US 2004/0110959 A1Published application

Antiangiogenic drug to treat cancer, arthritis and retinopathy

AssigneeAbbott Laboratories

InventorsMegumi Kawai, Jack Henkin, George S. Sheppard, Richard A. Craig

Life of this patent

Estimating the term…

Abstract

Compounds having Formula I 1 or pharmaceutically acceptable salts or prodrugs thereof, are useful for treating pathological states which arise from or are exacerbated by angiogenesis. The invention also relates to pharmaceutical compositions comprising these compounds and to methods of inhibiting angiogenesis in a mammal.

Claims17

Dependent claims

A compound of Formula I

4
or a pharmaceutically acceptable salt or prodrug thereof, where
L1 is selected from
(1) a covalent bond,
(2) —C(O)NR5(CH2)m—, where m is an integer from 0 to 4, and
R5 is selected from
(a) hydrogen and
(b) alkyl, and
(3) —N(R5)C(O)(CH2)m—,
where (2) and (3) are drawn with their left ends attached to R1;
R1 is selected from
(1) alkyl,
(2) alkyl substituted with 1, 2, or 3 substituents selected from
(a) —NO2
(b) —NR6R7 where R6 and R7 are independently selected from
(i) hydrogen,
(ii) alkyl,
(iii) arylalkyl,
(iv) an amino protecting group,
(v) alkanoyl, where the alkanoyl can be optionally substituted with —OR9,
(vi) (aryl)oyl,
(vii) alkoxycarbonyl, and
(viii) (heteroaryl)oyl, and
(c) alkoxycarbonyl,
(3) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from
(a) —NR6R7,
(b) alkyl, and
(c) alkyl substituted with 1, 2, or 3 substituents selected from —NR6R7,
(4) —NR6R7, and
(5) —OR9;
R2 and R3 are selected from
(1) hydrogen
(2) —(CH2)nC(O)R8 where n is an integer from 0 to 4, and
R8 is selected from
(a) —OR9 where R9 is selected from
(i) hydrogen,
(ii) alkyl, and
(iii) alkyl substituted with 1 or 2 substituents selected from the group consisting of aryl and
(b) —NR5R10 where R5 is defined previously, and RIO is selected from
(i) hydrogen,
(ii) alkyl,
(iii) alkyl substituted with 1, 2, or 3 substituents independently selected from
(1′) —CO2R9 and
(2′) —C(O)NR6R7
(iv) aryl, and
(v) arylalkyl,
where (iv) and (v) can be optionally substituted with 1, 2, 3, 4, or 5 substituents
independently selected from
(1′) alkyl,
(2′) alkanoyl,
(3′) —OR9,
(4′) —CO2R9,
(5′) alkanoyloxy,
(6′) carboxaldehyde,
(7′) cycloalkyl,
(8′) cycloalkenyl,
(9′) halo,
(10′) nitro,
(11′) perfluoroalkyl,
(12′) perfluoroalkoxy,
(13′) —NR6R7,
(14′) —SO2NR6R7,
(15′) —C(O)NR6R7,
(16′) aryloxy, and
(17′) aryl, and
(3) aryl, wherein the aryl is optionally substituted with 1, 2, or 3 substituents independently
selected from
(a) —NR6R7 and
(b) —CO2R9,
provided that at least one of R2 and R3 is other than hydrogen;
R4 is selected from
(1) hydrogen,
(2) alkyl,
(3) cycloalkyl,
(4) —CO2R5,
(5) aryl, and
(6) aryl substituted with at least one of W, X, Y, or Z where W, X, Y, and Z are independently selected from
(a) alkyl,
(b) alkanoyl,
(c) —OR9,
(d) —CO2R9,
(e) alkanoyloxy,
(f) carboxaldehyde,
(g) cycloalkyl,
(h) cycloalkenyl,
(i) halo,
(j)nitro,
(k) perfluoroalkyl,
(l) perfluoroalkoxy,
(m) —NR6R7,
(n) —SO2NR6R7,
(o) —C(O)NR6R7,
(p) aryloxy, and
(q) aryl.

91 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/616,628Filed 10 Jul 2003
Priority: 22 May 1998
Published: 10 Jun 2004
Term ends: Not estimatedThe source records don’t support an estimate.

Classification2 codes

C07C 237/22
Having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton: having nitrogen atoms of amino groups…
C07C
Acyclic or carbocyclic compounds

Family

Application60/086,491Us provisional application · filed 22 May 1998
Application09/316,856Division · filed 21 May 1999
Application10/616,628Division · filed 10 Jul 2003
US 6,632,961 B1Related patent
US 6,849,757 B2Related patent
US 2004/0110959 A1This patent

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

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Abstract

A compound of Formula I

4
or a pharmaceutically acceptable salt or prodrug thereof, where
L1 is selected from
(1) a covalent bond,
(2) —C(O)NR5(CH2)m—, where m is an integer from 0 to 4, and
R5 is selected from
(a) hydrogen and
(b) alkyl, and
(3) —N(R5)C(O)(CH2)m—,
where (2) and (3) are drawn with their left ends attached to R1;
R1 is selected from
(1) alkyl,
(2) alkyl substituted with 1, 2, or 3 substituents selected from
(a) —NO2
(b) —NR6R7 where R6 and R7 are independently selected from
(i) hydrogen,
(ii) alkyl,
(iii) arylalkyl,
(iv) an amino protecting group,
(v) alkanoyl, where the alkanoyl can be optionally substituted with —OR9,
(vi) (aryl)oyl,
(vii) alkoxycarbonyl, and
(viii) (heteroaryl)oyl, and
(c) alkoxycarbonyl,
(3) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from
(a) —NR6R7,
(b) alkyl, and
(c) alkyl substituted with 1, 2, or 3 substituents selected from —NR6R7,
(4) —NR6R7, and
(5) —OR9;
R2 and R3 are selected from
(1) hydrogen
(2) —(CH2)nC(O)R8 where n is an integer from 0 to 4, and
R8 is selected from
(a) —OR9 where R9 is selected from
(i) hydrogen,
(ii) alkyl, and
(iii) alkyl substituted with 1 or 2 substituents selected from the group consisting of aryl and
(b) —NR5R10 where R5 is defined previously, and RIO is selected from
(i) hydrogen,
(ii) alkyl,
(iii) alkyl substituted with 1, 2, or 3 substituents independently selected from
(1′) —CO2R9 and
(2′) —C(O)NR6R7
(iv) aryl, and
(v) arylalkyl,
where (iv) and (v) can be optionally substituted with 1, 2, 3, 4, or 5 substituents
independently selected from
(1′) alkyl,
(2′) alkanoyl,
(3′) —OR9,
(4′) —CO2R9,
(5′) alkanoyloxy,
(6′) carboxaldehyde,
(7′) cycloalkyl,
(8′) cycloalkenyl,
(9′) halo,
(10′) nitro,
(11′) perfluoroalkyl,
(12′) perfluoroalkoxy,
(13′) —NR6R7,
(14′) —SO2NR6R7,
(15′) —C(O)NR6R7,
(16′) aryloxy, and
(17′) aryl, and
(3) aryl, wherein the aryl is optionally substituted with 1, 2, or 3 substituents independently
selected from
(a) —NR6R7 and
(b) —CO2R9,
provided that at least one of R2 and R3 is other than hydrogen;
R4 is selected from
(1) hydrogen,
(2) alkyl,
(3) cycloalkyl,
(4) —CO2R5,
(5) aryl, and
(6) aryl substituted with at least one of W, X, Y, or Z where W, X, Y, and Z are independently selected from
(a) alkyl,
(b) alkanoyl,
(c) —OR9,
(d) —CO2R9,
(e) alkanoyloxy,
(f) carboxaldehyde,
(g) cycloalkyl,
(h) cycloalkenyl,
(i) halo,
(j)nitro,
(k) perfluoroalkyl,
(l) perfluoroalkoxy,
(m) —NR6R7,
(n) —SO2NR6R7,
(o) —C(O)NR6R7,
(p) aryloxy, and
(q) aryl.

91 more elements

Facts

Application

10/616,628Filed 10 Jul 2003

Priority

22 May 1998

Published

10 Jun 2004

Term ends

Not estimatedThe source records don’t support an estimate.

Classification2 codes

C07C 237/22
Having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton: having nitrogen atoms of amino groups…
C07C
Acyclic or carbocyclic compounds

Family

Application60/086,491Us provisional application · filed 22 May 1998

Application09/316,856Division · filed 21 May 1999

Application10/616,628Division · filed 10 Jul 2003

US 6,632,961 B1Related patent

US 6,849,757 B2Related patent

US 2004/0110959 A1This patent

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