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|Odanacatib |(2S)-N-(1-cyanocyclopropyl)-4-f...

基本信息

化学结构

分子式

C₂₅H₂₇F₄N₃O₃S

分子量

525.5587928

精确质量

525.17092562

电荷

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

计算属性

JChem

Acid pKa

6.213193

质子受体

质子供体

LogD (pH = 5.5)

3.2546234

LogD (pH = 7.4)

2.5531569

Log P

3.32841

摩尔折射率

126.9524

极化性

50.124634

极化表面积

99.06

可自由旋转的化学键

里宾斯基五规则

false

数据来源

产品目录

学术数据

数据来源

名称和标识

IUPAC传统名

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

别名

MK0822Odanacatib

IUPAC标准名

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

名称和标识

数据登录号

CAS号

603139-19-1

PubChem CID

10152654

PubChem SID

162038064

数据登录号

化合物性质

药理学性质

作用靶点

Cathepsin K

产品相关信息

成盐信息

Free Base

安全信息

保存条件

-20°C

化合物性质

分子相关蛋白质

暂无数据

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分子图谱

暂无数据

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描述信息

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.