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US 11,299,480 B2Granted
2-arylsulfonamido-N-arylacetamide derivatized STAT3 inhibitors
AssigneeUniversity of Hawaii
InventorsJames Turkson, Peibin Yue, Marcus Tius, Christine Brotherton-Pleiss, Francisco Javier Lopez Tapia
Life of this patent
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Abstract
The present disclosure provides pharmaceutical compositions comprising 2-arylsulfonamido-N-arylacetamide derivatized Stat3 inhibitors and certain pharmaceutically acceptable salts thereof, and methods of their use.
Claims29
A compound represented by Formula I:
- wherein R1 is selected from aryl or a 5 or 6-membered heteroaryl, where the heteroatoms are one or more O, N, S(A)2, where S is sulfur and A is selected from oxygen or an electron pair, the aryl or the 5 or 6-membered heteroaryl are optionally substituted with halo, CF3, C1-C6 alkyl, C1-C6 branched alkyl, aryl, heteroaryl, C3-C7 cycloalkyl, C3-C7 cycloalkenyl, three- to six-membered heterocycle, three- to seven-membered saturated heterocycle, fused C2-C5 alkylene, where one or more CH2 groups can be replaced with O, NR9, or S(A)2 where S is sulfur and A is selected from oxygen or an electron pair, the aryl or the 5 or 6-membered heteroaryl are optionally substituted naphthalene, optionally substituted indole, benzofuran, benzothiophene;
- R2 and R3 are independently selected from H or C1-C6 alkyl;
- where R2 and R3 can form a C3-C6 cycloalkane ring, where this C3-C6 cycloalkane ring can be substituted with 1 or more of C1-C6 alkyl, hydroxyl, NR9R10, or C1-C6 alkoxy;
- R5 is selected from H, (CH2)fNR9R10, (CH2)fOR9, (CH2)fCO2R9, or (CH2)fCO2NR9R10;
- R4 and R6 form a C3-C6 heterocycloalkane ring, where this C3-C6 heterocycloalkane ring can be substituted with 1 or more of C1-C6 alkyl, hydroxyl, NR9R10 and where one or more CH2 groups can be replaced with O, NR9, or S(A)2 where S is sulfur and A is selected from oxygen or an electron pair;
- or R4 and R6 form an optionally substituted pyrrole ring, wherein one or more CH groups of said pyrrole ring can be replaced with O, N, or S(A)2, where S is sulfur and A is selected from oxygen or an electron pair;
- R7 is selected from CF3, aryl or heteroaryl group where the aryl or heteroaryl group is substituted with 1-5 substituents selected from C1-C6 alkyl, halo, hydroxyl, CN, or CF3;
- R8 is substitution selected from one or more of H, C1-C6 alkyl, C1-C6 alkoxy, hydroxyl, halogen, OC(O)CH3, NR9R10, CN, CF3, CO2R9, CO2NR9R10, (CH2)fNR9R10, (CH2)fOR9, or (CH2)fCO2R9;
- R9 is selected from H or C1-C6 alkyl;
- R10 is selected from H, or C1-C6 alkyl;
- W is selected from CO2H, tetrazole, benzyl, C(O)NHOR10 or CF2OH;
- Q is C, CH, N, O, or S;
- where Q and R8 can form a heterocyclic ring;
- p is selected from 0 or 1, y is selected from 0 or 1, f is selected from 0 to 4;
- t is selected from 0 or 1;
- or a solvate, hydrate, or pharmaceutically acceptable salt thereof.
13 more elements
A compound represented by Formula II:
- wherein R11 is selected from aryl or heteroaryl,
- wherein the aryl or heteroaryl can be substituted with one or more of hydroxyl, carboxylic acid, carboxylate, benzohydroxamic acid, hydroxyl-substituted alkyl;
- wherein R12 is selected from (R)—CH(CH3), (S)—CHCH3, (S)—CH(CH2CH3), (R)—CH(CH2CH3), bridging cylcopropyl
- (S)—CH(CH2OH), (R)—CH(CH2OH), (R)—CH(CH2CH2OH), (S)—CH(CH2CH2OH), (S)—CH[(R)—CH(CH3)OH], (R)—CH[(S)—CH(CH3)OH], (S)—CH(CH2NH2), (R)—CH(CH2NH2), (S)—CH(CH2CO2H), or (R)—CH(CH2CO2H);
- or a solvate, hydrate, or pharmaceutically acceptable salt thereof.
2 more elements
A compound represented by Formula IV:
- wherein R14 is selected from a five- to seven-membered cycloalkyl or heteroxycloalkyl group, wherein the cycloalkyl group can be substituted with one or more of halo;
- wherein R15 is selected from substituted aryl, wherein the substitution is one or more of hydroxy, carboxylic acid, or benzohydroxamic acid;
- wherein R16 is (R)—CH(CH3);
- wherein Y is selected from CH or N;
- or a solvate, hydrate, or pharmaceutically acceptable salt thereof.
2 more elements
A compound represented by Formula VII:
- wherein W, X, Y, and Z each independently can include or exclude CH or N,
- wherein R21 is selected from optionally substituted aryl, optionally substituted heteroaryl, or an optionally substituted aryl fused with a heterocyclic ring,
- wherein the substituted aryl or substituted heteroaryl or the substituted aryl fused with a heterocyclic ring can be substituted with one or more of hydroxyl, carboxylic acid, carboxylate, hydroxamic acid, amide, alkyl amide, dialkylamide, alkoxyamino, alkyl carboxylic acid, C1-C6 alkyl, or halo,
- wherein n is selected from 1 to 3;
- or a solvate, hydrate, or pharmaceutically acceptable salt thereof.
2 more elements
A compound represented by Formula VIII:
- wherein W, X, Y, Z, and Q each independently can include or exclude CH or N,
- wherein d is selected from 0, 1, 2, 3, or 4,
- wherein R21 is selected from optionally substituted aryl, optionally substituted heteroaryl, or an optionally substituted aryl fused with a heterocyclic ring, and wherein R22 is halogen.
Dependencies are inferred from the claim text.