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US 2014/0350100 A1Published application
Glucagon-like peptide 1 (glp-1) receptor modulators and uses thereof in regulating blood glucose levels
AssigneesAcademia Sinica, Chi-Ming Liang
InventorsKlim King, Rong-Jie Chein
Life of this patent
Estimating the term…
Abstract
The present disclosure provides novel glucagon-like peptide-1 (GLP-1) receptor modulators such as compounds of Formula (I) or (II), and pharmaceutically acceptable salts thereof. The present disclosure also provides pharmaceutical compositions, kits, and uses that involve the GLP-1 receptor modulators for regulating blood glucose levels and/or treating diabetes via, e.g., modulating the endogenous signaling pathways mediated by the GLP-1 receptor.
Claims29
A compound of Formula (I):
- or a pharmaceutically acceptable salt thereof, wherein:
- GA is hydrogen, ═O, ═S, —OR″, —SR″, —N(R″)2, alkenyl, alkynyl, an amide group, an ester group, a phosphate group, an aldehyde group, a nitrile group, an imino group, a ketone group, a thione group, an isonitrile group, an isothiocyanide group, a carbamate group, a thiocarbamate group, or a cyclic or acyclic, substituted or unsubstituted, branched or unbranched, (hetero)aliphatic group having 1 to 6 carbon atoms, wherein each instance of R″ is independently hydrogen, a cyclic or acyclic, saturated or unsaturated, substituted or unsubstituted, branched or unbranched, (hetero)aliphatic group having 1 to 16 carbon atoms;
- RA1, RA2, RA3, RA4, RA5, RA6, RA7, RA8, RA9, and RA10 are each independently hydrogen, halogen, —OR″, —N(R″)2, a carboxyl group, or a cyclic or acyclic, substituted or unsubstituted, branched or unbranched, (hetero)aliphatic group having 1 to 6 carbons, or RA1 and RA2 are joined to form ═O, or RA3 and RA4 are joined to form alkenyl;
- RA11, RA13, RA15, and RA17 are each independently hydrogen, halogen, or a cyclic or acyclic, substituted or unsubstituted, branched or unbranched, (hetero)aliphatic group having 1 to 6 carbon atoms;
- RA12, RA14, and RA16 are each independently halogen, —N(R″)2, —SR″, —OR″, alkyl, alkenyl, alkynyl, an amide group, a carboxyl group, an ester group, an aldehyde group, a nitrile group, an imino group, a ketone group, a thione group, an isonitrile group, an isothiocyanide group, a urea group, a carbamate group, or a thiocarbamate group, or RA14 and RA15 are joined to form ═O or ═S;
- RA20 is hydrogen, halogen, or a cyclic or acyclic, substituted or unsubstituted, branched or unbranched, (hetero)aliphatic group having 1 to 6 carbon atoms;
- and
- RA21 is hydrogen, halogen, —N(R″)2, —SR″, —OR″, —CH2OR″, alkenyl, alkynyl, an amide group, a carboxyl group, an ester group, an aldehyde group, a nitrile group, an imino group, a ketone group, a thione group, an isonitrile group, an isothiocyanide group, a carbamate group, a thiocarbamate group, or a cyclic or acyclic, substituted or unsubstituted, branched or unbranched, (hetero)aliphatic group having 1 to 6 carbon atoms;
- provided that:
- (i) at least one of RA1, RA2, RA5, RA7, RA8, RA9, RA10, RA11, RA12, RA13, RA15, RA16, and RA17 is not hydrogen;
- (ii) at least one of RA3, RA4, and RA6 is not —CH3;
- or
- (iii) when RA21 is —CHO and GA is —OH or ═O, RA14 and RA15 are each not —CHO.
10 more elements
4-6. (canceled)
(canceled)
(canceled)
(canceled)
14-16. (canceled)
A compound of Formula (II):
- or a pharmaceutically acceptable salt thereof, wherein:
- G is hydrogen, ═O, ═S, —NR′H, —SR′, or —OR′, wherein R′ is hydrogen, an ester group, a ketone group, a thione group, or a cyclic or acyclic, saturated or unsaturated, substituted or unsubstituted, branched or unbranched, (hetero)aliphatic group having 1 to 16 carbon atoms;
- W is —O—, —S— or —NR′—;
- X and Y are each independently a single bond or a saturated or unsaturated, substituted or unsubstituted, branched or unbranched, (hetero)aliphatic group having 1 to 3 carbon atoms;
- R1, R2, R3, R4, R5, R6, R7, R8, R9, R12 and R13 are each independently hydrogen, halogen, or a cyclic or acyclic, substituted or unsubstituted, branched or unbranched, (hetero)aliphatic group having 1 to 6 carbon atoms, or R2 and R3 may join to form cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
- R10 and R11 are each independently hydrogen, halogen, an amino group, an amide group, an ester group, an aldehyde group, a nitrile, an imino group, a ketone group, a thione group, an isonitrile group, an isothiocyanide group, a carbamate group, a thiocarbamate group, or a cyclic or acyclic, saturated or unsaturated, substituted or unsubstituted, branched or unbranched, (hetero)aliphatic group having 1 to 6 carbon atoms;
- R14 is hydrogen or a saturated or unsaturated, substituted or unsubstituted, branched or unbranched, (hetero)aliphatic group having 1-16 carbon atoms;
- R15 is hydrogen or a saturated or unsaturated, substituted or unsubstituted, branched or unbranched, (hetero)aliphatic group having 1-6 carbon atoms;
- and
- R21 is
- or an aldehyde group;
- provided that:
- (i) at least one of R4, R5, R6, R7, R8, R9, and R10 is not hydrogen;
- (ii) R1 is not —CH3;
- or
- (iii) when R21 is —CHO and G is —OH or ═O, R11 is not —CHO.
13 more elements
20-21. (canceled)
23-24. (canceled)
(canceled)
28-29. (canceled)
Dependencies are inferred from the claim text.