Alacepril

Alacepril (INN) is an ACE inhibitor medication indicated as a treatment for hypertension. The medication metabolizes to captopril and desacetylalacepril.^[1] Alacepril is primarily used to treat hypertension, and in some cases, renovascular hypertension. It's often combined with other medications, particularly other blood pressure lowering classes of medications like thiazide diuretics to maximize its effectiveness.^[2]

Alacepril

Clinical data
AHFS/Drugs.com	International Drug Names
Routes of administration	Oral
ATC code	none
Legal status
Legal status	In general: ℞ (Prescription only)
Identifiers
IUPAC name (2S)-2-[[(2S)-1-[(2S)-3-acetylsulfanyl-2-methylpropanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoic acid
CAS Number	74258-86-9 N
PubChem CID	71992
ChemSpider	64993 Y
UNII	X39TL7JDPF
KEGG	D01900 Y
ChEMBL	ChEMBL2103775 N
CompTox Dashboard (EPA)	DTXSID3048576
Chemical and physical data
Formula	C20H26N2O5S
Molar mass	406.50 g·mol−1
3D model (JSmol)	Interactive image
SMILES C[C@H](CSC(=O)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)O
InChI InChI=1S/C20H26N2O5S/c1-13(12-28-14(2)23)19(25)22-10-6-9-17(22)18(24)21-16(20(26)27)11-15-7-4-3-5-8-15/h3-5,7-8,13,16-17H,6,9-12H2,1-2H3,(H,21,24)(H,26,27)/t13-,16+,17+/m1/s1 Y Key:FHHHOYXPRDYHEZ-COXVUDFISA-N Y
NY (what is this?)  (verify)

Mechanism of action

In vivo, when alacepril undergoes deacetylation, it loses a molecule similar to the amino acid phenylalanine which transforms it into captopril.^[3] Captopril then provides its blood pressure lowering effect through two ways. First, it inhibits the conversion of angiotensin 1, a precursor molecule, to angiotensin II, a vasoconstrictor that narrows blood vessels. Secondly, captopril prevents the breakdown of bradykinin, a vasodilator peptide that naturally relaxes blood vessels.^[4]

Synthesis

Thieme ChemDrug Synthesis:^[5] Patents:^[6][7][8] ~65%:^[9]

Amide formation between S-Acetylcaptopril [64838-55-7] (1) and (S)-tert-Butyl 2-amino-3-phenylpropanoate [16874-17-2] (2) gives PC86595505 (3). Deprotection with trifluoroacetic acid completed the synthesis of alacepril (4).