N-pivaloylcysteine derivatives for the treatment of presbyopia
AssigneeLento Bio, Inc.
InventorKristopher BARNES
Life of this patent
Estimating the term…
Abstract
The present invention is based on the discovery that N-pivaloylcysteine, and its derivatives, function to improve lens flexibility and treat presbyopia. N-pivaloylcysteine and N-(2-fluoro-2-methyl-1-oxopropyl)-cysteine showed improvement relative to N-acetylcysteine in reducing lens stiffness and in aqueous humor penetration. The invention includes N-pivaloylcysteine and its derivatives, their pharmaceutical compositions, and methods of administering them for the prevention of ophthalmic conditions related to lens stiffness, including presbyopia.
Claims21
-28. (canceled)
A compound of the formula:
- wherein
- each R1 is independently optionally substituted C1-6 alkyl, C1-6 aryl, halogen, a halogen-containing group, or an ammonium group;
- R2 is OR4, SR4, SeR4, or N(R4)2;
- R3 is SR4, SeR4, or SC(O)—R4, where R4 is hydrogen or optionally substituted C1-6 alkyl, and pharmaceutically acceptable salts thereof;
- and
- wherein one or more of the R1 substituents is a halogen or halogen-containing group.
The compound N-(2-fluoro-2-methyl-1-oxopropyl)-cysteine of the formula:
- or a pharmaceutically-acceptable salt or ester thereof.
A pharmaceutically acceptable ophthalmic composition comprising a compound according to claim 1 and one or more pharmaceutically acceptable excipients selected from the group consisting of tonicity modulators, buffers, surfactants, thickeners, corneal penetration enhancers, stabilizers, preservatives, antioxidants, solubilizers, suspending agents, pH adjusters, excipients, binders, fluidizers, lubricants, and solvents.
A method of reducing eye lens stiffness, comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of the formula:
- wherein
- each R1 is independently optionally substituted C1-6 alkyl, C1-6 aryl, halogen, a halogen-containing group, or an ammonium group;
- R2 is OR4, SR4, SeR4, or N(R4)2 and
- R3 is SR4, SeR4, or SC(O)—R4, where R4 is hydrogen or optionally substituted C1-6 alkyl, and pharmaceutically acceptable salts thereof.
A method of treating presbyopia, comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of the formula:
- wherein
- each R1 is independently optionally substituted C1-6 alkyl, C1-6 aryl, halogen, a halogen-containing group, or an ammonium group;
- R2 is OR4, SR4, SeR4, or N(R4)2 and
- R3 is SR4, SeR4, or SC(O)—R4, where R4 is hydrogen or optionally substituted C1-6 alkyl, and pharmaceutically acceptable salts thereof.
Dependencies are inferred from the claim text.