 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C16H22CLN3O2 |
| Molecular Weight | 323.82 |
| Exact Mass | 323.14 |
| CAS # | 112727-80-7 |
| PubChem CID | 119574 |
| Appearance | White to off-white solid powder |
| Density | 1.3g/cm3 |
| Boiling Point | 469.2ºC at 760mmHg |
| Flash Point | 237.6ºC |
| Vapour Pressure | 5.6E-09mmHg at 25°C |
| Index of Refraction | 1.614 |
| LogP | 3.054 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 22 |
| Complexity | 409 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | COC1=CC(N)=C(Cl)C=C1C(N[C@@H]2CCN3CCC[C@H]2C3)=O |
| InChi Key | GZSKEXSLDPEFPT-IINYFYTJSA-N |
| InChi Code | InChI=1S/C16H22ClN3O2/c1-22-15-8-13(18)12(17)7-11(15)16(21)19-14-4-6-20-5-2-3-10(14)9-20/h7-8,10,14H,2-6,9,18H2,1H3,(H,19,21)/t10-,14+/m0/s1 |
| Chemical Name | 4-amino-N-[(4R,5S)-1-azabicyclo[3.3.1]nonan-4-yl]-5-chloro-2-methoxybenzamide |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | 5-HT4 Receptor 115 nM (Ki) |
| ln Vitro | The selective 5-HT receptor antagonist [H3] GR 113808, which has a Ki value of 115 nM, is replaced by renzapride when it comes to binding to cloned human 5-HT4 receptors[3]. |
| ln Vivo | Both the delayed solid and liquid meal emptying are partially reversed by renzapride (BRL 24924) (100 µg iv)[2]. Renzapride (BRL 24924), at doses of 0.5–1 mg/kg, dramatically speeds up the rate at which a liquid meal labeled 51Cr exits the mouse stomach[4]. |
| Animal Protocol |
Animal/Disease Models: Dog (simulating gastroparesis)[2] Doses: 100 µg/kg Route of Administration: iv Experimental Results: Results in a partial reverse of both the delayed solid and liquid meals emptying. Animal/Disease Models: Mice (30-45g)[2] Doses: 0.5-1 mg/kg Route of Administration: po Experimental Results: Dramatically increase the rate of emptying of a 51Cr-labeled liquid meal from the murine stomach. |
| References |
[1]. Camilleri M, et al. Effect of renzapride on transit in constipation-predominant irritable bowel syndrome. Clin Gastroenterol Hepatol. 2004;2(10):895-904. [2]. Scarpellini E, et al. Renzapride: a new drug for the treatment of constipation in the irritable bowel syndrome. Expert Opin Investig Drugs. 2008;17(11):1663-1670. [3]. Nagakura Y, et al. Pharmacological properties of a novel gastrointestinal prokinetic benzamide selective for human 5-HT4 receptor versus human 5-HT3 receptor. Pharmacol Res. 1999;39(5):375-382. [4]. Mawe GM, et al. Blockade of 5-HT-mediated enteric slow EPSPs by BRL 24924: gastrokinetic effects. Am J Physiol. 1989;257(3 Pt 1):G386-G396. |
| Additional Infomation |
Renzapride is currently in Phase III clinical development in the United States for the treatment of constipation-predominant irritable bowel syndrome (IBS-C). It has been suggested that renzapride is effective in the treatment of irritable bowel syndrome with alternating stool pattern. It is being developed by Alizyme of the UK. Drug Indication For the treatment of constipation-predominant irritable bowel syndrome (IBS-C). Mechanism of Action Renzapride is a full serotonin 5-HT4 receptor agonist and partial serotonin 5-HT3 receptor antagonist. Pharmacodynamics Renzapride is a substituted benzamide which acts on the upper gastrointestinal tract. It has been shown to enhance stomach emptying in normal subjects; doses of 2 and 5 mg decreasing by 21 and 37% respectively the volume of gastric contents aspirated 80 min after a test meal. Renzapride was found to reduce the oro-caecal transit time as assessed by the lactulose/breath hydrogen method in a dose related manner from 0.2 to 5 mg; the later dose producing a 62% reduction. |
Solubility Data
| Solubility (In Vitro) | DMSO: 25 mg/mL (77.20 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.72 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (7.72 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (7.72 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0881 mL | 15.4407 mL | 30.8814 mL | |
| 5 mM | 0.6176 mL | 3.0881 mL | 6.1763 mL | |
| 10 mM | 0.3088 mL | 1.5441 mL | 3.0881 mL |