Angiotensin I-converting enzyme (ACE; EC 3.4.15.1) is a zinc-dipeptidyl carboxypeptidase that plays a key role in blood pressure regulation by converting the inactive decapeptide angiotensin I to the potent vasopressor octapeptide angiotensin II by cleavage of the carboxy-terminal dipeptide.1 It also inactivates the vasodepressor nonapeptide bradykinin.2,3 Thus, the inhibition of ACE has become a primary strategy in the treatment of hypertension, myocardical infarction, heart failure, and diabetic nephropathy.4 There are a number of commercially available ACE inhibitors, including captopril,5,6 lisinopril, and enalapril, which have established themselves in the therapy of hypertension and congestive heart failure.7,8 However, undesirable side effects such as persistent cough, loss of taste, and angioedema have been associated with current-generation ACE inhibitors.9,10 Therefore, the development of novel effective drugs for the treatment of hypertension and cardiovascular diseases still remains an important goal. The recent availability of the crystal structure of the testis ACE-lisinopril complex has opened the possibility of structure-guided design of second-generation, domain-selective ACE inhibitors.11 
USPTO Backgrounds
USPTO Backgrounds