Pyridone derivatives having tetrahydropyranylmethyl groups

Patent metadata

Field	Value
Publication number	US-10442797-B2
Application number	US-201515036981-A
Country	US
Kind code	B2
Filing date	Jul 6, 2015
Priority date	Jul 7, 2014
Publication date	Oct 15, 2019
Grant date	Oct 15, 2019

Abstract

The present disclosure provides novel compounds or salts thereof, or crystals of the compounds or the salts, which inhibit Axl and are useful in the treatment of a disease caused by hyperfunction of Axl, the treatment of a disease associated with hyperfunction of Axl, and/or the treatment of a disease involving hyperfunction of Axl.
The present disclosure provides pyridone derivatives having a tetrahydropyranylmethyl group represented by the following formula (I) having various substituents, or salts thereof, or crystals of the compounds or the salts, wherein R 1 , R 2 , R 3 , R 4 , R 5 , W, X, Y, and Z are each as defined in the specification:

First claim

The invention claimed is:

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof,
wherein
W, X, and Y are each independently C—H, C—F, or C—Cl,
Z is C—H, C—F, C—Cl, C—C 1 -C 6 alkyl group, or C—C 1 -C 6 alkoxy group,
R 1 is formula (II-1):

Q is C—H, or C—F,
T is C—H,
U is a nitrogen atom,
R 6 is a halogen atom, a C 1 -C 6 alkyl group, a C 3 -C 6 cycloalkyl group, a cyano group, or a trifluoromethoxy group,
R 2 is a hydrogen atom, a halogen atom, a C 1 -C 6 alkyl group, a C 1 -C 6 alkoxy group, or a cyano group,
R 3 is a hydrogen atom or a C 1 -C 6 alkyl group,
R 4 is a hydrogen atom, a halogen atom, or a C 1 -C 6 alkyl group,
R 5 is a group of formula (III-1):

R 8 and R 12 are each independently a hydrogen atom or a deuterium atom,
R 9 is a hydrogen atom, a halogen atom, or a C 1 -C 6 alkoxy group,
R 10 is 1,4-dioxan-2-ylmethoxy, and
R 11 is a hydrogen atom, a C 1 -C 6 alkoxy group, or a deuterium-substituted C 1 -C 6 alkoxy group.

2. The compound or salt of claim 1 , wherein the compound is N-[4-(2-Amino-5-{4-[(2R)-1,4-dioxan-2-ylmethoxy]-3-methoxyphenyl}pyridin-3-yl)-3-fluorophenyl]-5-methyl-4′-oxo-1′-(tetrahydro-2H-pyran-4-ylmethyl)-1′,4′-dihydro-2,3′-bipyridine-5′-carboxamide of the following formula:

or a pharmaceutically acceptable salt thereof.

3. The compound or salt of claim 1 , wherein the compound is N-[4-(2-Amino-5-{4-[(2S)-1,4-dioxan-2-ylmethoxy]-3-methoxyphenyl}pyridin-3-yl)-3-fluorophenyl]-5-methyl-4′-oxo-1′-(tetrahydro-2H-pyran-4-ylmethyl)-1′,4′-dihydro-2,3′-bipyridine-5′-carboxamide of the following formula:

or a pharmaceutically acceptable salt thereof.

4. A methanesulfonate, phosphate, naphthalene-1,5-disulfonate, or sulfate of the compound of claim 2 .

5. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

Assignees

• Daiichi Sankyo Co Ltd

Inventors

• Haginoya Noriyasu
• Suzuki Takashi
• Hayakawa Miho
• Ota Masahiro
• Tsukada Tomoharu
• Kobayashi Katsuhiro
• Ando Yosuke
• Jimbo Takeshi
• Nakamura Koichi

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P5/14

  of the thyroid hormones, e.g. T3, T4 · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title