Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C28H27Cl2N3O7S |
Molecular Weight | 620.501 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=C(OC)C=C(C=C1)S(=O)(=O)N2[C@@H](C(=O)N3CCC[C@H]3C(N)=O)[C@](O)(C4=CC(Cl)=CC=C24)C5=C(Cl)C=CC=C5
InChI
InChIKey=CEBYCSRFKCEUSW-NAYZPBBASA-N
InChI=1S/C28H27Cl2N3O7S/c1-39-23-12-10-17(15-24(23)40-2)41(37,38)33-21-11-9-16(29)14-19(21)28(36,18-6-3-4-7-20(18)30)25(33)27(35)32-13-5-8-22(32)26(31)34/h3-4,6-7,9-12,14-15,22,25,36H,5,8,13H2,1-2H3,(H2,31,34)/t22-,25-,28+/m0/s1
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/12436936Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/15823830 | https://www.ncbi.nlm.nih.gov/pubmed/14678081 | https://www.ncbi.nlm.nih.gov/pubmed/11035135
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12436936
Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/15823830 | https://www.ncbi.nlm.nih.gov/pubmed/14678081 | https://www.ncbi.nlm.nih.gov/pubmed/11035135
Relcovaptan is a potent, orally active nonpeptide vasopressin V1a antagonist that was undergoing clinical development with Sanofi-Synthélabo (formerly Sanofi) in France. SR49059 is specifically and selectively antagonizes the effect of vasopressin on the V1a receptor in animals’ and in humans. The drug has been shown to have an excellent safety profile in single and repeated dose toxicological studies in animals. In the human uterus in vitro, SR49059 caused a dose-dependent inhibition of vasopressin V1a receptor-mediated activity of myometrial strips and isolated uterine arteries. In vivo in nonpregnant women, an inhibition of vasopressin-induced uterine activity has been observed.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL1889 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21885275 |
13.0 nM [IC50] | ||
Target ID: CHEMBL1790 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12036368 |
178.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
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Binding of [3H] SR 49059, a potent nonpeptide vasopressin V1a antagonist, to rat and human liver membranes. | 1994 Feb 28 |
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Molecular cloning, sequencing, and functional expression of a cDNA encoding the human V1a vasopressin receptor. | 1994 Feb 4 |
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The human V3 pituitary vasopressin receptor: ligand binding profile and density-dependent signaling pathways. | 1997 Oct |
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Mapping peptide-binding domains of the human V1a vasopressin receptor with a photoactivatable linear peptide antagonist. | 1997 Oct 17 |
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Pharmacological characterization of the human vasopressin receptor subtypes stably expressed in Chinese hamster ovary cells. | 1998 Dec |
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Oxytocin and vasopressin constrict rat isolated uterine resistance arteries by activating vasopressin V1A receptors. | 1999 Jul 2 |
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Receptor binding of oxytocin and vasopressin antagonists and inhibitory effects on isolated myometrium from preterm and term pregnant women. | 1999 Oct |
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Vasopressin does not effect hypertension caused by long-term nitric oxide inhibition. | 2000 Feb |
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Conserved aromatic residues in the transmembrane region VI of the V1a vasopressin receptor differentiate agonist vs. antagonist ligand binding. | 2000 Jul |
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Nitric oxide, but not vasopressin V2 receptor-mediated vasodilation, modulates vasopressin-induced renal vasoconstriction in rats. | 2000 Mar |
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Binding properties of a selective tritiated vasopressin V2 receptor antagonist, [H]-SR 121463. | 2000 Oct |
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High concentrations of oxytocin cause vasoconstriction by activating vasopressin V1A receptors in the isolated perfused rat kidney. | 2001 Apr |
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Effects of YM471, a nonpeptide AVP V(1A) and V(2) receptor antagonist, on human AVP receptor subtypes expressed in CHO cells and oxytocin receptors in human uterine smooth muscle cells. | 2001 Jul |
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Vascular and renal effects of vasopressin and its antagonists in conscious rats with chronic myocardial infarction; evidence for receptor shift. | 2001 Jul 6 |
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A nonpeptide vasopressin V(1a) receptor antagonist, SR 49059, does not prevent cisplatin-induced emesis in piglets. | 2001 Jun |
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Placental transfer of SR49059 in the human dually perfused cotyledon in vitro. | 2001 Nov |
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Effects of nonpeptide V(1) vasopressin receptor antagonist SR-49059 on infarction volume and recovery of function in a focal embolic stroke model. | 2002 Dec |
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Interplay between presynaptic and postsynaptic activities is required for dendritic plasticity and synaptogenesis in the supraoptic nucleus. | 2002 Jan 1 |
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Vasopressin-induced facilitation of adrenergic responses in the rat mesenteric artery is V1-receptor dependent. | 2003 Feb |
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Oxytocin and fetal membranes in preterm labor: current concepts and clinical implication. | 2003 Jun |
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Identification of the binding sites of the SR49059 nonpeptide antagonist into the V1a vasopressin receptor using sulfydryl-reactive ligands and cysteine mutants as chemical sensors. | 2003 Oct 10 |
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Pancreatic vasopressin V1b receptors: characterization in In-R1-G9 cells and localization in human pancreas. | 2003 Sep |
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Participation of vasopressin in the development of cerebral vasospasm in a rat model of subarachnoid haemorrhage. | 2004 Apr |
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Functional rescue of the constitutively internalized V2 vasopressin receptor mutant R137H by the pharmacological chaperone action of SR49059. | 2004 Aug |
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Inhibitory effects of SR 49059 on oxytocin-and vasopressin-induced uterine contractions in non-pregnant women. | 2004 Jan |
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Vasotocin and vasopressin stimulation of the chloride secretion in the human bronchial epithelial cell line, 16HBE14o-. | 2005 Apr |
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The effect of relcovaptan (SR 49059), an orally active vasopressin V1a receptor antagonist, on uterine contractions in preterm labor. | 2005 Feb |
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Pharmacologic properties of YM218, a novel, potent, nonpeptide vasopressin V1A receptor-selective antagonist. | 2005 Jan |
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Selectivity of d[Cha4]AVP and SSR149415 at human vasopressin and oxytocin receptors: evidence that SSR149415 is a mixed vasopressin V1b/oxytocin receptor antagonist. | 2005 Nov |
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Protective effect of the V1a receptor antagonist SR49059 on brain edema formation following middle cerebral artery occlusion in the rat. | 2006 |
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Vasopressin receptor antagonists: pharmacological tools and potential therapeutic agents. | 2006 Apr |
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Evidence for a role of vasopressin in the control of aldosterone secretion in primary aldosteronism: in vitro and in vivo studies. | 2006 Apr |
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Vasopressin antagonists. | 2006 Aug |
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Pharmacologic chaperones as a potential treatment for X-linked nephrogenic diabetes insipidus. | 2006 Jan |
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Effects of YM218, a nonpeptide vasopressin V(1A) receptor-selective antagonist, on vasopressin-induced growth responses in human mesangial cells. | 2006 May 24 |
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Pharmacological chaperone activity of SR49059 to functionally recover misfolded mutations of the vasopressin V1a receptor. | 2006 May 26 |
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Functional rescue of vasopressin V2 receptor mutants in MDCK cells by pharmacochaperones: relevance to therapy of nephrogenic diabetes insipidus. | 2007 Jan |
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The modulation of aquaporin-4 by using PKC-activator (phorbol myristate acetate) and V1a receptor antagonist (SR49059) following middle cerebral artery occlusion/reperfusion in the rat. | 2008 |
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Modulation of AQP4 expression by the selective V1a receptor antagonist, SR49059, decreases trauma-induced brain edema. | 2008 |
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Effects of novel vasopressin receptor antagonists on renal function and cardiac hypertrophy in rats with experimental congestive heart failure. | 2008 Aug |
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Non-peptide arginine-vasopressin antagonists: the vaptans. | 2008 May 10 |
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[Vasopressin receptor antagonists and heart failure]. | 2009 Nov |
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cAMP/PKA-dependent increases in Ca Sparks, oscillations and SR Ca stores in retinal arteriolar myocytes after exposure to vasopressin. | 2010 Mar |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14678081
25, 75 or 200 mg
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16926443
MDCK II cells were seeded on 12 multiwell filters (Costar) at a density of 150,000 cells/cm2 and grown for 3 days. Cells were subsequently treated with the antagonists for 16 h, followed by three washes with ice-cold phosphate-buffered saline containing 1 mM MgCl2 and 0.1 mM CaCl2 (PBS-CM). The cells were then incubated for 1 h on ice with [3H]AVP (PerkinElmer Life Sciences, Boston, MA) and the antagonist (Relcovaptan) diluted in PBS-CM. Cells were washed three times with ice-cold PBS-CM, followed by excision of the filters and counting of the radioactivity
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NCI_THESAURUS |
C2180
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RELCOVAPTAN
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7809
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60943
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C1497
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300000034447
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150375-75-0
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C1GL8G6G0O
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CHEMBL419667
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DTXSID1045746
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DB13929
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ACTIVE MOIETY