UK-447841

UK-447841 is a neprilysin inhibitor (NEPI) which was under development for the treatment of female sexual dysfunction.^[1]^[2]^[3] It is taken as-needed orally.^[1] The drug is intended to work by inhibiting vasoactive intestinal peptide (VIP) hydrolysis by neprilysin (NEP).^[3] However, neprilysin is also involved in the metabolism of more than 50 other hormones and neuropeptides, for instance oxytocin among others.^[4]^[5] UK-447841 was under development by Pfizer.^[1]^[2] It reached phase 2 clinical trials prior to the discontinuation of its development in 2008.^[1]^[2]

Other namesUK447841; UK-447,841

Routes of
administrationOral^[1]

Drug classNeprilysin inhibitor

ATC code

None

Quick facts Clinical data, Other names ...

UK-447841
Clinical data

Other names	UK447841; UK-447,841
Routes of administration	Oral^[1]
Drug class	Neprilysin inhibitor
ATC code	None
Identifiers
IUPAC name (2S)-2-[[1-[3-(4-chlorophenyl)propylcarbamoyl]cyclopentyl]methyl]-4-methoxybutanoic acid
CAS Number	465528-01-2
PubChem CID	15978653
ChemSpider	13110134
UNII	T76DLY464G
ChEMBL	ChEMBL225085
CompTox Dashboard (EPA)	DTXSID701352306
Chemical and physical data
Formula	C₂₁H₃₀ClNO₄
Molar mass	395.92 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES COCC[C@H](CC1(CCCC1)C(=O)NCCCC2=CC=C(C=C2)Cl)C(=O)O
InChI InChI=1S/C21H30ClNO4/c1-27-14-10-17(19(24)25)15-21(11-2-3-12-21)20(26)23-13-4-5-16-6-8-18(22)9-7-16/h6-9,17H,2-5,10-15H2,1H3,(H,23,26)(H,24,25)/t17-/m1/s1 Key:UOGBJRPKRSUJRU-QGZVFWFLSA-N

References

[1]
"UK 447841". AdisInsight. 11 February 2014. Retrieved 27 January 2026.
[2]
"Delving into the Latest Updates on UK-447841 with Synapse". Synapse. 20 December 2025. Retrieved 27 January 2026.
[3]
El Bakali J, Maingot L, Dumont J, Host H, Hocine A, Cousaert N, et al. (2012). "Novel selective inhibitors of neutral endopeptidase: discovery by screening and hit-to-lead optimisation". MedChemComm. 3 (4): 469. doi:10.1039/c2md00287f. ISSN 2040-2503. Retrieved 27 January 2026. Recently selective inhibitors, such as UK414,495 (6) and UK-447,841 (7), were developed to inhibit VIP hydrolysis by hNEP, for the treatment of Female Sexual Arousal Disorder (FSAD).9 [...] Fig. 1 Structures of representative NEP inhibitors: 1 thiorphan (NEP selective), 2 omapatrilat (dual ACE/NEP inhibitor), 3 CGS 35601 (triple NEP/ACE/ECE inhibitor), 4 ilepatril (dual ACE/NEP inhibitor), 5 candoxatrilat (NEP selective), 6 UK-414,495 (NEP selective) and 7 UK447,841 (NEP selective).
[4]
Zhang X, Hu C, Tian E, Shen Y, Liu W, Li J (2024). "Comprehensive review on neprilysin (NEP) inhibitors: design, structure-activity relationships, and clinical applications". Frontiers in Pharmacology. 15 1501407. doi:10.3389/fphar.2024.1501407. PMC 11700742. PMID 39764460. NEPI affects the metabolism of various peptides, including amyloid peptides, corticotropin-releasing factor, luteinizing hormone-releasing hormone, oxytocin, and neurotensin (BayesGenis et al., 2016; Campbell, 2017). NEP plays a significant role in a variety of diseases affecting the natriuretic peptide system, the renin-angiotensin-aldosterone system (RAAS), and the kallikreinkinin system (Domenig et al., 2016; Ponikowski et al., 2016). Previous studies have confirmed that inhibiting NEP can elevate these peptides, Improving chronic heart failure treatment outcomes (Campbell, 2017).
[5]
Bozkurt B, Nair AP, Misra A, Scott CZ, Mahar JH, Fedson S (January 2023). "Neprilysin Inhibitors in Heart Failure: The Science, Mechanism of Action, Clinical Studies, and Unanswered Questions". JACC. Basic to Translational Science. 8 (1): 88–105. doi:10.1016/j.jacbts.2022.05.010. PMC 9911324. PMID 36777165. Neprilysin has putative roles in the modulation of peptides implicated in the cardiovascular system and in other systems related to amyloid deposition, opioid receptor and pain processing, gastrointestinal processes, metabolism, sperm motility, and skin aging. There are more than 50 peptide targets of neprilysin, which include vasodilatory peptides such as natriuretic peptides, bradykinin, adrenomedullin, and substance P; vasoconstrictor peptides such as angiotensin I and II, endothelin, and neurotensin; and other peptides implicated in pathways related to amyloid deposition, pain sensorium, mood, gastrointestinal processes, and metabolism, such as amyloid beta (Aβ) peptide, enkephalins, endomorphins, corticotropin, neuropeptide Y, gastrin, cholecystokinin-8, somatostatin, glucagon, vasoactive intestinal peptide (VIP), and oxytocin, among others (Central Illustration). [...] Oxytocin, a neuropeptide produced by the hypothalamus and secreted by the posterior pituitary gland, also undergoes hydrolysis by neprilysin. The significance of elimination of the breakdown of these peptides is unclear.

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References

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