Therapy for erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP)
AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsXiaochao Ma, Junjie Zhu, Jie Lu
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Abstract
Disclosed are novel compositions and methods of using the same for the treatment of Erythropoiefic protoporphyria (EPP) and X-linked protoporphyria (XLP). Disclosed are methods and compositions related to treating Erythropoietic protoporphyria and X-linked protoporphyria. Also described are therapeutic agents that can inhibit ABCG2. For example, provided herein are therapeutic agents defined by Formula I.
Claims8
A compound defined by Formula IA below
- wherein
- n is an integer of from 0 to 6;
- R6 and R7 are each independently selected from the group consisting of H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, are optionally substituted with 1, 2, 3, or 4 independently selected RA groups, or R6 and R7, together with the N atom to which they are attached, form a 4-9 membered heterocycloalkyl group or a 5-6 membered heteroaryl group, each optionally substituted with 1, 2, or 3 independently selected RA groups;
- and
- each RA is independently selected from OH, NO2, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-C1-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, thio, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl) carbamyl, carboxy, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di(C1-6 alkyl)aminosulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, di(C1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C1-6 alkylaminocarbonylamino, and di(C1-6 alkyl)aminocarbonylamino;
- or a pharmaceutically acceptable salt, ester, or N-oxide thereof.
A compound defined by Formula IB below
- wherein
- n is an integer of from 0 to 6;
- R8 and R9 are independently selected from the group consisting of H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, are optionally substituted with 1, 2, 3, or 4 independently selected RA groups, or R8 and R9, together with the atoms to which they are attached, form a 4-9 membered heterocycloalkyl group or a 5-6 membered heteroaryl group, each optionally substituted with 1, 2, or 3 independently selected RA groups;
- and
- each RA is independently selected from OH, NO2, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-C1-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, thio, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl) carbamyl, carboxy, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di(C1-6 alkyl)aminosulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, di(C1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C1-6 alkylaminocarbonylamino, and di(C1-6 alkyl)aminocarbonylamino;
- or a pharmaceutically acceptable salt, ester, or N-oxide thereof.
A compound defined by Formula IC below
- wherein
- n is an integer of from 0 to 6;
- R6 and R7 are each independently selected from the group consisting of H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, are optionally substituted with 1, 2, 3, or 4 independently selected RA groups, or R6 and R7, together with the N atom to which they are attached, form a 4-9 membered heterocycloalkyl group or a 5-6 membered heteroaryl group, each optionally substituted with 1, 2, or 3 independently selected RA groups;
- and
- each RA is independently selected from OH, NO2, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-C1-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, thio, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl) carbamyl, carboxy, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di(C1-6 alkyl)aminosulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, di(C1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C1-6 alkylaminocarbonylamino, and di(C1-6 alkyl)aminocarbonylamino;
- or a pharmaceutically acceptable salt, ester, or N-oxide thereof.
A compound defined by Formula ID below
- wherein
- n is an integer of from 0 to 6;
- X is selected from the group consisting of CH2, O and S;
- R10 is selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C(O)Rb, C3-10 cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, are optionally substituted with 1, 2, 3, or 4 independently selected RA groups;
- and
- each RA is independently selected from OH, NO2, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-C1-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, thio, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl) carbamyl, carboxy, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di(C1-6 alkyl)aminosulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, di(C1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C1-6 alkylaminocarbonylamino, and di(C1-6 alkyl)aminocarbonylamino;
- or a pharmaceutically acceptable salt, ester, or N-oxide thereof.
Dependencies are inferred from the claim text.