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US 8,133,880 B2Granted
Purine derivatives and methods of use thereof
AssigneeInotek Pharmaceuticals Corporation
InventorsPrakash Jagtap, Andrew L. Salzman, Csaba Szabo
Life of this patent
Estimating the term…
Abstract
The invention relates to Purine Derivatives having the formula; The invention also relates to pharmaceutical compositions comprising an effective amount of the Purine Derivative; and methods for treating or preventing an ischemic condition, reperfusion injury, a cellular proliferative disorder, a cardiovascular disease, a neurological disorder, a skin disorder, a radiation-induced injury, a wound, or an inflammatory disease comprising administering an effective amount of the Purine Derivative to a subject in need thereof.
Claims14
A compound having the formula
- or a pharmaceutically acceptable salt thereof,
- wherein
- A is —C(O)NHR3;
- B and C are —OH;
- D is
- A and B are trans with respect to each other;
- B and C are cis with respect to each other;
- C and D are cis or trans with respect to each other;
- R1 is —H, —C1-C10 alkyl, -aryl, —C3-C8 monocyclic cycloalkyl, —C3-C8 monocyclic cycloalkenyl, —C8-C12 bicyclic cycloalkyl, —C8-C12 bicyclic cycloalkenyl, or —(CH2)n-aryl;
- R2 is —NHNHCOR4, —NHNHCONHR4, —NHNHCOOR4, —NH—N═C(R9)R10, —NR5—N═C(R5)R6 or —NRS5—N(R7)R8;
- R3 is —C1-C10 alkyl, -aryl or -3- to 7-membered monocyclic heterocyclyl;
- R4 is —C1-C10 alkyl, -aryl, —(CH2)n-aryl, —(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl), —(CH2)n-(-3- to 7-membered monocyclic heterocyclyl heterocyclo) or —(CH2)n—(C8-C12-membered bicyclic heterocyclyl heterocycle);
- each occurrence of R5 is independently C1-C10 alkyl, —(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl), —(CH2)n—(C3-C7-membered monocyclic heterocyclyl heterocycle), (CH2)n—(C8-C12-membered bicyclic heterocyclyl heterocycle), phenylene-(C2-C10 alkynyl), -phenylene-(CH2)mCOOH, -phenylene-(CH2)m-(-3- to 7-membered monocyclic heterocyclyl heterocyclo), phenylene-(CH2)mCOO—(C1-C10 alkyl) or —C(O)—(C1-C10 alkyl), or R5 and R6, together with the carbon atom to which they are attached, join to form a cyclopentyl, 2-cyclopentenyl, 3-cyclopentenyl, cyclohexyl, 2-cyclohexenyl or 3-cyclohexenyl ring;
- R6 is —H, —C1-C10 alkyl, —(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl), —(CH2)n-(-3- to 7-membered monocyclic heterocyclyl heterocyclo), —(CH2)n-(-8- to 12-membered bicyclic heterocyclyl heterocycle), phenylene-(C2-C10 alkynyl), phenylene-(CH2)mCOOH, -phenylene-(CH2)m-(-3- to 7-membered monocyclic heterocyclyl heterocycle), or -phenylene-(CH2)mCOO—(C1-C10 alkyl);
- R7 is —C1-C10 alkyl, -aryl, —(CH2)n-aryl, —(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl), —(CH2)m-(-3- to 7-membered monocyclic heterocyclyl), (CH2)m-(-8- to 12-membered bicyclic heterocyclyl), phenylene-(C2-C10 alkyl alkynyl), -phenylene-(CH2)mCOOH, -phenylene-(CH2)m-(-3- to 7-membered monocyclic heterocyclyl), phenylene-(CH2)mCOO—(C1-C10 alkyl) or —C(O)—(C1-C10 alkyl), or R7 and R8, together with the nitrogen atom to which they are attached, join to form a -3- to 7-membered nitrogen-containing monocyclic heterocyclyl or a -8- to 1, 2-membered nitrogen-containing bicyclic heterocyclyl;
- R8 is C1-C10 alkyl, -aryl, —(CH2)n-aryl, —(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl), —(CH2)n-(-3- to 7-membered monocyclic heterocyclyl), (CH2)n-(-8- to 12-membered bicyclic heterocyclyl), phenylene-(C2-C10 alkyl alkynyl), -phenylene-(CH2)mCOOH, -phenylene-(CH2)m-(-3- to 7-membered monocyclic heterocyclyl), phenylene-(CH2)mCOO—(C1-C10 alkyl) or —C(O)—(C1-C10 alkyl);
- R9 is —C1-C10 alkyl, —(CH2)p—(C3-C8 monocyclic cycloalkenyl), —(CH2)p—(C8-C12 bicyclic cycloalkyl), —(CH2)p—(C8-C12 bicyclic cycloalkenyl), —(CH2)p-(-3- to 7-membered monocyclic heterocyclyl), (CH2)p-(-8 to 12-membered bicyclic heterocyclyl), phenylene-(C2-C10 alkynyl), -phenylene-(CH2)mCOOH, -phenylene-(CH2)m-(-3- to 7-membered monocyclic heterocyclyl), phenylene-(CH2)mCOO—(C1-C10 alkyl), —C(O)-phenyl or —C(O)—(C1-C10 alkyl), or R9 and R10, together with the carbon atom to which they are attached, join to form a cyclopentyl, 2-cyclopentenyl, 3-cyclopentenyl, cyclohexyl, 2-cyclohexenyl, 3-cyclohexenyl or 1,2,3,4-tetrahydronaphthalene group;
- R10 is —H, —C1-C10 alkyl, —(CH2)p—(C3-C8 monocyclic cycloalkenyl), —(CH2)p—(C8-C12 bicyclic cycloalkyl), —(CH2)p—(C8-C12 bicyclic cycloalkenyl), —(CH2)p—(-3- to 7-membered monocyclic heterocyclyl), (CH2)p-(-8- to 12-membered bicyclic heterocyclyl), phenylene-(C2-C10 alkynyl), —(CH2)m-phenylene-(CH2)mCOOH, -phenylene-(CH2)m-(-3- to 7-membered monocyclic heterocyclyl) or —(CH2)m-phenylene-(CH2)mCOO—(C1-C10 alkyl);
- each m is independently an integer ranging from 1 to 4;
- each n is independently an integer ranging from 1 to 5;
- and
- each p is independently an integer ranging from 0 to 5.
19 more elements
A compound or a pharmaceutically acceptable salt thereof having the formula:
- R1
- R9
- —H
- -4-cyclohexenyl
- —H
- -phenylene-4-(CH2CH2COOEt)
- —H
- -phenylene-4-(CH2CH2COOH)
- —H
- -phenylene-4-(—C≡C—CH2CH2CH2CH3)
- —H
- -(1-methyl)-1H-imidazol-5-yl
- —H
- -(1,3-dimethyl)-1H-pyrazol-5-yl
- —H
- -(1-methyl)-1H-pyrrol-4-yl-2-carboxylic acid
- methyl ester
- —H
- -(3,5-dimethyl)-isoxazol-4-yl
- —H
- -1H-imidazol-4-yl
- —H
- -(2-methyl)-furan-5-yl-3-carboxylic acid
- methyl ester
- —H
- -3,4-dihydro-2H-pyran-2-yl (racemate)
- —H
- -tetrahydrofuran-3-yl
- —H
- -furan-3-yl
- —H
- -furan-2-yl
- —H
- -tetrahydropyran-2-yl (racemate)
- —H
- -3,4-dihydro-2H-pyran-5-yl (racemate)
- —H
- -2H-chromen-3-yl
- —H
- —C(O)-phenyl
- —CH2CH3
- -isobutyl
- —H
- -3,4-dihydro-2H-pyran-2-(R)-yl
- —H
- -3,4-dihydro-2H-pyran-2-(S)-yl
- —H
- -(5-hydroxymethyl)-furan-2-yl
- —H
- -(5-CH2CH2COOH)-furan-2-yl
- —H
- -benzo[1,3]dioxole-4-yl
- —H
- -2,3-dihydro-benzo[1,4]dioxine-6-yl
- —H
- —CH2CH2CH(CH3)2
53 more elements
A compound having the structure:
- or a pharmaceutically acceptable salt thereof.
A compound having the structure:
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.