IP Library Granted Patent US 9,145,411
Granted Patent B2
US 9,145,411 · App. 13/957,470 · Granted Sep 29, 2015

Substituted amino-pyrimidine derivatives

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Quick Facts
Patent No.
US 9,145,411
App. No.
13/957,470
Granted
Sep 29, 2015
Kind
B2
Abstract

The present application provides novel substituted quinazoline and pyrido-pyrimidine compounds and pharmaceutically acceptable salts, prodrugs, and solvates thereof. Also provided are methods for preparing these compounds. These compounds are useful in co-regulating PI3K and/or mTOR activity by administering a therapeutically effective amount of one or more of the compounds to a patient. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the PI3K/AKT/mTOR pathway. Advantageously, these compounds perform as dual PI3K/mTOR inhibitors. A variety of conditions can be treated using these compounds and include diseases which are characterized by inflammation or abnormal cellular proliferation. In one embodiment, the disease is cancer.

Claims (157)

1. A compound of formula (I):

wherein:

R 1 is a substituted phenyl of the structure:

wherein:

n is 1 to 5;

each R 8 is independently selected from the group consisting of halogen, alkyl, aryl, alkylsulfonyl, alkylthio, alkylcarbonylamino, halogenated alkylcarbonylamino, alkylsulfonylamino, arylsulfonylamino, alkylaminocarbonyl, alkylaminocarbonylamino, alkylaminoalkylcarbonylamino, hydroxyalkylcarbonylamino, heteroarylcarbonylamino, heteroarylalkylcarbonylamino, heteroarylcarbonyl, heterocyclecarbonylamino, arylcarbonylamino, alkylsulfonylheterocyclecarbonyl, heterocyclecarbonyl, heterocycleaminocarbonyl, heteroarylalkylamino, hydroxyalkylamino, heterocyclealkylcarbonylamino, or cyanoalkylcarbonylamino;

R 2 is optionally substituted morpholine or thiomorpholine;

R 3 is H, F, Cl, CH 3 , or CH 3 O;

X is CH or N;

or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

2. The compound of claim 1 , wherein R 2 is morpholine.

3. The compound of claim 1 , which is of formulae (II), (III), or (IV):

4. The compound selected from the group consisting of:

5-(7-(3 (methylsulfonyl)phenyl)-4-morpholinoquinazolin-2-yl)pyrimidin-2-amine;

5-(6-fluoro-7-(3-(methylsulfonyl)phenyl)-4-morpholinoquinazolin-2-yl)pyrimidin-2-amine;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-7-yl)phenyl)acetamide;

4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-N-cyclopropylbenzamide;

(5-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)furan-2-yl)(4-methylpiperazin-1-yl)methanone;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)phenyl)-2-hydroxy-2-methylpropanamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)cyclopropanecarboxamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-4-fluorobenzenesulfonamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-7-yl)phenyl)-2-(4-hydroxypiperidin-1-yl)acetamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)morpholine-4-carboxamide;

1-(4-((2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one;

5-(4-morpholino-7-(pyrimidin-5-yl)quinazolin-2-yl)pyrimidin-2-amine;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)phenyl)acetamide;

5-(7-(1-methyl-1H-pyrazol-4-yl)-4-morpholinoquinazolin-2-yl)pyrimidin-2-amine;

1-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)phenyl)-3-methylurea;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)phenyl)methanesulfonamide;

5-(4-morpholino-7-(thiophen-3-yl)quinazolin-2-yl)pyrimidin-2-amine;

5-(7-(5-(methylsulfonyl)pyridin-3-yl)-4-morpholino-quinazolin-2-yl)pyrimidin-2-amine;

5-(7-(2-fluoropyridin-3-yl)-4-morpholinoquinazolin-2-yl)pyrimidin-2-amine;

5-(7-(3-(methylsulfonyl)phenyl)-4-morpholinopyrido[3,2-d]-pyrimidin-2-yl)pyrimidin-2-amine;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-7-yl)phenyl)methanesulfonamide;

5-(7-(1-methyl-1H-pyrazol-4-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-2-yl)pyrimidin-2-amine;

5-(4-morpholino-7-(pyrimidin-5-yl)pyrido[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine;

5-(7-(2-fluoropyridin-3-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-2-yl)pyrimidin-2-amine;

5-(7-(furan-2-yl)-4-morpholinopyrido[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine

5-(7-(5-methylfuran-2-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-2-yl)pyrimidin-2-amine;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-7-yl)phenyl)-N-methylacetamide;

1-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-3-methylurea;

1-(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-3-methylurea;

N-(5-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)pyridin-3-yl)acetamide;

N-(5-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)pyridin-3-yl)cyclopropanecarboxamide;

N-(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-3-fluorophenyl)cyclopropanecarboxamide;

4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-N-methylbenzamide;

5-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-N-(pyridin-3-yl)furan-2-carboxamide;

1-(4-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)benzoyl)piperazin-1-yl)ethanone;

(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)(4-(methylsulfonyl)piperazin-1-yl)-methanone;

4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-N-(thiazol-2-yl)benzamide;

4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-N-(pyridin-4-yl)benzamide;

(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)(4-hydroxypiperidin-1-yl)methanone;

(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)(4-hydroxypiperidin-1-yl)methanone;

3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-N,N-dimethylbenzamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)phenyl)-2-(dimethylamino)acetamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)phenyl)-2-hydroxypropanamide;

(S)—N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)phenyl)-2-hydroxypropanamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-hydroxypropanamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-(dimethylamino)acetamide;

(S)—N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-hydroxypropanamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-hydroxy-2-methylpropanamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-cyano-2-methylpropanamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-hydroxyacetamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-fluoropropanamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-2-fluorophenyl)acetamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-cyanoacetamide;

N-(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)acetamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-4-fluorophenyl)acetamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-2-methylphenyl)acetamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)cyclopentanecarboxamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)nicotinamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-5-methylfuran-2-carboxamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)cyclohexanecarboxamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-1-cyanocyclopropanecarboxamide;

N-(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)cyclopropanecarboxamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)tetrahydro-2H-pyran-4-carboxamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)pyrazine-2-carboxamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)adamantane-1-carboxamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-4-methylpentanamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)furan-2-carboxamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-4-(trifluoromethyl)nicotinamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-1,2,3-thiadiazole-4-carboxamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-4-hydroxycyclohexanecarboxamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-7-yl)-4-fluorophenyl)nicotinamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-4-fluorophenyl)-5-methylfuran-2-carboxamide;

N-(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-5-methylfuran-2-carboxamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-4-fluorobenzamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-3-methyl-1H-pyrazole-5-carboxamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)cyclobutanecarboxamide;

N-(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)nicotinamide;

N-(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)cyclobutanecarboxamide;

N-(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)furan-2-carboxamide;

N-(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-3-methyl-1H-pyrazole-5-carboxamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)cyclopropanesulfonamide;

N-(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)cyclopropanesulfonamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-(4-methylpiperazin-1-yl)acetamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-morpholinoacetamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-4-fluorophenyl)-2-(4-methylpiperazin-1-yl)-acetamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-7-yl)-2-fluorophenyl)-2-(4-methylpiperazin-1-yl)acetamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)phenyl)-4-methylpiperazine-1-carboxamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)phenyl)morpholine-4-carboxamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-4-methylpiperazine-1-carboxamide;

1-(4-((2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one;

1-(4-((2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)methyl)piperazin-1-yl)-2-hydroxy-2-methylpropan-1-one;

1-(4-((2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)methyl)piperazin-1-yl)ethanone;

N-(1-((2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)methyl)piperidin-4-yl)acetamide;

5-(4-morpholino-7-(piperazin-1-ylmethyl)pyrido[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-7-yl)-4-fluorophenyl)cyclopropanecarboxamide;

N-(5-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-7-yl)pyridin-3-yl)methanesulfonamide;

3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-7-yl)-N-(3-fluoropyridin-4-yl)benzamide;

3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-7-yl)-N-cyclopropylbenzamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-7-yl)phenyl)-5-fluoronicotinamide;

5-(7-(5-(4-methylpiperazin-1-yl)pyridin-3-yl)-4-morpholino-pyrido[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine;

5-(7-(3-(4-methylpiperazin-1-yl)phenyl)-4-morpholino-pyrido[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine;

3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-7-yl)-N-(2-(dimethylamino)ethyl)benzamide;

3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-7-yl)-N-methylbenzamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-7-yl)phenyl)propionamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-7-yl)phenyl)isobutyramide;

5-(4-morpholino-7-(3-(piperazin-1-yl)phenyl)pyrido[3,2-d]-pyrimidin-2-yl)pyrimidin-2-amine;

3-(4-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)piperazin-1-yl)-2,2-dimethyl-3-oxopropanenitrile;

1-(4-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)piperazin-1-yl)-2-hydroxy-2-methylpropan-1-one;

2-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)propan-2-ol;

(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-7-yl)phenyl)(4-methylpiperazin-1-yl)methanone;

6-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one;

1-(4-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)piperazin-1-yl)-2-(dimethylamino)-ethanone;

2-(4-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)piperazin-1-yl)ethanol;

N-(5-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-2-(4-methylpiperazin-1-yl)phenyl)acetamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-2-fluorophenyl)cyclopropanecarboxamide;

(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-7-yl)phenyl)(4-(2-hydroxyethyl)piperazin-1-yl)-methanone;

N-(5-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-2-(4-methylpiperazin-1-yl)phenyl)cyclopropane-carboxamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)pivalamide;

N-(5-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]-pyrimidin-7-yl)-2-fluorophenyl)acetamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-2,4-difluorophenyl)acetamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-4-fluorophenyl)-1-cyanocyclopropane-carboxamide;

N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-2-fluorophenyl)-1-cyanocyclopropane-carboxamide; and

N-(5-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-2-fluorophenyl)cyclopropanecarboxamide;

or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

5. The compound of claim 1 which is a prodrug of formula (I).

6. The compound of claim 5 , wherein the prodrug is a diester.

7. The compound of claim 4 which is a prodrug.

8. The compound of claim 7 , wherein the prodrug is a diester.

9. The compound of claim 1 , which is selected from the group consisting of:

1-((acetyl(3-(2-(2-aminopyrimidin-5-yl)-4-morpholino-pyrido[3,2-d]pyrimidin-7-yl)phenyl)carbamoyl)oxy)ethyl acetate;

((acetyl(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-phenyl)carbamoyl)oxy)methyl acetate; and

(((3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)(cyclopropanecarbonyl)carbamoyl)oxy)-methyl acetate.

10. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

11. A pharmaceutical composition comprising the compound of claim 4 and a pharmaceutically acceptable carrier.

12. A method for co-regulating PI3K and mTOR, said method comprising administering a therapeutically effective amount of the compound of claim 1 to a patient in need thereof.

13. A method for treating a condition treatable by inhibiting the PI3K/AKT/pathway, said method comprising administering a therapeutically effective amount of the compound of claim 1 to a patient in need thereof.

14. A method for treating a disease characterized by an abnormal cellular proliferation resulting from a dysregulated PI3K/AKT/mTOR pathway, said method comprising administering of a therapeutically effective amount of the compound of claim 1 to a patient in need thereof.

15. The method of claim 14 , wherein said disease is cancer.

16. The method of claim 14 , wherein said condition is an inflammatory disorder.

17. A method for co-regulating PI3K and mTOR, said method comprising administering a therapeutically effective amount of the compound of claim 4 to a patient in need thereof.

18. A method for treating a condition treatable by inhibiting the PI3K/AKT/pathway, said method comprising administering a therapeutically effective amount of the compound of claim 4 to a patient in need thereof.

19. A method for treating a disease characterized by an abnormal cellular proliferation resulting from a dysregulated PI3K/AKT/mTOR pathway, said method comprising administering of a therapeutically effective amount of the compound of claim 10 to a patient in need thereof.

20. The method of claim 19 , wherein said disease is cancer.

21. The method of claim 18 , wherein said condition is an inflammatory disorder.

Assignments (4)
RELEASE OF SECURITY INTEREST Recorded Apr 28, 2017
From: DEUTSCHE BANK AG NEW YORK BRANCH
To: ENDO PHARMACEUTICALS, INC.; ENDO PHARMACEUTICALS SOLUTIONS, INC.; ASTORA WOMEN'S HEALTH HOLDINGS, LLC
Reel/Frame 042362/0001 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 2, 2014
From: ENDO PHARMACEUTICALS INC.
To: ASANA BIOSCIENCES, LLC
Reel/Frame 033010/0256 →
GRANT OF SECURITY INTEREST IN PATENTS Recorded Mar 20, 2014
From: ENDO PHARMACEUTICALS SOLUTIONS, INC.; ENDO PHARMACEUTICALS, INC.; AMS RESEARCH CORPORATION; AMERICAN MEDICAL SYSTEMS, INC.; LASERSCOPE
To: DEUTSCHE BANK AG NEW YORK BRANCH, AS COLLATERAL AGENT
Reel/Frame 032491/0440 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 10, 2014
From: SMITH, ROGER ASTBURY; VENKATESAN, ARANAPAKAM; BEJUGAM, MALLESHAM; HOSAHALLI, SUBRAMANYA; NANDURI, SRINIVAS
To: ENDO PHARMACEUTICALS, INC.
Reel/Frame 032393/0770 →