Cardioselective Anti-Ischemic ATP-Sensitive Potassium Channel Openers. 3. Structure-Activity Studies on Benzopyranyl Cyanoguanidines: Modification of the Cyanoguanidine Portion

Journal of Medicinal Chemistry

Volumn 38, Issue 17, 1995, Pages 3236-3245

  Atwal, Karnail S ^a   Grover, Gary J ^a   Ahmed, Syed Z ^a   Sleph, Paul G ^a   Dzwonczyk, Steven ^a   Baird, Anne J ^a   Normandin, Diane E ^a  

^a BRISTOL MYERS SQUIBB PHARMACEUTICAL RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 PROPANOL; 5 HYDROXYDECANOIC ACID; ADENOSINE TRIPHOSPHATE; BENZOPYRANYLCYANOGUANIDINE DERIVATIVE; BMS 189365; CROMAKALIM; GLIBENCLAMIDE; MECLOFENAMIC ACID; METHOXAMINE; N (4 CHLOROPHENYL) N' CYANO N'' (6 CYANO 3,4 DIHYDRO 3 HYDROXY 2,2 DIMETHYL 2H 1 BENZOPYRAN 4 YL)GUANIDINE; N'' CYANO N (6 CYANO 3,4 DIHYDRO 3 HYDROXY 2,2 DIMETHYL 2H 1 BENZOPYRAN 4 YL) N' (1,1 DIMETHYLPROPYL)GUANIDINE; POTASSIUM CHANNEL; POTASSIUM CHANNEL BLOCKING AGENT; POTASSIUM CHANNEL STIMULATING AGENT; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; CARDIOSELECTIVITY; DRUG MECHANISM; DRUG POTENCY; HEART MUSCLE ISCHEMIA; NONHUMAN; POTASSIUM TRANSPORT; RAT; STRUCTURE ACTIVITY RELATION; VASODILATATION;

ADENOSINE TRIPHOSPHATE; ANIMAL; GUANIDINES; IN VITRO; MAGNETIC RESONANCE SPECTROSCOPY; MYOCARDIAL ISCHEMIA; POTASSIUM CHANNELS; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; VASODILATOR AGENTS;

EID: 0029166716     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm00017a007     Document Type: Article

References (23)

1. Parratt, J. R. Protection of the Heart by Ischemic Preconditioning: Mechanism and Possibilities for Pharmacological Exploitation. Trends Pharmacol. Sci. 1994, 15, 19-25.
2. Gross, G. J.; Auchampach, J. A. Blockade of ATP-Sensitive Potassium Channels Prevents Myocardial Preconditioning in Dogs. Circulation Res. 1990, 70, 223-233.
3. Auchampach, J. A. Grover, G. J.; Gross, G. J. Blockade of Ischemic Preconditioning in Dogs by the Novel ATP-dependent Potassium Channel Antagonist Sodium 5-Hydroxydecanoate. Cardiovas. Res. 1992, 26, 1054-1062.
4. Yao, Z; Gross, G. J. The ATP-Dependent Potassium Channel: An Endogenous Cardioprotective mechanism. J. Cardiovas. Pharmacol. 1994, 24, S28-S34.
5. Yao, Z.; Mizumura, T.; Mei, D. A.; Gross, G. J. Activation of KATP- Channels May Play a Role in the “Memory” of Ischemic Preconditioning (PC) in Anesthetized Dogs. Circulation 1994, 90 (4 Part 2), 1108.
6. Tomai, F.; Crea, F.; Gaspardone, A.; Versaci, F.; De Paulis, R.; Pentadepeppo, A.; Chiariello, L.; Gioffre, P. Ischemic Preconditioning During Coronary Artery Angioplasty is Prevented by Glybenclamide, a Selective ATP-Sensitive K+ channel Blocker. Circulation 1994, 90, 700-705.
7. Grover, G. J.; McCullough, J. R.; Henry, D. E.; Conder, M. L.; Sleph, P. G. Anti-i-Ischemic Effects of the Potassium Channel Activator Pinacidil and Cromakalim and the Reversal of these Effects with the Potassium Channel Blocker Glyburide. J. Pharmacol. Exp. Ther. 1989, 251, 98.
8. Auchampach, J. A.; Maruyama, M.; Cavero, I.; Gross, G. J. Pharmacological Evidence for a Role of ATP-Dependent Potassium Channels in Myocardial Stunning. Circulation 1992, 86, 311.
9. 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.
10. 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.
11. Atwal, K. S.; Ahmed S. Z.; O’Reilly, B. C. A Facile Synthesis of Cyanoguanidines from Thioureas. Tetrahedron Lett. 1989, 30, 7313-7316.
12. Atwal, K. S.; Moreland, S.; McCullough, J. R.; Ahmed, S. Z.; Normandin, D. E. Benzopyranyl-Cyanoguanidine Potassium Channel Openers. Bioorg. Med. Chem. Lett. 1992, 2, 87-90.
13. 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-l-benzopyrans. J. Med. Chem. 1986, 29, 2194-2201.
14. 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-2/7-1 -benzopyrans. J. Med. Chem. 1990, 33, 3023-3027.
15. 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-2ff-l-benzo- pyran-4-carboxamides and -thiocarboxamides and Their Analogs in Guinea Pig Trachealis. J. Med. Chem. 1991, 34, 2588-2594.
16. Atwal, K. S.; Moreland, S.; McCullough, J. R.; O’Reilly, B. C.; Ahmed, S. Z.; Normandin, D. E. Aryl Cyanoguanidine Potassium Channel Openers. Bioorg. Med. Chem. Lett. 1992, 2, 83-86.
17. 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.
18. Grover, G. J.; McCullough, J. R.; D’Alonzo, A. J.; Sargent, C. S.; Atwal, K. S. Cardioprotective Profile of the Cardiac-Selective ATP-Sensitive Potassium, Channel Opener BMS-180-448. J. Cardiovasc. Pharmacol. 1994, 25, 40-50.
19. Ashwood, V. A.; Cassidy, F; Evans, J. M.; Gagliardi, S.; Stemp, G. Synthesis and Antihypertensive Activity of Pyran Oxygen and Amide Nitrogen Replacement Analogues of the Potassium Channel Activator Cromakalim. J. Med. Chem. 1991, 34, 3261-3267.
20. Toombs, C. F.; Moore, T. F.; Shebuski, R. J. Cardioprotection with U-89232 is not Reversible with Glibenclamide: Evidence of a Novel Anti-ischemic Agent Derived from Cromakalim. Pharmacology 1994, 49, 96-104.
21. Grover, G. J.; Sargent, C. S.; McCullough, J. R.; Atwal, K. S. In vitro Anti-ischemic Profile of Activity of a Novel Cardioselective Katp Opener, BMS-180-448. The Pharmacologist 1993, 35, 178.
22. 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.
23. Grover, G. J.; D’Alonzo, A. J.; Sleph, P. G.; Dzwonczyk, S.; Hess, T. A.; Darbenzio, R. B. The Cardioprotective and Electrophysiological Effects of Cromakalim are Attenuated by Maclofenamate Through a Cyclooxygenase Independent Mechanism. J. Pharmacol. Exp. Ther. 1994, 269, 536-540.