Suppression and regeneration promoting effect of low molecular weight compound on cancer and fibrosis

Patent metadata

Field	Value
Publication number	US-2019055249-A1
Application number	US-201615760374-A
Country	US
Kind code	A1
Filing date	Sep 16, 2016
Priority date	Sep 18, 2015
Publication date	Feb 21, 2019
Grant date	—

Abstract

To obtain a novel therapeutic drug for a malignant tumor or fibrosis. Used is a compound represented by formula (1), a salt thereof, or a solvate thereof. Also used is a therapeutic drug for a malignant tumor or a therapeutic drug for fibrosis, comprising a compound represented by formula (1), a salt thereof, or a solvate thereof.

First claim

1 . A compound, a salt thereof, or a solvate thereof, the compound represented by formula (1):

wherein substituents R 1 and R 2 are represented by the following case (a) or (b):
(a) R 1 is optionally substituted phenyl, and
R 2 is H, optionally substituted phenyl, or —C(O)NHR 3 where the R 3 is H, C 1-6 alkyl, or optionally substituted benzyl; or

(b) R 1 is optionally substituted naphthyl or optionally substituted phenyl, and
R 2 is optionally substituted phenyl or —C(O)NHR 4 where the R 4 is H, C 1-6 alkyl, or optionally substituted siloxybenzyl.

2 . The compound, the salt thereof, or the solvate thereof according to claim 1 , wherein
the R 1 of case (a) is phenyl having a substituent R 5 where the R 5 is at least one substituent selected from the group consisting of H, halogen, nitro, amino, 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, and C 1-6 alkoxyamino; the R 2 of case (a) is H, phenyl having a substituent R 5 , —C(O)NHR 3 where the R 3 is benzyl having a substituent R 6 where the R 6 is at least one substituent selected from the group consisting of H, halogen, nitro, amino, 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, C 1-6 alkoxyamino, C 1-6 alkoxy-substituted C 1-6 alkoxy, C 1-6 alkoxyphenyl-substituted C 1-6 alkoxy, tri(C 1-6 alkylsiloxy)C 1-6 alkyl, C 1-6 alkyldiphenylsiloxy C 1-6 alkyl, triphenylsiloxy C 1-6 alkyl, tri(C 1-6 alkyl)siloxy, C 1-6 alkyldiphenylsiloxy, and triphenylsiloxy; the R 1 of case (b) is phenyl having a substituent R 5 or naphthyl; and the R 2 of case (b) is phenyl having a substituent R 5 or —C(O)NHR 4 where the R 4 is H, C 1-6 alkyl, or siloxybenzyl having a substituent R 5 .

3 . The compound, the salt thereof, or the solvate thereof according to claim 2 , wherein
the R 2 of case (a) is —C(O)NH(CH 2 C 6 H 5 ); the R 1 of case (b) is naphthyl; and the R 2 of case (b) is nitrophenyl or —C(O)NHR 4 where the R 4 is H or siloxybenzyl having a substituent R 5 .

4 . The compound, the salt thereof, or the solvate thereof according to claim 1 , wherein
the R 1 of case (a) is phenyl having at least one substituent selected from the group consisting of F, Cl, nitro, OH, and methoxy; the R 2 of case (a) is —C(O)NH(CH 2 C 6 H 5 ); the R 1 of case (b) is naphthyl; and the R 2 of case (b) is —C(O)NH 2 , nitrophenyl, or (tert-butyldimethylsiloxy)benzyl.

5 . A method of treating a malignant tumor, comprising the step of administering to a patient the compound, the salt thereof, or the solvate thereof according to claim 1 .

6 . A method of treating fibrosis, comprising the step of administering to a patient the compound, the salt thereof, or the solvate thereof according to claim 1 .

7 . A method for producing hepatocytes, comprising the step of causing the compound, the salt thereof, or the solvate thereof according to claim 1 to contact a mesenchymal stem cell.

8 - 9 . (canceled)

10 . A method of treating a malignant tumor, comprising the step of administering simultaneously or separately to a patient 5-FU and a compound, a salt thereof, or a solvate thereof, the compound represented by formula (2):

wherein R 7 and R 8 are the same or different and each represent optionally substituted C 1-6 alkyl or optionally substituted C 2-6 alkenyl.

11 . A method of treating a malignant tumor, comprising the step of:
administering to a patient a compound, a salt thereof, or a solvate thereof, wherein the patient has already received 5-FU, the compound represented by formula (2):

wherein R 7 and R 8 are the same or different and each represent optionally substituted C 1-6 alkyl or optionally substituted C 2-6 alkenyl, or
administering to a patient 5-FU, wherein the patient has already received a compound, a salt thereof, or a solvate thereof, the compound represented by formula (2).

Assignees

• Nat Univ Corp Tottori Univ
• Kanoncure Inc

Inventors

• Shiota Goshi
• Itaba Noriko
• Morimoto Minoru
• Oka Hiroyuki
• Abe Kenichiro
• Shimizu Hiroki
• Kouno Yoohei
• Yokogi Satoshi

Classifications

• A61K31/085

  having an ether linkage to aromatic ring nuclear carbon · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• A61K31/519

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

• A61K31/695

  Silicon compounds · CPC title