(1R)-N-(prop-2-yn-1-yl)-2,3-dihydro-1H-inden-1-amine

• ChemBase ID: 1192
• Molecular Formular: C12H13N
• Molecular Mass: 171.23832
• Monoisotopic Mass: 171.10479942
• SMILES: N([C@@H]1CCc2c1cccc2)CC#C
• Canonical SMILES: C#CCN[C@@H]1CCc2c1cccc2
• InChI: InChI=1S/C12H13N/c1-2-9-13-12-8-7-10-5-3-4-6-11(10)12/h1,3-6,12-13H,7-9H2/t12-/m1/s1
• InChIKey: RUOKEQAAGRXIBM-GFCCVEGCSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (1R)-N-(prop-2-yn-1-yl)-2,3-dihydro-1H-inden-1-amine
• IUPAC Traditional name: rasagiline
• Brand Name: Azilect
• Synonyms: RAS; Rasagiline; (R)-N-(2-Propynyl)-2,3-dihydroinden-1-amine

Database IDs

• CAS Number: 136236-51-6
• MDL Number: MFCD00866571
• PubChem SID: 160964654; 46506045
• PubChem CID: 3052776

CALCULATED PROPERTIES

JChem

• H Acceptors: 1
• H Donor: 1
• LogD (pH = 5.5): -0.6091183
• LogD (pH = 7.4): 0.9995979
• Log P: 2.303902
• Molar Refractivity: 54.467 cm^3
• Polarizability: 21.04538 Å^3
• Polar Surface Area: 12.03 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.26
• LOG S: -3.84
• Solubility (Water): 2.49e-02 g/l

PROPERTIES

Safety Information

• Storage Warning: IRRITANT
• TSCA Listed: false

Product Information

• Purity: 95+%; 97%

DETAILS

DrugBank - DB01367

• Drug Groups: approved
• Description: Rasagiline is an irreversible inhibitor of monoamine oxidase and is used as a monotherapy in early Parkinson's disease or as an adjunct therapy in more advanced cases.
• Indication: For the treatment of the signs and symptoms of idiopathic Parkinsons disease as initial monotherapy and as adjunct therapy to levodopa.
• Pharmacology: Rasagiline is a propargylamine and an irreversible inhibitor of monoamine oxidase (MAO). MAO, a flavin-containing enzyme, regulates the metabolic degradation of catecholamines and serotonin in the CNS and peripheral tissues. It is classified into two major molecular species, A and B, and is localized in mitochondrial membranes throughout the body in nerve terminals, brain, liver and intestinal mucosa. MAO-A is found predominantly in the GI tract and liver, and regulates the metabolic degradation of circulating catecholamines and dietary amines. MAO-B is the major form in the human brain and is responsible for the regulation of the metabolic degradation of dopamine and phenylethylamine. In ex vivo animal studies in brain, liver and intestinal tissues rasagiline was shown to be a potent,selective, and irreversible monoamine oxidase type B (MAO-B) inhibitor. At the recommended therapeutic doses, Rasagiline was also shown to be a potent and irreversible inhibitor of MAO-B in platelets. The selectivity of rasagiline for inhibiting only MAO-B (and not MAO-A) in humans and the sensitivity to tyramine during rasagiline treatment at any dose has not been sufficiently characterized to avoid restriction of dietary tyramine and amines contained in medications.
• Toxicity: Signs and symptoms of overdosage may include, alone or in combination, any of the following: drowsiness, dizziness, faintness, irritability, hyperactivity, agitation, severe headache, hallucinations, trismus, opisthotonos, convulsions, and coma; rapid and irregular pulse, hypertension, hypotension and vascular collapse; precordial pain, respiratory depression and failure, hyperpyrexia, diaphoresis, and cool, clammy skin.
• Affected Organisms: Humans and other mammals
• Biotransformation: Rasagiline undergoes almost complete biotransformation in the liver prior to excretion. In vitro experiments indicate that both routes of rasagiline metabolism are dependent on the cytochrome P450 (CYP) system, with CYP 1A2 being the major isoenzyme involved in rasagiline metabolism.
• Absorption: Rasagiline is rapidly absorbed following oral administration. The absolute bioavailability of rasagiline is about 36%.
• Half Life: Rasagiline has a mean steady-state half life of 3 hours but there is no correlation of pharmacokinetics with its pharmacological effect because of its irreversible inhibition of MAO-B.
• Protein Binding: Plasma protein binding ranges from 88-94% with mean extent of binding of 61-63% to human albumin over the concentration range of 1-100 ng/ml.
• Elimination: Rasagiline undergoes almost complete biotransformation in the liver prior to excretion. Glucuronide conjugation of rasagiline and its metabolites, with subsequent urinary excretion, is the major elimination pathway. After oral administration of 14C-labeled rasagiline, elimination occurred primarily via urine and secondarily via feces (62% of total dose in urine and 7% of total dose in feces over 7 days), with a total calculated recovery of 84% of the dose over a period of 38 days. Less than 1% of rasagiline was excreted as unchanged drug in urine.
• Distribution: * 87 L
• References: Weinreb O, Amit T, Bar-Am O, Youdim MB: RASAGILINE; A NOVEL ANTI-PARKINSONIAN MONOAMINE OXIDASE-B INHIBITOR WITH NEUROPROTECTIVE ACTIVITY. Prog Neurobiol. 2010 Jun 19. [Pubmed] ; Leegwater-Kim J, Bortan E: The role of rasagiline in the treatment of Parkinson's disease. Clin Interv Aging. 2010 May 25;5:149-56. [Pubmed] ; Chen JJ, Swope DM, Dashtipour K: Comprehensive review of rasagiline, a second-generation monoamine oxidase inhibitor, for the treatment of Parkinson's disease. Clin Ther. 2007 Sep;29(9):1825-49. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Chen JJ, Swope DM, Dashtipour K: Comprehensive review of rasagiline, a second-generation monoamine oxidase inhibitor, for the treatment of Parkinson's disease. Clin Ther. 2007 Sep;29(9):1825-49. Pubmed
• Weinreb O, Amit T, Bar-Am O, Youdim MB: RASAGILINE; A NOVEL ANTI-PARKINSONIAN MONOAMINE OXIDASE-B INHIBITOR WITH NEUROPROTECTIVE ACTIVITY. Prog Neurobiol. 2010 Jun 19. Pubmed
• Leegwater-Kim J, Bortan E: The role of rasagiline in the treatment of Parkinson's disease. Clin Interv Aging. 2010 May 25;5:149-56. Pubmed