Agents for treating disorders involving ryanodine receptors
AssigneeARMGO Pharma, Inc.
InventorsSandro BELVEDERE, Jiaming YAN
Life of this patent
Estimating the term…
Abstract
The present disclosure relates to 1,4-benzothiazepine derivatives and use thereof to treat conditions associated with ryanodine receptors that regulate calcium channel functioning in cells.
Claims35
A compound of Formula (I):
- wherein
- each R1a, R1b, R1c, and R1d is independently alkyl, haloalkyl, haloalkoxy, alkenyl, alkynyl, cycloalkyl, aryl, benzyl, heteroaryl, heterocyclyl, —CN, —NO2, —N3, —NR3R4, —OR5, —SO3H, —SO2R6, —OSO2R6, —S(O)R6, or —SR7, each of which is independently substituted or unsubstituted, or hydrogen or halogen;
- R2 is alkyl, haloalkyl, haloalkoxy, alkenyl, alkynyl, cycloalkyl, aryl, benzyl, heteroaryl, heterocyclyl, —C(O)NR3R4, —C(O)C(O)NR3R4, —C(O)R8, —C(O)OR8, or —C(O)C(O)OR8, each of which is independently substituted or unsubstituted;
- each R3 and R4 is independently alkyl, haloalkyl, haloalkoxy, alkenyl, alkynyl, cycloalkyl, aryl, benzyl, heteroaryl, or heterocyclyl, each of which is independently substituted or unsubstituted, or hydrogen or halogen;
- or R3 and R4 together with the nitrogen atom to which R3 and R4 are attached form a heterocyclic or heteroaromatic ring, which is unsubstituted or substituted;
- and
- each R5, R6, R7, and R8 is independently alkyl, haloalkyl, haloalkoxy, alkenyl, alkynyl, cycloalkyl, aryl, benzyl, heteroaryl, or heterocyclyl, each of which is independently substituted or unsubstituted, or hydrogen or halogen;
- or a pharmaceutically-acceptable salt thereof,
- provided that
- (a) compounds wherein (i) R1a, R1b, R1c, and R1d are each hydrogen;
- (ii) R1b is OH or methoxy;
- or (iii) R2 is —C(O)OtBu or —C(O)OCH2Ph, are excluded;
- (b) when R1d is methyl, then R2 is not 4-methoxybenzyl;
- and
- (c) when R1a is methyl, Cl, CN, or F, or when R1b is Br, then R2 is not methyl, —C(═O)H, —C(═O)Me, —C(═O)Et, or —C(═O)Ph.
5-8. (canceled)
15-18. (canceled)
The compound of claim 0, wherein R3 and R4 together with the nitrogen atom to which R3 and R4 are attached form a heterocyclic ring, which is unsubstituted or substituted.
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31-36. (canceled)
A method of treating a condition, the method comprising administering to a subject in need thereof a therapeutically-effective amount of a compound of Formula (I):
- wherein
- each R1a, R1b, R1c, and R1d is independently alkyl, haloalkyl, haloalkoxy, alkenyl, alkynyl, cycloalkyl, aryl, benzyl, heteroaryl, heterocyclyl, —CN, —NO2, —N3, —NR3R4, —OR5, —SO3H, —SO2R6, —OSO2R6, —S(O)R6, or —SR7, each of which is independently substituted or unsubstituted, or hydrogen or halogen;
- R2 is alkyl, haloalkyl, haloalkoxy, alkenyl, alkynyl, cycloalkyl, aryl, benzyl, heteroaryl, heterocyclyl, —C(O)NR3R4, —C(O)C(O)NR3R4, —C(O)R8, —C(O)OR8, or —C(O)C(O)OR8, each of which is independently substituted or unsubstituted;
- each R3 and R4 is independently alkyl, haloalkyl, haloalkoxy, alkenyl, alkynyl, cycloalkyl, aryl, benzyl, heteroaryl, or heterocyclyl, each of which is independently substituted or unsubstituted, or hydrogen or halogen;
- or R3 and R4 together with the nitrogen atom to which R3 and R4 are attached form a heterocyclic or heteroaromatic ring, which is unsubstituted or substituted;
- and
- each R5, R6, R7, and R8 is independently alkyl, haloalkyl, haloalkoxy, alkenyl, alkynyl, cycloalkyl, aryl, benzyl, heteroaryl, or heterocyclyl, each of which is independently substituted or unsubstituted, or hydrogen or halogen;
- or a pharmaceutically-acceptable salt thereof,
- provided that
- (a) compounds wherein (i) R1a, R1b, R1c, and R1d are each hydrogen;
- (ii) R1b is OH or methoxy;
- or (iii) R2 is —C(O)OtBu or —C(O)OCH2Ph, are excluded;
- (b) when R1d is methyl, then R2 is not 4-methoxybenzyl, and
- (c) when R1a is methyl, Cl, CN, or F, or when Rb is Br, then R2 is not methyl, —C(═O)H, —C(═O)Me, —C(═O)Et, or —C(═O)Ph.
39-60. (canceled)
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65-75. (canceled)
77-85. (canceled)
Dependencies are inferred from the claim text.