Tetracyclic compound

Patent metadata

Field	Value
Publication number	US-9440922-B2
Application number	US-201514619242-A
Country	US
Kind code	B2
Filing date	Feb 11, 2015
Priority date	Jun 10, 2009
Publication date	Sep 13, 2016
Grant date	Sep 13, 2016

Abstract

A compound represented by the general Formula (I) below, or a salt or solvate thereof, which is useful as an ALK inhibitor, and is useful for prophylaxis or treatment of a disease accompanied by abnormality in ALK, for example, cancer, cancer metastasis, depression or cognitive function disorder:

(meanings of the symbols that are included in the formula are as given in the specification).

First claim

The invention claimed is:

1. A pharmaceutical for the treatment of cancer, cancer metastasis, or depression, comprising one or more pharmaceutically acceptable carriers and as an active ingredient a compound represented by Formula (I):

wherein,
A 5 is selected from NR 5 , O and S;
A 4 , A 7 , and A 9 represent CR 4 , CR 7 , and CR 9 respectively, or wherein A 4 is N and A 7 and A 9 represent CR 7 and CR 9 respectively;
R 1 and R 10 each independently represent [1] a hydrogen atom, [2] a cyano group, [3] a halogen atom or [4] a 4- to 10-membered heterocycloalkyl group which may be substituted by 4- to 10-membered heterocycloalkyl group(s);
R 2 is selected from the group consisting of:
(1) a hydrogen atom,
(2) a C 1-8 alkyl group,
(3) a C 2-8 alkenyl group,
(4) a C 2-8 alkynyl group,
(5) a cyano group,
(6) a halogen atom,
(7) a (C 1-8 alkyl) m2 -amino group which may be substituted by C 1-8 alkylsulfonyl group(s),
m2: 0˜2, and

(8) a nitro group;
R 3 is selected from the group consisting of:
(1) a hydrogen atom,
(2) a C 1-8 alkyl group which may be substituted by [1] halogen atom(s), [2] hydroxy group(s) or [3] C 1-8 alkoxy group(s),
(3) a C 6-10 aryl group,
(4) a cyano group,
(5) a C 1-8 alkanoyl group which may be substituted by C 6-10 aryl group(s),
I. (6) a (C1-8 alkyl) m3a -aminocarbonyl group which may be substituted by one or more R 3A ,
II. R 3A : [1] a C 6-10 aryl group, [2] a C 1-8 alkoxy group, [3] a 5- to 14-membered heteroaryl group, or [4] a C 6-10 arylsulfonyl group,
III. m3a: 0˜2,
(7) a hydroxycarbonyl group,
(8) a C 1-8 alkoxycarbonyl group which may be substituted by [1] hydroxy group(s) or [2] C 1-8 alkoxy group(s),
(9) a halogen atom,
(10) a (C 1-8 alkyl) m3b -amino group which may be substituted by C 6-10 aryl group(s),
m3b: 0˜2,
(11) a C 1-8 alkylcarbonyl (C 0-8 alkyl) amino group which may be substituted by [1] C 6-10 aryl group(s) or [2] C 6-10 aryloxy group(s),
(12) a C 6-10 arylcarbonyl (C 0-8 alkyl) amino group which may be substituted by C 1-8 alkyl group(s) which may be substituted by halogen atom(s),
(13) a (C 1-8 alkyl) m3c -aminocarbonyl (C 0-8 alkyl) amino group which may be substituted by C 6-10 aryl group(s),
m3c: 0˜2,
(14) a nitro group,
(15) a hydroxy group,
(16) a C 1-8 alkoxy group which may be substituted by one or more R 3B ,
R 3B : [1] a hydroxy group, [2] a C 1-8 alkoxy group, [3] a C 6-10 aryl (C 0-8 alkyl) aminocarbonyl group, [4] a (C 1-8 alkyl) m3d -amino group, or [5] a halogen atom,
m3d: 0˜2,
(17) a 4- to 10-membered heterocycloalkyloxy group,
(18) a 5- to 14-membered heteroaryloxy group,
(19) a (C 1-8 alkyl) m3e -aminocarbonyloxy group which may be substituted by C 6-10 aryl group(s)
m3e: 0˜2,
(20) a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group,
(21) a C 1-8 alkylsulfonyloxy group which may be substituted by halogen atom(s),
(22) a C 1-8 alkylthio group,
(23) a C 1-8 alkylsulfonyl group which may be substituted by C 6-10 aryl group(s),
(24) a 5- to 14-membered heteroaryl group which may be substituted by C 1-8 alkyl group(s) which may be substituted by C 1-8 alkoxy group(s),
(25) a C 1-8 alkoxycarbonyl (C 0-8 alkyl) amino group which may be substituted by C 1-8 alkoxy group(s),
(26) a C 6-10 aryloxycarbonyl (C 0-8 alkyl) amino group which may be substituted by C 1-8 alkyl group(s) which may be substituted by halogen atom(s),
(27) a C 6-10 aryl (C 0-8 alkyl) aminocarbonyl (C 0-8 alkyl) amino group which may be substituted by one or more R 3C ,
R 3C : [1] a C 1-8 alkyl group which may be substituted by halogen atom(s), or [2] a C 1-8 alkoxy group,
(28) a C 3-8 cycloalkyl (C 0-8 alkyl) aminocarbonyloxy group, and
(29) a C 6-10 aryl (C 0-8 alkyl) aminocarbonyloxy group which may be substituted by substituent(s) selected from the group consisting of [1] a C 1-8 alkyl group and [2] a C 1-8 alkoxy group;
R 4 is selected from the group consisting of:
(1) a hydrogen atom,
(2) a C 1-8 alkyl group which may be substituted by halogen atom(s),
(3) a C 2-8 alkenyl group,
(4) a C 2-8 alkynyl group,
(5) a C 3-8 cycloalkyl group,
(6) a cyano group,
(7) an aminocarbonyl group,
(8) a (C 1-8 alkyl) m4a -aminocarbonyl group,
m4a: 1˜2,
(9) a hydroxycarbonyl group,
(10) a C 1-8 alkoxycarbonyl group,
(11) a halogen atom,
(12) a (C 1-8 alkyl) m4b -amino group,
m4b: 0˜2,
(13) a hydroxy group, and
(14) a C 1-8 alkoxy group which may be substituted by hydroxy group(s);
R 5 is selected from the group consisting of:
(1) a hydrogen atom,
(2) a C 1-8 alkyl group which may be substituted by one or more R 5A ,
R 5A : [1] a hydroxycarbonyl group, [2] a C 1-8 alkoxycarbonyl group, [3] a hydroxy group, [4] a C 1-8 alkoxy group, [5] a (C 1-8 alkyl) m5 -amino group, [6] a C 6-10 aryl group, or [7] a C 1-8 alkylthio group,
m5: 0˜2,
(3) a C 2-8 alkenyl group,
(4) a C 2-8 alkynyl group,
(5) a C 3-8 cycloalkyl group, and
(6) a C 1-8 alkylsulfonyl group;
R 6 and R 6′ are each independently selected from the group consisting of:
(1) a C 1-8 alkyl group which may be substituted by halogen atom(s),
(2) a C 2-8 alkenyl group, and
(3) a C 2-8 alkynyl group; or
R 6 and R 6′ are taken together with the carbon atoms to which they are bound to form:
(4) a C 3-8 cycloalkyl group, or
(5) a 4- to 10-membered heterocycloalkyl group which may be substituted by C 1-8 alkyl C 6-10 aryl sulfonyl group(s) which may be substituted by C 1-8 alkyl group(s);
R 7 is selected from the group consisting of:
(1) a hydrogen atom,
(2) a halogen atom,
IV. (3) a C 1-8 alkoxy group which may be substituted by one or more R 7A ,
V. R 7A : [1] a (C 1-8 alkyl)m7a-amino group, [2] a hydroxy, [3] a 4- to 10-membered heterocycloalkyl group which may be substituted by C 1-8 alkyl group(s),
VI. m7a: 0˜2,
(4) a C 1-8 alkylsulfonyl group,
(5) a nitro group, and
(6) a hydroxyl group;
R 8 is selected from the group consisting of:
(1) a hydrogen atom,
(2) a C 1-8 alkyl group which may be substituted by one or more R 8A ,
R 8A : [1] a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 8A1 , [2] a (C 1-8 alkyl) m8a -amino group which may be substituted by a halogen atom, or [3] a hydroxy group,
m8a:0˜2,

R 8A1 : [1] a C 1-8 alkyl group, [2] a C 1-8 alkylsulfonyl group, [3] a (C 1-8 alkyl) m8b -aminosulfonyl group, [4] an oxo group, [5] a C 1-8 alkoxycarbonyl, or [6] a C 1-8 alkoxycarbonyl (C 0-8 alkyl) aminosulfonyl,
m8b: 0˜2,
(3) a C 2-8 alkenyl group,
(4) a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 8B ,
R 8B :

<1> a C 1-8 alkyl group which may be substituted by one or more R 8B1 ,
<2> a C 2-8 alkeynyl group,
<3> a C 2-8 alkynyl group,
<4> a C 3-8 cycloalkyl group which may be substituted by [1] cyano group(s) or [2] C 1-8 alkyl group(s),
<5> a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 8B2 ,
<6> a C 1-8 alkoxy group which may be substituted by substituent(s) selected from the group consisting of [1] a C 1-8 alkoxy group and [2] a C 3-8 cycloalkyl group,
<7> a C 1-8 alkoxycarbonyl group,
<8> a C 1-8 alkylsulfonyl group,
<9> a 5- to 14-membered heteroarylsulfonyl group,
<10> an oxo group,
<11> a cyano group,
<12> a C 1-8 alkanoyl group which may be substituted by one or more R 8B3 ,
<13> a C 3-8 cycloalkylcarbonyl group,
<14> a (C 1-8 alkyl) m8c -aminosulfonyl group,
<15> a C 1-8 alkylsulfonyl (C 0-8 alkyl) amino group,
<16> a (C 1-8 alkyl) m8d -amin

Assignees

• Chugai Pharmaceutical Co Ltd

Inventors

• Kinoshita Kazutomo
• Asoh Kohsuke
• Furuichi Noriyuki
• Ito Toshiya
• Kawada Hatsuo
• Ishii Nobuya
• Sakamoto Hiroshi
• Hong Woosang
• Park Minjeong
• Ono Yoshiyuki
• Kato Yasuharu
• Morikami Kenji
• Emura Takashi
• Oikawa Nobuhiro

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

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

• A61P25/24

  Antidepressants · CPC title