US 6,632,961 B1Granted

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 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.

Claims5

Dependent claims

An inhibitor of microvascular endothelial cell migration of Formula I

where
L1 is selected from
(1) —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
(2) —N(R5)C(O)(CH2)m—, where (1) and (2) are drawn with their left ends attached to R1;
R1 is selected from
(1) alkyl substituted with 1 or 2 substituents selected from
(a) —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 substituted with —OR9,
(vi) (aryl)oyl,
(vii) alkoxycarbonyl,
and
(viii) (heteroaryl)oyl,
and
(b) alkoxycarbonyl,
(2) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from
(a) —NR6R7,
(b) alkyl, and
(c) alkyl substituted with 1 or 2 —NR6R7 substituents,
(3) —NR6R7, and
(4) —OR9 where R9 is selected from
(i) hydrogen,
(ii) alkyl,
and
(iii) alkyl substituted with 1 or 2 aryl substituents;
R2 is selected from
(1) —(CH2)nC(O)R8 where n is an integer from 0 to 4, and R8 is selected from
(a) —OR9
and
(b) —NR5R10 where R5 is defined previously, and R10 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
(vi) 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′) —SO2NR R
(15′) —C(O)NR6R7,
(16′) aryloxy,
and
(17′) aryl,
and
(2) aryl, wherein the aryl is optionally substituted with 1, 2, or 3 substituents independently selected from
(a) —NR6R7
and
(b) —CO2R9;
provided that when R2 is —CO2H and R1 is substituted alkyl, the alkyl is substituted with 2 substituents;
R3 is hydrogen, and
R4 is selected from
(1) hydrogen, and
(2) alkyl;
all of the foregoing with the proviso that compounds in which
L1 is —C(O)NR5(CH2)m— where m is 0 and R5 is hydrogen;
R1 is alkyl substituted with —NR6R7 where R6 and R7 are hydrogen;
R2 is —(CH2)nC(O)R8 where n is 0, R8 is OR9, and R9 is ethyl;
R3 is hydrogen;
and
R4 is hydrogen,
are excluded therefrom.

78 more elements

Dependencies are inferred from the claim text.

patentgrep

Loading patent…

Abstract

An inhibitor of microvascular endothelial cell migration of Formula I

where
L1 is selected from
(1) —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
(2) —N(R5)C(O)(CH2)m—, where (1) and (2) are drawn with their left ends attached to R1;
R1 is selected from
(1) alkyl substituted with 1 or 2 substituents selected from
(a) —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 substituted with —OR9,
(vi) (aryl)oyl,
(vii) alkoxycarbonyl,
and
(viii) (heteroaryl)oyl,
and
(b) alkoxycarbonyl,
(2) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from
(a) —NR6R7,
(b) alkyl, and
(c) alkyl substituted with 1 or 2 —NR6R7 substituents,
(3) —NR6R7, and
(4) —OR9 where R9 is selected from
(i) hydrogen,
(ii) alkyl,
and
(iii) alkyl substituted with 1 or 2 aryl substituents;
R2 is selected from
(1) —(CH2)nC(O)R8 where n is an integer from 0 to 4, and R8 is selected from
(a) —OR9
and
(b) —NR5R10 where R5 is defined previously, and R10 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
(vi) 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′) —SO2NR R
(15′) —C(O)NR6R7,
(16′) aryloxy,
and
(17′) aryl,
and
(2) aryl, wherein the aryl is optionally substituted with 1, 2, or 3 substituents independently selected from
(a) —NR6R7
and
(b) —CO2R9;
provided that when R2 is —CO2H and R1 is substituted alkyl, the alkyl is substituted with 2 substituents;
R3 is hydrogen, and
R4 is selected from
(1) hydrogen, and
(2) alkyl;
all of the foregoing with the proviso that compounds in which
L1 is —C(O)NR5(CH2)m— where m is 0 and R5 is hydrogen;
R1 is alkyl substituted with —NR6R7 where R6 and R7 are hydrogen;
R2 is —(CH2)nC(O)R8 where n is 0, R8 is OR9, and R9 is ethyl;
R3 is hydrogen;
and
R4 is hydrogen,
are excluded therefrom.

78 more elements