Angiotension II Receptor Blocker

Index Background - RAS(Renin-Angiotensin System) Angiotensin II Receptor Blocker(Sartan compound) Introduction Chemistry Assay data

Hypertension 혈관 수축에 의한 고혈압 Angiotension II 에 의한 혈관수축 혈관 내에 혈류량에 의한 고혈압 Aldosterone 에 의한 이온 재흡수 및 물의 잔류

Angiotensin? Octapeptide Produced by RAS Key role in the Pathophtsiology of hypertension. Vasoactive hormone. Regulate the cardiovascular homeostasis by acting on both the vascular resistance and the blood volume.

RAS(Renin-Angiotensin System)

Angiotensin II Receptor Blocker (Sartan compound)

Tetrazole included sartan compound Valsartan Losartan Candesartan Fimasartan OlmesartanIrbesartan

Angiotensin II Receptor Blocker (Sartan compound) Other form sartan compound(Imidazole included) EprosartanTelmisartanAzilsartan

Angiotensin II Receptor Blocker (Sartan compound)

Introduction Angiotensin II is an octapeptide produced by the renin- angiotensin system, which plays a key role in the pathophysiology of hypertension. AngII is produced in vivo from angiotensin I by the angiotensin converting enzyme(ACE) EX) Enalapril, Captopril. This ACE is not a very selective enzymes. EnalaprilCaptopril

Introduction Thus the specific block of Ang II actions at the receptor level represents a potentially convenient approach to modulate the RAS. The parallel discovery of losartan and eprosartan, potent and orally active nonpeptide Ang II antagonists. Most of these compounds have the biphenyl fragment bearing an acidic moiety(tetrazole ring, COOH, SO2NHCO) in common and differ in the nature of the pendent heterocyclic system (valasartan lakcs the heterocyclic moiety) connected to the para position of the distal phenyl by means of a methylene group.

Introduction

A>Effects of the modification of the distal phenyl ring

B>Effects of the modification of the acidic moiety

C>Effects of the introduction of a substituent in the ortho position with respect to the acidic moiety

D>Effects of the modification of the lipophilic substituent in position 2 of the imidazo[4,5-b]- pyridine nucleus.

Summuary Losartan 의 유사체를 만들어 Angiotensin 2 receptor blocker 로서 역할을 하는 물질을 합성하 였다. Biphenyl system 에 amine 기를 도입했을때 2f 물질 이 그나마 약효가 있는것을 발견해서 새로운 타 겟으로 설정하였다. 4b 는 2f 와 비슷한 약효를 보였고 Loasartan 과도 유사한 약효가 보였다. Binding mode 를 살펴서 물질과 receptor 간의 binding site 를 살펴보았다.