Esters of 8-methyl-8-azabicyclo[3.2.1] octan-3-yl 3-hydroxy-2-phenylpropanoate
AssigneeADS Therapeutics LLC
InventorsJinsong Ni, Rong Yang, Wenkui Fang
Life of this patent
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Abstract
In one general aspect, the present disclosure provides fatty acid esters of atropine, or a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprising these esters is also provided. In one example, the composition comprises a semifluorinated alkane vehicle, such as perfluorohexyloctane (F6H8). Method of using the fatty esters of atropine include medical fields where atropine is known to be useful. In one example, the disclosure provides methods of using the compound as cycloplegic agent and/or as mydriatic.
Claims12
A compound of Formula (I):
- or a pharmaceutically acceptable salt thereof, wherein:
- R3 is selected from H, C1-6 alkyl, and C1-6 haloalkyl;
- each R2 is independently selected from C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, OH, NO2, CN, halo, amino, C1-3 alkylamino, di(C1-3 alkyl)amino, carbamyl, carboxy, aminosulfonyl, and aminosulfonylamino;
- n is selected from 0, 1, 2, 3, 4, and 5;
- and
- R1 is selected from C7-34 alkyl, C7-34 alkenyl, C7-34 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 5-14 membered heteroaryl, and C6-10 aryl, wherein said C7-34 alkyl, C7-34 alkenyl, and C7-34 alkynyl are each optionally substituted with 1 or 2 substituents independently selected from C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 5-14 membered heteroaryl, and C6-10 aryl, and each of said C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 5-14 membered heteroaryl, and C6-10 aryl is optionally substituted with 1, 2, or 3 substituents independently selected from C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, OH, NO2, CN, halo, amino, C1-3 alkylamino, di(C1-3 alkyl)amino, carbamyl, carboxy, aminosulfonyl, and aminosulfonylamino;
- with a proviso that the compound of Formula (I) is not atropine oleate or hyoscyamine oleate.
A method for causing a condition selected from cycloplegic refraction and mydriasis in the eye of the subject, for relieving an eye floater symptom in a subject, for patching therapy for children with amblyopia or lazy eye, or for treating or preventing a condition selected from painful ciliary muscle spasm in the eye and a myopia progression, the method comprising administering to an eye of the subject an ophthalmic composition comprising a compound of Formula (I):
- or a pharmaceutically acceptable salt thereof, wherein:
- R3 is selected from H, C1-6 alkyl, and C1-6 haloalkyl;
- each R2 is independently selected from C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, OH, NO2, CN, halo, amino, C1-3 alkylamino, di(C1-3 alkyl)amino, carbamyl, carboxy, aminosulfonyl, and aminosulfonylamino;
- n is selected from 0, 1, 2, 3, 4, and 5;
- and
- R1 is selected from C7-34 alkyl, C7-34 alkenyl, C7-34 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 5-14 membered heteroaryl, and C6-10 aryl, wherein said C7-34 alkyl, C7-34 alkenyl, and C7-34 alkynyl are each optionally substituted with 1 or 2 substituents independently selected from C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 5-14 membered heteroaryl, and C6-10 aryl, and each of said C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 5-14 membered heteroaryl, and C6-10 aryl is optionally substituted with 1, 2, or 3 substituents independently selected from C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, OH, NO2, CN, halo, amino, C1-3 alkylamino, di(C1-3 alkyl)amino, carbamyl, carboxy, aminosulfonyl, and aminosulfonylamino.
A pharmaceutical composition comprising:
- i) a compound of Formula (I):
- or a pharmaceutically acceptable salt thereof, wherein:
- R3 is selected from H, C1-6 alkyl, and C1-6 haloalkyl;
- each R2 is independently selected from C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, OH, NO2, CN, halo, amino, C1-3 alkylamino, di(C1-3 alkyl)amino, carbamyl, carboxy, aminosulfonyl, and aminosulfonylamino;
- n is selected from 0, 1, 2, 3, 4, and 5;
- and
- R1 is selected from C7-34 alkyl, C7-34 alkenyl, C7-34 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 5-14 membered heteroaryl, and C6-10 aryl, wherein said C7-34 alkyl, C7-34 alkenyl, and C7-34 alkynyl are each optionally substituted with 1 or 2 substituents independently selected from C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 5-14 membered heteroaryl, and C6-10 aryl, and each of said C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 5-14 membered heteroaryl, and C6-10 aryl is optionally substituted with 1, 2, or 3 substituents independently selected from C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, OH, NO2, CN, halo, amino, C1-3 alkylamino, di(C1-3 alkyl)amino, carbamyl, carboxy, aminosulfonyl, and aminosulfonylamino;
- and
- ii) a pharmaceutically acceptable carrier comprising a semifluorinated alkane.
Dependencies are inferred from the claim text.