(2S)-N-(1-cyanocyclopropyl)-4-fluoro-4-methyl-2-{[(1S)-2,2,2-trifluoro-1-[4-(4-methanesulfonylphenyl)phenyl]ethyl]amino}pentanamide

• ChemBase ID: 73144
• Molecular Formular: C25H27F4N3O3S
• Molecular Mass: 525.5587928
• Monoisotopic Mass: 525.17092562
• SMILES: c1c(ccc(c1)c1ccc(cc1)[C@H](N[C@H](C(=O)NC1(C#N)CC1)CC(C)(C)F)C(F)(F)F)S(=O)(=O)C
• Canonical SMILES: N#CC1(CC1)NC(=O)[C@H](CC(F)(C)C)N[C@H](C(F)(F)F)c1ccc(cc1)c1ccc(cc1)S(=O)(=O)C
• InChI: InChI=1S/C25H27F4N3O3S/c1-23(2,26)14-20(22(33)32-24(15-30)12-13-24)31-21(25(27,28)29)18-6-4-16(5-7-18)17-8-10-19(11-9-17)36(3,34)35/h4-11,20-21,31H,12-14H2,1-3H3,(H,32,33)/t20-,21-/m0/s1
• InChIKey: FWIVDMJALNEADT-SFTDATJTSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (2S)-N-(1-cyanocyclopropyl)-4-fluoro-4-methyl-2-{[(1S)-2,2,2-trifluoro-1-[4-(4-methanesulfonylphenyl)phenyl]ethyl]amino}pentanamide
• IUPAC Traditional name: (2S)-N-(1-cyanocyclopropyl)-4-fluoro-4-methyl-2-{[(1S)-2,2,2-trifluoro-1-[4-(4-methanesulfonylphenyl)phenyl]ethyl]amino}pentanamide
• Synonyms: MK0822; Odanacatib

Database IDs

• CAS Number: 603139-19-1
• PubChem SID: 162038064
• PubChem CID: 10152654

CALCULATED PROPERTIES

• Acid pKa: 6.213193
• H Acceptors: 5
• H Donor: 2
• LogD (pH = 5.5): 3.2546234
• LogD (pH = 7.4): 2.5531569
• Log P: 3.32841
• Molar Refractivity: 126.9524 cm^3
• Polarizability: 50.124634 Å^3
• Polar Surface Area: 99.06 Å^2
• Rotatable Bonds: 10
• Lipinski's Rule of Five: false

PROPERTIES

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: Cathepsin K

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S1115

Research Area

• Description: Neurological Disease

Biological Activity

• Description: Odanacatib (MK 0822) is a potent, selective, and neutral inhibitor of human and rabbit cathepsin K with IC50 of 0.2 nM and 1 nM , respectively.
• Targets: Human Cathepsin K; Rabbit Cathepsin K
• IC50: 0.2 nM; 1 nM ^[1]
• In Vitro: In vitro, Odanacatib shows the high inhibitory activity and selectivity on cathepsin K with IC50 values of 0.2 nM and 1 nM for human cathepsin K and rabbit cathepsin K, respectively. Furthermore, Odanacatib also shows similar potencies in whole human cell enzyme occupancy assays with corrected IC50 of 5 nM. ^[1] A recent study shows that Odanacatib results in reduction of Osteoclast (OC) resorption activity by interrupting intracellular vesicular trafficking. ^[2]
• In Vivo: In preclinical rats, Odanacatib (10 mg/kg) exhibits excellent pharmacokinetics with clearance (Cl: 2 mL kg^-1 min^-1), low volume of distribution (V_dss: 1.1 L kg^-1), half-life (T_1/2: 6 hours) and oral bioavailability (F: 8%), respectively. Besides, Odanacatib also exhibits excellent metabolic stability in rat hepatocytes with a 96% recovery of the parent identity. ^[1] Odanacatib (ODN) administrated by p.o. prevents bone loss in ovariectomized (OVX) rabbits in a dose-related manner. Moreover, Odanacatib (9?μM/day) leads to a significant increase in proximal femur bone mineral density (BMD) (7.8%), femoral neck BMD (10.8%) and the greater trochanter BMD (6.5%). ^[3] In the estrogen-deficient, skeletally mature rhesus monkeys, long-term treatment with Odanacatib effectively inhibits bone turnover without reducing osteoclast number and maintains normal biomechanical properties of the spine of OVX nonhuman primates. ^[4]
• Clinical Trials: Odanacatib (MK 0822) is currently in Phase I clinical trials in patients with Osteoporosis. Combination of Odanacatib (MK 0822), cholecalciferol andcalcium carbonate is currently in Phase II clinical trials in patients with Osteoporosis Postmenopausal.
• Features: Odanacatib (MK 0822) is a potent, selective, and neutral cathepsin K inhibitor.

Protocol

• Protocol: Animal Study ^[3]
• Animal Models: Ovariectomized (OVX) rabbit model
• Formulation: Odanacatib is provided in a diet formulae.
• Doses: ≤9?μM/day
• Administration: Administered via p.o.

References

• References: [1] Gauthier JY, et al. Bioorg Med Chem Lett. 2008, 18(3), 923-928.
• References: [2] Leung P, et al. Bone. 2011, 49(4), 623-635.
• References: [3] Pennypacker BL, et al. J Bone Miner Res. 2011, 26(2):252-262.
• References: [4] Masarachia PJ, et al. J Bone Miner Res. 2012, 27(3), 509-523.

REFERENCES

• Gauthier JY, et al. Bioorg Med Chem Lett. 2008, 18(3), 923-928.
• Leung P, et al. Bone. 2011, 49(4), 623-635.
• Pennypacker BL, et al. J Bone Miner Res. 2011, 26(2):252-262.
• Masarachia PJ, et al. J Bone Miner Res. 2012, 27(3), 509-523.