US 2008/0293705 A1Published application

A1 adenosine receptor antagonists

AssigneeEndacea, Inc.

InventorsConstance Neely Wilson, John J. Partridge

Life of this patent

Estimating the term…

Abstract

Compounds of the general formula (I) are described: wherein A is a 5- or 6-membered aromatic or heteroaromatic ring. Compositions comprising such compounds and methods of use thereof are also described.

Claims55

Dependent claims

A hydrate of a compound of formula (I):

wherein:
A is a 5- or 6-membered heteroaromatic ring containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S;
R2 is of the formula (i):
(CH2)r-A′-R4 (i)
wherein:
A′ is a 6-membered aromatic ring or heteroaromatic ring containing 1 to 4 nitrogen atoms;
r is an integer ranging from 1 to 20;
R4 is selected from the group consisting of H, NH2, (CH2)sOH, wherein s is an integer ranging from 1 to 8, R14COOH, wherein R14 is an alkylene or alkylidene group having 1 to 8 carbon atoms, halo, NHR8, NR8R9, NHCOR8, NR8COR9, SO3H and PO3H2;
R3 is selected from the group consisting of H, NH2, R15COOH, wherein R15 is an alkylene or alkylidene group having 1 to 8 carbon atoms, and (CH2)tOH, wherein t is an integer ranging from 1 to 8, halo, NHR8, NR8R9, NHCOR8, NR8COR9, SO3H and PO3H2;
q is an integer ranging from 1 to 8;
and
R1 is a C1-C8 alkanyl group, C2-C8-alkenyl- or C2-C8-alkynyl-group which is optionally substituted by —CN, —CH2NR6R7OH, —OR8, —NR6R7, —NHCOR8, NHCONR6R7, halogen, —OCOR8, —OCH2COOH, —OCH2COOR8, —SO2R5, —S—R5, —OCH2—CONR6R7, —OCH2CH2OH, —SO2—CH2—CH2—O—COR8, —OCH2—CH2—NR6R7, —SO2—CH2—CH2—OH, —CONHSO2R8, —CH2CONHSO2R8, —OCH2CH2OR8, —COOH, —COOR8, —CONR6R7, —CHO, —SR8, —SOR8, —SO2R8, —SO3H, —PO3H2, —SO2NR6R7, —OCH2—CH2OCOR8, —CH═NOH, —CH═NOR8, —COR9, —CH(OH)R9, —CH(OR8)2, —CH═CH—R10, —OCONR6R7,
R5 is C1-C4-alkyl, optionally substituted by OH, OCOR8, NH2, NR6R7 or NHCOR8,
R6 and R7 are each independently hydrogen, an optionally substituted C3-6-cycloalkyl group, a branched or unbranched alkyl-, alkenyl- or alkynyl group having up to 10 carbon atoms, which may optionally be substituted by hydroxy, phenyl, substituted phenyl, amino, or it denotes —(CH2)m—NHCOOR8, wherein m=1, 2, 3 or 4;
R8 is hydrogen, C1-C8-alkyl or C2-C8-alkenyl or C2-C8-alkynyl optionally substituted with CO2H, a benzyl- or phenyl-group, which is optionally mono- or polysubstituted by OCH3;
R9 is C1-C8-alkyl or C2-C8-alkenyl or C2-C8-alkynyl optionally substituted with CO2H, optionally substituted phenyl, optionally substituted benzyl, C3-C6-cycloalkyl;
and
R10 is —COOR8, —CH2OR8, —CONR6R7, hydrogen, C1-C3-alkyl, optionally substituted phenyl, —CH2NR6R7;
and
wherein the hydrate is in a salt form.

17 more elements

A hydrate of a compound of formula (I):

wherein:
A is a 5- or 6-membered aromatic ring;
R2 is of the formula (i):
(CH2)r-A′-R4 (i)
wherein:
A′ is a 6-membered aromatic ring or a heteroaromatic ring containing 1 to 4 nitrogen atoms;
r is an integer ranging from 1 to 20;
R4 is selected from the group consisting of NH2, halo, NHR8, NR8R9, NHCOR8, NR8COR9, SO3H, and PO3H2;
R3 is selected from the group consisting of H, NH2, R15COOH, wherein R15 is an alkylene or alkylidene group having 1 to 8 carbon atoms, and (CH2)tOH, wherein t is an integer ranging from 1 to 8, halo, NHR8, NR8R9, NHCOR8, NR8COR9, SO3H and PO3H2;
q is an integer ranging from 1 to 8;
and
R1 is a C1-C8 alkanyl-group, C2-C8-alkenyl-, or C2-C8-alkynyl-group which is optionally substituted by —CN, —CH2NR6R7OH, —OR8, —NR6R7, —NHCOR8, —NHCONR6R7, halogen, —OCOR8, —OCH2COOH, —OCH2COOR8, —SO2R5, —S—R5, —OCH2—CONR6R7, —OCH2CH2OH, —SO2—CH2—CH2—O—COR8, —OCH2—CH2—NR6R7, —SO2—CH2—CH2—OH, —CONHSO2R8, —CH2CONHSO2R8, —OCH2CH2OR8, —COOH, —COOR8, —CONR6R7, —CHO, —SR8, —SOR8, —SO2R8, —SO3H, —PO3H2, —SO2NR6R7, —OCH2—CH2OCOR8, —CH═NOH, —CH═NOR8, —COR9, —CH(OH)R9, —CH(OR8)2, —CH═CH—R10, —OCONR6R7,
R5 is C1-C4-alkyl, optionally substituted by OH, OCOR8, NH2, NR6R7 or NHCOR8,
R6 and R7 are each independently hydrogen, an optionally substituted C3-6-cycloalkyl group, a branched or unbranched alkyl-, alkenyl- or alkynyl group having up to 10 carbon atoms, which may optionally be substituted by hydroxy, phenyl, substituted phenyl, amino or it denotes —(CH2)m—NHCOOR8, wherein m=1, 2, 3 or 4;
R8 is hydrogen, C1-C8-alkyl or C2-C8-alkenyl or C2-C8-alkynyl optionally substituted with CO2H, a benzyl- or phenyl-group, which is optionally mono- or polysubstituted by OCH3;
R9 is C1-C8-alkyl or C2-C8-alkenyl or C2-C8-alkynyl optionally substituted with CO2H, optionally substituted phenyl, optionally substituted benzyl, C3-C6-cycloalkyl;
and
R10 is —COOR8, —CH2OR8, —CONR6R7, hydrogen, C1-C3-alkyl, optionally substituted phenyl, —CH2NR6R7;
and
wherein the hydrate is in a salt form.

17 more elements

An assay-type probe of a compound of formula (I):

wherein:
A is a 5- or 6-membered heteroaromatic ring containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S;
R2 is of the formula (i):
(CH2)r-A′-R4 (i)
wherein:
A′ is a 6-membered aromatic ring or heteroaromatic ring containing 1 to 4 nitrogen atoms;
r is an integer ranging from 1 to 20;
R4 is selected from the group consisting of H, NH2, (CH2)sOH, wherein s is an integer ranging from 1 to 8, R14COOH, wherein R14 is an alkylene or alkylidene group having 1 to 8 carbon atoms, halo, NHR8, NR8R9, NHCOR8, NR8COR9, SO3H and PO3H2;
R3 is selected from the group consisting of H, NH2, R15COOH, wherein R15 is an alkylene or alkylidene group having 1 to 8 carbon atoms, and (CH2)tOH, wherein t is an integer ranging from 1 to 8, halo, NHR8, NR8R9, NHCOR8, NR8COR9, SO3H and PO3H2;
q is an integer ranging from 1 to 8;
and
R1 is a C1-C8 alkanyl group, C2-C8-alkenyl- or C2-C8-alkynyl-group which is optionally substituted by —CN, —CH2NR6R7OH, —OR8, —NR6R7, —NHCOR8, NHCONR6R7, halogen, —OCOR8, —OCH2COOH, —OCH2COOR8, —SO2R5, —S—R5, —OCH2—CONR6R7, —OCH2CH2OH, —SO2—CH2—CH2—O—COR8, —OCH2—CH2—NR6R7, —SO2—CH2—CH2—OH, —CONHSO2R8, —CH2CONHSO2R8, —OCH2CH2OR8, —COOH, —COOR8, —CONR6R7, —CHO, —SR8, —SOR8, —SO2R8, —SO3H, —PO3H2, —SO2NR6R7, —OCH2—CH2OCOR8, —CH═NOH, —CH═NOR8, —COR9, —CH(OH)R9, —CH(OR8)2, —CH═CH—R10, —OCONR6R7,
R5 is C1-C4-alkyl, optionally substituted by OH, OCOR8, NH2, NR6R7 or NHCOR8,
R6 and R7 are each independently hydrogen, an optionally substituted C3-6-cycloalkyl group, a branched or unbranched alkyl-, alkenyl- or alkynyl group having up to 10 carbon atoms, which may optionally be substituted by hydroxy, phenyl, substituted phenyl, amino, or it denotes —(CH2)m—NHCOOR8, wherein m=1, 2, 3 or 4;
R8 is hydrogen, C1-C8-alkyl or C2-C8-alkenyl or C2-C8-alkynyl optionally substituted with CO2H, a benzyl- or phenyl-group, which is optionally mono- or polysubstituted by OCH3;
R9 is C1-C8-alkyl or C2-C8-alkenyl or C2-C8-alkynyl optionally substituted with CO2H, optionally substituted phenyl, optionally substituted benzyl, C3-C6-cycloalkyl;
and
R10 is —COOR8, —CH2OR8, —CONR6R7, hydrogen, C1-C3-alkyl, optionally substituted phenyl, —CH2NR6R7,
wherein the compound of formula (I) is labeled by a detectable radioactive or non-radioactive group.

16 more elements

An assay-type probe of a compound of formula (I):

wherein:
A is a 5- or 6-membered aromatic ring;
R2 is of the formula (i):
(CH2)r-A′-R4 (i)
wherein:
A′ is a 6-membered aromatic ring or a heteroaromatic ring containing 1 to 4 nitrogen atoms;
r is an integer ranging from 1 to 20;
R4 is selected from the group consisting of NH2, halo, NHR8, NR8R9, NHCOR8, NR8COR9, SO3H and PO3H2;
R3 is selected from the group consisting of H, NH2, R15COOH, wherein R15 is an alkylene or alkylidene group having 1 to 8 carbon atoms, and (CH2)tOH, wherein t is an integer ranging from 1 to 8, halo, NHR8, NR8R9, NHCOR9, NR8COR9, SO3H and PO3H2;
q is an integer ranging from 1 to 8;
and
R1 is a C1-C8 alkanyl-group, C2-C8-alkenyl-, or C2-C8-alkynyl-group which is optionally substituted by —CN, —CH2NR6R7OH, —OR8, —NR6R7, —NHCOR8, —NHCONR6R7, halogen, —OCOR8, —OCH2COOH, —OCH2COOR8, —SO2R5, —S—R5, —OCH2—CONR6R7, —OCH2CH2OH, —SO2—CH2—CH2—O—COR8, —OCH2—CH2—NR6R7, —SO2—CH2—CH2—OH, —CONHSO2R8, —CH2CONHSO2R8, —OCH2CH2OR8, —COOH, —COOR8, —CONR6R7, —CHO, —SR8, —SOR8, —SO2R8, —SO3H, —PO3H2, —SO2NR6R7, —OCH2—CH2OCOR8, —CH═NOH, —CH═NOR8, —COR9, —CH(OH)R9, —CH(OR8)2, —CH═CH—R10, —OCONR6R7,
R5 is C1-C4-alkyl, optionally substituted by OH, OCOR8, NH2, NR6R7 or NHCOR8,
R6 and R7 are each independently hydrogen, an optionally substituted C3-6-cycloalkyl group, a branched or unbranched alkyl-, alkenyl- or alkynyl group having up to 10 carbon atoms, which may optionally be substituted by hydroxy, phenyl, substituted phenyl, amino or it denotes —(CH2)m—NRCOOR8, wherein m=1, 2, 3 or 4;
R8 is hydrogen, C1-C8-alkyl or C2-C8-alkenyl or C2-C8-alkynyl optionally substituted with CO2H, a benzyl- or phenyl-group, which is optionally mono- or polysubstituted by OCH3;
R9 is C1-C8-alkyl or C2-C8-alkenyl or C2-C8-alkynyl optionally substituted with CO2H, optionally substituted phenyl, optionally substituted benzyl, C3-C6-cycloalkyl;
and
R10 is —COOR8, —CH2OR8, —CONR6R7, hydrogen, C1-C3-alkyl, optionally substituted phenyl, —CH2NR6R7,
wherein the compound of formula (I) is labeled by a detectable radioactive or non-radioactive group.

16 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/186,857Filed 6 Aug 2008
Priority: 19 Feb 2003
Published: 27 Nov 2008
Term ends: Not estimatedThe source records don’t support an estimate.

Classification7 codes

C07D 473/04
With oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6: two oxygen atoms
A61P 11/06
Drugs for disorders of the respiratory system: antiasthmatics
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents
A61P 37/02
Drugs for immunological or allergic disorders: immunomodulators

Family

Application60/448,212Us provisional application · filed 19 Feb 2003
Application10/780,296Continuation · filed 17 Feb 2004
Application11/690,579Continuation · filed 23 Mar 2007
Application12/186,857Continuation
US 2005/0119258 A1Published application
US 2007/0161629 A1Published application
US 7,202,252 B2Related patent
US 7,423,041 B2Related patent
US 2008/0293705 A1This patent

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

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Abstract

A hydrate of a compound of formula (I):

wherein:
A is a 5- or 6-membered heteroaromatic ring containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S;
R2 is of the formula (i):
(CH2)r-A′-R4 (i)
wherein:
A′ is a 6-membered aromatic ring or heteroaromatic ring containing 1 to 4 nitrogen atoms;
r is an integer ranging from 1 to 20;
R4 is selected from the group consisting of H, NH2, (CH2)sOH, wherein s is an integer ranging from 1 to 8, R14COOH, wherein R14 is an alkylene or alkylidene group having 1 to 8 carbon atoms, halo, NHR8, NR8R9, NHCOR8, NR8COR9, SO3H and PO3H2;
R3 is selected from the group consisting of H, NH2, R15COOH, wherein R15 is an alkylene or alkylidene group having 1 to 8 carbon atoms, and (CH2)tOH, wherein t is an integer ranging from 1 to 8, halo, NHR8, NR8R9, NHCOR8, NR8COR9, SO3H and PO3H2;
q is an integer ranging from 1 to 8;
and
R1 is a C1-C8 alkanyl group, C2-C8-alkenyl- or C2-C8-alkynyl-group which is optionally substituted by —CN, —CH2NR6R7OH, —OR8, —NR6R7, —NHCOR8, NHCONR6R7, halogen, —OCOR8, —OCH2COOH, —OCH2COOR8, —SO2R5, —S—R5, —OCH2—CONR6R7, —OCH2CH2OH, —SO2—CH2—CH2—O—COR8, —OCH2—CH2—NR6R7, —SO2—CH2—CH2—OH, —CONHSO2R8, —CH2CONHSO2R8, —OCH2CH2OR8, —COOH, —COOR8, —CONR6R7, —CHO, —SR8, —SOR8, —SO2R8, —SO3H, —PO3H2, —SO2NR6R7, —OCH2—CH2OCOR8, —CH═NOH, —CH═NOR8, —COR9, —CH(OH)R9, —CH(OR8)2, —CH═CH—R10, —OCONR6R7,
R5 is C1-C4-alkyl, optionally substituted by OH, OCOR8, NH2, NR6R7 or NHCOR8,
R6 and R7 are each independently hydrogen, an optionally substituted C3-6-cycloalkyl group, a branched or unbranched alkyl-, alkenyl- or alkynyl group having up to 10 carbon atoms, which may optionally be substituted by hydroxy, phenyl, substituted phenyl, amino, or it denotes —(CH2)m—NHCOOR8, wherein m=1, 2, 3 or 4;
R8 is hydrogen, C1-C8-alkyl or C2-C8-alkenyl or C2-C8-alkynyl optionally substituted with CO2H, a benzyl- or phenyl-group, which is optionally mono- or polysubstituted by OCH3;
R9 is C1-C8-alkyl or C2-C8-alkenyl or C2-C8-alkynyl optionally substituted with CO2H, optionally substituted phenyl, optionally substituted benzyl, C3-C6-cycloalkyl;
and
R10 is —COOR8, —CH2OR8, —CONR6R7, hydrogen, C1-C3-alkyl, optionally substituted phenyl, —CH2NR6R7;
and
wherein the hydrate is in a salt form.

17 more elements

Facts

Application

12/186,857Filed 6 Aug 2008

Priority

19 Feb 2003

Published

27 Nov 2008

Term ends

Not estimatedThe source records don’t support an estimate.

Classification7 codes

C07D 473/04
With oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6: two oxygen atoms
A61P 11/06
Drugs for disorders of the respiratory system: antiasthmatics
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents
A61P 37/02
Drugs for immunological or allergic disorders: immunomodulators

Family

Application60/448,212Us provisional application · filed 19 Feb 2003

Application10/780,296Continuation · filed 17 Feb 2004

Application11/690,579Continuation · filed 23 Mar 2007

Application12/186,857Continuation

US 2005/0119258 A1Published application

US 2007/0161629 A1Published application

US 7,202,252 B2Related patent

US 7,423,041 B2Related patent

US 2008/0293705 A1This patent

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