Structure-activity relationship of N,N′-disubstituted pyrimidinetriones as CaV1.3 calcium channel-selective antagonists for Parkinson's disease

Journal of Medicinal Chemistry

Volumn 56, Issue 11, 2013, Pages 4786-4797

  Kang, Soosung ^a   Cooper, Garry ^a,b   Dunne, Sara Fernandez ^a   Luan, Chi Hao ^a   Surmeier, D James ^b   Silverman, Richard B ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

^b NORTHWESTERN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 ( EXO NORBORNYL) 3 (3 (TRIFLUOROMETHYL)PHENETHYL) PYRIMIDINE 2,4,6 (1H,3H,5H) TRIONE; 1 ((1 (4 CHLOROPHENYL)CYCLOPROPYL)METHYL) 3 CYCLOPENTYLPYRIMIDINE 2,4,6 (1H,3H,5H) TRIONE; 1 (1 (3 CHLOROPHENYL)PROPAN 2 YL) 3 ( ENDO NORBONYL) PYRIMIDINE 2,4,6 (1H,3H,5H) TRIONE; 1 (2 (3 CHLOROPHENYL) 2 METHYLPROPYL) 3 CYCLOPENTYLPYRIMIDINE 2,4,6 (1H,3H,5H) TRIONE; 1 (2 (3 CHLOROPHENYL)PROPYL) 3 ( ENDO NORBONYL) PYRIMIDINE 2,4,6 (1H,3H,5H) TRIONE; 1 (2 (3,5 DICHLOROPHENYL)ETHYL) 3 ( ENDO NORBONYL) PYRIMIDINE 2,4,6 (1H,3H,5H) TRIONE; 1 (3 CHLOROPHENETHYL) 3 (1 CYCLOHEXYLETHYL) PYRIMIDINE 2,4,6 (1H,3H,5H)TRIONE; 1 (3 CHLOROPHENETHYL) 3 (1 CYCLOHEXYLETHYL)PYRIMIDINE 2,4,6(1H,3H,5H)TRIONE; 1 (3,5 BIS(TRIFLUOROMETHYL)PHENETHYL) 3 CYCLOPENTYLPYRIMIDINE 2,4,6(1H,3H,5H) TRIONE; 1 (4 CHLOROPHENETHYL) 3 (1 CYCLOHEXYLETHYL)PYRIMIDINE 2,4,6(1H,3H,5H)TRIONE; 1 (BICYCLO [2.2.1]HEPTAN 2 YL) 3 (3 CHLOROPHENETHYL)PYRAMIDINE 2,4,6(1H,3H,5H)TRIONE; 1 (BICYCLO [2.2.1]HEPTAN 2 YL) 3 (3 TRIFLUOROMETHYL)PHENETHYL) PYRAMIDINE 2,4,6(1H,3H,5H)TRIONE; 1 (BICYCLO [2.2.1]HEPTAN 2 YL) 3 (4 CHLOROPHENETHYL)PYRAMIDINE 2,4,6(1H,3H,5H)TRIONE; 1 CYCLOPENTYL 3 (2 METHYL 2 (3 TRIFLUOROMETHYL)PHENYL) PROPYL)PYRIMIDINE 2,4,6 (1H,3H,5H) TRIONE; 1 CYCLOPENTYL 3 (3,4 DICHLOROPHENETHYL)PYRIMIDINE 2,4,6 (1H,3H,5H) TRIONE; 1 CYCLOPENTYL 3 (3,5 DICHLOROPHENETHYL)PYRIMIDINE 2,4,6 (1H,3H,5H) TRIONE; ANTIPARKINSON AGENT; CALCIUM CHANNEL BLOCKING AGENT; DILTIAZEM; ISRADIPINE; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VERAPAMIL;

ALKYLATION; ARTICLE; BINDING AFFINITY; BIOLOGICAL ACTIVITY; CONTROLLED STUDY; DRUG BINDING SITE; DRUG SELECTIVITY; ENANTIOMER; HUMAN; HUMAN CELL; HYDROPHILICITY; NONHUMAN; NUCLEOTIDE SEQUENCE; PARKINSON DISEASE; RAT; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

ANTIPARKINSON AGENTS; CALCIUM CHANNEL BLOCKERS; CALCIUM CHANNELS; CALCIUM CHANNELS, L-TYPE; HEK293 CELLS; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; PYRIMIDINONES; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSFECTION;

EID: 84879049515     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm4005048     Document Type: Article

References (33)

1. Casamassima, F.; Hay, A. C.; Benedetti, A.; Lattanzi, L.; Cassano, G. B.; Perlis, R. H. L-type calcium channels and psychiatric disorders, a brief review Am. J. Med. Genet., Part B 2010, 153B, 1373-1390
2. Catterall, W. A.; Perez-Reyes, E.; Snutch, T. P; Striessnig, J. International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels Pharmacol. Rev. 2005, 57, 411-425 (Pubitemid 43036432)
3. Lipscombe, D.; Helton, T. D; Xu, W. L-type calcium channels: the low down J. Neurophysiol. 2004, 92, 2633-2641 (Pubitemid 40340475)
4. Sinnegger-Brauns, M. J.; Huber, I. G.; Koschak, A.; Wild, C.; Obermair, G. J.; Einzinger, U.; Hoda, J.-C.; Sartori, S. B.; Striessnig, J. Expression and 1,4-dihydropyridine-binding properties of brain L-type calcium channel isoforms Mol. Pharmacol. 2009, 75, 407-414
5. Zuccotti, A.; Clementi, S.; Reinbothe, T.; Torrente, A.; Vandael, D. H.; Pirone, A. Structural and functional differences between L-type calcium channels: crucial issues for future selective targeting Trends Pharmacol. Sci. 2011, 32, 366-375
6. 2+ channels Pfluegers Arch. 2010, 460, 361-374
7. 2+ channels is dependent on a Shank-binding domain J. Neurosci. 2005, 25, 1050-1062 (Pubitemid 40268947)
8. Chan, C. S.; Guzman, J. N.; Ilijic, E.; Mercer, J.; Rick, C.; Tkatch, T.; Meredith, G.; Surmeier, D. J. Rejuvenation protects neurons in mouse models of Parkinson's disease Nature 2007, 447, 1081-1086 (Pubitemid 47014425)
9. Riederer, P.; Wuketich, S. Time course of nigrostriatal degeneration in Parkinson's disease. A detailed study of influential factors in human brain amine analysis J. Neural Transm. 1976, 38, 277-301
10. Fearnley, J. M.; Lees, A. J. Ageing and Parkinson's disease: substantia nigra regional selectivity Brain 1991, 114, 2283-2301
11. Guzman, J. N.; Sanchez-Padilla, J.; Wokosin, D.; Kondapalli, J.; Ilijic, E.; Schumacker, P. T.; Surmeier, D. J. Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1 Nature 2010, 468, 696-700
12. Guzman, J. N.; Sánchez-Padilla, J.; Chan, C. S.; Surmeier, D. J. Robust pacemaking in substantia nigra dopaminergic neurons J. Neurosci. 2009, 29, 11011-11009
13. Jankovic, J. Parkinson's disease: clinical features and diagnosis J. Neurol., Neurosurg. Psychiatry 2008, 79, 368-376 (Pubitemid 351441488)
14. Epstein, M. Calcium antagonists: still appropriate as first line antihypertensive agents Am. J. Hypertens. 1996, 9, 110-121 (Pubitemid 26108111)
15. 2+] using the fluorometric imaging plate reader (FLIPR) Methods Mol. Biol. 1999, 114, 125-133
16. Minta, A.; Kao, J. P. Y; Tsien, R. Y. Fluorescent indicators for cytosolic calcium based on rhodamine and fluorescein chromophores J. Biol. Chem. 1989, 264, 8171-8178 (Pubitemid 19137304)
17. Triggle, D. J. 1,4-Dihydropyridines as calcium channel ligands and privileged structures Cell. Mol. Neurobiol. 2003, 23, 293-303 (Pubitemid 36676276)
18. Triggle, D. J.; Hawthorn, M.; Gopalakrishnan, M.; Minarini, A.; Avery, S.; Rutledge, A.; Bangalore, R.; Zheng, W. Synthetic organic ligands active at voltage-gated calcium channels Ann. N.Y. Acad. Sci. 1991, 635, 123-138
19. V1.2 Bioorg. Med.Chem. 2010, 18, 3147-3158
20. V1.2 by 1,4-dihydropyrimidines and 4 H -pyrans as dihydropyridine mimics, Bioorg. Med. Chem. [Online early access]. DOI: 10.1016/j.bmc.2013.04.054. Published Online: Apr 28, 2013.
21. V1.3-selective L-type calcium channel antagonists as potential new therapeutics for Parkinson's disease Nat. Commun. 2012, 3, 1146
22. Wöhler, F. Ueber künstliche bildung des harnstoffs Ann. Phys. Chem. 1828, 88, 253
23. Biltz, H.; Wittek, H. Alkylierte und acylierte barbitursauren Ber. 1921, 54B, 1035
24. Poll, T.; Sobczak, A.; Hartmann, H.; Helmchen, G. Diastereoface- discriminative metal coordination in asymmetric synthesis: d -pantolactone as practical chiral auxiliary for Lewis acid catalyzed Diels-Alder reactions Tetrahedron Lett. 1985, 26, 3095-3098
25. Poll, T.; Abdel Hady, A. F.; Karge, R.; Linz, G.; Weetman, J.; Helmchen, G. N-Substituted hydroxysuccinhides from (S)-malic acid as new reagents for asymmetric Diels-Alder additions to enoates Tetrahedron Lett. 1989, 30, 5595-5598
26. Eda, M.; Takemoto, T.; Ono, S.-I.; Okada, T.; Kosaka, K.; Gohda, M.; Matzno, S.; Nakamura, N.; Fukaya, C. Novel potassium-channel openers: preparation and pharmacological evaluation of racemic and optically active N -(6-amino-3-pyridyl)- N ′-bicycloalkyl- N ″-cyanoguanidine derivatives J. Med. Chem. 1994, 37, 1983-1990 (Pubitemid 24233611)
27. Bollu, V.; Boren, B. C.; Dalgar, J. E.; Flatt, B. T.; Haq, N.; Hudson, S.; Mohan, R.; Morrissey, M.; Pratt, B.; Wang, T.-L. Triazole and Imidazole Derivatives for Use as TGR5 Agonists in the Treatment of Diabetes and Obesity. PCT Int. Appl. 2011071565, Jun 16, 2011.
28. Meier, H.; Bender, E.; Brueggemeier, U.; Flamme, I.; Karthaus, D.; Kolkhof, P.; Meibom, D.; Schneider, D.; Voehringer, V.; Fuerstner, C.; Keldenich, J.; Lang, D.; Pook, E.; Schmerk, C. Preparation of 4-Arylimidazol-2-ones and 5-Aryl-1,2,4-triazolones as Vasopressin Receptor Inhibitors. PCT Int. Appl. 2007134862, Nov 29, 2007.
29. Nugent, T. C.; Ghosh, A. K.; Wakchaure, V. N.; Mohanty, R. B. Asymmetric reductive amination: convenient access to enantioenriched alkyl-alkyl or aryl-alkyl substituted α-chiral primary amines Adv. Synth. Catal. 2006, 348, 1289-1299 (Pubitemid 44166114)
30. Moss, N.; Gauthier, J.; Ferland, J.-M. The enantioselective synthesis of neopentylamine derivatives Synlett 1995, 2, 142-144
31. Frahm, A. W.; Knupp, G. Asymmetric Synthesis of cis-2-substituted cyclohexanamines with high optical purity Tetrahedron Lett. 1981, 22, 2633-2636
32. Knupp, G.; Frahm, A. W. Synthesis and absolute configuration of 2-substituted cyclohexylamine Chem. Ber. 1984, 117, 2076-2098
33. 2+ channels by two different mechanisms J. Physiol. 1999, 521.1, 31-42