US 9,315,521 B2Granted

Pyrimidines as novel therapeutic agents

AssigneeUniversite Laval

InventorsGiorgio Attardo, Sasmita Tripathy, Martin Gagnon

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Abstract

The present invention features compounds having the Formula (Ia) and (Ib) (e.g., a compound of any of Formulas ((Ia-2)-(Ia-21)), including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, pharmaceutically acceptable salts, and compositions thereof. The invention also features methods for treating or preventing pain (e.g., neuropathic pain), inflammation, or epilepsy in a patient by administering an effective amount of a compound of Formula (Ia) or (Ib). The invention also features a method for treating or preventing pain (e.g., neuropathic pain), inflammation, or epilepsy in a patient that includes administering to a patient in need thereof an effective amount of a compound of Formula (IIa) or (IIb) (e.g., a compound of any of Formulas ((IIa-2)-(IIa-6)). The compounds described herein (e.g., a compound of Formulas (Ia), (Ib), (IIa), or (IIb)) can also be used as anticonvulsants.

Claims12

Dependent claims

A method for treating or preventing inflammation in a patient, said method comprising administering to the patient in need thereof an effective amount of a compound having the following structure

or its tautomer
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein:
W is O, S, NH, N-terminal linked amino acid, or CH2;
Q1 is —O—, —NH—, —S—, —SO—, —SO2—, —CH2, —CH2CH2—, —CH═CH—, —OCH2—, —SCH2—, —SOCH2—, or —SO2CH2—, wherein Q1 is not —O— when W is O or S;
R1 is —H, OH, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, —(CH2)nOZ, —C(O)Z, —C(O)OZ, —C(O)NHZ, —C(O)N(Z)2, —(CR1AR1B)r2OPO(OZ)2, —(CR2AR2B)r3PO(OZ)2, or C-terminal linked amino acid;
each R1A, R1B, R2A, and R2B is, independently, —H or —C1-5 alkyl;
R2 and R3 are each, independently, —H, -D, —OH, -halogen, —CN, —NO2, —SH, —C1-C8 alkyl, —CF3, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2, or R2 and R3, together with the carbon atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle;
each Z is, independently, —H, —C1-C8 alkyl, —C4-C12 alkcycloalkyl, —C3-C9 alkheterocyclyl, wherein the heterocyclyl is 3 to 9 membered, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocycle, —C2-C8 alkenyl, or —C2-C8 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle;
each n is 1 or 2;
each r2 is an integer between 1-3;
each r3 is an integer between 0-2;
A1 and A2 are each, independently, —H, -D, -halogen, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, or —C7-C14 arylalkyl;
and
A3 is a 3- to 9-membered aromatic or non aromatic carbocycle or heterocycle.

11 more elements

A method for treating epilepsy in a patient, said method comprising administering to the patient in need thereof an effective amount of a compound having the following structure

or its tautomer
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein:
W is O, S, NH, N-terminal linked amino acid, or CH2;
Q1 is —O—, —NH—, —S—, —SO—, —SO2—, —CH2, —CH2CH2—, —CH═CH—, —OCH2—, —SCH2—, —SOCH2—, or —SO2CH2—, wherein Q1 is not —O— when W is O or S;
R1 is —H, OH, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, —(CH2)nOZ, —C(O)Z, —C(O)OZ, —C(O)NHZ, —C(O)N(Z)2, —(CR1AR1B)r2OPO(OZ)2, —(CR2AR2B)r3PO(OZ)2, or C-terminal linked amino acid;
each R1A, R1B, R2A, and R2B is, independently, —H or —C1-5 alkyl;
R2 and R3 are each, independently, —H, -D, —OH, -halogen, —CN, —NO2, —SH, —C1-C8 alkyl, —CF3, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2, or R2 and R3, together with the carbon atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle;
each Z is, independently, —H, —C1-C8 alkyl, —C4-C12 alkcycloalkyl, —C3-C9 alkheterocyclyl, wherein the heterocyclyl is 3 to 9 membered, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocycle, —C2-C8 alkenyl, or —C2-C8 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle;
each n is 1 or 2;
each r2 is an integer between 1-3;
each r3 is an integer between 0-2;
A1 and A2 are each, independently, —H, -D, -halogen, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, or —C7-C14 arylalkyl;
and
A3 is a 3- to 9-membered aromatic or non aromatic carbocycle or heterocycle.

11 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/693,345Filed 22 Apr 2015 · division
Priority: 21 May 2009
Published: US 2015/0225423 A113 Aug 2015
Granted: 19 Apr 2016
Term ends: Not estimatedThe source records don’t support an estimate.

Classification22 codes

C07D 513/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61K 31/435
Having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins: having six-membered rings with one nitrogen as the only ring hetero atom
A61K 31/497
Non-condensed pyrazines: containing further heterocyclic rings
A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings

Family

Application61/180,253Us provisional application · filed 21 May 2009
Application61/285,003Us provisional application · filed 9 Dec 2009
Application61/289,628Us provisional application · filed 23 Dec 2009
Application12/784,975Parent of this division · filed 21 May 2010
US 2015/0225423 A1Pre-grant publication · published 13 Aug 2015
US 9,040,538 B2Parent of this division
US 2010/0298336 A1Published application
US 9,315,521 B2This patent

From the US filing history. Foreign family members aren’t listed.