|
|
| | AnaMorelin hydrochloride Basic information |
| Product Name: | AnaMorelin hydrochloride | | Synonyms: | AnaMorelin hydrochloride;ONO-7643 hydrochloride;RC 1291 hydrochloride;AnaMorelin HCl;(3R)-1-(2-Methylalanyl-D-tryptophyl)-3-(phenylmethyl)-3-piperidinecarboxylic acid trimethylhydrazide monohydrochloride;RC 1291 HCl;Anamorelin (RC-1291) HCl;Anamorelin hydrochloride
(RC-1291 hydrochloride | | CAS: | 861998-00-7 | | MF: | C31H43ClN6O3 | | MW: | 583.16452 | | EINECS: | | | Product Categories: | | | Mol File: | 861998-00-7.mol |  |
| | AnaMorelin hydrochloride Chemical Properties |
| storage temp. | Store at -20°C | | solubility | DMSO:28.0(Max Conc. mg/mL);48.01(Max Conc. mM) | | form | Powder | | color | White to off-white | | InChIKey | VFYAEUWJFGTGGO-LQVXCNOLNA-N | | SMILES | C(N[C@H](CC1C2=C(NC=1)C=CC=C2)C(N1CCC[C@](CC2=CC=CC=C2)(C(=O)N(N(C)C)C)C1)=O)(=O)C(N)(C)C.[H]Cl |&1:2,18,r| |
| | AnaMorelin hydrochloride Usage And Synthesis |
| Description | Anamorelin Monohydrochloride, also known as ONO-7643, RC-1291, and ST-1291, is a drug developed by Novo Nordisk A/S and later licensed by Helsinn Healthcare SA and Ono Pharmaceutical Co. Anamorelin is used for the treatment of cancer anorexia and cachexia syndrome (CACS), a cancer-related side effect manifested by loss of appetite, weight loss, muscle wasting, and reduced quality of life. | | Uses | Anamorelin Hydrochloride can be used in biological study and therapeutic use for treatment of cancer-anorexia-cachexia in non-small-cell lung carcinoma patients. | | Mechanism of action | Anamorelin is an agonist for growth hormone secretin receptor-1a (GHSR-1a), which mimics the N-terminal active parent nucleus of growth hormone-releasing peptide (ghrelin).Ghrelin, a 28-amino-acid peptide secreted primarily by the stomach, is the endogenous ligand for GHSR-1a.By binding to its receptor, Anamorelin stimulates multiple pathways that positively regulate body weight, muscle mass, appetite and metabolism. | | Synthesis | The synthesis of Anamorelin begins with 2,2-dimethylhydrazine (19.1), which is first synthesised as intermediates 19.3 and 19.9 and then prepared by coupling, saponification and deprotection reactions.
The synthesis of 19.12 was achieved by reacting amino acids 19.10 and 19.11 under conventional coupling conditions followed by saponification with 5% NaOH in methyl tertiary butyl ether (MTBE) to give 19.12 in an overall yield of 86% for the two-step reaction. The acid 19.12 was then coupled with the amine 19.9 with the same coupling conditions to produce the amide 19.13. Screening of the conditions for removal of the N-Boc protecting group showed that rapid deprotection was achieved using methanesulfonic acid in either ethanol or methanol with minimal formation of by-products. After the reaction was quenched with a warm aqueous solution of potassium hydroxide, it was slowly cooled to give crystals of the free base, which could be isolated using a purity of more than 99.5%. Finally, the hydrochloride salt was formed by dissolving the free base in isopropyl alcohol acetate and adding a chemical equivalent of aqueous hydrochloric acid. The mixture was gently heated and then cooled to room temperature to give Anamorelin monohydrochloride in the crystalline state (19).
 | | in vivo | In rats, Anamorelin (ANAM) at an oral dose of 3, 10, or 30 mg/kg once daily significantly increases both food intake and body weight from Day 2 to Day 7 of treatment compared with the vehicle control. The cumulative change in food intake and weight gain increases dose-dependently, and these changes are significant at all dose levels (P<0.05) compared to the control. Administration of Anamorelin at a single oral dose of 3, 10, or 30 mg/kg induces a dose-dependent increase in plasma GH levels and GH AUC0-6h in rats[1]. |
| | AnaMorelin hydrochloride Preparation Products And Raw materials |
|