IP Library Granted Patent US 9,713,613
Granted Patent B2
US 9,713,613 · App. 14/940,584 · Granted Jul 25, 2017

Methods and compositions for the treatment of cancer and related hyperproliferative disorders

Inventors: Motonari Uesugi (Osaka, JP); Salih J. Wakil (Houston, TX); Lutfi Abu-Elheiga (Houston, TX); Mizuki Watanabe (Kyoto, JP)
A61K31/5025A61K31/426A61K31/427A61K31/428A61K31/437A61K31/44A61K31/4439A61K31/454A61K31/4709A61K31/496C07D213/06C07D213/16C07D213/76C07D235/14C07D277/22C07D277/24C07D277/66C07D417/04C07D417/12C07D417/14C07D471/04C07D487/04
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Quick Facts
Patent No.
US 9,713,613
App. No.
14/940,584
Granted
Jul 25, 2017
Kind
B2
Abstract

The present invention relates to methods of treating a disease related to cell hyper-proliferation via administration of a therapeutically effective amount of a compound having a general tripartite structure A-B-C. In the tripartite structure A, B, and C are identical or non-identical structures, for example, but not limited to, heterocyclic, phenyl or benzyl ring structures with or without substitutions and are described in detail herein. The methods may utilize particular compounds, for example, having a piperidinyl, a pyrrolinyl or pyridinyl A ring, a thiazole B ring, and a phenyl C ring which may be further substituted independently.

Claims (36)

1. A method for treating a cancer in a patient in need thereof, comprising the step of administering to the patient, in a pharmaceutically acceptable medium, a therapeutically effective amount of a compound according to the chemical structure:

wherein R is H, isopropyl, benzyl, cyclohexyl, cyclopropylmethyl, —COMe, tert-butyloxycarbonyl, or methylsulfonyl, or a pharmaceutically acceptable salt or a stereoisomer thereof or a combination thereof;

wherein the cancer is a cancer of the respiratory tract, brain, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid, or parathyroid, or the cancer is lymphoma, sarcoma, melanoma, leukemia, multiple myeloma, or a distant metastasis of a solid tumor.

2. The method of claim 1 , wherein the chemical structure of the compound is:

3. The method of claim 1 , wherein the compound is:

N-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl)methanesulfonamide,

4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine,

N-isopropyl-4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine,

N-4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenylacetamide,

N-(cyclopropylmethyl)-4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine,

N-benzyl-4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine, or

N-cyclohexyl-4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine.

4. A method for treating a disease related to cell hyper-proliferation in a patient in need thereof, comprising the step of administering to the patient, in a pharmaceutically acceptable medium, a therapeutically effective amount of a compound that is:

4-(4-bromophenyl)-2-(pyrrolidin-2-yl)thiazole,

4-(4-bromophenyl)-2-(1-propylpyrrolidin-2-yl)thiazole,

tert-butyl 2-(4-(4-bromophenyl)thiazol-2-yl)pyrrolidine-1-carboxylate,

benzyl 2-(4-(4-bromophenyl)thiazol-2-yl)pyrrolidine-1-carboxylate,

benzyl (R)-2-(4-(4-(methylsulfonamido)phenyl)thiazol-2-yl)pyrrolidine-1-carboxylate,

3-(4-(4-bromophenyl)thiazol-2-yl)-1-propylpiperidine,

tert-butyl 3-(4-(4-bromophenyl)thiazol-2-yl)piperidine-1-carboxylate,

benzyl 3-(4-(4-bromophenyl)thiazol-2-yl)piperidine-1-carboxylate,

benzyl 4-(4-(4-bromophenyl)thiazol-2-yl)piperidine-1-carboxylate,

benzyl 3-(4-(4-(methylsulfonamido)phenyl)thiazol-2-yl)piperidine-1-carboxylate,

benzyl 4-(4-(4-(methylsulfonamido)phenyl)thiazol-2-yl)piperidine-1-carboxylate,

3-chloro-4-methyl-N-(6-(4-(3-(trifluoromethyl)benzyl)piperazin-1-yl)pyridin-3-yl)benzenesulfonamide,

(4-(5-chloro-2-methylphenyl)piperazin-1-yl)(4-(tosylamino)phenyl) methanone,

4-(4-((1-methyl-1H-benzo[d]imidazole-2-yl)methyl)piperazin-1-yl)-N-tosylbenzenamine,

4-chloro-N-(4-(4-((1-methyl-1H-benzo[d]imidazol-2-yl)methyl)piperazin-1-yl)phenyl) benzenesulfonamide;

or

4-(3-(pyridin-2-yl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-N-tosylbenzenamine;

(Z)-4-(3-cyano-3-(4-(2,4-dimethylphenyl)thiazol-2-yl)allyl)-N-(thiazol-2-yl)benzenesulfonamide.

5. The method of claim 4 , wherein the disease related to cell hyper-proliferation is cancer.

6. The method of claim 5 , wherein the cancer is a cancer of the breast, respiratory tract, brain, reproductive organs, prostate, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid, or parathyroid, or the cancer is lymphoma, sarcoma, melanoma, leukemia, multiple myeloma, or a distant metastasis of a solid tumor.

7. The method of claim 2 , where the cancer is liver cancer.

8. The method of claim 2 , where the cancer is leukemia.

9. The method of claim 2 , where the cancer is multiple myeloma.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 20, 2019
From: WAKIL, SALIH J.; ABU-ELHEIGA, LUTFI
To: BAYLOR COLLEGE OF MEDICINE
Reel/Frame 050108/0510 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 20, 2019
From: UESUGI, MOTONARI
To: BAYLOR COLLEGE OF MEDICINE; KYOTO UNIVERSITY
Reel/Frame 050108/0521 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 20, 2019
From: WATANABE, MIZUKI
To: KYOTO UNIVERSITY
Reel/Frame 050108/0535 →
Continuity (7)
Continuation 14052074 · Oct 11, 2013
Continuation In Part 14013918 · Aug 29, 2013
Continuation In Part 13484702 · May 31, 2012
Continuation 12024530 · Feb 1, 2008
Provisional Application 61012310 · Dec 7, 2007
Provisional Application 60887994 · Feb 2, 2007
Related Publication 20160136164A1 · May 19, 2016