View source for Alacepril

{{Short description|Antihypertensive drug of the ACE inhibitor class}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 477316241
| IUPAC_name = (2''S'')-2-<nowiki>[[</nowiki>(2''S'')-1-[(2''S'')-3-acetylsulfanyl-2-methylpropanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoic acid
| image = Alacepril.svg

<!--Clinical data-->
| tradename =  
| Drugs.com = {{drugs.com|international|alacepril}}
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category =  
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status = Rx-only
| routes_of_administration = Oral

<!--Pharmacokinetic data-->
| bioavailability =  
| protein_bound =  
| metabolism =  
| elimination_half-life =  
| excretion =

<!--Identifiers-->
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 74258-86-9
| ATC_prefix = none
| ATC_suffix =  
| ATC_supplemental =  
| PubChem = 71992
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 2103775
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank =  
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 64993
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = X39TL7JDPF
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D01900

<!--Chemical data-->
| chemical_formula =  
| C=20 | H=26 | N=2 | O=5 | S=1 
| smiles = C[C@H](CSC(=O)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)O
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = FHHHOYXPRDYHEZ-COXVUDFISA-N
}}

'''Alacepril''' ([[International Nonproprietary Name|INN]]) is an [[ACE inhibitor]] medication indicated as a treatment for hypertension. The medication metabolizes to [[captopril]] and desacetylalacepril.<ref>{{Cite web |date=24 August 2010 |title=Alacepril |url=https://www.micromedexsolutions.com/micromedex2/librarian/CS/33581F/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSYNC/EBE7F1/ND_PG/evidencexpert/ND_B/evidencexpert/ND_AppProduct/evidencexpert/ND_T/evidencexpert/PFActionId/evidencexpert.IntermediateToDocumentLink?docId=18737-x&contentSetId=30&title=Alacepril&servicesTitle=Alacepril |access-date=23 June 2022 |website=IBM Micromedex}}</ref> 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 diuretic]]s to maximize its effectiveness.<ref>{{Cite web |title=Alacepril |url=https://drugcentral.org/drugcard/101 | quote = It is an angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. It used for the treatment of essential or renovascular hypertension (usually administered with other drugs, particularly thiazide diuretics). |access-date= 13 April 2024 | work = DrugCentral online drug compendium }}</ref>

== Mechanism of action ==
In vivo, when alacepril undergoes [[Histone acetylation and deacetylation|deacetylation]], it loses a molecule similar to the amino acid phenylalanine which transforms it into captopril.<ref>{{cite book | vauthors = Campese VM, Lakdawala RS | chapter = The Challenges of Blood Pressure Control in Dialysis Patients | veditors = Nissenson AR, Fine RN  |title=Handbook of dialysis therapy |date=2017 | pages = 603–626.e2 |publisher=Elsevier | edition=5th |location=Philadelphia, PA | quote = The sulfhydryl agents, such as alacepril, delapril, and moveltopril, are prodrugs and thus are converted to captopril in vivo. These sulfhydryl-containing compounds have a slower onset and longer duration of action than captopril. |isbn=978-0-323-39154-2 | doi = 10.1016/B978-0-323-39154-2.00053-9 }}</ref> 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.<ref>{{cite journal | vauthors = Odaka C, Mizuochi T | title = Angiotensin-converting enzyme inhibitor captopril prevents activation-induced apoptosis by interfering with T cell activation signals | journal = Clinical and Experimental Immunology | volume = 121 | issue = 3 | pages = 515–522 | date = September 2000 | pmid = 10971519 | doi = 10.1046/j.1365-2249.2000.01323.x | pmc = 1905724 }}</ref>
==Synthesis==
[[File:Alacepril synthesis.svg|thumb|center|500px|[https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-01-0048 Thieme] [https://www.chemdrug.com/article/8/3284/16419376.html ChemDrug] Synthesis:<ref>Castaer, J.; Mannhold, R.; Alacepril. Drugs Fut 1986, 11, 5, 357.</ref> Patents:<ref>Tadahiro Sawayama, et al. EP0007477 (1982 to Dainippon Pharmaceutical Co Ltd).</ref><ref>Tadahiro Sawayama, et al. {{US patent|4248883}} (1981 to Dainippon Pharmaceutical Co Ltd).</ref><ref>Nicoletta Almirante, et al. WO2004106300 (Nicox SA). Page 65.</ref> ~65%:<ref>Ishikura, Minoru; Ohta, Tsukasa; Terashima, Masanao (1985). "A novel synthesis of 4-aryl- and 4-heteroarylpyridines via diethyl(4-pyridyl)borane". CHEMICAL & PHARMACEUTICAL BULLETIN. 33 (11): 4755–4763. doi:10.1248/cpb.33.4755.</ref>]]
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).
== References ==
{{Reflist|2}}

== External links ==
*{{Commons category-inline}}

{{ACE inhibitors}}
{{Angiotensin receptor modulators}}

[[Category:ACE inhibitors]]
[[Category:Carboxamides]]
[[Category:Enantiopure drugs]]
[[Category:Pyrrolidines]]

{{cardiovascular-drug-stub}}