N-{(2S)-2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanoyl}glycine
Alvimopan
CAS: 156053-89-3
Molecular Formula: C25H32N2O4
N-{(2S)-2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanoyl}glycine - Names and Identifiers
| Name | Alvimopan |
| Synonyms | Ly246736 Alvimopan Alvimopan anhydrous AlviMopan (ADL 8-2698) 170098-38-1 (Dihydrate) N-{(2S)-2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanoyl}glycine 2-((S)-2-benzyl-3-((3R,4R)-4-(3-hydroxyphenyl)-3,4-diMethylpiperidin-1-yl)propanaMido)acetic acid N-[(2S)-2-[[(3R,4R)-4-(3-Hydroxyphenyl)-3,4-diMethyl-1-piperidinyl]Methyl]-1-oxo-3-phenylpropyl]glycine Glycine, N-((2S)-2-(((3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl)methyl)-1-oxo-3-phenylpropyl)- 2-([(2S)-2-([(3R,4R)-4-(3-Hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]methyl)-3-phenylpropanoyl]amino)acetic acid |
| CAS | 156053-89-3 |
| EINECS | 1312995-182-4 |
| InChI | InChI=1/C25H32N2O4/c1-18-16-27(12-11-25(18,2)21-9-6-10-22(28)14-21)17-20(24(31)26-15-23(29)30)13-19-7-4-3-5-8-19/h3-10,14,18,20,28H,11-13,15-17H2,1-2H3,(H,26,31)(H,29,30)/t18-,20-,25+/m0/s1 |
N-{(2S)-2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanoyl}glycine - Physico-chemical Properties
| Molecular Formula | C25H32N2O4 |
| Molar Mass | 424.53 |
| Density | 1.166±0.06 g/cm3(Predicted) |
| Melting Point | 200-204°C |
| Boling Point | 684.1±55.0 °C(Predicted) |
| Flash Point | 367.5 °C |
| Solubility | DMSO (Slightly), Methanol (Slightly, Sonicated, Heated) |
| Appearance | Solid |
| Color | White |
| pKa | 3.39±0.10(Predicted) |
| Storage Condition | 2-8°C |
| Use | A gastroprokinetic, peripheral μ-opioid receptor antagonist. |
N-{(2S)-2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanoyl}glycine - Introduction
Alvimopan is a gastroprokinetic, peripheral ?μ-opioid receptor antagonist.
Last Update：2022-10-16 17:14:10
N-{(2S)-2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanoyl}glycine - Reference Information
| Overview | Avemopan (alvimopan), the chemical name is 2-[[(2S)-2-[[(3R,4R)-4-(3-hydroxyphenyl)-3, 4-dimethylpiperidine-1-yl] methyl]-3-phenylpropionyl] amino] acetic acid dihydrate, it is a highly selective peripheral opioid receptor antagonist jointly developed by GlaxoSmithKline (GSK) in the United Kingdom and Adolor in the United States. It was approved by the US FDA in May 2008 to promote the large intestine or small intestine. Recovery of gastrointestinal function in patients after stage I anastomosis after partial resection. Since this product can selectively inhibit gastrointestinal opioid receptors and will not reduce the central analgesic effect of opioid receptor agonists, it does not affect the analgesic effect of opioid systemic drugs, and has good safety and tolerance. |
| preparation method | 1. using 3-[(3R,4R)-3, 4-dimethylpiperidine-4-yl] phenol and 2-benzyl ethyl acrylate as raw materials, 2-benzyl -3-[(3R,4R)-4-(3-hydroxyphenyl)-3, 4-dimethylpiperidine-1-yl] ethyl propionate, and then hydrolyzed, condensed, chiral column preparation and separation, hydrolyzed to Evelomopan. The products in each step of the method need column chromatography purification; in addition, about 50% of the optical isomers generated by the Michael addition reaction need to be separated and removed by manual preparation in the condensation step, which is cumbersome and not suitable for industrial production. 2. (S)-2-benzyl -3-[(3R,4R)-3, 4-dimethylpiperidine-4-yl] phenol is successively added with methyl acrylate, substituted with strong base diisopropylamide lithium (LDA), and salt is used to prepare (S)-2-benzyl -3-[(3R,4R)-4-(3-hydroxyphenyl)-3, 4-Dimethylpiperidine-1-yl] ethyl propionate hydrochloride, 3 hydrolyzed to obtain (S)-2-benzyl -3-[(3R,4R)-4-(3-hydroxyphenyl)-3, 4-dimethylpiperidine-1-yl] propionic acid monohydrate, and then condensed with glycine isobutyl ester p-toluenesulfonate to obtain 2-[[(2S)-2-[[(3R,4R)-4-(3-hydroxyphenyl)-3, 4-dimethylpiperidin-1-yl] methyl]-3-phenylpropionyl]-amino] isobutyl acetate, and then hydrolyzed to obtain Avimopan. |
| mechanism of action | there are three opioid receptors μ, κ, and δ that regulate gastrointestinal function in intestinal reflex. μ opioid receptors are the main receptors for gastrointestinal motility and intestinal transport time. They can achieve the cellular function of intestinal plexus through a variety of signal pathways including K ion channels, membrane hyperpolarization, inhibition of Ca2 ion channels and reduction of cyclic adenosine monophosphate (cAMP). Opioids bind to intestinal opioid receptors to slow intestinal peristalsis and increase muscle tone and non-peristaltic contraction of intestinal smooth muscle. Surgical trauma can also stimulate the secretion of endogenous opioid peptides, which bind to gastrointestinal μ opioid receptors to inhibit gastrointestinal activity. Exogenous and endogenous factors stimulate μ opioid receptor activation, leading to gastrointestinal dysfunction. This product is a peripheral μ opioid receptor antagonist, which can selectively bind to μ opioid receptors on the gastrointestinal wall and inhibit the stimulation of receptor activation on mesenteric transmission activity. At the same time, this product has no biological affinity with other non-opioid receptors such as adrenoceptor (α1, α2, β), dopamine receptor (D1, D2), benzodiazepine receptor, serotonin receptor, histamine receptor (H1), γ-aminobutyric acid and muscarinic receptor. |
| pharmacodynamics | pharmacokinetics the bioavailability of oral avemopan is extremely poor, only 6%, most of the drugs are in the gastrointestinal tract, to ensure that the drugs play a role locally. After oral administration of 12mg of avemopan, the human body absorbs a small amount, Cmax is 14ng · ml-1 , tmax is 1.5~3.0h ,t1/2 is 1.3h. After the drug is absorbed, it is quickly removed, and the drug cannot penetrate the blood-brain barrier. The drug is partially metabolized under the action of intestinal bacteria, the liver does not participate in drug metabolism, and the original drug and metabolites are excluded by feces. |
| pharmacological effects | using radioligand method in vitro, the affinity of this product to μ receptor is higher than that to δ receptor and κ receptor (Ki is 0.77, 4.4,40 nmol · L-1 respectively). Radiolabeled and cloned human μ opioid receptors have high affinity with KD value of 0.35nmol · L-1. This product can inhibit the binding of μ opioid receptor to [3 5S] -GTPγS, μ opioid receptor can reduce the amount of cAMP, and this product has antagonistic effect on it. Comparing [3H] naloxone or [3H] morphine with [3H] this product and human μ opioid receptor binding, [3H] this product dissociates slowly, indicating a higher affinity with the receptor. The antagonistic effect of this product on peripheral and central μ opioid receptors was evaluated in animal models. Studies have proved that this product has a long-term inhibitory effect on morphine-induced gastrointestinal dysfunction in mice. This product only inhibits the analgesic effect of morphine at high doses, and passes through the blood-brain barrier at very high blood concentrations. The results show that the interaction between this product and peripheral receptors is 200 times that of central receptors, indicating that it mainly has antagonistic effect on peripheral μ opioid receptors. The pharmacological effects of this product were evaluated by gavage of mouse charcoal powder. The results showed that it has peripheral antagonism but no central antagonism, and has therapeutic effect on morphine-induced constipation for more than 8 h. The use of morphine withdrawal induced jumping behavior for evaluation, this product does not change the analgesic effect of morphine. This product is administered orally, and the bioavailability is very low, only 6%. This product mainly exists in the form of amphoteric molecules, so this molecular feature prevents this product from being absorbed in the gastrointestinal tract or acting on the central nervous system through the blood-brain barrier. |
| drug interaction | in vitro studies show that this product and its metabolites have no inhibitory effect on CYP1A2,CYP2C9,CYP2C19,CYP3A4,CYP2D6 and CYP2E1, but have no inducing effect on CYP1A2,CYP2B6,CYP2C9,CYP2C19 and CYP3A4. In theory, there is no effect on the combination of CYP enzyme inhibition or induction drugs and this product, but there is no clinical research data to prove it. This product and its metabolites are the substrates of p-glycoprotein. At present, there is no clinical study on the combination of this product and strong inhibitors of p-glycoprotein (e. g. verapamil, cyclosporine, itraconazole, quinine, diltiazem, benzedil, etc.). Population pharmacokinetic analysis showed that the combined use of acid blockers or antibiotics did not affect the pharmacokinetic parameters of this product. The blood concentration of the metabolite of this product is low, and the metabolite has no pharmacodynamic effect, so it has no effect. Intravenous morphine in clinical practice, combined use of this product, has no effect on the pharmacokinetic parameters of morphine and its metabolite morphine -6-glucuronic acid. |
| clinical application | 1. for the treatment of postoperative intestinal obstruction; 2. Opioid-induced intestinal dysfunction. |
| adverse reactions | the most common adverse reactions are nausea, vomiting and hypotension. (2015-12-21) |
| use | a peripheral μ-opioid receptor antagonist. Gastroprokinetic. |
| toxic substance data | information provided by: pubchem.ncbi.nlm.nih.gov (external link) |
Last Update：2024-04-09 15:16:48
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Multiple Specifications
Product Name: Alvimopan Visit Supplier Webpage Request for quotationCAS: 156053-89-3
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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