| Identification | Back Directory | [Name]
(2S,4R)-1-[(R)-5-CHLORO-1-(2,4-DIMETHOXY-BENZENESULFONYL)-3-(2-METHOXY-PHENYL)-2-OXO-2,3-DIHYDRO-1H-INDOL-3-YL]-4-HYDROXY-PYRROLIDINE-2-CARBOXYLIC ACID DIMETHYLAMIDE | [CAS]
439687-69-1 | [Synonyms]
Nelivaptan
SSR 149415
SSR 149415 - Nelivaptan
Nelivaptan(SSR-149,415)
(2S,4R)-1-[(3R)-5-chloro-1-(2,4-dimethoxyphenyl)sulfonyl-3-(2-methoxyphenyl)-2-oxoindol-3-yl]-4-hydroxy-N,N-dimethylpyrrolidine-2-carboxamide
(2S,4R)-1-[(3R)-5-Chloro-1-[(2,4-dimethoxyphenyl)sulfonyl]-2,3-dihydro-3-(2-methoxyphenyl)-2-oxo-1H-indol-3-yl]-4-hydroxy-N,N-dimethyl-2-pyrrolidinecarboxamide
2-PYRROLIDINECARBOXAMIDE, 1-[(3R)-5-CHLORO-1-[(2,4-DIMETHOXYPHENYL)SULFONYL]-2,3-DIHYDRO-3-(2-METHOXYPHENYL)-2-OXO-1H-INDOL-3-YL]-4-HYDROXY-N,N-DIMETHYL-, (2S,4R)-
(2S,4R)-1-[(R)-5-CHLORO-1-(2,4-DIMETHOXY-BENZENESULFONYL)-3-(2-METHOXY-PHENYL)-2-OXO-2,3-DIHYDRO-1H-INDOL-3-YL]-4-HYDROXY-PYRROLIDINE-2-CARBOXYLIC ACID DIMETHYLAMIDE | [Molecular Formula]
C30H32ClN3O8S | [MDL Number]
MFCD06199090 | [MOL File]
439687-69-1.mol | [Molecular Weight]
630.11 |
| Chemical Properties | Back Directory | [Boiling point ]
799.7±70.0 °C(Predicted) | [density ]
1.414±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
63.01mg/ml in DMSO; 63.01mg/ml in ethanol | [form ]
Solid | [pka]
14.14±0.40(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
SSR 149415 is a vasopressin V1b receptor antagonist. | [Biological Activity]
SSR149415 is an orally activeselective vasopressin V1b receptor antagonist (human/r at Ki in nM = 1.5/1.3/V1b91/1050/V1a1412/2897/V2174/270/OT) th at inhibits 30 nM AVP-induced Ca2+ response in human and r at V1b CHO transfectants (Ki = 1.26/2.0 nM). SSR149415 suppresses AVP-mediated physiological responses in vivoincluding corticotropin secretion (1-30 mg/kg p.o. or i.p. in rats) upon exogenous AVP administration (0.3 μg/kg alone or 0.03 μg/kg with 0.1 μg corticoliberin/kg via i.v.)restraint stress-Induced corticotropin secretion (EC50 = 10 mg/kg i.p. in rats)and in a murine model of anxiety (four-plate test; 1-10 mg/kg i.p. or 3-10 mg/kg p.o. acute or 10 mg/kg/day p.o.). | [in vivo]
Nelivaptan (1-30 mg/kg; 30 min i.p. or 2 h p.o. before an exogenous AVP injection) inhibits exogenous AVP-induced increase in plasma corticotropin in Sprague-Dawley rats[1].
Nelivaptan (1-10 mg/kg; p.o.; 1, 2, 3, 4, and 6 h before the AVP challenge) produces powerful dose-dependent inhibition of the corticotropin increase in response to exogenous AVP plus corticotropin-releasing factor (CRF) in Sprague-Dawley rats[1].
Nelivaptan (1-10 mg/kg; i.p. 30 min or 60 min before test; or p.o. for 7 days) displays anxiolytic-like activity after acute and 7-day repeated administrations in male NMRI mice [1].
Nelivaptan (30 mg/kg; i.p.; daily for two weeks) retains efficacy in reducing both measured indices of depression-like behavior (learned helplessness and anhedonia), even when neurogenesis is blocked in male Wistar rats with chronic mild stress[2].
| Animal Model: | Male Wistar rats (300-400 g, aged 3 months) with chronic mild stress[2] | | Dosage: | 30 mg/kg | | Administration: | Intraperitoneal injection (i.p.); daily for two weeks | | Result: | Chronic administration reversed learned helplessness and anhedonia even when methylazoxymethanol (MAM) was administered.
Attenuated these depressive-like behaviors after 1 week.
Restored the density of Ki-67-positive cells to control levels.
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| Animal Model: | Male Sprague-Dawley CD rats (275-300 g)[1] | | Dosage: | 1, 3, 10, 30 mg/kg | | Administration: | Intraperitoneal injection (i.p.) or Oral gavage (p.o.); 30 min i.p. or 2 h p.o. before an exogenous AVP injection | | Result: | Antagonized AVP-induced corticotropin secretion in a dose-dependent manner by both intraperitoneal and oral routes.
The inhibition was significant from 10 mg/kg p.o. and 3 mg/kg i.p. upwards.
The inhibitory action lasted significantly for more than 2 h at 10 mg/kg i.p. and up to 4 h at 10 mg/kg p.o..
Had no effect on basal corticotropin plasma levels up to 30 mg/kg p.o..
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| Animal Model: | Male Sprague-Dawley CD rats (275-300 g)[1] | | Dosage: | 1, 3, 10 mg/kg | | Administration: | Oral gavage (p.o.); 1, 2, 3, 4, and 6 h before the AVP challenge (10 mg/kg) | | Result: | Produced powerful dose-dependent inhibition of the corticotropin increase in response to exogenous AVP plus corticoliberin; the effect was significant from the dose of 3 mg/kg p.o.. Complete blockade was achieved at 10 mg/kg.
Showed a fast onset of action, the inhibitory effect was maximal at 1 h after administration.
The inhibitory effect on corticotropin secretion lasted significantly more than 4 h, demonstrating a long-lasting oral effect in a specific V1b-related model.
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| Animal Model: | Male NMRI mice (20 g)[1] | | Dosage: | 1, 3, 10 mg/kg | | Administration: | Intraperitoneal injection (i.p.) or Oral gavage (p.o.); i.p. (1, 3, 10 mg/kg) 30 min or 60 min befeore; p.o. (10 mg/kg) for 7 days, | | Result: | In the acute experiments, i.p. and p.o. compound increased the number of punished crossings showing marked anxiolytic effects.
Post hoc analysis revealed that these effects reached statistical significance from 3 mg/kg p.o. and i.p.
The anxiolytic-like activity was still significantly maintained when given repeatedly at 10 mg/kg p.o. for 7 days.
The oral time course of the anxiolytic-like action performed at 10 mg/kg indicated that effects lasted for more than 4 h.
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| [storage]
Store at -20°C |
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| Company Name: |
BOC Sciences
|
| Tel: |
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| Website: |
https://www.bocsci.com |
| Company Name: |
Merck KGaA
|
| Tel: |
21-20338288 |
| Website: |
www.sigmaaldrich.cn |
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