Carbazeran
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MedKoo CAT#: 524551

CAS#: 70724-25-3

Description: Carbazeran is an Aldehyde oxidase (AO) substrate and potent phosphodiesterase PDE-II and PDE-III inhibitor that produces concentration-dependent positive inotropic responses. Carbazeran shows chronotropic and inotropic effect in vivo (EC50 = 100 μM, ionotropic effects, independent of adrenergic mechanisms). It potently inhibits cAMP hydrolysis. In humans, the compound is almost completely cleared via 4-hydroxylation to the phthalazinone metabolite by AO.


Chemical Structure

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Carbazeran
CAS# 70724-25-3

Theoretical Analysis

MedKoo Cat#: 524551
Name: Carbazeran
CAS#: 70724-25-3
Chemical Formula: C18H24N4O4
Exact Mass: 360.18
Molecular Weight: 360.410
Elemental Analysis: C, 59.99; H, 6.71; N, 15.55; O, 17.76

Price and Availability

Size Price Availability Quantity
5mg USD 265 2 Weeks
25mg USD 800 2 Weeks
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Synonym: Carbazeran; UK 31557; UK-31557; UK31557; UK 31,557; UK-31,557; UK31,557.

IUPAC/Chemical Name: 1-(6,7-dimethoxyphthalazin-1-yl)piperidin-4-yl ethylcarbamate

InChi Key: QJGVXJYGDBSPSJ-UHFFFAOYSA-N

InChi Code: InChI=1S/C18H24N4O4/c1-4-19-18(23)26-13-5-7-22(8-6-13)17-14-10-16(25-3)15(24-2)9-12(14)11-20-21-17/h9-11,13H,4-8H2,1-3H3,(H,19,23)

SMILES Code: c1(c(OC)cc2c(c1)c(nnc2)N1CCC(CC1)OC(NCC)=O)OC

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target:
In vitro activity:
In vivo activity:

Preparing Stock Solutions

The following data is based on the product molecular weight 360.41 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol:
In vivo protocol:

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1: Uehara S, Yoneda N, Higuchi Y, Yamazaki H, Suemizu H. Human Aldehyde Oxidase 1-Mediated Carbazeran Oxidation in Chimeric TK-NOG Mice Transplanted with Human Hepatocytes. Drug Metab Dispos. 2020 Jul;48(7):580-586. doi: 10.1124/dmd.120.091090. Epub 2020 May 1. PMID: 32357972.


2: Xie J, Saburulla NF, Chen S, Wong SY, Yap ZP, Zhang LH, Lau AJ. Evaluation of Carbazeran 4-Oxidation and O6-Benzylguanine 8-Oxidation as Catalytic Markers of Human Aldehyde Oxidase: Impact of Cytosolic Contamination of Liver Microsomes. Drug Metab Dispos. 2019 Jan;47(1):26-37. doi: 10.1124/dmd.118.082099. Epub 2018 Oct 18. PMID: 30337443.


3: Kaye B, Rance DJ, Waring L. Oxidative metabolism of carbazeran in vitro by liver cytosol of baboon and man. Xenobiotica. 1985 Mar;15(3):237-42. doi: 10.3109/00498258509045354. PMID: 4024658.


4: Critchley DJ, Rance DJ, Beedham C. Biotransformation of carbazeran in guinea pig: effect of hydralazine pretreatment. Xenobiotica. 1994 Jan;24(1):37-47. doi: 10.3109/00498259409043219. PMID: 8165820.


5: Shahid M, Rodger IW. Chronotropic and inotropic actions of amrinone, carbazeran and isobutylmethyl xanthine: role of phosphodiesterase inhibition. Br J Pharmacol. 1989 Sep;98(1):291-301. doi: 10.1111/j.1476-5381.1989.tb16894.x. PMID: 2478244; PMCID: PMC1854668.


6: Kaye B, Offerman JL, Reid JL, Elliott HL, Hillis WS. A species difference in the presystemic metabolism of carbazeran in dog and man. Xenobiotica. 1984 Dec;14(12):935-45. doi: 10.3109/00498258409151492. PMID: 6531941.


7: Manevski N, Balavenkatraman KK, Bertschi B, Swart P, Walles M, Camenisch G, Schiller H, Kretz O, Ling B, Wettstein R, Schaefer DJ, Pognan F, Wolf A, Litherland K. Aldehyde oxidase activity in fresh human skin. Drug Metab Dispos. 2014 Dec;42(12):2049-57. doi: 10.1124/dmd.114.060368. Epub 2014 Sep 23. PMID: 25249692.


8: Uno Y, Uehara S, Murayama N, Yamazaki H. Genetic variants of aldehyde oxidase (AOX) 1 in cynomolgus and rhesus macaques. Xenobiotica. 2021 Apr;51(4):494-499. doi: 10.1080/00498254.2021.1874564. Epub 2021 Jan 17. PMID: 33434089.


9: Taylor CR, Baird JR, Blackburn KJ, Cambridge D, Constantine JW, Ghaly MS, Hayden ML, McIlhenny HM, Moore PF, Olukotun AY, Pullman LG, Salsburg DS, Saxton CA, Shevde S. Comparative pharmacology and clinical efficacy of newer agents in treatment of heart failure. Am Heart J. 1981 Sep;102(3 Pt 2):515-32. doi: 10.1016/0002-8703(81)90740-7. PMID: 7023221.


10: Kato S, Shah A, Plesescu M, Miyata Y, Bolleddula J, Chowdhury S, Zhu X. Prediction of Human Disproportionate and Biliary Excreted Metabolites Using Chimeric Mice with Humanized Liver. Drug Metab Dispos. 2020 Oct;48(10):934-943. doi: 10.1124/dmd.120.000128. Epub 2020 Jul 14. PMID: 32665417.


11: Hoey M, Houslay MD. Identification and selective inhibition of four distinct soluble forms of cyclic nucleotide phosphodiesterase activity from kidney. Biochem Pharmacol. 1990 Jul 15;40(2):193-202. doi: 10.1016/0006-2952(90)90678-e. PMID: 2165400.


12: el Allaf D, D'Orio V, Carlier J. The new inotropic phosphodiesterase inhibitors. Arch Int Physiol Biochim. 1984 Nov;92(4):S69-79. doi: 10.3109/13813458409071165. PMID: 6085243.


13: Fu C, Di L, Han X, Soderstrom C, Snyder M, Troutman MD, Obach RS, Zhang H. Aldehyde oxidase 1 (AOX1) in human liver cytosols: quantitative characterization of AOX1 expression level and activity relationship. Drug Metab Dispos. 2013 Oct;41(10):1797-804. doi: 10.1124/dmd.113.053082. Epub 2013 Jul 15. PMID: 23857892.


14: Subash S, Singh DK, Ahire DS, Khojasteh SC, Murray BP, Zientek MA, Jones RS, Kulkarni P, Smith BJ, Heyward S, Cronin CN, Prasad B. Dissecting parameters contributing to the underprediction of aldehyde oxidase-mediated metabolic clearance of drugs. Drug Metab Dispos. 2023 Jul 10:DMD-AR-2023-001379. doi: 10.1124/dmd.123.001379. Epub ahead of print. PMID: 37429730.


15: Smith GW, Hall JC, West PA. Lack of inotropic selectivity of phosphodiesterase enzyme inhibitors in-vitro. J Pharm Pharmacol. 1987 Sep;39(9):748-51. doi: 10.1111/j.2042-7158.1987.tb06985.x. PMID: 2890746.


16: Hutzler JM, Yang YS, Albaugh D, Fullenwider CL, Schmenk J, Fisher MB. Characterization of aldehyde oxidase enzyme activity in cryopreserved human hepatocytes. Drug Metab Dispos. 2012 Feb;40(2):267-75. doi: 10.1124/dmd.111.042861. Epub 2011 Oct 26. PMID: 22031625.


17: Price B, Pyne NJ, Houslay MD. Proteolysis of cyclic AMP phosphodiesterase-II attenuates its ability to be inhibited by compounds which exert positive inotropic actions in cardiac tissue. Biochem Pharmacol. 1987 Dec 1;36(23):4047-54. doi: 10.1016/0006-2952(87)90560-0. PMID: 2825712.


18: Beedham C, Bruce SE, Critchley DJ, al-Tayib Y, Rance DJ. Species variation in hepatic aldehyde oxidase activity. Eur J Drug Metab Pharmacokinet. 1987 Oct- Dec;12(4):307-10. doi: 10.1007/BF03189919. PMID: 3130251.


19: Sharma R, Strelevitz TJ, Gao H, Clark AJ, Schildknegt K, Obach RS, Ripp SL, Spracklin DK, Tremaine LM, Vaz AD. Deuterium isotope effects on drug pharmacokinetics. I. System-dependent effects of specific deuteration with aldehyde oxidase cleared drugs. Drug Metab Dispos. 2012 Mar;40(3):625-34. doi: 10.1124/dmd.111.042770. Epub 2011 Dec 21. PMID: 22190693.


20: Tan WK, Tan ARY, Sivanandam P, Goh EJH, Yap ZP, Saburulla NF, Austin-Muttitt K, Mullins JGL, Lau AJ. In Vitro Inhibition of Human Aldehyde Oxidase Activity by Clinically Relevant Concentrations of Gefitinib and Erlotinib: Comparison with Select Metabolites, Molecular Docking Analysis, and Impact on Hepatic Metabolism of Zaleplon and Methotrexate. J Pharmacol Exp Ther. 2020 Aug;374(2):295-307. doi: 10.1124/jpet.120.265249. Epub 2020 May 11. PMID: 32393528.