LPAAT-beta inhibitors and uses thereof
AssigneeCell Therapeutics, Inc.
InventorsBaoqing Gong, John Tulinsky, Lynn Bonham, J. Peter Klein, Robert E. Finney, David M. Hollenback, Scott A. Shaffer, Norina M. Tang, Thayer H. White, David W. Leung
Life of this patent
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Abstract
The invention relates to triazines and the use thereof to inhibit lysophosphatidic acid acyltransferase β (LPAAT-β) activity. The invention further relates to methods of treating cancer using said triazines. The invention also relates to methods for screening for LPAAT-β activity.
Claims39
A compound of the Formula:
- 15
- wherein,
- R1 is halo, hydroxy, alkylmercapto, mercapto, alkoxy, aryloxy or substituted amino;
- R2, R3, R4 and R5, each of which may be same or different, are hydrogen, alkyl, substituted alkyl, alkenyl, alkynyl, aryl or substituted aryl;
- or
- R2 and R3 or R4 and R5, together with the nitrogen to which they are attached, form a piperidine, piperazine, or a morpholine ring;
- or
- pharmaceutically acceptable salts thereof.
A compound selected from the group consisting of 6-chloro-N-(4-methoxy-phenyl)-N′-p-tolyl-[1,3,5]triazine-2,4-diamine, N-butyl-6-chloro-N′-(4-chlorophenyl)-[1,3,5]triazine-2,4-diamine, 6-chloro-N-isopropyl-N′-p-tolyl[1,3,5]triazine-2,4-diamine, N-tert-butyl-6-chloro-N′-phenyl-[1,3,5]triazine-2,4-diamine, (4-chloro-6-morpholin-4-yl-[1,3,5]triazin-2-yl)-naphthalen-1-yl-amine, N-tert-butyl-6-chloro-N′-p-tolyl-[1,3,5]triazine-2,4-diamine, 6-chloro-N-cyclohexyl-N′-isopropyl-[1,3,5]triazine-2,4-diamine, 2-(4-chloro-6-phenylamino[1,3,5]triazin-2-yl-amino)-2-methyl-propan-1-ol, 6-chloro-N-isopropyl-N′-phenyl[1,3,5]triazine-2,4-diamine, 6-chloro-N-(4-chloro-phenyl)-N′-cyclohexyl[1,3,5]triazine-2,4-diamine, N-allyl-6-chloro-N′-cyclohexyl-[1,3,5]triazine-2,4-diamine, 2-(4-chloro-6-phenylamino-[1,3,5]triazin-2-yl-amino)-ethanol, N-tert-butyl-6-chloro-N′-cyclopentyl-[1,3,5]triazine-2,4-diamine, 6-chloro-N-(4-methoxyphenyl)-N′-phenyl-[1,3,5]triazine-2,4-diamine, N-benzo[1,3]dioxol-5-yl-6-chloro-N′-(4-chlorophenyl)-[1,3,5]triazine-2,4-diamine, 6-chloro-N-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-N′-phenyl-[1,3,5]triazine-2,4-diamine, N-benzo[1,3]dioxol-5-yl-6-chloro-N′-phenyl-[1,3,5]triazine-2,4-diamine, 6-chloro-N-indan-5-yl-N′-phenyl-[1,3,5]triazine-2,4-diamine, 6-chloro-N-(4-chlorophenyl)-N′-propyl-[1,3,5]triazine-2,4-diamine, N-(4-chloro-phenyl)-6-methoxyN′-propyl-[1,3,5]triazine-2,4-diamine and N-(4-chloro-phenyl)-6-methylsulfanyl-N′-phenyl-[1,3,5]triazine-2,4-diamine.
A method for inhibiting LPAAT-β (lysophosphatidic acid acyltransferase β) comprising contacting LPAAT-β with an effective amount of a compound of the Formula:
- 16
- wherein,
- R1 is halo, hydroxy, alkylmercapto, mercapto, alkoxy, aryloxy or substituted amino;
- R2, R3, R4 and R5, each of which may be same or different, are hydrogen, alkyl, substituted alkyl, alkenyl, alkynyl, aryl or substituted aryl;
- or
- R2 and R3 or R4 and R5, together with the nitrogen to which they are attached, form a piperidine, piperazine, or a morpholine ring;
- or
- pharmaceutically acceptable salts thereof;
- thereby inhibiting LPAAT-β.
A method of inhibiting cell proliferation comprising contacting a cell with an effective amount of a compound of the Formula:
- 17
- wherein,
- R1 is halo, hydroxy, alkylmercapto, mercapto, alkoxy, arylox or substituted amino;
- R2, R3, R4 and R5, each of which may be same or different, are hydrogen, alkyl, substituted alkyl, alkenyl, alkynyl, aryl or substituted aryl;
- or
- R2 and R3 or R4 and R5, together with the nitrogen to which they are attached, form a piperidine, piperazine, or a morpholine ring;
- or
- pharmaceutically acceptable salts thereof;
- thereby inhibiting the proliferation of the cell.
A method for treating cancer, comprising administering to an animal in need thereof, an effective amount of a compound of the Formula:
- 18
- wherein,
- R1 is halo, hydroxy, alkylmercapto, mercapto, alkoxy, aryloxy or substituted amino;
- R2, R3, R4 and R5, each of which may be same or different, are hydrogen, alkyl, substituted alkyl, alkenyl, alkynyl, aryl or substituted aryl;
- or
- R2 and R3 or R4 and R5, together with the nitrogen to which they are attached, form a piperidine, piperazine, or a morpholine ring;
- or
- pharmaceutically acceptable salts thereof;
- wherein the cancer is treated.
A method for screening a patient for LPAAT-β activity, said method comprising detecting the presence or absence of an increased amount of LPAAT-β RNA, DNA or protein relative to a predetermined control, whereby the presence of said increased amount is indicative of cancer susceptibility in said patient.
A method of inhibiting cell proliferation comprising the inhibition of LPAAT-β.
A vaccine preparation capable of inducing an anti-tumor immune response comprising a pharmaceutically acceptable carrier and an anti-tumor immune response-inducing effective amount of LPAAT-β protein.
A method for screening a patient for LPAAT-β activity, said method comprising detecting the presence or absence of an increased amount of a phospholipid of defined acyl-chain composition relative to a predetermined control, whereby the presence of said increased amount is indicative of cancer susceptibility in said patient.
Dependencies are inferred from the claim text.