Cardioselective antiischemic ATP-sensitive potassium channel (K(ATP)) openers. 6. Effect of modifications at C6 of benzopyranyl cyanoguanidines

Journal of Medicinal Chemistry

Volumn 42, Issue 18, 1999, Pages 3711-3717

  Ding, Charles Z ^a   Rovnyak, George C ^a   Misra, Raj N ^a   Grover, Gary J ^a   Miller, Arthur V ^a   Ahmed, Syed Z ^a   Kelly, Yolanda ^a   Normandin, Diane E ^a   Sleph, Paul G ^a   Atwal, Karnail S ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BMS 191095; CROMAKALIM; GLIBENCLAMIDE; N (4 CHLOROPHENYL) N' CYANO N'' (6 CYANO 3,4 DIHYDRO 3 HYDROXY 2,2 DIMETHYL 2H 1 BENZOPYRAN 4 YL)GUANIDINE; POTASSIUM CHANNEL; POTASSIUM CHANNEL BLOCKING AGENT; POTASSIUM CHANNEL STIMULATING AGENT; UNCLASSIFIED DRUG;

ARTICLE; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; HEART MUSCLE ISCHEMIA; HEART PROTECTION; ISCHEMIC HEART DISEASE; STRUCTURE ACTIVITY RELATION; VASODILATATION;

ANIMALS; BENZOPYRANS; CARDIOTONIC AGENTS; GLYBURIDE; GUANIDINES; HEART; MUSCLE CONTRACTION; MYOCARDIAL ISCHEMIA; POTASSIUM CHANNELS; RATS; VASODILATION; VASODILATOR AGENTS;

EID: 0033539130     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990196h     Document Type: Article

References (28)

1. (a) Coetzee, W. A. ATP-Sensitive Potassium Channels and Myocardial Ischemia: Why Do They Open? Cardiovasc. Drugs Ther. 1992, 6, 201-208.
2. (b) Hearse, D. J. Activation of ATP-sensitive Potassium Channels: a Novel Pharmacological Approach to Myocardial Protection. Cardiovasc. Res. 1995, 30, 1-17.
3. ATP Openers. J. Cardiovasc. Pharmacol. 1994, 24 (Suppl. 4), S12-S17.
4. (d) Atwal, K. S. Advances in the Structure-Activity Relation-ships, Mechanism of Action, and Therapeutic Utilities of ATP-Sensitive Potassium Channel Openers. Drug Dev. Res. 1994, 33, 250-262.3.
5. (a) For BMS-180448 (2a): Atwal, K. S.; Grover, G. J.; Ahmed, S. Z.; Ferrara, F. N.; Harper, T. W.; Kim, K. S.; Sleph, P. G.; Dzwonczyk, S.; Russell, A. D.; Moreland, S.; McCullough, J. R.; Normandin, D. E. Cardioselective anti-ischemic ATP-sensitive potassium channel openers. J. Med. Chem. 1993, 36, 3971-3974.
6. ATP) Openers. 5. Identification of 4-(N-Aryl)-Substituted Benzopyran Derivatives with High Selectivity. J. Med. Chem. 1997, 40, 24-34
7. Atwal, K. S.; Grover, G. J. BMS-180448, A Glyburide-Reversible Cardioprotective Agent with Minimal Vasodilator Activity. Cardiovasc. Drug Rev. 1995, 13, 123-136.
8. Atwal, K. S.; Grover, G. J.; Ferrara, F. N.; Ahmed, S. Z.; Sleph, P. G.; Dzwonczyk, S.; Normandin, D. E. Cardioselective anti-ischemic ATP-sensitive potassium channel openers. 2. Structure-Activity Studies on Benzopyranyl Cyanoguanidines; Modification of the Benzopyran. J. Med. Chem. 1995, 38, 1966-1973.
9. Atwal, K. S.; Grover, G. J.; Ahmed, S. Z.; Sleph, P. G.; Dzwonczyk, S.; Baird, A. J.; Normandin, D. E. Cardioselective anti-ischemic ATP-sensitive potassium channel openers 3. Structure-Activity Studies on Benzopyranyl Cyanoguanidines; Modification of the Cyanoguanidine Portion. J. Med. Chem. 1996, 38, 3238-3245.
10. ATP) openers. 5. Identification of 4-(N-Aryl)-Substituted Benzopyran Derivatives with High Selectivity. J. Med. Chem. 1997, 40, 24-34.
11. Lee, N. H.; Muci, A. R.; Jacobsen, E. R. Enantiomerically Pure Epoxychromans via Asymmetric Catalysis. Tetrahedron Lett. 1991, 32, 5055.
12. Atwal, K. S.; Ahmed S. Z.; O'Reilly, B. C. A Facile Synthesis of Cyanoguanidines from Thioureas. Tetrahedron Lett. 1989, 30, 7313-7316.
13. Ding, C. Z. A Convenient Synthesis of 6-Substituted-2,2-Dimethyl-2H-1-Benzopyrans. Synth. Comm. 1996, 26, 4267-4273.
14. Lei, H.; Stoakes, M. S.; Schwabacher, A. W. Palladium Catalyzed Preparation of Monoaryl and Diarylphosphinates from Methyl Phosphinate. Synthesis 1992, 1255-60.
15. Grover, G. J.; Newburger, J.; Sleph, P. G.; Dzwonczyk, S.; Taylor, S. C.; Ahmed, S. Z.; Atwal, K. S. Cardioprotective Effects of the Potassium Channel Opener Cromakalim: Stereoselectivity and Effects on Myocardial Adenine Nucleotides. J. Pharmacol. Exp. Ther. 1991, 257, 156-162.
16. ATP) Openers. Curr. Pharm. Des. 1996, 2, 585-595.
17. (a) Grover, G. J.; Dzwonczyk, S.; Sleph, P. G. Reduction of Ischemic Damage in Isolated Rat Hearts by the Potassium Channel Opener RP 52891. Eur. J. Pharmacol. 1990, 69, 571-581.
18. (b) Sargent, C. A.; Smith, M. A.; Dzwonczyk, S.; Sleph, P. G.; Grover, G. J. Effect of Potassium Channel Blockade on the Anti-Ischemic Actions of Mechanistically Diverse Agents. J. Pharmacol. Exp. Ther. 1991, 259, 97-103.
19. ATP: An Inward Rectifier Subunit Plus the Sulfonylurea receptor. Science 1995, 270, 1166.
20. (b) Inagaki, N.; Gonoi, T.; Clement, J. P., IV; Wang, C.; Aguilar-Bryan, L.; Bryan J.; Seino, S. A Family of Sulfonylurea Receptors Determines the Pharmacological Properties of ATP-Sensitive K+ Channels. Neuron 1996, 16, 1011-1017.
21. (a) Dickinson, K. E. J.; Bryson, C. C.; Cohen, R. B.; Rogers, L.; Green, D. W.; Atwal, K. S. Nucleotide Regulation and Characterization of Potassium Channel Opener Binding to Skeletal Muscle Membranes. Mol. Pharmacol. 1997, 52, 1473-1481.
22. ATP) Openers to Cardiac Membranes: Correlation of Binding Affinities with Cardioprotective and Smooth Muscle Relaxing Potencies. J. Med. Chem. 1998, 41, 271-275.
23. Schwanstecher, M.; Sieverding, C.; Dorschner, H.; Gross, I.; Aguilar-Bryan. L.; Schwanstecher, C.; Bryan, J. Potassium Channel Openers Require ATP to bind to and act Through Sulfonylurea Receptors. EMBO J. 1998, 17, 5529-5535.
24. (a) Ashwood, V. A.; Buckingham, R. E.; Cassidy, F.; Evans, J. M.; Faruk, E. A.; Hamilton, T. C.; Nash, D. J.; Stemp, G.; Willcock, K. Synthesis and Antihypertensive Activity of 4-(Cyclic amido)-2H-1-benzopyrans. J. Med. Chem. 1986, 29, 2194-2201.
25. (b) Burrell, G.; Cassidy, F.; Evans, J. M.; Lightowler, D.; Stemp, G. Variation in the Aromatic Ring of Cromakalim: Antihypertensive Activity of Pyranopyridines and 6-Alkyl-2H-1-benzopyrans. J. Med. Chem. 1990, 33, 3023-3027.
26. (c) Arch, J. R. S.; Buckle, D. R.; Carey, C.; P.-Dobrzanski, H.; Faller, A.; Foster, K. A.; H.-Frydrych, C. S. V.; Pinto, I. L.; Smith, D. G.; Taylor, S. G. Relaxant Activity of 6-Cyano-2,2-dimethyl-2H-1-benzopyran-4-carboxamides and -thiocarboxamides and Their Analogues in Guinea Pig Trachealis. J. Med. Chem. 1991, 34, 2588-2594.
27. (d) Godfrey, J. D., Jr.; Mueller, R. H.; Sedergran, T. C.; Soundarajan, N.; Colandrea, V. J. Improved Synthesis of Aryl 1,1-Dimethylproparyl Ethers. Tetrahedron Lett. 1994, 35, 6405-6408.
28. Debruin, K E.; Tang, C-L. W.; Johnson, D. M.; Wilde, R. L. Kinetic facial Selectivity in Nucleophilic Displacements at Tetracoordinate Phosphorus: Kinetic and Stereochemistry in the Reaction of Sodium Ethoxide with O,S-Dimethyl Phenylphosphonothioate. J. Am. Chem. Soc. 1989, 111, 5871-5879.