Alvimopan
Names
[ CAS No. ]:
156053-89-3
[ Name ]:
Alvimopan
[Synonym ]:
Alvimopan
N-{(2S)-2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanoyl}glycine
Glycine, N-[(2S)-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]-1-oxo-2-(phenylmethyl)propyl]-
N-{(2S)-2-Benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]propanoyl}glycine
Unii-Q153V49p3z
Biological Activity
[Description]:
Alvimopan(LY 246736; ADL 8-2698) is a peripherally acting mu-opioid receptor (PAM-OR, IC50= 1.7 nM) antagonist for accelerating gastrointestinal recovery after surgery. IC50 Value: 1.7 nM (Mu-type opioid receptor) [1]Target: mu-opioid receptorin vitro: The dissociation rate of alvimopan from the micro opioid receptor (t(1/2)=30--44 min) was comparable to that of the long acting partial agonist buprenorphine (t(1/2)=44 min), but was slower than those of the antagonists naloxone (t(1/2)=0.82 min) and N-methylnaltrexone (t(1/2)=0.46 min) [2].in vivo: Alvimopan did not significantly accelerate GI-3 compared with placebo [6 mg: hazard ratio (HR) = 1.20, p = 0.080; 12 mg: HR = 1.24, p = 0.038). However, after adjustment for significant covariates (sex/surgical duration), benefits were significant for both doses (6 mg: HR = 1.24, p = 0.037; 12 mg: HR = 1.26, p = 0.028). Alvimopan also significantly accelerated time to GI-2 (6 mg: HR = 1.37, p = 0.008; 12 mg: HR = 1.33, p = 0.018) and DCO (6 mg: HR = 1.31, p = 0.008; 12 mg: HR = 1.28, p = 0.015) [3]. Alvimopan (1 and 3 mg/kg) significantly reversed this delayed GI transit when administered 45 min prior to surgery. However, the effects of alvimopan were less pronounced when administered following surgery [4].Toxicity:The most common treatment-emergent adverse events across all treatment groups were nausea, vomiting, and hypotension; the incidence of nausea and vomiting was reduced by 53 percent in thealvimopan 12-mg group [5].Clinical trial: Intercostal Nerve Block With Liposome Bupivacaine in Subjects Undergoing Posterolateral Thoracotomy. Phase 3
[Related Catalog]:
[References]
[1]. NCBI BioAssay: 325959
[2]. Cassel JA, et al. [(3)H]Alvimopan binding to the micro opioid receptor: comparative binding kinetics of opioid antagonists. Eur J Pharmacol. 2005 Sep 27;520(1-3):29-36.
[3]. Viscusi ER, et al. Alvimopan, a peripherally acting mu-opioid receptor antagonist, compared with placebo in postoperative ileus after major abdominal surgery: results of a randomized, double-blind, controlled study. Surg Endosc. 2006 Jan;20(1):64-70.
[4]. Fukuda H, et al. The selective mu opioid receptor antagonist, alvimopan, improves delayed GI transit of postoperative ileus in rats. Brain Res. 2006 Aug 2;1102(1):63-70.
[5]. Delaney CP, et al. Phase III trial of alvimopan, a novel, peripherally acting, mu opioid antagonist, for postoperative ileus after major abdominal surgery. Dis Colon Rectum. 2005 Jun;48(6):1114-25; discussion 1125-6; author reply 1127-9.
[Related Small Molecules]
Chemical & Physical Properties
[ Density]:
1.2±0.1 g/cm3
[ Boiling Point ]:
684.1±55.0 °C at 760 mmHg
[ Melting Point ]:
210-213ºC
[ Molecular Formula ]:
C25H32N2O4
[ Molecular Weight ]:
424.533
[ Flash Point ]:
367.5±31.5 °C
[ Exact Mass ]:
424.236206
[ PSA ]:
89.87000
[ LogP ]:
3.38
[ Vapour Pressure ]:
0.0±2.2 mmHg at 25°C
[ Index of Refraction ]:
1.572
[ Storage condition ]:
2-8°C
Safety Information
[ Symbol ]:
GHS07, GHS09
[ Signal Word ]:
Warning
[ Hazard Statements ]:
H315-H319-H400
[ Precautionary Statements ]:
P273-P280-P305 + P351 + P338-P337 + P313-P391
[ RIDADR ]:
UN 3077 9 / PGIII
[ HS Code ]:
2933399090
Synthetic Route
Precursor & DownStream
Customs
[ HS Code ]: 2933399090
[ Summary ]:
2933399090. other compounds containing an unfused pyridine ring (whether or not hydrogenated) in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%