Synthesis and selective coronary vasodilatory activity of 3,4-dihydro- 2,2-bis(methoxymethyl)-2H-1-benzopyran-3-ol derivatives: Novel potassium channel openers

Journal of Medicinal Chemistry

Volumn 39, Issue 19, 1996, Pages 3797-3805

  Cho, Hidetsura ^a   Katoh, Susumu ^a   Sayama, Shinsuke ^a   Murakami, Kengo ^a   Nakanishi, Hiroyuki ^a   Kajimoto, Yasuyuki ^a   Ueno, Hiroshi ^a   Kawasaki, Hisashi ^a   Aisaka, Kazuo ^a   Uchida, Itsuo ^a  

^a JAPAN TOBACCO INC   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

4 [(1,6 DIHYDRO 1 METHYL 6 OXO 3 PYRIDAZINYL)AMINO] 3 HYDROXY 2,2 BIS(METHOXYMETHYL)CHROMAN 6 CARBONITRILE; 6 CYANO 3,4 DIHYDRO 4 [(1,6 DIHYDRO 1 METHYL 6 OXO 3 PYRIDAZINYL)AMINO] 2,2 BIS(METHOXYMETHYL) 2H 1 BENZOPYRAN 3 OL; BENZOPYRAN DERIVATIVE; CORONARY VASODILATING AGENT; GLIBENCLAMIDE; LEMAKALIM; METHACHOLINE; NICORANDIL; NIFEDIPINE; POTASSIUM CHANNEL STIMULATING AGENT; UNCLASSIFIED DRUG;

ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; CORONARY ARTERY BLOOD FLOW; CORONARY ARTERY DILATATION; DOG; DRUG SYNTHESIS; ELECTROCARDIOGRAM; FEMALE; HEART RATE; INTRACORONARY INFUSION; INTRAVENOUS DRUG ADMINISTRATION; MALE; MEAN ARTERIAL PRESSURE; NONHUMAN; ORAL DRUG ADMINISTRATION; RAT; ST SEGMENT ELEVATION; STRUCTURE ACTIVITY RELATION; SYSTEMIC CIRCULATION;

ANIMALS; BENZOPYRANS; BLOOD PRESSURE; CORONARY CIRCULATION; CORONARY VESSELS; DOGS; FEMALE; HEART RATE; ION CHANNEL GATING; MALE; MODELS, MOLECULAR; MOLECULAR STRUCTURE; POTASSIUM CHANNELS; PYRIDAZINES; RATS; RATS, SPRAGUE-DAWLEY; STRUCTURE-ACTIVITY RELATIONSHIP; SWINE; VASODILATOR AGENTS;

EID: 9544238081     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960270l     Document Type: Article

References (22)

1. Robertson, D. W.; Steinberg, M. I. Potassium Channel Modulators: Scientific Applications and Therapeutic Promise. J. Med. Chem. 1990, 33, 1529-1541.
2. Bergmann, R.; Gericke, R. Synthesis and Antihypertensive Activity of 4-(1,2-Dihydro-2-oxo-1-pyridyl)-2H-1-benzopyrans and Related Compounds, New Potassium Channel Activators. J. Med. Chem. 1990, 33, 492-504.
3. + Channel Opener with Less Incidence of Tachycardia. Cardiovasc. Drug Rev. 1991, 9, 372-384.
4. Lebel, M.; Grose, J. H.; Lacourciere, Y. Effect of Short-Term Administration of Cromakalim on Renal Hemodynamics and Eicosanoid Excretion in Essential Hypertension. Am. J. Hypertens. 1991, 4, 740-744.
5. Toombs, C. F.; Norman, N. R.; Groppi, V. E.; Lee, K. S.; Gadwood, R. C.; Shebuski, R. J. Limitation of Myocardial Injury with the Potassium Channel Opener Cromakalim and the Nonvasoactive Analog U-89, 232: Vascular vs Cardiac Actions in Vitro and in Vivo. J. Pharmacol. Exp. Ther. 1992, 263, 1261-1268. Atwal, K. S.; Grover, G. J.; Ferrara, F. N.; Ahmed, S. Z.; Sleph, P. G.; Dzwonczyk, S.; Normandin, D. E. Cardioselective Antiischemic ATP-Sensitive Potassium Channel Openers. 2. Structure-Activity Studies on Benzopyranylcyanoguanidines: Modification of the Benzopyran Ring. J. Med. Chem. 1995, 38, 1966-1973.
6. Toombs, C. F.; Norman, N. R.; Groppi, V. E.; Lee, K. S.; Gadwood, R. C.; Shebuski, R. J. Limitation of Myocardial Injury with the Potassium Channel Opener Cromakalim and the Nonvasoactive Analog U-89, 232: Vascular vs Cardiac Actions in Vitro and in Vivo. J. Pharmacol. Exp. Ther. 1992, 263, 1261-1268. Atwal, K. S.; Grover, G. J.; Ferrara, F. N.; Ahmed, S. Z.; Sleph, P. G.; Dzwonczyk, S.; Normandin, D. E. Cardioselective Antiischemic ATP-Sensitive Potassium Channel Openers. 2. Structure-Activity Studies on Benzopyranylcyanoguanidines: Modification of the Benzopyran Ring. J. Med. Chem. 1995, 38, 1966-1973.
7. Katoh, S.; Sayama, S.; Shibata, S.; Yamaki, T.; Uchida, I. JP 5186458A (Appl. JP 91188374, April 26, 1991).
8. Ellis, G. P.; Show, D. Benzopyrones. Part VIII. Mono- and Ditetrazol-5-yl-chromones. The Infrared Cyano-Absorption of Some 4-Oxo-chromencarbonitriles. J. Chem. Soc., Perkin Trans. I 1972, 779-783.
9. Petrusova, M.; Mihalov, V.; Kocis, P.; Fedoronko, M. Preparation and Identification of Aldolization Products of 1,3-Dimethoxy-2-propanone. Chem. Papers 1985, 39, 763-768.
10. Lee, N. H.; Muci, A. R.; Jacobsen, E. N. Enantiomerically Pure Epoxychromans via Asymmetric Catalysis. Tetrahedron Lett. 1991, 32, 5055-5058. Zang, W.; Jacobsen, E. N. Asymmetric Olefin Epoxidation with Sodium Hypochlorite Catalyzed by Easily Prepared Chiral Mn(III) Salen Complexes. J. Org. Chem. 1991, 56, 2296-2298.
11. Lee, N. H.; Muci, A. R.; Jacobsen, E. N. Enantiomerically Pure Epoxychromans via Asymmetric Catalysis. Tetrahedron Lett. 1991, 32, 5055-5058. Zang, W.; Jacobsen, E. N. Asymmetric Olefin Epoxidation with Sodium Hypochlorite Catalyzed by Easily Prepared Chiral Mn(III) Salen Complexes. J. Org. Chem. 1991, 56, 2296-2298.
12. Katoh, S.; Cho, H.; Sayama, S.; Kajimoto, Y.; Shibata, S.; Mizushima, J.; Yamaki, T.; Uchida, I. WO 9502589.
13. 50 values of the less polar diastereomers are shown in Table 1. The more polar diastereomers of compounds 10 and 12 were inactive even after injection at a dose of 30 μg, while the more polar diastereomer of compound 13 exhibited the same potency and duration of action as the less polar one.
14. Gericke, R.; Harting, J.; Lues, I.; Schittenhelm, C. 3-Methyl-2H-1-benzopyran, Potassium Channel Activators. J. Med. Chem. 1991, 34, 3074-3085.
15. Horie, T.; Kinjo, K.; Ueda, T. Studies on Pyridazine Derivatives I. Synthesis and Antimicrobial Activity of 6-Substituted 3-Aminopyridazine and its Sulfonamido Derivatives. Chem. Pharm. Bull. 1962, 10, 580-591.
16. 9 and shown to have one-thirtieth of the activity of compound 3 itself.
17. Baumgarth, M.; Bergmann, R.; Gericke, R.; Harting, J.; Lues, I. JP 4300880A.
18. It is speculated that nitric oxide released from nicorandil potently relaxes coronary arteries.
19. + Channel Activators in vitro. J. Autonomic Pharmacol. 1989, 9, 71-78.
20. Cho, H.; Sayama, S.; Katoh, S.; Aisaka, K.; Uchida, I. WO 9513272.
21. Rubinstein, H.; Skarbek, J. E.; Fener, H. Reactions of 3-Carboxyacryloyl-hydrazines and the Formation of Maleimides, Isomaleimides, and Pyridazinones. J. Org. Chem. 1971, 36, 3372-3376.
22. Izawa, T.; Kashiwabara, T.; Nakajima, S.; Ogawa, N. EP 0388528A.