AVE0991
AVE0991 Basic information
- Product Name:
- AVE0991
- Synonyms:
-
- AVE0991
- N-[(Ethylamino)carbonyl]-3-[4-[(5-formyl-4-methoxy-2-phenyl-1H-imidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)-2-thiophenesulfonamide
- 2-Thiophenesulfonamide, N-[(ethylamino)carbonyl]-3-[4-[(5-formyl-4-methoxy-2-phenyl-1H-imidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)-
- N-(Ethylcarbamoyl)-3-(4-((5-formyl-4-methoxy-2-phenyl-1H-imidazol-1-yl)methyl)phenyl)-5-isobutylthiophene-2-sulfonamide
- AVE 0991, 10 mM in DMSO
- CAS:
- 304462-19-9
- MF:
- C29H32N4O5S2
- MW:
- 580.72
- Mol File:
- 304462-19-9.mol
AVE0991 Chemical Properties
- Melting point:
- 191-192℃
- Density
- 1.31±0.1 g/cm3(Predicted)
- storage temp.
- under inert gas (nitrogen or Argon) at 2–8 °C
- solubility
- ≥29.04 mg/mL in DMSO
- form
- solid
- pka
- 5.12±0.10(Predicted)
- color
- Off-white to yellow
AVE0991 Usage And Synthesis
Uses
AVE 0991 is a nonpeptide and orally active angiotensin-(1-7) receptor agonist with an IC50 of 21 nM[1].
Biological Activity
ave 0991 is an agonist of angiotensin-(1-7) receptor [1].as an ang-(1–7) mimic, ave0991 acts as a nonpeptide agonist of angiotensin-(1-7) receptor. in water-loaded mice (c57bl/6), ave0991(0.58 nmol/g)produces a significant decrease of water dieresis. the antidiuretic effect of ave was associated with an increase in urine osmolality. it also occurs in water-loaded swiss mice. the antidiuretic action of ave can be blocked by the ang ii antagonists completely, demonstrating the specificity of ave 0991. since ang ii promotes atherogenesis and ang-(1–7) opposites ang ii action, it is reported that ave 0991 can inhibit atherogenesis in apolipoprotein e (apoe)-knockout mice model [1, 2].
in vitro
AVE 0991 is a nonpeptide compound that evokes effects similar to Ang-(1-7) on the endothelium. AVE 0991 and unlabeled Ang-(1-7) compete for high-affinity binding of [ 125 I]-Ang-(1-7) to bovine aortic endothelial cell membranes with IC 50 s of 21±35 and 220±280 nM, respectively . Peak concentrations of NO and O 2 - release by AVE 0991 sodium salt and Ang-(1-7) (both 10 μM) are not significantly different (NO: 295 ±20 and 270±25 nM; O 2 - : 18±2 and 20±4 nM). However, the released amount of bioactive NO is ≈5 times higher for AVE 0991 in comparison to Ang-(1-7).
in vivo
AVE 0991 (0.58 nmol/g) produces a significant decrease of water diuresis in WT mice compared with vehicle-treated animals (0.06±0.03 mL versus 0.27±0.05; n=9 for each group; P<0.01). The antidiuretic effect of AVE 0991 (AVE) is associated with an increase in urine osmolality (1669±231.0 mOsm/KgH2O versus 681.1±165.8 mOsm/KgH2O in vehicle-treated mice; P<0.01). The genetic deletion of Mas abolishes the antidiuretic effect of AVE 0991 during water loading (0.37±0.10 mL [n=9] versus 0.27±0.03 mL [n=11] in AVE 0991-treated mice). As observed with C57BL/6 mice, administration of AVE 0991 (0.58 nmol/g) in water-loaded Swiss mice also produces a significant decrease of the urinary volume compared with vehicle-treated animals (0.13±0.05 mL [n=16] versus 0.51±0.04 mL [n=40]; P<0.01)[2]. One week of treatment with AVE-0991 produces a significant decrease in perfusion pressure (56.55±0.86 vs. 68.73±0.69 mmHg in vehicle-treated rats) and an increase in systolic tension (11.40±0.05 vs. 9.84±0.15 g in vehicle-treated rats), rate of tension rise (+dT/dt; 184.30±0.50 vs. 155.20±1.97 g/s in vehicle-treated rats), rate of tension fall (?dT/dt; 179.60±1.39 vs. 150.80±2.42 g/s in vehicle-treated rats). A slight increase in heart rate (HR) is also observed (220.40±0.71 vs. 214.20±0.74 beats/min in vehicle-treated rats[3].
target
angiotensin-(1-7) receptor
References
[1] sergio veloso brant pinheiro, ana cristina simoes e silva, walkyria oliveira sampaio, renata dutra de paula, elizabeth pereira mendes, elizabete dias bontempo, joao bosco pesquero, thomas walther, natalia alenina, michael bader, markus bleich, robson augusto souza santos. nonpeptide ave 0991 is an angiotensin-(1–7) receptor mas agonist in the mouse kidney. hypertension. 2004, 44: 490-496.
[2] j. toton-zuranska, m. gajda, g. pyka-fosciak, k. kus, m. pawlowska, a. niepsuj, p. wolkow, r. olszanecki, j. jawien, r. korbut. ave 0991- angiotensin-(1-7) receptor agonist, inhibits atherogenesis in apoe-knockout mice. journal of physiology and pharmacology. 2010, 61(2):181-183.
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