GLP-1 potentiators from hedychium coronarium and their applications
A compound for controlling blood glucose level has a structure shown in Formula I: wherein R5-R8 are as defined herein. A method for controlling blood glucose level includes administering to a subject in need thereof a compound of Formula I. The method further includes administering to the subject a GLP-1 receptor ligand. The compound and the GLP-1 receptor ligand may be administered together. The compound may be Galanal A or Galanal B. The GLP-1 receptor ligand may be GLP-1 or exendin-4.
1. A compound for controlling blood glucose level, wherein the compound has a structure shown in Formula I:
wherein
R 8 is H, —OH, or —O—R′;
R 5 is C 2 -C 4 alkenyl or C 7 -C 10 alkenyl, which is straight-chained or branched and is optionally substituted with one or more substituents selected from —OR′, —NR′R″, —SR′, oxo (═O), thioxo (═S), —CONR′R″, —CO 2 R′, or —CR′R″OH, wherein R′ and R″ are independently H, C 1 -C 10 alkyl or C 2 -C 10 alkenyl; or R 5 is a 5- or 6-membered ring that is a cycloalkyl or cycloalkenyl ring or a heterocyclic ring with one or more hetero atoms selected from N, O, or S, wherein the 5- or 6-membered ring is optionally substituted with one or more substituent selected from —OR′, —NR′R″, —SR′, oxo (═O), thioxo (═S), —CONR′R″, —CN, —CO 2 R′, or —CR′R″OH; and
R 6 and R 7 are independently selected from H (provided that R 6 and R 7 are not both H), C 1 -C 10 alkyl or C 2 -C 10 alkenyl, which is straight-chained or branched and is optionally substituted with one or more substituents selected from —OR′, —NR′R″, —SR′, oxo (═O), thioxo (═S), —CONR′R″, —CN, —CO 2 R′, or —CR′R″OH, or R 6 and R 7 jointly form ═CH 2 ;
wherein R′ and R″ are independently H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, cycloalkyl or C 6 -C 10 aryl;
or wherein
R 7 is —CHO, and R 5 and R 6 jointly form a ring, which is a 5 or 6-membered ring made of C, O, N, or S atoms or a combination thereof, wherein the ring has 0 or 1 double bond, and wherein the ring is optionally substituted with one or more alkyl side chains of 1-10 carbons (C 1 -C 10 ), and wherein the ring and/or the one or more alkyl side chains independently are optionally substituted with one or more substituents selected from —OR′, —NR′R″, —SR′, oxo (═O), thioxo (═S), —CONR′R″, —CN, —CO 2 R′, or —CR′R″OH.
2. The compound of claim 1 , wherein R 6 and R 7 jointly form ═CH 2 and the compound has a structure shown in Formula II:
3. A method for controlling blood glucose level, comprising administering to a subject in need thereof a compound of formula I shown below and a glucagon-like peptide-1 (GLP-1) receptor ligand,
wherein
R 8 is H, —OH, or —O—R′;
R 5 is C 1 -C 10 alkyl or C 2 -C 10 alkenyl, which is straight-chained or branched and is optionally substituted with one or more substituents selected from —OR′, —NR′R″, —SR′, oxo (═O), thioxo (═S), —CONR′R″, —CN, —CO 2 R′, or —CR′R″OH, wherein R′ and R″ are independently H, C 1 -C 10 alkyl or C 2 -C 10 alkenyl; or R 5 is a 5-, 6- or 7-membered ring that is a cycloalkyl or cycloalkenyl ring or a heterocyclic ring with one or more hetero atoms selected from N, O, or S, wherein the 5-, 6-, or 7-membered ring is optionally substituted with one or more substituent selected from —OR′, —NR′R″, —SR′, oxo (═O), thioxo (═S), —CONR′R″, —CN, —CHO, —CO 2 R′, or —CR′R″OH; and
R 6 and R 7 are independently selected from H (provided that R 6 and R 7 are not both H), C 1 -C 10 alkyl or C 2 -C 10 alkenyl, which is straight-chained or branched and is optionally substituted with one or more substituents selected from —OR′, —NR′R″, —SR′, oxo (═O), thioxo (═S), —CONR′R″, —CN, —CHO, —CO 2 R′, or —CR′R″OH, or R 6 and R 7 jointly form ═CH 2 ;
wherein R′ and R″ are independently H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 3 -C 10 cycloalkyl or C 6 -C 10 aryl;
or wherein
R 7 is —CHO, and R 5 and R 6 jointly form a ring, which is a 5, 6 or 7-membered ring made of C, O, N, or S atoms or a combination thereof, wherein the ring has 0 or 1 double bond, and wherein the ring is optionally substituted with one or more alkyl side chains of 1-10 carbons (C 1 -C 10 ), and wherein the ring and/or the one or more alkyl side chains independently are optionally substituted with one or more substituents selected from —OR′, —NR′R″, —SR′, oxo (═O), thioxo (═S), —CONR′R″, —CN, —CHO, —CO 2 R′, or —CR′R″OH.
4. The method of claim 3 , wherein the GLP-1 receptor ligand is GLP-1 or exendin-4.
5. The method of claim 3 , wherein the compound and the GLP-1 receptor ligand are administered together.
6. The method of claim 3 , wherein the compound is one selected from the following compounds:
7. The method of claim 6 , wherein the compound is
8. The method of claim 6 , wherein the compound is