Deacetyl-N,O-didemethyldiltiazem

• CAT Number: I025670
• CAS Number: 86408-42-6
• Molecular Formula: C18H20N2O3S
• Molecular Weight: 344.43
• Purity: 98%
• Synonyms: Deacetyl-N,O-didemethyldiltiazem; Deacetyl-N,O-didesmethyldiltiazem; N,O-Didemethyldeacetyldiltiazem; o-Desmethyldeacetylnordiltiazem.
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Storage: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
• IUPAC Name: (2S,3S)-3-hydroxy-2-(4-hydroxyphenyl)-5-[2-(methylamino)ethyl]-2,3-dihydro-1,5-benzothiazepin-4-one
• InChI: InChI=1S/C18H20N2O3S/c1-19-10-11-20-14-4-2-3-5-15(14)24-17(16(22)18(20)23)12-6-8-13(21)9-7-12/h2-9,16-17,19,21-22H,10-11H2,1H3/t16-,17+/m1/s1
• InChIKey: ZTRZZXJIQHVVGS-SJORKVTESA-N
• SMILES: CNCCN1C2=CC=CC=C2S[C@H]([C@H](C1=O)O)C3=CC=C(C=C3)O

Deacetyl-N,O-didemethyldiltiazem(CAT: I025670) is a metabolite of diltiazem, a calcium channel blocker, widely utilized in cardiovascular pharmacology research. This compound plays a crucial role in studying the pharmacokinetics, metabolism, and biological activity of diltiazem, particularly its effects on calcium ion influx in cardiac and vascular smooth muscle cells. Researchers leverage Deacetyl-N,O-didemethyldiltiazem to explore its role in modulating heart rate, reducing vascular resistance, and investigating therapeutic approaches for hypertension, angina, and arrhythmias. Its relevance to drug metabolism and efficacy makes it a valuable tool for advancing preclinical studies in cardiovascular drug development and safety assessments.

Reference

1: Zarev Y, Foubert K, Ionkova I, Apers S, Pieters L. Isolation and Structure Elucidation of Glucosylated Colchicinoids from the Seeds of Gloriosa superba by LC-DAD-SPE-NMR. J Nat Prod. 2017 Apr 28;80(4):1187-1191. doi: 10.1021/acs.jnatprod.6b01024. Epub 2017 Feb 17. PubMed PMID: 28211687.
2: Kumbhar BV, Borogaon A, Panda D, Kunwar A. Exploring the Origin of Differential Binding Affinities of Human Tubulin Isotypes αβII, αβIII and αβIV for DAMA-Colchicine Using Homology Modelling, Molecular Docking and Molecular Dynamics Simulations. PLoS One. 2016 May 26;11(5):e0156048. doi: 10.1371/journal.pone.0156048. eCollection 2016. PubMed PMID: 27227832; PubMed Central PMCID: PMC4882049.
3: Ho CT, Chang YJ, Yang LX, Wei PL, Liu TZ, Liu JJ. A Novel Microtubule-Disrupting Agent Induces Endoplasmic Reticular Stress-Mediated Cell Death in Human Hepatocellular Carcinoma Cells. PLoS One. 2015 Sep 10;10(9):e0136340. doi: 10.1371/journal.pone.0136340. eCollection 2015. PubMed PMID: 26355599; PubMed Central PMCID: PMC4565632.
4: Ab O, Whiteman KR, Bartle LM, Sun X, Singh R, Tavares D, LaBelle A, Payne G, Lutz RJ, Pinkas J, Goldmacher VS, Chittenden T, Lambert JM. IMGN853, a Folate Receptor-α (FRα)-Targeting Antibody-Drug Conjugate, Exhibits Potent Targeted Antitumor Activity against FRα-Expressing Tumors. Mol Cancer Ther. 2015 Jul;14(7):1605-13. doi: 10.1158/1535-7163.MCT-14-1095. Epub 2015 Apr 22. PubMed PMID: 25904506.
5: Hong EE, Erickson H, Lutz RJ, Whiteman KR, Jones G, Kovtun Y, Blanc V, Lambert JM. Design of Coltuximab Ravtansine, a CD19-Targeting Antibody-Drug Conjugate (ADC) for the Treatment of B-Cell Malignancies: Structure-Activity Relationships and Preclinical Evaluation. Mol Pharm. 2015 Jun 1;12(6):1703-16. doi: 10.1021/acs.molpharmaceut.5b00175. Epub 2015 Apr 27. PubMed PMID: 25856201.
6: Rai A, Gupta TK, Kini S, Kunwar A, Surolia A, Panda D. CXI-benzo-84 reversibly binds to tubulin at colchicine site and induces apoptosis in cancer cells. Biochem Pharmacol. 2013 Aug 1;86(3):378-91. doi: 10.1016/j.bcp.2013.05.024. Epub 2013 Jun 6. PubMed PMID: 23747346.
7: Davis JA, Rock DA, Wienkers LC, Pearson JT. In vitro characterization of the drug-drug interaction potential of catabolites of antibody-maytansinoid conjugates. Drug Metab Dispos. 2012 Oct;40(10):1927-34. doi: 10.1124/dmd.112.046169. Epub 2012 Jun 29. PubMed PMID: 22752008.
8: Yeung PK, Alcos A, Marcoux T, Tang J. Comparing pharmacokinetics and metabolism of diltiazem in normotensive Sprague Dawley and Wistar Kyoto rats vs. spontaneously hypertensive rats in vivo. Drug Metabol Drug Interact. 2011;26(3):119-25. doi: 10.1515/DMDI.2011.012. Epub 2011 Sep 20. PubMed PMID: 21929464.
9: Al-Katib AM, Aboukameel A, Mohammad R, Bissery MC, Zuany-Amorim C. Superior antitumor activity of SAR3419 to rituximab in xenograft models for non-Hodgkin’s lymphoma. Clin Cancer Res. 2009 Jun 15;15(12):4038-45. doi: 10.1158/1078-0432.CCR-08-2808. Epub 2009 Jun 9. PubMed PMID: 19509168.
10: Nevarez DM, Mengistu YA, Nawarathne IN, Walker KD. An N-aroyltransferase of the BAHD superfamily has broad aroyl CoA specificity in vitro with analogues of N-dearoylpaclitaxel. J Am Chem Soc. 2009 Apr 29;131(16):5994-6002. doi: 10.1021/ja900545m. PubMed PMID: 19382815.
11: Tassone P, Goldmacher VS, Neri P, Gozzini A, Shammas MA, Whiteman KR, Hylander-Gans LL, Carrasco DR, Hideshima T, Shringarpure R, Shi J, Allam CK, Wijdenes J, Venuta S, Munshi NC, Anderson KC. Cytotoxic activity of the maytansinoid immunoconjugate B-B4-DM1 against CD138+ multiple myeloma cells. Blood. 2004 Dec 1;104(12):3688-96. Epub 2004 Aug 3. PubMed PMID: 15292058.
12: Tassone P, Gozzini A, Goldmacher V, Shammas MA, Whiteman KR, Carrasco DR, Li C, Allam CK, Venuta S, Anderson KC, Munshi NC. In vitro and in vivo activity of the maytansinoid immunoconjugate huN901-N2′-deacetyl-N2′-(3-mercapto-1-oxopropyl)-maytansine against CD56+ multiple myeloma cells. Cancer Res. 2004 Jul 1;64(13):4629-36. PubMed PMID: 15231675.
13: Stockis A, De Bruyn S, Gengler C, Rosillon D. Nitazoxanide pharmacokinetics and tolerability in man during 7 days dosing with 0.5 g and 1 g b.i.d. Int J Clin Pharmacol Ther. 2002 May;40(5):221-7. PubMed PMID: 12051574.
14: Stockis A, Allemon AM, De Bruyn S, Gengler C. Nitazoxanide pharmacokinetics and tolerability in man using single ascending oral doses. Int J Clin Pharmacol Ther. 2002 May;40(5):213-20. PubMed PMID: 12051573.
15: Yeung PK, Feng JD, Buckley SJ. Effect of administration route and length of exposure on pharmacokinetics and metabolism of diltiazem in dogs. Drug Metabol Drug Interact. 2001;18(3-4):251-62. PubMed PMID: 11791888.
16: Rodriguez RJ, Miranda CL. Isoform specificity of N-deacetyl ketoconazole by human and rabbit flavin-containing monooxygenases. Drug Metab Dispos. 2000 Sep;28(9):1083-6. PubMed PMID: 10950853.
17: Gelmi ML, Mottadelli S, Pocar D, Riva A, Bombardelli E, De Vincenzo R, Scambia G. N-deacetyl-N-aminoacylthiocolchicine derivatives: synthesis and biological evaluation on MDR-positive and MDR-negative human cancer cell lines. J Med Chem. 1999 Dec 16;42(25):5272-6. PubMed PMID: 10602712.
18: Rodriguez RJ, Proteau PJ, Marquez BL, Hetherington CL, Buckholz CJ, O’Connell KL. Flavin-containing monooxygenase-mediated metabolism of N-deacetyl ketoconazole by rat hepatic microsomes. Drug Metab Dispos. 1999 Aug;27(8):880-6. PubMed PMID: 10421614.
19: Yeung PK, Feng JD, Buckley SJ. Pharmacokinetics and hypotensive effect of diltiazem in rabbits: comparison of diltiazem with its major metabolites. J Pharm Pharmacol. 1998 Nov;50(11):1247-53. PubMed PMID: 9877310.
20: Yeung PK, Feng JD, Buckley SJ. Pharmacokinetics and hypotensive effect of deacetyl N-monodesmethyl diltiazem (M2) in rabbits after a single intravenous administration. Eur J Drug Metab Pharmacokinet. 1998 Jan-Mar;23(1):27-31. PubMed PMID: 9625269.