CAS 603139-19-1|(2S)-N-(1-cyanocyclopropyl)-4-fluoro-4-methyl-2-{[(1S)-2,2,2-trifluoro-1-[4-(4-methanesulfonylphenyl)phenyl]ethyl]amino}pentanamide|MK0822|(2S)-N-(1-cyanocyclopropyl)-4-fluoro-4-meth...

General Information

Structure

Molecular Formula

C₂₅H₂₇F₄N₃O₃S

Molecular Mass

525.5587928

Exact Mass

525.17092562

Charge

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

Canonic 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

Isomeric 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

Calculated Properties

JChem

Acid pKa

6.213193

H Acceptors

H Donor

LogD (pH = 5.5)

3.2546234

LogD (pH = 7.4)

2.5531569

Log P

3.32841

Molar Refractivity

126.9524

Polarizability

50.124634

Polar Surface Area

99.06

Rotatable Bonds

Lipinski's Rule of Five

false

Data Source

Commercial Catalog

Academic Data

Data Source

Names and Identifiers

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

MK0822Odanacatib

IUPAC name

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

Names and Identifiers

Registration numbers

CAS Number

603139-19-1

PubChem CID

10152654

PubChem SID

162038064

Registration numbers

Properties

Safety Information

Storage Condition

-20°C

Product Information

Salt Data

Free Base

Pharmacology Properties

Target

Cathepsin K

Properties

Related Proteins

No Data Available

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Molecular Spectra

No Data Available

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Molecule 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

IC₅₀

0.2 nM

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.