IntroductionAbout 40 years ago, inappropriate stomach acid level was a very significant problem. At that time, very few medical treatments were available for this type of gastroesophageal reflux disease (GRED). For this type of disease Heartburn was the most common type of symptom and peptic ulcer was one of the most common types of disease. If left untreated, it can be life-threatening. This time, the only cure for the disease was to administer antacid drugs. But this only had a temporary effect. With the advancement of drug chemistry, new drugs have come to the market for gastric diseases whose effect lasts for a long time. These drugs generally target different types of receptors like histamine (H2) receptor, proton pump receptors, etc. This review, they showed the development of new antacid drug by structure-activity relationship such as omeprazole and esoprazole. Development History The breakthrough in GRED-like diseases occurred in the late 1970s, when the antisecretory drug cimetidine was developed, which is the histamine (H2) antagonist that plays an important role in the secretion of gastric juice. After that, cimetidine-like compounds with the same type of mechanism of action have good potential for GRED but the effect is temporary. But this reduces the need for surgery. Currently, the pharmaceutical company Astra is trying to develop a compound that inhibits the proton pump in the acid secretion of the pariental cells of the stomach, which is most important in the acid secretion stage. After a long examination of the molecules, they arrived at the drug called Omeprazole, first launched as Losec in Europe in 1988 and in 1990 as Prilosec in the United States. This type of medication is... middle of article... those with a stomach tumor use high doses of proton pump inhibitor medications. References: 1. www.wikipedia.org2. Lindberg, P. et al. Omeprazole, the first proton pump inhibitor. Med. Res. Rev.10, 15 (1990)3. Saccomani, G., Crago, S., Mihas, A., Dailey, DW & Sachs, G. Localization of porcine gastric plasma membrane tissues and cells by antibody techniques. Acta Physiol. Scand. (Supplement) 293-305 (1978)4. Lindberg, P., Brandstrom, A. and Wallmark, B. Structure-activity relationships of omeprazole analogues and their mechanism of action. Pharmacol Trends. Sci. 8, 399-402 (1987)5. Andersson, T., Rohss, K., Bredberg, E. and Hassan – Alin, M. Pharmacokinetics and pharmacodynamics of esomeprazole, the S isomer of omeprazole. Food. Pharmacol. There. 15, 1563-1569 (2001)6. An Introduction to Medicinal Chemistry (4th Edition) By Graham L Patrick, Oxford University Press