Dihydroquinazolinone compound or pharmacologically acceptable salt, and cell growth inhibitor

Patent metadata

Field	Value
Publication number	US-11566017-B2
Application number	US-201816958066-A
Country	US
Kind code	B2
Filing date	Dec 26, 2018
Priority date	Dec 27, 2017
Publication date	Jan 31, 2023
Grant date	Jan 31, 2023

Abstract

Provided is a cell proliferation inhibitor comprising a compound of the formula (1) or a pharmacologically acceptable salt thereof:wherein J1 and J2 each represent CH or N, with the proviso that J1 and J2 are not simultaneously CH; r represents 0 to 4; each R101 is the same or different when r is 2 or more, and R101 represents a C1-6 alkyl group optionally substituted with a halogen atom or the like; s represents 0 to 5; each R102 is the same or different when s is 2 or more, and R102 represents a halogen atom or the like; R103 represents a hydrogen atom, a C1-6 alkyl group, a C3-6 cycloalkyl group, or a C3-6 cycloalkyl C1-6 alkyl group; and R101 and R103 are optionally linked together to form a five- to seven-membered ring hetero ring when R101 is present at the 8-position.

First claim

The invention claimed is:

1. A composition comprising a compound of the following formula (1) or a pharmacologically acceptable salt thereof:

wherein J 1 is CH or N, and J 2 is N;
r represents 0 to 4;
each R 101 is the same or different when r is 2 or more, and represents a halogen atom, a C 1-6 alkyl group optionally substituted with a halogen atom, OR 111 , or a group represented by the formula: —N(R 112a )—R 112b ,
where R 111 , R 112a and R 112b are each independently a hydrogen atom or a C 1-6 alkyl group;
s represents 0 to 5;
each R 102 is the same or different when s is 2 or more, and represents a halogen atom, a C 1-6 alkyl group, OR 113 , a group represented by the formula: —N(R 114a )—R 114b , a group represented by the formula: —NH—C(═O)—R 115 , a group represented by the formula: —C(═O)—R 116 , an optionally substituted aryl group, an optionally substituted heteroaryl group, a nitro group, or a cyano group,
where R 113 is a hydrogen atom, an optionally substituted alkyl group, an optionally substituted aryl group, an optionally substituted arylalkyl group, or an optionally substituted heteroaryl group,
R 114a and R 114b are each independently a hydrogen atom or a C 1-6 alkyl group,
R 115 is an optionally substituted alkyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, or a group represented by the formula: —NH—R 121 ,
R 116 is an optionally substituted alkyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, OR 122 , or a group represented by the formula: —N(R 123a )—R 123b ),
R 121 is an optionally substituted alkyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group,
R 122 is a hydrogen atom, an optionally substituted alkyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group, and
R 123a and R 123b are each independently a hydrogen atom, an optionally substituted alkyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group, or R 123a and R 123b are linked together to form a cyclic amine;
R 103 represents a hydrogen atom, a C 1-6 alkyl group, a C 3-6 cycloalkyl group, or a C 3-6 cycloalkyl C 1-6 alkyl group; and
R 101 and R 103 are optionally linked together to form a five- to seven-membered hetero ring when R 101 is present at the 8-position; and
a diluent or a pharmaceutically acceptable excipient.

2. The composition of claim 1 , wherein the compound of the formula (1) is a compound of the following formula (1a):

wherein J 1 is CH or N, and J 2 is N;
r represents 0 to 4;
each R 101 is the same or different when r is 2 or more, and represents a halogen atom, a C 1-6 alkyl group optionally substituted with a halogen atom, OR 111 , or a group represented by the formula: —N(R 112a )—R 112b ),
where R 111 , R 112a and R 112b are each independently a hydrogen atom or a C 1-6 alkyl group;
s represents 0 to 5;
each R 102 is the same or different when s is 2 or more, and represents a halogen atom, a C 1-6 alkyl group, OR 113 , a group represented by the formula: —N(R 114a )—R 114b , a group represented by the formula: —NH—C(═O)—R 115 , a group represented by the formula: —C(═O)—R 116 , an optionally substituted aryl group, an optionally substituted heteroaryl group, a nitro group, or a cyano group,
where R 113 is a hydrogen atom, an optionally substituted alkyl group, an optionally substituted aryl group, an optionally substituted arylalkyl group, or an optionally substituted heteroaryl group,
R 114a and R 114b are each independently a hydrogen atom or a C 1-6 alkyl group,
R 115 is an optionally substituted alkyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, or a group represented by the formula: —NH—R 121 , R 116 is an optionally substituted alkyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, OR 122 , or a group represented by the formula: —N(R 123a )—R 123b ,
R 121 is an optionally substituted alkyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group,
R 122 is a hydrogen atom, an optionally substituted alkyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group, and
R 123a and R 123b are each independently a hydrogen atom, an optionally substituted alkyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group, or R 123a and R 123b ) are linked together to form a cyclic amine;
R 103 represents a hydrogen atom, a C 1-6 alkyl group, a C 3-6 cycloalkyl group, or a C 3-6 cycloalkyl C 1-6 alkyl group; and
R 101 and R 103 are optionally linked together to form a five- to seven-membered hetero ring when R 101 is present at the 8-position,
with the exception of cases where J 1 represents CH, J 2 represents N, r is 0, R 103 is a hydrogen atom or a methyl group, R 102 is present at the p-position, and R 102 is a methoxy group.

3. The composition of claim 1 , wherein in the formula (1), r is 0; or r is 1, R 101 is present at the 7-position or the 8-position and R 101 represents a C 1-3 alkyl group optionally substituted with a halogen atom, or a hydroxy group; or r is 1, R 101 is present at the 8-position and R 101 and R 103 are linked together to form a five- or six-membered hetero ring.

4. The composition of claim 1 , wherein in the formula (1), R 103 represents a hydrogen atom, a C 1-3 alkyl group or a C 3-6 cycloalkyl C 1-3 alky group; or r is 1, R 101 is present at the 8-position and R 101 and R 103 are linked together to form a five- or six-membered hetero ring.

5. The composition of claim 1 , wherein in the formula (1), s is 0; or s is 1 and R 102 represents a halogen atom, OR 113 in which R 113 is an optionally substituted C 1-3 alkyl group, or an optionally substituted aryl group.

6. The composition of claim 1 , wherein in the formula (1), J 1 and J 2 each represent N.

7. A method for inhibiting cell proliferation, the method comprising contacting a cell with a compound of the following formula (1) or a pharmacologically acceptable salt thereof:

wherein J 1 is CH or N, and J 2 is N;
r represents 0 to 4;
each R 101 is the same or different when r is 2 or more, and represents a halogen atom, a C 1-6 alkyl group optionally substituted with a halogen atom, OR 111 , or a group represented by the formula: —N(R 112a )—R 112b ,
where R 111 , R 112a and R 112b are each independently a hydrogen atom or a C 1-6 alkyl group;
s represents 0 to 5;
each R 102 is the same or different when s is 2 or more, and represents a halogen atom, a C 1-6 alkyl group, OR 113 , a group represented by the formula: —N(R 114a )—R 114b , a group represented by the formula: —NH—C(═O)—R 115 , a group represented by the formula: —C(═O)—R 116 , an optionally substituted aryl group, an optionally substituted heteroaryl group, a nitro group, or a cyano group,
where R 113 is a hydrogen atom, an optionally substituted alkyl group, an optionally substituted aryl group, an optionally substituted arylalkyl g

Assignees

• Riken
• Japanese Found For Cancer Res
• Yakult Honsha Kk

Inventors

• Yoshida Minoru
• Seimiya Hiroyuki
• YASHIRODA Yoko
• Washizuka Kenichi
• Shirai Fumiyuki
• Yoshimoto Nobuko
• Kazami Junichi

Classifications

• C07D403/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D498/06

  Peri-condensed systems · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/22

  for herpes viruses · CPC title