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Inhibition of thromboxane synthase (TXAS), especially in human platelets, has been a clinical objective for many years. 1-Alkyl (N-alkyl)-imidazole derivatives have been recognized as TXAS inhibitors since the early 1980s.1,2,3 Ozagrel is a 1-alkyl imidazole derivative that acts as a selective inhibitor of TXAS with an IC50 of 11 nM. The beneficial effects of TXAS inhibition by ozagrel include improved motor coordination after experimental stroke,4 and antihypertensive effects in spontaneously hypertensive rats.5
1
Iizuka, K., Akahane, K., Momose, D., et al. Highly selective inhibitors of thromboxane synthase. 1. Imidazole derivatives. J Med Chem241139-1148(1981 Nov 20).
2
Wright, W.B., Tomcufcik, A.S., Chan, P.S., et al. Thromboxane synthase inhibitors and antihypertensive agents. 4,N-[(1H-imidazol-1-yl)alkyl] derivatives of quinazoline-2,4(1H,3H)-diones, quinazolin-4(3H)-ones, and 1,2,3-benzotriazin-4(3H)-ones. J Med Chem302277-2283(1987 May 6).
3
Wright, W.B., Press, J.B., Chan, P.S., et al. Thromboxane synthetase inhibitors and antihypertensive agents. 1. N-[(1H-imidazol-1-yl)alkyl]aryl amides and N-[(1H-imidazol-1,2,4-triazol-1-yl)alkyl]aryl amides. J Med Chem29523-530(1986).
4
Ichikawa, K., Tazawa, S., Hamano, S., et al. Effect of ozagrel on locomotor and motor coordination after transient cerebral ischemia in experimental animal models. Pharmacology59257-265(1999).
5
Press, J.B., Wright, W.B., Chan, P.S., et al. Thromboxane synthetase inhibitors and antihypertensive agents. 2. N-[(1H-Imidazol-1-yl)alkyl]-1H-isoindole-1,3(2H)-diones and N-[(1H-1,2,4-triazol-1-yl)alkyl]-1H-isoindole-1,3(2H)-diones as unique antihypertensive agents. J Med Chem29(5)816-819(1986).
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in continental US; may vary elsewhere
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OC(=O)\C=C/c1ccc(cc1)Cn1ccnc1
Background Reading
Ichikawa, K., Tazawa, S., Hamano, S., et al. Effect of ozagrel on locomotor and motor coordination after transient cerebral ischemia in experimental animal models. Pharmacology59257-265(1999).
Wright, W.B., Tomcufcik, A.S., Chan, P.S., et al. Thromboxane synthase inhibitors and antihypertensive agents. 4,N-[(1H-imidazol-1-yl)alkyl] derivatives of quinazoline-2,4(1H,3H)-diones, quinazolin-4(3H)-ones, and 1,2,3-benzotriazin-4(3H)-ones. J Med Chem302277-2283(1987 May 6).
Iizuka, K., Akahane, K., Momose, D., et al. Highly selective inhibitors of thromboxane synthase. 1. Imidazole derivatives. J Med Chem241139-1148(1981 Nov 20).
Wright, W.B., Press, J.B., Chan, P.S., et al. Thromboxane synthetase inhibitors and antihypertensive agents. 1. N-[(1H-imidazol-1-yl)alkyl]aryl amides and N-[(1H-imidazol-1,2,4-triazol-1-yl)alkyl]aryl amides. J Med Chem29523-530(1986).
Press, J.B., Wright, W.B., Chan, P.S., et al. Thromboxane synthetase inhibitors and antihypertensive agents. 2. N-[(1H-Imidazol-1-yl)alkyl]-1H-isoindole-1,3(2H)-diones and N-[(1H-1,2,4-triazol-1-yl)alkyl]-1H-isoindole-1,3(2H)-diones as unique antihypertensive agents. J Med Chem29(5)816-819(1986).