Inhibitory effect of low molecular weight compound on cancer and fibrosis

Patent metadata

Field	Value
Publication number	US-2018028536-A1
Application number	US-201515128608-A
Country	US
Kind code	A1
Filing date	Mar 25, 2015
Priority date	Mar 28, 2014
Publication date	Feb 1, 2018
Grant date	—

Abstract

A novel therapeutic drug for malignant tumors, cancer stem cells, or fibrosis is obtained. A therapeutic drug for malignant tumors or cancer stem cells is used that includes at least one compound selected from the group consisting of compounds represented by formulas (1), (2), and (5), a salt thereof, or a solvate thereof. Alternatively, a therapeutic drug for fibrosis can be used that includes at least one compound selected from the group consisting of compounds represented by formulas (1), (2), and (5), a salt thereof, or a solvate thereof.

First claim

1 . A method of treating a malignant tumor, comprising the step of administering to a subject at least one compound selected from the group consisting of compounds represented by formulas (1), (2), and (5), a salt thereof, or a solvate thereof:

wherein
R 1 , R 2 , R 4 , R 5 , and R 6 are the same or different and each represent H, halogen, nitro, cyano, OH, optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted C 1-6 alkoxy, aryl, or heteroaryl;
R 3 and R 7 are the same or different and each represent H, optionally substituted C 1-6 alkyl, or optionally substituted C 2-6 alkenyl;
ring A is optionally substituted aryl or optionally substituted heteroaryl;
R 8 and R 9 are the same or different and each represent optionally substituted C 1-6 alkyl or optionally substituted C 2-6 alkenyl;
m and q are the same or different and each represent an integer of any of 1 to 4;
n is an integer of any of 1 to 3; and
p and r are the same or different and each represent an integer of any of 1 to 5.

2 . The method of treating a malignant tumor according to claim 1 , wherein the R 1 , R 2 , R 4 , R 5 , and R 6 are the same or different and each represent H, halogen, nitro, cyano, OH, C 1-6 alkyl, C 1-6 halogenoalkyl, C 1-6 hydroxyalkyl, C 1-6 alkylamino, 01-6 alkoxy, 01-6 halogenoalkoxy, C 1-6 hydroxyalkoxy, or C 1-6 alkoxyamino, or C 1-6 alkoxy-substituted C 1-6 alkoxy, C 1-6 alkoxyphenyl-substituted C 1-6 alkoxy, (trialkylsiloxy) C 1-6 alkyl, or (alkyl diphenyl siloxy) C 1-6 alkyl;
the R 3 and R 7 are H; the ring A is naphthyl, phenyl substituted by five halogens, or furyl substituted by one methyl; and the R 8 and R 9 are the same or different and each represent C 1-6 alkyl.

3 . The method of treating a malignant tumor according to claim 1 , wherein in the formula (1),
the R 1 , R 2 , and R 3 are each H, the R 4 is at position 4 and represents H, F, Cl, nitro, OH, CH 2 OH, methoxy, methoxymethoxy, or tert-butyl dimethyl siloxymethyl; the formula (2) is represented by the following formula (4); and the formula (5) is represented by the following formula (6):

4 . A method of treating a cancer stem cell, comprising the step of administering to a subject at least one compound selected from the group consisting of compounds represented by formulas (1), (2), and (5), a salt thereof, or a solvate thereof:

wherein
R 1 , R 2 , R 4 , R 5 , and R 6 are the same or different and each represent H, halogen, nitro, cyano, OH, optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted C 1-6 alkoxy, aryl, or heteroaryl;
R 3 and R 7 are the same or different and each represent H, optionally substituted C 1-6 alkyl, or optionally substituted C 2-6 alkenyl;
ring A is optionally substituted aryl or optionally substituted heteroaryl;
R 8 and R 9 are the same or different and each represent optionally substituted C 1-6 alkyl or optionally substituted C 2-6 alkenyl;
m and q are the same or different and each represent an integer of any of 1 to 4;
n is an integer of any of 1 to 3; and
p and r are the same or different and each represent an integer of any of 1 to 5.

5 . The method of treating a cancer stem cell according to claim 4 , wherein the R 1 , R 2 , R 4 , R 5 , and R 6 are the same or different and each represent H, halogen, nitro, cyano, OH, C 1-6 alkyl, C 1-6 halogenoalkyl, C 1-6 hydroxyalkyl, C 1-6 alkylamino, C 1-6 alkoxy, C 1-6 halogenoalkoxy, C 1-6 hydroxyalkoxy, or C 1-6 alkoxyamino, or C 1-6 alkoxy-substituted C 1-6 alkoxy, C 1-6 alkoxyphenyl-substituted C 1-6 alkoxy, (trialkylsiloxy) C 1-6 alkyl, or (alkyl diphenyl siloxy) C 1-6 alkyl;
the R 3 and R 7 are H; the ring A is naphthyl, phenyl substituted by five halogens, or furyl substituted by one methyl; and the R 8 and R 9 are the same or different and each represent C 1-6 alkyl.

6 . The method of treating a cancer stem cell according to claim 4 , wherein in the formula (1),
the R 1 , R 2 , and R 3 are each H, the R 4 is at position 4 and represents H, F, Cl, nitro, OH, CH 2 OH, methoxy, methoxymethoxy, or tert-butyl dimethyl siloxymethyl; the formula (2) is represented by the following formula (4); and the formula (5) is represented by the following formula (6):

7 . A method of treating fibrosis, comprising the step of administering to a subject at least one compound selected from the group consisting of compounds represented by formulas (1, 2, and 5), a salt thereof, or a solvate thereof:

wherein
R 1 , R 2 , R 4 , R 5 , and R 6 are the same or different and each represent H, halogen, nitro, cyano, OH, optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted C 1-6 alkoxy, aryl, or heteroaryl;
R 3 and R 7 are the same or different and each represent H, optionally substituted C 1-6 alkyl, or optionally substituted C 2-6 alkenyl;

ring A is optionally substituted aryl or optionally substituted heteroaryl;
R 8 and R 9 are the same or different and each represent optionally substituted C 1-6 alkyl or optionally substituted C 2-6 alkenyl;
m and q are the same or different and each represent an integer of any of 1 to 4;
n is an integer of any of 1 to 3; and
p and r are the same or different and each represent an integer of any of 1 to 5.

8 . The method of treating fibrosis according to claim 7 , wherein the R 1 , R 2 , R 4 , R 5 , and R 6 are the same or different and each represent H, halogen, nitro, cyano, OH, C 1-6 alkyl, C 1-6 halogenoalkyl, C 1-6 hydroxyalkyl, C 1-6 alkylamino, C 1-6 alkoxy, C 1-6 halogenoalkoxy, C 1-6 hydroxyalkoxy, or C 1-6 alkoxyamino, or C 1-6 alkoxy-substituted C 1-6 alkoxy, C 1-6 alkoxyphenyl-substituted C 1-6 alkoxy, (trialkylsiloxy) C 1-6 alkyl, or (alkyl diphenyl siloxy) C 1-6 alkyl;
the R 3 and R 7 are H; the ring A is naphthyl, phenyl substituted by five halogens, or furyl substituted by one methyl; and the R 8 and R 9 are the same or different and each represent C 1-6 alkyl.

9 . The method of treating fibrosis according to claim 7 , wherein in the formula (1),
the R 1 , R 2 , and R 3 are each H, the R 4 is at position 4 and represents H, F, Cl, nitro, OH, CH 2 OH, methoxy, methoxymethoxy, or tert-butyl dimethyl siloxymethyl; the formula (2) is represented by the following formula (4); and the formula (5) is represented by the following formula (6):

Assignees

• Nat Univ Corp Tottori Univ
• Kanoncure Inc

Inventors

• Shiota Goshi
• Itaba Noriko
• Kanki Keita
• Seto Kenzo
• Shimizu Hiroki
• Kouno Yohei
• Kunita Shinya
• Adumi Zyunya
• Sakabe Tomohiko
• Abe Kenichiro
• Morimoto Minoru
• Oka Hiroyuki

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P19/04

  for non-specific disorders of the connective tissue · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• A61K31/16

  Amides, e.g. hydroxamic acids · CPC title

• A61K31/09

  having two or more such linkages · CPC title