1. A method for modulating immune response in a biological sample, comprising the steps
of:
a. obtaining a first biological sample and determining TIGIT overexpression in the
biological sample;
b. obtaining a second biological sample, independently, and determining PD-L1 and/or
PD-L2 overexpression in the biological sample; and
c. contacting the first biological sample and the second biological sample, independently,
with the compound of formula (I) or a stereoisomer thereof or a pharmaceutically
acceptable salt thereof:

for modulating immune response in the biological sample,
wherein,
R1 represents hydrogen, -(C1-C6)alkyl optionally substituted with -OH, -COOH, aryl,
heteroaryl, or aryl-OH;
R2 represents hydrogen, -(C1-C6)alkyl optionally substituted with -OH, -SH, C(O)NH2,
-COOH, aryl, heteroaryl, or aryl-OH;
Ra represents hydrogen; or Ra and R2 taken together with the atom to which they are
attached form a pyrrolidine ring;
R3 represents hydrogen or a group represented by formula (I’),
(I’);
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----- represents point of attachment;
Rb represents hydrogen; or Rb and Rc taken together with the atoms to which they are
attached form a pyrrolidine ring; and
Rc represents hydrogen, -(C1-C6)alkyl optionally substituted with -OH, -C(O)NH2,
COOH, aryl, or aryl-OH.
2. The method as claimed in claim 1, wherein the compound is represented by compound
of formula (IA),
;
wherein, R1, R2, Ra, Rb, and Rc are as defined in claim 1.
3. The method as claimed in claim 1, wherein
R1 represents -(C1-C6)alkyl optionally substituted with -OH, -COOH, imidazolyl,
phenyl, or (p-OH)phenyl;
R2 represents hydrogen, -(C1-C6)alkyl substituted with -OH, -SH, -COOH, phenyl,
imidazolyl, or (p-OH)phenyl;
Ra represents hydrogen; or Ra and R2 taken together with the atom to which they are
attached form a pyrrolidine ring;
Rb represents hydrogen; or Rb and Rc taken together with the atoms to which they are
attached form a pyrrolidine ring; and
Rc represents hydrogen, -(C1-C6)alkyl optionally substituted with -OH, -C(O)NH2, -
COOH, phenyl, or (p-OH)phenyl.
4. The method as claimed in any one of claims 1 to 3, wherein the compound is
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Compound No. Structure
1
;
2
;
3
;
4
;
5
;
6
;
7
;
86
Compound No. Structure
8
;
9
;
10
;
11
;
12
;
13
;
14
;
87
Compound No. Structure
15
;
16
;
17
;
18
;
19
; or
20
;
or a pharmaceutically acceptable salt or a stereoisomer thereof.
5. The method as claimed in claim 1, wherein the biological sample is selected from whole
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blood, plasma, serum, cells (e.g., tumor cells), saliva, urine, stool and tissue.
6. The method as claimed in claims 1 to 5, wherein the immune response is mediated by
both TIGIT signalling pathway and PD-1 signalling pathway.
7. The method as claimed in claim 6, wherein the immune response mediated by both
TIGIT signalling pathway and PD-1 signalling pathway is selected from cancer,
immune disorders, immunodeficiency disorders, inflammatory disorders, infectious
diseases, and transplant rejection.
8. The method as claimed in claim 7, wherein the cancer is selected from blastoma, breast
cancer, epithelial cancer, colon cancer, lung cancer, melanoma, prostate cancer, renal
cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, uterine
cancer, ovarian cancer, colorectal cancer, rectal cancer, cancer of the anal region, cancer
of the peritoneum, stomach cancer, testicular cancer, carcinoma of the fallopian tubes,
carcinoma of the endometrium, cervical cancer, vaginal cancer, vulval cancer, cancer
of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer
of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland,
sarcoma, cancer of the urethra, cancer of the penis, chronic or acute leukemia, solid
tumors of childhood, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, cutaneous T
cell lymphoma, mesothelioma, thymic carcinoma, myeloma, cancer of the bladder,
cancer of the ureter, carcinoma of the renal pelvis, liver cancer, pancreatic cancer, posttransplant lymphoproliferative disorder (PTLD), neoplasm of the central nervous
system (CNS), tumor angiogenesis, spinal axis tumor, brain stem glioma, pituitary
adenoma, epidermoid cancer, salivary gland carcinoma, squamous cell cancer,
abnormal vascular proliferation associated with phakomatoses, edema (such as that
associated with brain tumors), Meigs’ syndrome, Merkel cell carcinoma, and
environmentally induced cancers.
9. The method as claimed in claim 7, wherein the infectious disease is selected from at
least one bacterium selected from anthrax, Bacilli, Bordetella, Borrelia, botulism,
Brucella, Burkholderia, Campylobacter, Chlamydia, cholera, Clostridium, Conococcus,
Corynebacterium, diptheria, Enterobacter, Enterococcus, Erwinia, Escherichia,
Francisella, Haemophilus, Heliobacter, Klebsiella, Legionella, Leptospira,
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leptospirosis, Listeria, Lyme’s disease, meningococcus, Mycobacterium, Mycoplasma,
Neisseria, Pasteurella, Pelobacter, plague, Pneumonococcus, Proteus, Pseudomonas,
Rickettsia, Salmonella, Serratia, Shigella, Staphylococcus, Streptococcus, tetanus,
Treponema, Vibrio, Yersinia, and Xanthomonas; at least one virus selected from
arboviral encephalitis virus, adenovirus, herpes simplex type I, herpes simplex type 2,
Varicella-zoster virus, Epstein-barr virus, cytomegalovirus, herpesvirus type 8,
papillomavirus, BK virus, coronavirus, echovirus, JC virus, smallpox, Hepatitis B,
bocavirus, parvovirus B19, astrovirus, Norwalk virus, coxsackievirus, Hepatitis A,
poliovirus, rhinovirus, severe acute respiratory syndrome virus, Hepatitis C, yellow
fever, dengue virus, West Nile virus, rubella, Hepatitis E, human immunodeficiency
virus (HIV), human T-cell lymphotropic virus (HTLV), influenza, guanarito virus,
Junin virus, Lassa virus, Machupo virus, Sabia virus, Crimean- Congo hemorrhagic
fever virus, ebola virus, Marburg virus, measles virus, molluscum virus, mumps virus,
parainfluenza, respiratory syncytial virus, human metapneumovirus, Hendra virus,
Nipah virus, rabies, Hepatitis D, rotavirus, orbivirus, coltivirus, vaccinia virus, and
Banna virus; a fungal infection selected from thrush, Aspergillus (fumigatus, niger,
etc.), Blastomyces dermatitidis, Candida (albicans, krusei, glabrata, tropicalis, etc.),
Coccidioides immitis, Cryptococcus (neoformans, etc.), Histoplasma capsulatum,
Mucorales (mucor, absidia, rhizophus), Paracoccidioides brasiliensis,, sporotrichosis,
Sporothrix schenkii, zygomycosis, chromoblastomycosis, lobomycosis, mycetoma,
onychomycosis, piedra pityriasis versicolor, tinea barbae, tinea capitis, tinea corporis,
tinea cruris, tinea favosa, tinea nigra, tinea pedis, otomycosis, phaeohyphomycosis, and
rhinosporidiosis; and at least one parasite selected from Acanthamoeba, Babesia
microti, Balantidium coli, Entamoeba hystolytica, Giardia lamblia, Cryptosporidium
muris, Trypanosomatida gambiense, Trypanosomatida rhodesiense, Trypanosoma
brucei, Trypanosoma cruzi, Leishmania mexicana, Leishmania braziliensis,
Leishmania tropica, Leishmania donovani, Toxoplasma gondii, Plasmodium vivax,
Plasmodium ovale, Plasmodium malariae, Plasmodium falciparum, Pneumocystis
carinii, Trichomonas vaginalis, Histomonas meleagridis, Secementea, Trichuris
trichiura, Ascaris lumbricoides, Enterobius vermicularis, Ancylostoma duodenale,
Naegleria fowleri, Necator americanus, Nippostrongylus brasiliensis, Strongyloides
stercoralis, Wuchereria bancrofti, Dracunculus medinensis, blood flukes, liver flukes,
intestinal flukes, lung flukes, Schistosoma mansoni, Schistosoma haematobium,
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Schistosoma japonicum, Fasciola hepatica, Fasciola gigantica, Heterophyes
heterophyes, and Paragonimus westermani.
10. The method as claimed in claims 1 to 4, wherein the compound
is
(Compound 19) or a pharmaceutically acceptable salt thereof.