Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C29H41NO7 |
Molecular Weight | 515.6383 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COCCOC[C@H](CC1(CCCC1)C(=O)N[C@H]2CC[C@H](CC2)C(O)=O)C(=O)OC3=CC=C4CCCC4=C3
InChI
InChIKey=ZTWZVMIYIIVABD-OEMFJLHTSA-N
InChI=1S/C29H41NO7/c1-35-15-16-36-19-23(27(33)37-25-12-9-20-5-4-6-22(20)17-25)18-29(13-2-3-14-29)28(34)30-24-10-7-21(8-11-24)26(31)32/h9,12,17,21,23-24H,2-8,10-11,13-16,18-19H2,1H3,(H,30,34)(H,31,32)/t21-,23-,24+/m0/s1
Molecular Formula | C29H41NO7 |
Molecular Weight | 515.6383 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: https://www.drugbank.ca/drugs/DB00616Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/1315825 | https://www.ncbi.nlm.nih.gov/pubmed/10937982 | https://www.ncbi.nlm.nih.gov/pubmed/21515054 | https://www.ncbi.nlm.nih.gov/pubmed/2529858 | https://www.ncbi.nlm.nih.gov/pubmed/26082640
Sources: https://www.drugbank.ca/drugs/DB00616
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/1315825 | https://www.ncbi.nlm.nih.gov/pubmed/10937982 | https://www.ncbi.nlm.nih.gov/pubmed/21515054 | https://www.ncbi.nlm.nih.gov/pubmed/2529858 | https://www.ncbi.nlm.nih.gov/pubmed/26082640
Candoxatril is the orally-active prodrug of candoxatrilat (UK-73967), a potent neutral endopeptidase (NEP) inhibitor. Neutral endopeptidase inhibitors such as Candoxatril have a dual mechanism of action. They inhibit two metalloprotease enzymes, neutral endopeptidase, and ACE, resulting in an increased availability of natriuretic peptides that exhibit vasodilatory effects and, possibly, tissue protective effects. Candoxatril is the first drug of its kind to be released for clinical trials regarding heart failure. This is because Candoxatril produces favorable hemodynamic effects in patients with chronic heart failure. It has been demonstrated that Candoxatril is associated with a beneficial hemodynamic effect that is useful both for rest and exercise. In several different studies, candoxatril has been shown to improve performance in people with heart failure. In one study, 12 different patients were selected, all with moderately severe heart failure. On day one of this study, the candoxatril had increased plasma ANP levels, suppressed aldosterone and decreased right atrial and pulmonary capillary wedge pressures. After treatment for 10 days, patients health had improved with an increase of basal ANP and a decrease of aldosterone, along with a reduced body weight that could be a reflection of chronic natriuretic, diuretic effects, or both. It was decided that on day 10 of the study, the effects of candoxatril were similar to that on day one.
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2529858
Curator's Comment: # Pfizer Central Research
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1944 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21515054 |
7.8 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
---|---|---|
Chronic endopeptidase inhibition in DOCA-salt hypertension: mechanism of cardiovascular protection. | 2003 Aug |
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[The new class of drugs-- metalloprotease inhibitors -- in the treatment of heart failure]. | 2004 |
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Natriuretic and antialdosterone actions of chronic oral NEP inhibition during progressive congestive heart failure. | 2005 May |
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Natriuretic and renoprotective effect of chronic oral neutral endopeptidase inhibition in acute renal failure. | 2010 Jan |
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Effect of Treatment of Sprague Dawley Rats with AVE7688, Enalapril, or Candoxatril on Diet-Induced Obesity. | 2011 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10937982
200 mg candoxatril capsules twice daily.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1443870
The acute effect of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) on pulmonary vascular tone in normoxia and acute hypoxia in the absence and presence of a specific inhibitor of neutral endopeptidase 24.11 (NEI, UK 73, 967, candoxatrilat; Pfizer) in the isolated and blood-perfused rat lung preparation was studied. Baseline pulmonary artery pressure (Ppa) was 16.4 +/- 0.3 mm Hg in lungs from normoxic control rats and 22.5 +/- 0.3 mm Hg in lungs from rats kept in hypoxia (FIO2 = 10%) for 7 days. Acute hypoxic pulmonary vasoconstriction (HPV delta Ppa) was similar in normoxic control rats (9.5 +/- 0.6 mm Hg) and chronically hypoxic rats (9.8 +/- 0.9 mm Hg). NEI at 0.07 and 0.2 mg had no effect on baseline Ppa or HPV delta Ppa. Synthetic BNP at 10 nM had no effect on baseline Ppa but produced a 2.8 +/- 0.2 mm Hg reduction in HPV delta Ppa alone and 2.7 +/- 0.2 mm Hg reduction in the presence of 0.07 mg NEI in normoxic control rats. In contrast, ANP at 10 nM produced a significantly greater decrease in HPV delta Ppa in the presence of 0.07 mg NEI (4.8 +/- 0.3 mm Hg, p < 0.05) compared with ANP alone (2.9 +/- 0.4 mm Hg), and similar results were also observed in chronically hypoxic rats.
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 15:51:20 GMT 2023
by
admin
on
Fri Dec 15 15:51:20 GMT 2023
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Record UNII |
ACP75508EE
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Record Status |
Validated (UNII)
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Record Version |
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100000081621
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C171870
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DB00616
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m3015
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123122-55-4
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C062766
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CANDOXATRIL
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CC-75
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6558
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CHEMBL35084
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3353
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ACP75508EE
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SUB06072MIG
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