N-{2-[(8S)-1H,2H,6H,7H,8H-indeno[5,4-b]furan-8-yl]ethyl}propanamide

• ChemBase ID: 855
• Molecular Formular: C16H21NO2
• Molecular Mass: 259.34344
• Monoisotopic Mass: 259.15722892
• SMILES: O1c2c(c3[C@@H](CCc3cc2)CCNC(=O)CC)CC1
• Canonical SMILES: CCC(=O)NCC[C@@H]1CCc2c1c1CCOc1cc2
• InChI: InChI=1S/C16H21NO2/c1-2-15(18)17-9-7-12-4-3-11-5-6-14-13(16(11)12)8-10-19-14/h5-6,12H,2-4,7-10H2,1H3,(H,17,18)/t12-/m0/s1
• InChIKey: YLXDSYKOBKBWJQ-LBPRGKRZSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: N-{2-[(8S)-1H,2H,6H,7H,8H-indeno[5,4-b]furan-8-yl]ethyl}propanamide
• IUPAC Traditional name: ramelteon; rozerem
• Brand Name: Rozerem
• Synonyms: N-[-[(8S)-1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl]propanamide; ramelteon; TAK-375; Ramelteon; Rozerem; Ramelteon(TAK-375)

Database IDs

• CAS Number: 196597-26-9
• PubChem SID: 160964318; 46505923
• PubChem CID: 208902

CALCULATED PROPERTIES

JChem

• Acid pKa: 15.82243
• H Acceptors: 2
• H Donor: 1
• LogD (pH = 5.5): 2.5705578
• LogD (pH = 7.4): 2.5705583
• Log P: 2.5705583
• Molar Refractivity: 75.5185 cm^3
• Polarizability: 29.00936 Å^3
• Polar Surface Area: 38.33 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.03
• LOG S: -4.2
• Solubility (Water): 1.64e-02 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; Dichloromethane; Ethanol; Methanol
• Apperance: White Solid
• Melting Point: 108-110°C
• Hydrophobicity(logP): 2.4

Safety Information

• Storage Condition: -20°C; -20°C Freezer

Pharmacology Properties

• Target: MT

Product Information

• Salt Data: Free Base

DETAILS

DrugBank - DB00980

• Drug Groups: approved; investigational
• Description: Ramelteon is the first in a new class of sleep agents that selectively binds to the melatonin receptors in the suprachiasmatic nucleus (SCN). It is used for insomnia, particularly delayed sleep onset. Ramelteon has not been shown to produce dependence and has shown no potential for abuse.
• Indication: For the treatment of insomnia characterized by difficulty with sleep onset.
• Pharmacology: Ramelteon is the first selective melatonin agonist. It works by mimicking melatonin (MT), a naturally occuring hormone that is produced during the sleep period and thought to be responsible for the regulation of circadian rhythm underlying the normal sleep-wake cycle. Ramelteon has a high affinity for the MT₁ and MT₂ receptors. The MT₁ and MT₂ receptors are located in the brain's suprachiasmatic nuclei (SCN),which is known as the body's "master clock" because it regulates the 24-hour sleep-wake cycle. Ramelteon has an active metabolite that is less potent but circulates in higher concentrations than the parent compound. The metabolite also has weak affinity for the 5HT2b receptor.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic
• Absorption: Rapid, total absorption is at least 84%.
• Half Life: ~1-2.6 hours
• Protein Binding: ~82% (in human serum)
• Elimination: Following oral administration of radiolabeled ramelteon, 84% of total radioactivity was excreted in urine and approximately 4% in feces, resulting in a mean recovery of 88%.; Less than 0.1% of the dose was excreted in urine and feces as the parent compound.
• Distribution: * 73.6 L
• References: Karim A, Tolbert D, Cao C: Disposition kinetics and tolerance of escalating single doses of ramelteon, a high-affinity MT1 and MT2 melatonin receptor agonist indicated for treatment of insomnia. J Clin Pharmacol. 2006 Feb;46(2):140-8. [Pubmed] ; Miyamoto M: Pharmacology of ramelteon, a selective MT1/MT2 receptor agonist: a novel therapeutic drug for sleep disorders. CNS Neurosci Ther. 2009 Winter;15(1):32-51. [Pubmed] ; Pandi-Perumal SR, Srinivasan V, Spence DW, Moscovitch A, Hardeland R, Brown GM, Cardinali DP: Ramelteon: a review of its therapeutic potential in sleep disorders. Adv Ther. 2009 Jun;26(6):613-26. Epub 2009 Jun 30. [Pubmed] ; Borja NL, Daniel KL: Ramelteon for the treatment of insomnia. Clin Ther. 2006 Oct;28(10):1540-55. [Pubmed] ; Roth T, Stubbs C, Walsh JK: Ramelteon (TAK-375), a selective MT1/MT2-receptor agonist, reduces latency to persistent sleep in a model of transient insomnia related to a novel sleep environment. Sleep. 2005 Mar 1;28(3):303-7. [Pubmed] ; Simpson D, Curran MP: Ramelteon: a review of its use in insomnia. Drugs. 2008;68(13):1901-19. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1259

Research Area: Cancer
Biological Activity:
Ramelteon is a melatonin receptor agonist with both high affinity for melatonin MT1 (IC50 =28.5 ± 8.55 pM)and MT2 (20.1 ± 9.25 pM)receptors and selectivity over the MT3 receptor. [1]The activity of ramelteon at the MT1 and MT2 receptors is believed to contribute to its sleep-promoting properties. Ramelteon has no appreciable affinity for the GABA receptor complex or for receptors that bind neuropeptides, cytokines, serotonin, dopamine, noradrenaline, acetylcholine, and opiates. [2]

Toronto Research Chemicals - R110051

Melatonin MT1/MT2 receptor agonist. Sedative, hypnotic.

REFERENCES

• Karim A, Tolbert D, Cao C: Disposition kinetics and tolerance of escalating single doses of ramelteon, a high-affinity MT1 and MT2 melatonin receptor agonist indicated for treatment of insomnia. J Clin Pharmacol. 2006 Feb;46(2):140-8. Pubmed
• Miyamoto M: Pharmacology of ramelteon, a selective MT1/MT2 receptor agonist: a novel therapeutic drug for sleep disorders. CNS Neurosci Ther. 2009 Winter;15(1):32-51. Pubmed
• Pandi-Perumal SR, Srinivasan V, Spence DW, Moscovitch A, Hardeland R, Brown GM, Cardinali DP: Ramelteon: a review of its therapeutic potential in sleep disorders. Adv Ther. 2009 Jun;26(6):613-26. Epub 2009 Jun 30. Pubmed
• Roth T, Stubbs C, Walsh JK: Ramelteon (TAK-375), a selective MT1/MT2-receptor agonist, reduces latency to persistent sleep in a model of transient insomnia related to a novel sleep environment. Sleep. 2005 Mar 1;28(3):303-7. Pubmed
• Borja NL, Daniel KL: Ramelteon for the treatment of insomnia. Clin Ther. 2006 Oct;28(10):1540-55. Pubmed
• Simpson D, Curran MP: Ramelteon: a review of its use in insomnia. Drugs. 2008;68(13):1901-19. Pubmed
• http://en.wikipedia.org/wiki/Ramelteon
• Yukuhiro, N., et al.: Brain Res., 59, 1027 (2004)
• Cajochen, C., et al.: Curr. Opin. Invest. Drugs, 6, 114 (2004)
• Kato, K., et al.: Neuropharmacology, 48, 301 (2004)