Tolvaptan

Tolvaptan
(IUPAC) ime
	N-(4[(5R*)-7-chloro-5-hydroxy-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl]carbonyl3-methylphenyl)-2-methylbenzamide
Klinički podaci
Identifikatori
CAS broj	150683-30-0
ATC kod	C03XA01
PubChem	216237
ChemSpider	187438
ChEMBL	CHEMBL344159
Hemijski podaci
Formula	C26H25ClN2O3
Mol. masa	448.941 g/mol
SMILES	eMolekuli & PubHem
InChI
	InChI=1S/C26H25ClN2O3/c1-16-6-3-4-7-20(16)25(31)28-19-10-11-21(17(2)14-19)26(32)29-13-5-8-24(30)22-15-18(27)9-12-23(22)29/h3-4,6-7,9-12,14-15,24,30H,5,8,13H2,1-2H3,(H,28,31) ; Key: GYHCTFXIZSNGJT-UHFFFAOYSA-N
Sinonimi	N4-[(6R*)-9-chloro-6-hydroxy-2-azabicyclo[5.4.0]undeca-8,10,12-triene-2-carbonyl]-3-methyl-phenyl2-methyl-benzamide
Farmakokinetički podaci
Bioraspoloživost	nepoznata (40% je apsorbovano)
Vezivanje za proteine plazme	99%
Metabolizam	Hepatički (CYP3A4-posredovano)
Poluvreme eliminacije	12 časova
Farmakoinformacioni podaci
Licenca	US FDA:link
Trudnoća	C(US)
Pravni status	℞-only (SAD)
Način primene	Oralno

Tolvaptan (INN), OPC-41061, je selektivni kompetitivni antagonist arginin vazopresinskog receptora 2 koji se koristi u lečenju hiponatremije (niskih nivoa krvnog natrijuma) vezanih za kongestivno zatajenje srca, cirozu, i sindrom neodgovarajućeg izlučivanja antidiuretskog hormona (SIADH). FDA je odobrila tolvaptan 16 maja 2009, i u prodaji je od strane kompanije Otsuka Farmaceutikal pod imenom Samsca.

Tolvaptan je relativno brzo prošao kroz klinička ispitivanja^[7] za policistično oboljenje bubrega. Tokom ispitivanja iz 2004 je primećeno da kad se tolvaptan dozira sa tradicionalnim diureticima, dolazi do povećanja izlučivanja suvišnih fluida i poboljšanja nivoa krvnog natrijuma kod pacijenata sa zatajenjem srca, bez nuspojava poput hipotenzije (niskog krvnog pritiska) ili hipokalemije (sniženih nivoa krvnog kalijuma), i bez uzrokovanja nuspojava u bubrežnim funkcijama.^[8]

Hemija

Hemijska sinteza:^[9]

Stereokemija

Tolvaptan je racemat, tj. Smjesa 1: 1 sljedećih dva enantiomera:^[10]

Enantiomeri Tolvaptan
CAS-Number: 331947-66-1	CAS-Number: 331947-44-5

Reference

↑ WHO International Working Group for Drug Statistics Methodology (27. 8. 2008.). „ATC/DDD Classification (FINAL): New ATC 5th level codes”. WHO Collaborating Centre for Drug Statistics Methodology. Arhivirano iz originala na datum 2008-05-06. Pristupljeno 5. 9. 2008.
↑ Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit
↑ Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.
↑ Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit
↑ Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit
↑ Shoaf S, Elizari M, Wang Z et al. (2005). „Tolvaptan administration does not affect steady state amiodarone concentrations in patients with cardiac arrhythmias”. J Cardiovasc Pharmacol Ther 10 (3): 165–71. DOI:10.1177/107424840501000304. PMID 16211205.
↑ „Otsuka Maryland Research Institute, Inc.”.
↑ Gheorghiade M, Gattis W, O'Connor C et al. (2004). „Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial”. Journal of the American Medical Association 291 (16): 1963–71. DOI:10.1001/jama.291.16.1963. PMID 15113814.
↑ Kondo, K.; Ogawa, H.; Yamashita, H.; Miyamoto, H.; Tanaka, M.; Nakaya, K.; Kitano, K.; Yamamura, Y.; Nakamura, S.; Onogawa, T.; et al.; Bioor. Med. Chem. 1999, 7, 1743.
↑ Rote Liste Service GmbH (Hrsg.): Rote Liste 2017 - Arzneimittelverzeichnis für Deutschland (einschließlich EU-Zulassungen und bestimmter Medizinprodukte). Rote Liste Service GmbH, Frankfurt/Main, 2017, Aufl. 57, ISBN 978-3-946057-10-9, S. 222.

Spoljašnje veze

	Portal Medicina
	Portal Hemija

Šablon:Diuretici Šablon:Neuropeptidni ligandi

[1] WHO International Working Group for Drug Statistics Methodology (27. 8. 2008.). „ATC/DDD Classification (FINAL): New ATC 5th level codes”. WHO Collaborating Centre for Drug Statistics Methodology. Arhivirano iz originala na datum 2008-05-06. Pristupljeno 5. 9. 2008.

[2] Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit

[3] Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.

[4] Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit

[5] Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit

[pk-6] Shoaf S, Elizari M, Wang Z et al. (2005). „Tolvaptan administration does not affect steady state amiodarone concentrations in patients with cardiac arrhythmias”. J Cardiovasc Pharmacol Ther 10 (3): 165–71. DOI:10.1177/107424840501000304. PMID 16211205.

[7] „Otsuka Maryland Research Institute, Inc.”.

[ACTIV-8] Gheorghiade M, Gattis W, O'Connor C et al. (2004). „Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial”. Journal of the American Medical Association 291 (16): 1963–71. DOI:10.1001/jama.291.16.1963. PMID 15113814.

[9] Kondo, K.; Ogawa, H.; Yamashita, H.; Miyamoto, H.; Tanaka, M.; Nakaya, K.; Kitano, K.; Yamamura, Y.; Nakamura, S.; Onogawa, T.; et al.; Bioor. Med. Chem. 1999, 7, 1743.

[Rote_Liste-10] Rote Liste Service GmbH (Hrsg.): Rote Liste 2017 - Arzneimittelverzeichnis für Deutschland (einschließlich EU-Zulassungen und bestimmter Medizinprodukte). Rote Liste Service GmbH, Frankfurt/Main, 2017, Aufl. 57, ISBN 978-3-946057-10-9, S. 222.

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