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US 2025/0019352 A1Published application
Pharmacological agents for treating ophthalmic diseases
AssigneePlex Pharmaceuticals, Inc.
InventorsSantosh C. SINHA, Sridhar Govinda PRASAD, Albert REMACLE, Boris RATNIKOV
Life of this patent
Estimating the term…
Abstract
Methods for treating ophthalmic diseases and disorders such as treating presbyopia or cataract in a subject in need thereof. The methods require administering to the subject an effective amount of a composition comprising a compound that inhibits the formation of high molecular weight aggregates of human α-A-crystallin and/or human α-B-crystallin.
Claims34
A compound of formula (I):
- or a pharmaceutically acceptable salt thereof,
- wherein
- A1 and A2 are, each independently, a six-membered aromatic or heteroaromatic ring comprising at least one heteroatom and at least one carbon atom;
- each of m and n is, independently, any number from 0 to 4;
- R1a is attached to one or more carbon atoms of A1;
- and R1b is attached to one or more carbon atoms of A2,
- R1a and R1b are, each independently, selected from the group consisting of:
- hydrogen;
- (C1-C6)alkyl;
- halo(C1-C6)alkyl;
- (C1-C6)alkoxy;
- halo(C1-C6)alkoxy;
- hydroxy(C1-C6)alkyl;
- (C1-C6)alkoxy(C1-C6)alkyl;
- (C2-C5)alkenyl;
- (C2-C5)alkynyl;
- SO2R2;
- CO2R2;
- NH2;
- (R2)(R2) wherein each R2 may be the same or different, (C1-C6)alkylamine;
- (C1-C6)dialkylamine;
- NHCOR2;
- hydroxyl;
- halogen;
- CN;
- NO2;
- (C3-C6)cycloalkyl, halo(C3-C6)cycloalkyl, and hydroxy(C3-C6)cycloalkyl;
- wherein more than one R1a may exist, and if more than one R1a is present, then each R1a may be the same or different,
- wherein more than one R1b may exist, and if more than one R1b is present, then each R1b may be the same or different, and
- wherein R2 is selected from hydrogen, (C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl, (C3-C6)cycloalkyl, halo(C3-C6)cycloalkyl, hydroxy(C3-C6)cycloalkyl, and (CH2)1-3CO2H.
27 more elements
A compound selected from the group consisting of:
- or a pharmaceutically acceptable salt thereof.
A compound of formula (II)
- or a pharmaceutically acceptable salt thereof,
- wherein
- A is a 5-10 membered heteroaryl or heteroaromatic ring comprising at least one heteroatom and at least one carbon atom, wherein A may be a monocyclic or bicyclic ring, wherein A is optionally substituted with one or more R1 groups, wherein each R1 is attached to one or more carbon atoms of A, and wherein when more than one R1 is present, then each R1 may be the same or different,
- R1 is optional, but when present, R1 is independently selected from the group consisting of:
- hydrogen;
- (C1-C6)alkyl;
- halo(C1-C6)alkyl;
- (C1-C6)alkoxy;
- halo(C1-C6)alkoxy;
- hydroxy(C1-C6)alkyl;
- (C1-C6)alkoxy(C1-C6)alkyl;
- (C2-C5)alkenyl;
- (C2-C5)alkynyl;
- SO2R2;
- (CH2)0-4CO2R2;
- NH2;
- NHR2;
- N(R2)(R2) wherein each R2 may be the same or different;
- (C1-C6)alkylamine;
- di(C1-C6)alkylamine;
- NHCOR2;
- hydroxyl;
- halogen;
- CN;
- and NO2;
- wherein R2 is selected from:
- hydrogen, (C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl, (C2-C5)alkenyl, (C1-C5)alkynyl, (C3-C6)cycloalkyl, halo(C3-C6)cycloalkyl, and hydroxy(C3-C6)cycloalkyl;
- W is a direct bond, CO, CS, or (CRARB)p, and
- X is a direct bond, 0, NH, or (CRARB)p,
- wherein each of RA and RB is independently selected from the group consisting of:
- hydrogen, halogen, and hydroxyl, wherein RA and RB may be the same or different,
- wherein p is any number between 0 and 4;
- and
- each of r and t is independently any number between 1 and 3.
31 more elements
A compound selected from the group consisting of:
- or a pharmaceutically acceptable salt thereof.
A compound of formula (III)
- or a pharmaceutically acceptable salt thereof,
- wherein
- A3 is a 5- or 6-membered aromatic or heteroaromatic ring comprising at least one heteroatom and at least one carbon atom, wherein A3 is optionally substituted with one or more R1 groups, wherein each R1 is attached to one or more carbon atoms of A3, and wherein when more than one R1 is present, then each R1 may be the same or different,
- R1 is attached to one or more carbon atoms of A3, and R1 is independently selected from the group consisting of:
- hydrogen;
- (C1-C6)alkyl;
- halo(C1-C6)alkyl;
- (C1-C6)alkoxy;
- halo(C1-C6)alkoxy;
- hydroxy(C1-C6)alkyl;
- (C1-C6)alkoxy(C1-C6)alkyl;
- (C2-C5)alkenyl;
- (C2-C5)alkynyl;
- SO2R2;
- (CH2)0-4CO2R2;
- NH2;
- NHR2;
- N(R2)(R2) wherein each R2 may be the same or different;
- (C1-C6)alkylamine;
- di(C1-C6)alkylamine;
- NHCOR2;
- hydroxyl;
- halogen;
- CN;
- and NO2;
- wherein R2 is selected from:
- hydrogen, (C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl, (C2-C5)alkenyl, (C2-C5)alkynyl, (C3-C6)cycloalkyl, halo(C3-C6)cycloalkyl, and hydroxy(C3-C6)cycloalkyl;
- and
- R3 and R4 are each independently selected from the group consisting of:
- hydrogen;
- (C1-C10) alkyl;
- halo(C1-C6)alkyl;
- hydroxy(C1-C6)alkyl;
- (C1-C6)alkoxy(C1-C6)alkyl;
- (C2-C5)alkenyl;
- (C2-C5)alkynyl;
- (C3-C6)cycloalkyl;
- halo(C3-C6)cycloalkyl;
- hydroxy(C3-C6)cycloalkyl;
- (CHR5)nCO2R5;
- or R3 and R4 together, with the nitrogen to which they are attached to, join together to form a 5-10 membered aromatic or heterocyclic ring or cyclic ring linked to the nitrogen with (CH2)1-4, optionally substituted at one or more ring atoms with (C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl, hydroxyl, CN, halogen, NH2;
- (C1-C6)alkylamine;
- di(C1-C6)alkylamine;
- and NO2,
- wherein R5 is independently selected from the group consisting of:
- hydrogen and a (C1-C6)alkyl and
- wherein n is any number from 0 and 4.
44 more elements
A compound selected from the group consisting of:
- or a pharmaceutically acceptable salt thereof.
A compound of formula (IV)
- formula (IV):
- or a pharmaceutically acceptable salt thereof,
- wherein
- A4 and A5 are each independently a 6-14 membered aromatic or heteroaromatic ring comprising at least one heteroatom and at least one carbon atom, wherein each of A4 and A5 are independently optionally substituted with R1a and R1b, respectively,
- wherein R1a and R1b are each independently optionally attached to one or more carbon atoms of the A4 and A5, respectively, and R1a and R1b are each independently selected from the group consisting of:
- hydrogen;
- (C1-C6)alkyl;
- halo(C1-C6)alkyl;
- (C1-C6)alkoxy;
- halo(C1-C6)alkoxy;
- hydroxy(C1-C6)alkyl;
- (C1-C6)alkoxy(C1-C6)alkyl;
- (C2-C5)alkenyl;
- (C2-C5)alkynyl;
- CO2R2;
- NH2;
- NHR2;
- N(R2)(R2) wherein each R2 may be the same or different (C1-C6)alkylamine;
- di(C1-C6)alkylamine;
- NHCOR2;
- hydroxyl;
- halogen;
- CN;
- and NO2;
- wherein R2 is selected from the group consisting of:
- hydrogen, (C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl, (C3-C6)cycloalkyl, halo(C3-C6)cycloalkyl, and hydroxy(C3-C6)cycloalkyl;
- each of R3a and R3b is independently hydrogen or (C1-C3)alkyl;
- and
- each of X1 and X2 is independently CHR4, wherein R4 is hydrogen or (C1-C3)alkyl, wherein X1 and X2 are the same or different
26 more elements
A compound selected from the group consisting of:
- or a pharmaceutically acceptable salt thereof.
A compound of formula (V):
- or a pharmaceutically acceptable salt thereof,
- wherein:
- XA is N or O;
- XB is S or CH;
- XC is N or CH;
- R1c is selected from the group consisting of:
- (CH2)1-3NH2, (CH2)1-3NH(R2), (CH2)1-3NR2R3, (CH2)1-3(C1-C6)alkylamine, and (CH2)1-3di(C1-C6)alkylamine, and N═CR2R3, wherein R2 and R3 are independently hydrogen or (C1-C6)alkyl and may be the same or different;
- R4a and R4b are each independently hydrogen or (C1-C6)alkyl, and R4a and R4b may be the same or different,
- R5 is (C1-C6)alkyl, (C2-C5)alkenyl, (C2-C5)alkynyl, or CH2CN;
- R6 is NH2, NHR2, N(R2)(R2) wherein each R2 may be the same or different, NO2 or (C1-C6)alkyl, wherein R2 is selected from the group consisting of:
- hydrogen, (C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl, (C3-C6)cycloalkyl, halo(C3-C6)cycloalkyl, and hydroxy(C3-C6)cycloalkyl;
- v is any number from 0 to 3;
- and
- x is any number from 0 to 3.
11 more elements
A compound selected from the group consisting of:
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.