Where do angiotensin receptor blockers (ARBs) come from?

Angiotensin receptor blockers (ARBs) were developed to selectively inhibit the binding of angiotensin II (A-II) to angiotensin II type 1 (AT₁) receptors.^1-7 In 1982, the class of chemical compounds 1-benzylimidazole-5-acetic acids was found which antagonized A-II and reduced elevated blood pressure in lab animals.^8,9 The discovery of N-(biphenylyl-methyl)imidazoles and the development of derivatives created potent antihypertensives that could be administered orally.^6,7,9-13 Losartan was the first of a new class of oral antihypertensive agents called angiotensin receptor blockers, approved by the FDA in 1995.^1,3,9,14-16

^References

1. Goldberg MR, Bradstreet TE, McWilliams EJ, et al. Biochemical effects of losartan, a nonpeptide angiotensin II receptor antagonist, on the renin-angiotensin-aldosterone system in hypertensive patients. Hypertension 1995; 25 (1): 37-46.
2. Guthrie GP, Jr. Angiotensin receptors: physiology and pharmacology. Clin Cardiol 1995; 18 (6 Suppl 3): Iii 29-34.
3. Timmermans PB, Duncia JV, Carini DJ, et al. Discovery of losartan, the first angiotensin II receptor antagonist. J Hum Hypertens 1995; 9 Suppl 5: S3-18.
4. Fyhrquist F, Metsarinne K, Tikkanen I. Role of angiotensin II in blood pressure regulation and in the pathophysiology of cardiovascular disorders. J Hum Hypertens 1995; 9 Suppl 5: S19-24.
5. Oparil S, Williams D, Chrysant SG, Marbury TC, Neutel J. Comparative efficacy of olmesartan, losartan, valsartan, and irbesartan in the control of essential hypertension. J Clin Hypertens (Greenwich) 2001; 3 (5): 283-291, 318.
6. Wexler RR, Carini DJ, Duncia JV, et al. Rationale for the chemical development of angiotensin II receptor antagonists. Am J Hypertens 1992; 5 (12 pt 2): 209s-220s.
7. Timmermans PB, Carini DJ, Chiu AT, et al. The discovery of a new class of highly specific nonpeptide angiotensin II receptor antagonists. Am J Hypertens 1991; 4 (4 pt 2): 275s-281s.
8. Bauer JH, Reams GP. The angiotensin II type 1 receptor antagonists. A new class of antihypertensive drugs. Arch Intern Med 1995; 155 (13): 1361-1368.
9. Wexler RR, Greenlee WJ, Irvin JD, et al. Nonpeptide angiotensin II receptor antagonists:  the next generation in antihypertensive therapy. J Med Chem 1996; 39 (3): 625-656.
10. Ries UJ, Mihm G, Narr B, et al. 6-Substituted benzimidazoles as new nonpeptide angiotensin II receptor antagonists: synthesis, biological activity, and structure-activity relationships. J Med Chem 1993; 36 (25): 4040-4051.
11. Carini DJ, Duncia JV, Aldrich PE, et al. Nonpeptide angiotensin II receptor antagonists: the discovery of a series of N-(biphenylylmethyl)imidazoles as potent, orally active antihypertensives. J Med Chem 1991; 34 (8): 2525-2547.
12. Newman DJ, Cragg GM, Snader KM. Natural products as sources of new drugs over the period 1981−2002. J Nat Prod 2003; 66 (7): 1022-1037.
13. Timmermans PB, Wong PC, Chiu AT, et al. Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev 1993; 45 (2): 205-251.
14. Goa KL, Wagstaff AJ. Losartan potassium: a review of its pharmacology, clinical efficacy and tolerability in the management of hypertension. Drugs 1996; 51 (5): 820-845.
15. Carr AA, Prisant LM. Losartan: first of a new class of angiotensin antagonists for the management of hypertension. J Clin Pharmacol 1996; 36 (1): 3-12.
16. Goldberg AI, Dunlay MC, Sweet CS. Safety and tolerability of losartan potassium, an angiotensin II receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and angiotensin-converting enzyme inhibitors for the treatment of systemic hypertension. Am J Cardiol 1995; 75 (12): 793-795.