LACTAM-MODIFIED POLYPEPTIDE COMPOUNDS
A class of lactam-modified polypeptide compounds and the use thereof in the preparation of a drug for treating related diseases.
1 . A compound represented by the following formula or a pharmaceutically acceptable salt thereof,
SEQ ID NO1: YAibEGT FTSDY SIAibLD KK 1 AZ 0 K 0 Z 1 FZ 2 E 0 W LZ 3 AGG PSSGA PPPS 0
SEQ ID NO2: YAibEGT FTSDY SIAibLD KE 0 AQK 0 AFVK 1 W LIAGG PSSGA PPPS 0
SEQ ID NO3: YAibEGT FTSDY SIE 0 LD KK 0 AQK 1 AFVQW LIAGG PSSGA PPPS 0
SEQ ID NO4: YAibEGT FTSDY SIE 0 LD K 0 IAQK 1 AFVQW LIAGG PSSGA PPPS 0
wherein
Aib has a structure of
S 0 is selected from
Z 0 is selected from glutamine (Q) and asparagine (N);
Z 1 is selected from alanine (A) and glutamic acid (E);
Z 2 is selected from valine (V) and isoleucine (I);
Z 3 is selected from isoleucine (I) and leucine (L);
E 0 and K 0 indicate that the carboxyl group on the side chain of the glutamic acid and the amino group on the side chain of the lysine jointly form a lactam structure, and in this case, K 0 Z 1 FZ 2 E 0 has a structure of
E 0 AQK 0 has a structure of
E 0 LDKK 0 has a structure of
and E 0 LDK 0 has a structure of
K 1 indicates that the amino group on the side chain of the lysine is connected to —X—X 1 —X 2 , and has a structure of
X is selected from
R 1 and R 2 are each independently selected from H and CH 3 ;
X 1 is selected from
X 2 is selected from
m, n and p are each independently selected from 2 and 3;
s is selected from 2 and 3;
q is selected from 15, 16, 17, 18 and 19.
2 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , which is selected from:
3 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein X is selected from —C(═O)—CH 2 —.
4 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein m, n and p are each independently selected from 2.
5 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein s is independently selected from 2.
6 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein q is independently selected from 15 and 17.
7 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein X 1 is selected from
8 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein X 2 is selected from
9 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein —X—X 1 —X 2 is selected from
10 . A compound represented by the following formula or a pharmaceutically acceptable salt thereof, selected from:
11 . A method for treating obesity and diabetes in a subject in need thereof, comprising: administering the compound or the pharmaceutically acceptable salt thereof according to claim 1 to the subject.
12 . The compound or the pharmaceutically acceptable salt thereof according to claim 2 , wherein X is selected from —C(O)—CH 2 —.
13 . The compound or the pharmaceutically acceptable salt thereof according to claim 2 , wherein m, n and p are each independently selected from 2.
14 . The compound or the pharmaceutically acceptable salt thereof according to claim 2 , wherein s is independently selected from 2.
15 . The compound or the pharmaceutically acceptable salt thereof according to claim 2 , wherein q is independently selected from 15 and 17.
16 . The compound or the pharmaceutically acceptable salt thereof according to claim 2 , wherein X 1 is selected from
17 . The compound or the pharmaceutically acceptable salt thereof according to claim 2 , wherein X 2 is selected from
18 . The compound or the pharmaceutically acceptable salt thereof according to claim 2 , wherein —X—X 1 —X 2 is selected from
19 . A method for treating obesity and diabetes in a subject in need thereof, comprising: administering the compound or the pharmaceutically acceptable salt thereof according to claim 10 to the subject.