US2016194295A1PendingUtilityA1
1,3,4-Oxadiazole and 1,3,4-Thiadiazole Derivatives as Immunomodulators
Est. expirySep 6, 2033(~7.2 yrs left)· nominal 20-yr term from priority
Inventors:Pottayil Govindan Nair SasikumarMuralidhara RamachandraSeetharamaiah Setty Sudarshan Naremaddepalli
A61P 31/00A61K 31/433C07D 285/12A61K 31/4245A61K 2300/00A61P 35/00A61K 45/06C07D 271/10
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Claims
Abstract
The present invention relates to 1,3,4-oxadiazole and 1,3,4-thiadiazole compounds as therapeutic agents capable of inhibiting the programmed cell death 1 (PD1) signalling pathway. The invention also refers to derivatives of the therapeutic agents. The invention also encompasses the use of the said therapeutic agents and derivatives for treatment of disorders via immunopotentiation comprising inhibition of immunosuppressive signal induced due to PD-1, PD-L1, or PD-L2 and therapies using them.
Claims
exact text as granted — not AI-modified1 : A compound of formula (I)
wherein,
R 1 is a side chain of an amino acid Ser, Thr, Phe, Ala or Asn;
X is S or O;
R 2 is hydrogen or —CO-Aaa;
Aaa is an amino acid residue Ser, Asn or Thr; wherein a C-terminus thereof is a free terminus, is amidated or is esterified;
R 3 is a side chain of an amino acid Ser, Ala, Glu, Gln, Asn or Asp;
is an optional bond;
R 4 and R 5 independently are hydrogen or absent;
or a pharmaceutically acceptable salt or a stereoisomer thereof.
2 : The compound according to claim 1 is a compound of formula (IA):
or a pharmaceutically acceptable salt or a stereoisomer thereof; wherein,
R 1 is a side chain of an amino acid Ser, Thr, Phe, Ala or Asn;
X is S or O;
R 2 is hydrogen or —CO-Aaa;
R 3 is a side chain of an amino acid Ser, Ala, Glu, Gln, Asn or Asp;
Aaa is an amino acid residue Ser, Asn or Thr; wherein a C-terminus thereof is a free terminus, is amidated or is esterified.
3 : The compound according to claim 1 , is a compound of formula (IB):
or a pharmaceutically acceptable salt or a stereoisomer thereof; wherein,
R 1 is a side chain of an amino acid Ser, Thr, Phe, Ala or Asn;
R 3 is a side chain of an amino acid Ser, Ala, Glu, Gln, Asn or Asp;
Aaa is an amino acid residue Ser, Asn or Thr; wherein a C-terminus thereof is a free terminus, is amidated or is esterified.
4 : The compound according to claim 1 , is a compound of formula (IC):
or a pharmaceutically acceptable salt or a stereoisomer thereof; wherein,
R 1 is a side chain of an amino acid Ser, Thr, Phe, Ala or Asn;
R 3 is a side chain of an amino acid Ser, Ala, Glu, Gln, Asn or Asp;
Aaa is an amino acid residue Ser, Asn or Thr; wherein a C-terminus thereof is a free terminus, is amidated or is esterified.
5 : The compound according to claim 1 , wherein X is O.
6 : The compound according to claim 1 , wherein X is S.
7 : The compound according to claim 1 , wherein
R 1 is a side chain of Ser or Thr; R 2 is —CO-Aaa; Aaa is an amino acid residue Ser or Thr; wherein the C-terminus is free; R 3 is a side chain of Asn, Gln, Glu or Asp.
8 : The compound according to claim 1 , wherein R 2 is hydrogen.
9 : A compound according to claim 1 selected from the group consisting of
Com-
pound
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Structure
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or a pharmaceutically acceptable salt or a stereoisomer thereof.
10 : A pharmaceutical composition comprising at least one compound according to claim 1 or a pharmaceutically acceptable salt or a stereoisomer thereof, and a pharmaceutically acceptable carrier or excipient.
11 : The pharmaceutical composition according to claim 10 , comprising at least one additional pharmaceutical agent wherein the said additional pharmaceutical agent is an anticancer agent, chemotherapy agent, or antiproliferative compound.
12 . (canceled)
13 : A method of treating a cancer or infectious disease in a subject, comprising administering to the subject therapeutically effective amount of the pharmaceutical composition according to claim 10 .
14 : The method according to claim 13 , wherein the cancer is bone cancer, cancer of the head or neck, pancreatic cancer, skin cancer, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, uterine cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, non-Hodgkin's lymphoma, 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 of soft tissue, cancer of the urethra, cancer of the penis, chronic or acute leukemias including acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, solid tumours of childhood, lymphocytic lymphoma, cancer of the bladder, cancer of the kidney or ureter, carcinoma of the renal pelvis, neoplasm of the central nervous system (CNS), primary CNS lymphoma, tumour angiogenesis, spinal axis tumour, brain stem glioma, pituitary adenoma, Kaposi's sarcoma, epidermoid cancer, squamous cell cancer, T-cell lymphoma, or environmentally induced cancers including those induced by asbestos, or combinations of said cancers.
15 : The method according to claim 13 , wherein the infectious disease is a bacterial infectious disease, a viral infectious disease or a fungal infectious disease.
16 : A method of modulating an immune response mediated by PD-1 signaling pathway in a subject, comprising administering to the subject therapeutically effective amount of a compound according to claim 1 .
17 : A method of inhibiting growth of tumour cells and/or metastasis in a subject, comprising administering to the subject a therapeutically effective amount of a compound according to claim 1 .
18 : The method of claim 15 , wherein the tumour cells are of a cancer selected from the group consisting of breast cancer, colon cancer, lung cancer, melanoma, prostate cancer and renal cancer.
19 : The method of claim 15 , wherein the tumour cells comprise bone cancer, cancer of the head or neck, pancreatic cancer, skin cancer, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, uterine cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, non-Hodgkin's lymphoma, 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 of soft tissue, cancer of the urethra, cancer of the penis, chronic or acute leukemias including acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, solid tumours of childhood, lymphocytic lymphoma, cancer of the bladder, cancer of the kidney or ureter, carcinoma of the renal pelvis, neoplasm of the central nervous system (CNS), primary CNS lymphoma, tumour angiogenesis, spinal axis tumour, brain stem glioma, pituitary adenoma, Kaposi's sarcoma, epidermoid cancer, squamous cell cancer, T-cell lymphoma, or environmentally induced cancers including those induced by asbestos, or combinations of said cancers.
20 : A method of treating an infectious disease in a subject comprising administering to the subject a therapeutically effective amount of compound according to claim 1 .
21 : A method of treating bacterial, viral and fungal infections in a subject comprising administering to the subject a therapeutically effective amount of a compound according to claim 1 .Cited by (0)
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