Heterocyclic amide compound, preparation method therefor and use thereof

1 . A compound of formula (IA), an optical isomer thereof or a pharmaceutically acceptable salt thereof,

wherein,

L 1 is selected from the group consisting of —O—, —NH— and a single bond;

R 1 is selected from the group consisting of H and C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with 1, 2 or 3 R;

R 2 and R 3 are each independently selected from the group consisting of H,

C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl and 5-6 membered heteroaryl, wherein the C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl or 5-6 membered heteroaryl is optionally substituted with 1, 2 or 3 R;

L 2 is selected from the group consisting of a single bond, —O—, —S—, —NH— and —NHC(═O)—;

R 4 is selected from the group consisting of

m is selected from the group consisting of 1, 2, 3, 4, 5 and 6;

R 5 is independently selected from the group consisting of OH, NH 2 , —CH 2 NH 2 ,

R 6 and R 7 are included in each instance of repeating unit of variable m, and in each instance,

R 6 and R 7 are each independently selected from the group consisting of H, halogen, N 3 , OH, SH, NH 2 , CN,

C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio and C 1-6 alkylamino, wherein the C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio or C 1-6 alkylamino is optionally substituted with 1, 2 or 3 R;

R 8 is selected from the group consisting of H, halogen, N 3 , OH, SH, NH 2 , CN,

and C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with 1, 2 or 3 R;

or, R 3 and R 8 are linked to form a 5-6 membered heterocyclic ring;

R 9 and R 12 are each independently selected from the group consisting of H and C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with 1, 2 or 3 R;

R 10 , R 11 , R 13 and R 14 are each independently selected from the group consisting of H, halogen, N 3 , OH, SH, NH 2 , CN and C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with 1, 2 or 3 R;

or, R 9 and R 13 are linked to form a carbon chain comprising 3-7 carbon atoms;

T is selected from the group consisting of N and CH;

R is independently selected from the group consisting of H, halogen, N 3 , OH, SH, NH 2 , CN,

C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, 5-6 membered heterocycloalkyl, phenyl and 5-10 membered heteroaryl, wherein the C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, 5-6 membered heterocycloalkyl, phenyl or 5-10 membered heteroaryl is optionally substituted with 1, 2 or 3 R′;

R′ is selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 and CH 3 ;

the 5-6 membered heterocycloalkyl, 5-6 membered heteroaryl, 4-10 membered heterocycloalkyl or 5-10 membered heteroaryl contains 1, 2 or 3 heteroatoms or heteroatom groups independently selected from the group consisting of —O—, —NH—, —S— and N.

2 . The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 1 , selected from:

wherein,

L 1 is selected from the group consisting of —O—, —NH— and a single bond;

R 1 is selected from the group consisting of H and C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with 1, 2 or 3 R;

R 2 and R 3 are each independently selected from the group consisting of H,

C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl and 5-6 membered heteroaryl, wherein the C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl or 5-6 membered heteroaryl is optionally substituted with 1, 2 or 3 R;

L 2 is selected from the group consisting of a single bond, —O—, —S—, —NH— and —NHC(═O)—;

R 4 is selected from the group consisting of

m is selected from the group consisting of 1, 2, 3, 4, 5 and 6;

R 5 is independently selected from the group consisting of OH, NH 2 , —CH 2 NH 2 ,

R 6 and R 7 are included in each instance of repeating unit of variable m, and in each instance,

R 6 and R 7 are each independently selected from the group consisting of H, halogen, N 3 , OH, SH, NH 2 , CN,

C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio and C 1-6 alkylamino, wherein the C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio or C 1-6 alkylamino is optionally substituted with 1, 2 or 3 R;

R 9 is independently selected from the group consisting of H and C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with 1, 2 or 3 R;

R 13 is independently selected from the group consisting of H, halogen, N 3 , OH, SH, NH 2 , CN and C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with 1, 2 or 3 R;

or, R 9 and R 13 are linked to form a carbon chain comprising 3-7 carbon atoms;

R is independently selected from the group consisting of H, halogen, N 3 , OH, SH, NH 2 , CN,

C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, 5-6 membered heterocycloalkyl, phenyl and 5-10 membered heteroaryl, wherein the C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, 5-6 membered heterocycloalkyl, phenyl or 5-10 membered heteroaryl is optionally substituted with 1, 2 or 3 R′;

R′ is selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 and CH 3 ;

the 5-6 membered heterocycloalkyl, 5-6 membered heteroaryl, 5-10 membered heterocycloalkyl or 5-10 membered heteroaryl contains 1, 2 or 3 heteroatoms or heteroatom groups independently selected from the group consisting of —O—, —NH—, —S— and N.

3 . The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 1 , wherein R is independently selected from the group consisting of H, halogen, N 3 , OH, SH, NH 2 , CN,

C 1-3 alkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 alkylamino, morpholinyl, phenyl, imidazolyl and indolyl, wherein the C 1-3 alkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 alkylamino, morpholinyl, phenyl, imidazolyl or indolyl is optionally substituted with 1, 2 or 3 R′.

4 . The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 3 , wherein R is independently selected from the group consisting of H, F, Cl, Br, I, N 3 , OH, SH, NH 2 , CN, Me,

5 . The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 1 , wherein R 1 is selected from the group consisting of H, Me,

6 . The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 5 , wherein the structural unit

is selected from the group consisting of H,

7 . The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 1 , wherein R4 is selected from the group consisting of

8 . The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 1 , wherein R4 is selected from the group consisting of

9 . The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 1 , wherein R 6 and R 7 are included in each instance of repeating unit of variable m, and in each instance, R 6 and R 7 are each independently selected from the group consisting of H, halogen, N 3 , OH, SH, NH 2 , CN,

C 1-3 alkyl, C 1-3 alkoxy,

C 1-3 alkylthio and C 1-3 alkylamino, wherein the C 1-3 alkyl, C 1-3 alkoxy, C 1-3 alkylthio or C 1-3 alkylamino is optionally substituted with 1, 2 or 3 R.

10 . The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 9 , wherein R 6 and R 7 are included in each instance of repeating unit of variable m, and in each instance, R 6 and R 7 are each independently selected from the group consisting of H, F, Cl, Br, I, N 3 , OH, SH, NH 2 , CN, Me,

11 . The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the structural unit

is selected from the group consisting of —CH 2 —,

12 . The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is selected from the group consisting of:

13 . A pharmaceutical composition, comprising the compound or the pharmaceutically acceptable salt thereof according to claim 1 .

14 . A method for the treatment of a STING-mediated disease or a STING-mediated tumor complication in a subject in need thereof, comprising administering the compound or the pharmaceutically acceptable salt thereof according to claim 1 to the subject, wherein the STING-mediated disease comprises a disease selected from the group consisting of cancer, inflammation, infectious diseases and immune-related diseases.

15 . The method according to claim 14 , wherein the cancer is selected from the group consisting of adrenocortical carcinoma, anal carcinoma, anorectal carcinoma, anal canal carcinoma, appendiceal carcinoma, cerebellar astrocytoma, cerebral astrocytoma, basal cell carcinoma, skin carcinoma (non-melanoma), biliary tract carcinoma, extrahepatic bile duct carcinoma, intrahepatic bile duct carcinoma, bladder carcinoma, osteoarticular carcinoma, osteosarcoma, malignant fibrous histiocytoma, brain carcinoma, brain tumors, brain stem glioma, ependymoma, medulloblastoma, visual pathway and hypothalamic gliomas, breast carcinoma, bronchial adenoma, nervous system carcinoma, nervous system lymphoma, central nervous system carcinoma, central nervous system lymphoma, cervical carcinoma, chronic lymphocytic leukemia, chronic myelogenous leukemia, chronic myeloproliferative disease, colon carcinoma, colorectal carcinoma, cutaneous T-cell lymphoma, lymphoid tumors, granuloma fungoides, Sezary syndrome, endometrial carcinoma, esophageal carcinoma, extracranial germ cell tumors, extragonadal germ cell tumors, eye carcinoma, intraocular melanoma, retinoblastoma, gallbladder carcinoma, gastric carcinoma, gastrointestinal carcinoids, gastrointestinal stromal tumors (GIST), germ cell tumors, ovarian germ cell tumors, head and neck carcinoma, hepatocellular carcinoma, Hodgkin lymphoma, islet cell tumors, Kaposi's sarcoma, kidney carcinoma, laryngeal carcinoma, acute lymphocytic leukemia, acute myelogenous leukemia, hairy cell leukemia, lip and oral cavity carcinoma, liver carcinoma, lung carcinoma, non-small-cell lung carcinoma, small cell lung carcinoma, non-Hodgkin's lymphoma, primary central nervous system lymphoma, Waldenstrom macroglobulinemia, melanoma, mesothelioma, metastatic squamous carcinoma, tongue carcinoma, multiple endocrine tumor syndrome, myelodysplastic syndrome, multiple myeloma, nasopharyngeal carcinoma, neuroblastoma, oropharyngeal carcinoma, ovarian carcinoma, ovarian epithelial carcinoma, ovarian low malignant potential tumors, pancreatic carcinoma, pancreatic islet cell pancreatic carcinoma, sinus and nasal cavity carcinoma, parathyroid carcinoma, penile carcinoma, pharyngeal carcinoma, pheochromocytoma, pinealoma, pituitary tumors, plasma cell tumors, pleuropulmonary blastoma, prostate carcinoma, rectal carcinoma, renal pelvis and ureter transitional cell carcinoma, retinoblastoma, rhabdomyosarcoma, salivary gland carcinoma, Ewing's sarcoma, Kaposi's sarcoma, synovial sarcoma, uterine carcinoma, uterine sarcoma, small intestine carcinoma, soft tissue sarcoma, squamous cell carcinoma, supratentorial primitive neuroectodermal tumors, testicular carcinoma, throat carcinoma, thymoma, urinary tract carcinoma, endometriosis, vaginal carcinoma, vulval carcinoma, and Wilm's tumors.

16 . The method according to claim 14 , wherein the STING-mediated tumor complication is selected from malignant pleural effusion and ascites.