^a   De Cesco, Stéphane ^a   Airaghi, Francesco ^a   Kurian, Jerry ^a   Schiavini, Paolo ^a   Rocheleau, Sylvain ^a   Huskić, Igor ^a   Auclair, Karine ^a   Mittermaier, Anthony ^a   Moitessier, Nicolas ^a  

^a MCGILL UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

1 [2 (BENZYLOXY) 3 OXO 2,3,3A,4,5,7A HEXAHYDRO 1H ISOINDOLE 4 CARBONYL]PYRROLIDINE 2 CARBONITRILE; 1 [2 BENZYL 3 OXO 2,3,3A,4,5,7A HEXAHYDRO 1H ISOINDOLE 4 CARBONYL]PYRROLIDINE 2 CARBONITRILE; 1 [2 BENZYL 5 METHYL 3 OXO 2,3,3A,4,5,7A HEXAHYDRO 1H ISOINDOLE 4 CARBONYL]PYRROLIDINE 2 CARBONITRILE; 2 BENZYL 6 METHYL 7 (PYRROLIDINE 1 CARBONYL) 2,3,3A,6,7,7A HEXAHYDRO 1H ISOINDOL 1 ONE; 2 BENZYL 7 (PYRROLIDINE 1 CARBONYL) 2,3,3A,6,7,7A HEXAHYDRO 1H ISOINDOL 1 ONE; 3 OXO HEXAHYDRO 1H ISOINDOLE 4 CARBOXYLIC ACID; BENZYL [4 (2 CYANOPYRROLIDINE 1 CARBONYL) 3 OXO 1,3,3A,4,5,7A HEXAHYDRO 2H ISOINDOL 2 YL]CARBAMATE; BENZYL [4 (2 CYANOPYRROLIDINE 1 CARBONYL)5 METHYL 3 OXO 1,3,3A,4,5,7A HEXAHYDRO 2H ISOINDOL 2 YL]CARBAMATE; CARBOXYLIC ACID; ISOINDOLE DERIVATIVE; N [4 (2 CYANOPYRROLIDINE 1 CARBONYL) 3 OXO 1,3,3A,4,5,7A HEXAHYDRO 2H ISOINDOL 2 YL] 2 PHENYLACETAMIDE; PROLYL ENDOPEPTIDASE INHIBITOR; RAC 2 (BENZYLOXY) 3 OXO 2,3,3A,4,5,7A HEXAHYDRO 1H ISOINDOLE 4 CARBOXYLIC ACID; RAC 2 (BENZYLOXY) 7 (PYRROLIDINE 1 CARBONYL) 2,3,3A,6,7,7A HEXAHYDRO 1H ISOINDOL 1 ONE; RAC 2 BENZYL 3 OXO 2,3,3A,4,5,7A HEXAHYDRO 1H ISOINDOLE 4 CARBOXYLIC ACID; RAC 2 BENZYL 5 METHYL 3 OXO 2,3,3A,4,5,7A HEXAHYDRO 1H ISOINDOLE 4 CARBOXYLIC ACID; RAC 2 [[(BENZOYLOXY)CARBONYL]AMINO] 3 OXO 2,3,3A,4,5,7A HEXAHYDRO 1H ISOINDOLE 4 CARBOXYLIC ACID; RAC 2 [[(BENZOYLOXY)CARBONYL]AMINO] 5 METHYL 3 OXO 2,3,3A,4,5,7A HEXAHYDRO 1H ISOINDOLE 4 CARBOXYLIC ACID; RAC 3 OXO 2 (2 PHENYLACETAMIDO) 2,3,3A,4,5,7A HEXAHYDRO 1H ISOINDOLE 4 CARBOXYLIC ACID; RAC BENZYL [3 OXO 4 (PYRROLIDINE 1 CARBONYL) 1,3,3A,4,5,7A HEXAHYDRO 2H ISOINDOL 2 YL]CARBAMATE; RAC BENZYL [5 METHYL 3 OXO 4 (PYRROLIDINE 1 CARBONYL) 1,3,3A,4,5,7A HEXAHYDRO 2H ISOINDOL 2 YL]CARBAMATE; RAC BENZYL [7 CYANO 1 OXO 3,3A,7,7A TETRAHYDRO 1H ISOINDOL 2(6H) YL]CARBAMATE; RAC N [3 OXO 4 (PYRROLIDINE 1 CARBONYL) 1,3,3A,4,5,7A HEXAHYDRO 2H ISOINDOL 2 YL] 2 PHENYLACETAMIDE; UNCLASSIFIED DRUG; BRIDGED BICYCLO COMPOUNDS; PROLYL ENDOPEPTIDASE; PROTEINASE INHIBITOR; SERINE PROTEINASE;

ARTICLE; CALCULATION; CHIRALITY; COVALENT BOND; CRYSTALLOGRAPHY; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IC50; IN VITRO STUDY; MOLECULAR DOCKING; NONHUMAN; STEREOCHEMISTRY; CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECTS; HUMAN; STEREOISOMERISM;

BRIDGED BICYCLO COMPOUNDS; CARBOXYLIC ACIDS; HUMANS; ISOINDOLES; MOLECULAR DOCKING SIMULATION; MOLECULAR STRUCTURE; PROTEASE INHIBITORS; SERINE ENDOPEPTIDASES; STEREOISOMERISM;

EID: 84969570434     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b01296     Document Type: Article

References (45)

1. Lawandi, J.; Gerber-Lemaire, S.; Juillerat-Jeanneret, L.; Moitessier, N. Inhibitors of prolyl oligopeptidases for the therapy of human diseases: Defining diseases and inhibitors J. Med. Chem. 2010, 53, 3423-3438 10.1021/jm901104g
2. Lambeir, A. M. Translational research on prolyl oligopeptidase inhibitors: The long road ahead Expert Opin. Ther. Pat. 2011, 21, 977-981 10.1517/13543776.2011.587803
3. López, A.; Tarragó, T.; Giralt, E. Low molecular weight inhibitors of Prolyl Oligopeptidase: A review of compounds patented from 2003 to 2010 Expert Opin. Ther. Pat. 2011, 21, 1023-1044 10.1517/13543776.2011.577416
4. Cunningham, D. F.; OConnor, B. Identification and initial characterisation of a N-benzyloxycarbonyl-prolyl-prolinal (Z-Pro-prolinal)-insensitive 7-(N-benzyloxycarbonyl-glycyl-prolyl-amido)-4- methylcoumarin (Z-Gly-Bro-NH-Mec)-hydrolysing peptidase in bovine serum Eur. J. Biochem. 1997, 244, 900-903 10.1111/j.1432-1033.1997.00900.x
5. Toide, K.; Shinoda, M.; Iwamoto, Y.; Fujiwara, T.; Okamiya, K.; Uemura, A. A novel propyl endopeptidase inhibitor, JTP-4819, with potential for treating Alzheimers disease Behav. Brain Res. 1997, 83, 147-151 10.1016/S0166-4328(97)86059-7
6. Jarho, E. M.; Venäläinen, J. I.; Huuskonen, J.; Christiaans, J. A. M.; Garcia-Horsman, J. A.; Forsberg, M. M.; Jarvinen, T.; Gynther, J.; Männistö, P. T.; Wallén, E. A. A. A cyclopent-2-enecarbonyl group mimics proline at the P2 position of prolyl oligopeptidase inhibitors J. Med. Chem. 2004, 47, 5605-5607 10.1021/jm049503w
7. Jalkanen, A. J.; Hakkarainen, J. J.; Lehtonen, M.; Venäläinen, T.; Kääriäinen, T. M.; Jarho, E.; Suhonen, M.; Forsberg, M. M. Brain pharmacokinetics of two prolyl oligopeptidase inhibitors, JTP-4819 and KYP-2047, in the rat Basic Clin. Pharmacol. Toxicol. 2011, 109, 443-451 10.1111/j.1742-7843.2011.00747.x
8. Venäläinen, J. I.; Garcia-Horsman, J. A.; Forsberg, M. M.; Jalkanen, A.; Wallén, E. A. A.; Jarho, E. M.; Christiaans, J. A. M.; Gynther, J.; Männistö, P. T. Binding kinetics and duration of in vivo action of novel prolyl oligopeptidase inhibitors Biochem. Pharmacol. 2006, 71, 683-692 10.1016/j.bcp.2005.11.029
9. Barelli, H.; Petit, A.; Hirsch, E.; Wilk, S.; De Nanteuil, G.; Morain, P.; Checler, F. S 17092-1, a highly potent, specific and cell permeant inhibitor of human proline endopeptidase Biochem. Biophys. Res. Commun. 1999, 257, 657-661 10.1006/bbrc.1999.0366
10. Van Der Veken, P.; Fülöp, V.; Rea, D.; Gerard, M.; Van Elzen, R.; Joossens, J.; Cheng, J. D.; Baekelandt, V.; De Meester, I.; Lambeir, A. M.; Augustyns, K. P2-substituted N-acylprolylpyrrolidine inhibitors of prolyl oligopeptidase: Biochemical evaluation, binding mode determination, and assessment in a cellular model of synucleinopathy J. Med. Chem. 2012, 55, 9856-9867 10.1021/jm301060g
11. Lambeir, A. M. Interaction of prolyl oligopeptidase with α-synuclein CNS Neurol. Disord.: Drug Targets 2011, 10, 349-354 10.2174/187152711794653878
12. Myöhänen, T. T.; Hannula, M. J.; Van Elzen, R.; Gerard, M.; Van Der Veken, P.; García-Horsman, J. A.; Baekelandt, V.; Männistö, P. T.; Lambeir, A. M. A prolyl oligopeptidase inhibitor, KYP-2047, reduces α-synuclein protein levels and aggregates in cellular and animal models of Parkinsons disease Br. J. Pharmacol. 2012, 166, 1097-1113 10.1111/j.1476-5381.2012.01846.x
13. Hannula, M. J.; Myöhänen, T. T.; Tenorio-Laranga, J.; Männistö, P. T.; Garcia-Horsman, J. A. Prolyl oligopeptidase colocalizes with α-synuclein, β-amyloid, tau protein and astroglia in the post-mortem brain samples with Parkinsons and Alzheimers diseases Neuroscience 2013, 242, 140-150 10.1016/j.neuroscience.2013.03.049
14. Lawandi, J.; Toumieux, S.; Seyer, V.; Campbell, P.; Thielges, S.; Juillerat-Jeanneret, L.; Moitessier, N. Constrained peptidomimetics reveal detailed geometric requirements of covalent prolyl oligopeptidase inhibitors J. Med. Chem. 2009, 52, 6672-6684 10.1021/jm901013a
15. De Cesco, S.; Deslandes, S.; Therrien, E.; Levan, D.; Cueto, M.; Schmidt, R.; Cantin, L. D.; Mittermaier, A.; Juillerat-Jeanneret, L.; Moitessier, N. Virtual screening and computational optimization for the discovery of covalent prolyl oligopeptidase inhibitors with activity in human cells J. Med. Chem. 2012, 55, 6306-6315 10.1021/jm3002839
16. Lawandi, J.; Toumieux, S.; Seyer, V.; Campbell, P.; Thielges, S.; Juillerat-Jeanneret, L.; Moitessier, N. Constrained peptidomimetics reveal detailed geometric requirements of covalent prolyl oligopeptidase inhibitors J. Med. Chem. 2009, 52, 6672-6684 10.1021/jm901013a
17. Johnson, D. S.; Weerapana, E.; Cravatt, B. F. Strategies for discovering and derisking covalent, irreversible enzyme inhibitors Future Med. Chem. 2010, 2, 949-964 10.4155/fmc.10.21
18. Zhou, S.; Chan, E.; Duan, W.; Huang, M.; Chen, Y. Z. Drug bioactivation, covalent binding to target proteins and toxicity relevance Drug Metab. Rev. 2005, 37, 41-213 10.1081/DMR-200028812
19. Guterman, L. Covalent Drugs Form Long-Lived Ties Chem. Eng. News 2011, 89, 19-26
20. Kalgutkar, A. S.; Dalvie, D. K. Drug discovery for a new generation of covalent drugs Expert Opin. Drug Discovery 2012, 7, 561-581 10.1517/17460441.2012.688744
21. Robertson, J. G. Mechanistic basis of enzyme-targeted drugs Biochemistry 2005, 44, 5561-5571 10.1021/bi050247e
22. Singh, J.; Petter, R. C.; Baillie, T. A.; Whitty, A. The resurgence of covalent drugs Nat. Rev. Drug Discovery 2011, 10, 307-317 10.1038/nrd3410
23. Potashman, M. H.; Duggan, M. E. Covalent modifiers: An orthogonal approach to drug design J. Med. Chem. 2009, 52, 1231-1246 10.1021/jm8008597
24. Smith, A. J. T.; Zhang, X.; Leach, A. G.; Houk, K. N. Beyond picomolar affinities: Quantitative aspects of noncovalent and covalent binding of drugs to proteins J. Med. Chem. 2009, 52, 225-233 10.1021/jm800498e
25. Fleming, F. F.; Yao, L.; Ravikumar, P. C.; Funk, L.; Shook, B. C. Nitrile-containing pharmaceuticals: Efficacious roles of the nitrile pharmacophore J. Med. Chem. 2010, 53, 7902-7917 10.1021/jm100762r
26. Huot, M.; Moitessier, N. Expedient synthesis of novel bicyclic peptidomimetic scaffolds Tetrahedron Lett. 2010, 51, 2820-2823 10.1016/j.tetlet.2010.03.066
27. Szeltner, Z.; Rea, D.; Renner, V.; Fülöp, V.; Polgár, L. Electrostatic effects and binding determinants in the catalysis of prolyl oligopeptidase: Site-specific mutagenesis at the oxyanion binding site J. Biol. Chem. 2002, 277, 42613-42622 10.1074/jbc.M208043200
28. Therrien, E.; Weill, N.; Tomberg, A.; Corbeil, C. R.; Lee, D.; Moitessier, N. Docking ligands into flexible and solvated macromolecules. 7. Impact of protein flexibility and water molecules on docking-based virtual screening accuracy J. Chem. Inf. Model. 2014, 54, 3198-3210 10.1021/ci500299h
29. Racys, D. T.; Rea, D.; Fülöp, V.; Wills, M. Inhibition of prolyl oligopeptidase with a synthetic unnatural dipeptide Bioorg. Med. Chem. 2010, 18, 4775-4782 10.1016/j.bmc.2010.05.012
30. Singh, T.; Biswas, D.; Jayaram, B. AADS-An automated active site identification, docking, and scoring protocol for protein targets based on physicochemical descriptors J. Chem. Inf. Model. 2011, 51, 2515-2527 10.1021/ci200193z
31. Tomberg, A.; De Cesco, S.; Huot, M.; Moitessier, N. Solvent effect in diastereoselective intramolecular Diels-Alder reactions Tetrahedron Lett. 2015, 56, 6852-6856 10.1016/j.tetlet.2015.10.086
32. Nguyen, L. A.; He, H.; Pham-Huy, C. Chiral drugs: An overview Int. J. Biomed. Sci. 2006, 2, 85-100
33. Morrison, J. F. Kinetics of the reversible inhibition of enzyme-catalysed reactions by tight-binding inhibitors Biochim. Biophys. Acta 1969, 185, 269-286 10.1016/0005-2744(69)90420-3
34. Schiavini, P.; Pottel, J.; Moitessier, N.; Auclair, K. Metabolic instability of cyanothiazolidine-based prolyl oligopeptidase inhibitors: A structural assignment challenge and potential medicinal chemistry implications ChemMedChem 2015, 10, 1174-1183 10.1002/cmdc.201500114
35. Wong, Y. C.; Qian, S.; Zuo, Z. Regioselective biotransformation of CNS drugs and its clinical impact on adverse drug reactions Expert Opin. Drug Metab. Toxicol. 2012, 8, 833-854 10.1517/17425255.2012.688027
36. Kalgutkar, A. S.; Gardner, I.; Obach, R. S.; Shaffer, C. L.; Callegari, E.; Henne, K. R.; Mutlib, A. E.; Dalvie, D. K.; Lee, J. S.; Nakai, Y.; ODonnell, J. P.; Boer, J.; Harriman, S. P. A comprehensive listing of bioactivation pathways of organic functional groups Curr. Drug Metab. 2005, 6, 161-225 10.2174/1389200054021799
37. Stepan, A. F.; Walker, D. P.; Bauman, J.; Price, D. A.; Baillie, T. A.; Kalgutkar, A. S.; Aleo, M. D. Structural alert/reactive metabolite concept as applied in medicinal chemistry to mitigate the risk of idiosyncratic drug toxicity: A perspective based on the critical examination of trends in the top 200 drugs marketed in the United States Chem. Res. Toxicol. 2011, 24, 1345-1410 10.1021/tx200168d
38. Gill, S. C.; von Hippel, P. H. Calculation of protein extinction coefficients from amino acid sequence data Anal. Biochem. 1989, 182, 319-326 10.1016/0003-2697(89)90602-7
39. Morrison, J. F. Kinetics of the reversible inhibition of enzyme-catalysed reactions by tight-binding inhibitors Biochimica et Biophysica Acta (BBA)-Enzymology 1969, 185, 269-286 10.1016/0005-2744(69)90420-3
40. Corbeil, C. R.; Englebienne, P.; Moitessier, N. Docking ligands into flexible and solvated macromolecules. 1. Development and validation of FITTED 1.0 J. Chem. Inf. Model. 2007, 47, 435-449 10.1021/ci6002637
41. Therrien, E.; Englebienne, P.; Arrowsmith, A. G.; Mendoza-Sanchez, R.; Corbeil, C. R.; Weill, N.; Campagna-Slater, V.; Moitessier, N. Integrating medicinal chemistry, organic/combinatorial chemistry, and computational chemistry for the discovery of selective estrogen receptor modulatorswith FORECASTER, a novel platform for drug discovery J. Chem. Inf. Model. 2012, 52, 210-224 10.1021/ci2004779
42. Sheldrick, G. M. A short history of SHELX Acta Crystallogr., Sect. A: Found. Crystallogr. 2008, 64, 112-122 10.1107/S0108767307043930
43. Farrugia, L. J. WinGX suite for small-molecule single-crystal crystallography J. Appl. Crystallogr. 1999, 32, 837-838 10.1107/S0021889899006020
44. Gulías, M.; Durán, J.; López, F.; Castedo, L.; Mascarenas, J. L. Palladium-Catalyzed [4 + 3] Intramolecular Cycloaddition of Alkylidenecyclopropanes and Dienes J. Am. Chem. Soc. 2007, 129, 11026-11027 10.1021/ja0756467
45. Mellor, J. M.; Wagland, A. M. Synthesis of hydroisoindoles via intramolecular Diels-Alder reactions of functionalised amido trienes J. Chem. Soc., Perkin Trans. 1 1989, 997-1005 10.1039/p19890000997