US2023382932A1PendingUtilityA1
Cyclopentane-Based Modulators of STING (Stimulator of Interferon Genes)
Est. expiryMar 15, 2038(~11.7 yrs left)· nominal 20-yr term from priority
Inventors:Martin James WythesIndrawan James McalpineRyan PatmanEugene Yuanjin RuiAndrew FensomeAndreas MadernaMehran JalaieKetan Gajiwala
C07F 9/65744A61K 47/6801A61P 35/00C07H 19/213C07H 19/23A61K 31/7042
84
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
Compounds of the general formula (I):or a pharmaceutically acceptable salt thereof, processes for the preparation of these compounds, compositions containing these compounds, and the uses of these compounds.
Claims
exact text as granted — not AI-modifiedWe claim:
1 . A compound of formula (I):
or a pharmaceutically acceptable salt thereof, wherein
each J is independently oxygen (O) or sulfur (S);
R 1 is selected from:
R 2 is selected from:
W is OH, SH, O − M + or S − M + , where M + represents a cationic counter-ion;
X is OH, SH, O − M + or S − M + , where M + represents a cationic counter-ion;
each Y is independently selected from hydrogen, halogen, C 1 -C 6 alkyl, substituted C 1 -C 6 alkyl, N(R 3 ) 2 , and OR 4 , or the two Y substituents join to form a 3-5 membered spirocyclic ring system comprising 0-1 heteroatoms;
each Z is independently selected from hydrogen, halogen, C 1 -C 6 alkyl, substituted C 1 -C 6 alkyl, N(R 3 ) 2 , and OR 4 , or the two Z substituents join to form a 3-5 membered spirocyclic ring system comprising 0-1 heteroatoms; and
R 3 and R 4 are each independently hydrogen or C 1 -C 6 alkyl.
2 . A compound of formula (II):
or a pharmaceutically acceptable salt thereof, wherein
R 1 is selected from:
R 2 is selected from:
W is OH, SH, O − M + or S − M + , where M + represents a cationic counter-ion;
X is OH, SH, O − M + or S − M + , where M + represents a cationic counter-ion;
each Y is independently selected from hydrogen, halogen, C 1 -C 6 alkyl, substituted C 1 -C 6 alkyl, N(R 3 ) 2 , and OR 4 , or the two Y substituents join to form a 3-5 membered spirocyclic ring system comprising 0-1 heteroatoms;
each Z is independently selected from hydrogen, halogen, C 1 -C 6 alkyl, substituted C 1 -C 6 alkyl, N(R 3 ) 2 , and OR 4 , or the two Z substituents join to form a 3-5 membered spirocyclic ring system comprising 0-1 heteroatoms; and
R 3 and R 4 are each independently hydrogen or C 1 -C 6 alkyl.
3 . The compound or salt of claim 1 , wherein M + is selected from the group consisting of sodium, potassium, calcium, ammonium, triethylammonium, trimethylammonium and magnesium.
4 . The compound or salt of claim 1 , wherein each counter-ion M + is the same.
5 . The compound or salt of claim 1 , wherein R 1 is
and R 2 is
6 . The compound or salt of claim 1 , wherein R 1 is
and R 2 is
7 . The compound or salt of claim 1 , wherein R 1 is
and R 2 is
8 . The compound or salt of claim 1 , wherein R 1 is
and R 2 is
9 . The compound or salt of claim 1 , wherein R 1 is
and R 2 is
10 . The compound or salt of claim 1 , wherein R 1 is
and R 2 is
11 . The compound or salt of claim 1 , wherein R 1 is
and R 2 is
12 . The compound or salt of claim 1 , wherein R 1 is
and R 2 is
13 . The compound or salt of claim 1 , wherein R 1 is
and R 2 is
14 . The compound or salt of claim 1 , wherein R 1 is
and R 2 is
15 . The compound or salt of claim 1 , wherein R 1 is
and R 2 is
16 . The compound or salt of claim 1 , wherein R 1 is
and R 2 is
17 . The compound or salt of claim 1 , wherein R 1 is
and R 2 is
18 . The compound or salt of claim 1 , wherein one or both Y is halogen.
19 . The compound or salt of claim 1 , wherein one Y is hydrogen and the other Y is a halogen.
20 . The compound or salt of claim 19 , wherein said halogen is fluorine.
21 . The compound or salt of claim 1 , wherein one Z is hydrogen and the other Z is OR 4 .
22 . The compound or salt of claim 1 , wherein W is —SH and X is —SH.
23 . The compound or salt of claim 1 , wherein W is —OH and X is —OH.
24 . The compound or salt of claim 1 , wherein W is —SH and X is —OH.
25 . The compound or salt of claim 1 , wherein W is —OH and X is —SH.
26 . A compound selected from:
or a pharmaceutically acceptable salt thereof.
27 . A compound selected from:
or a pharmaceutically acceptable salt thereof.
28 . A compound selected from:
or a pharmaceutically acceptable salt thereof.
29 . A single diastereomer of a compound or salt according to any one of claims 1 , 2 and 26 - 28 .
30 . A pharmaceutical composition comprising a compound or salt according to any one of claims 1 and 26 , and a pharmaceutically acceptable carrier.
31 . A pharmaceutical composition comprising a compound or salt according to any one of claims 1 and 26 , wherein said compound is a component of an antibody-drug conjugate.
32 . A pharmaceutical composition comprising a compound or salt according to any one of claims 1 and 26 , wherein said compound is a component of a particle-based delivery system.
33 . A method of treating abnormal cell growth in a mammal, the method comprising administering to the mammal a therapeutically effective amount of a compound or salt according to any one of claims 1 and 26 .
34 . The method of claim 33 , wherein said compound or salt is a component of an antibody-drug conjugate.
35 . The method of claim 33 , wherein said compound or salt is a component of a particle-based delivery system.
36 . The method of claim 33 , wherein the abnormal cell growth is cancer.
37 . The method of claim 36 , wherein the cancer is lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, colon cancer, breast 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, 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, prostate cancer, chronic or acute leukemia, lymphocytic lymphomas, cancer of the bladder, cancer of the kidney or ureter, renal cell carcinoma, carcinoma of the renal pelvis, neoplasms of the central nervous system (CNS), primary CNS lymphoma, spinal axis tumors, brain stem glioma, or pituitary adenoma.
38 . Use of a compound or salt according to any one of 1 and 26 for the preparation of a medicament useful in the treatment of abnormal cell growth in a mammal.
39 . The use according to claim 38 , wherein said abnormal cell growth is cancer.
40 . The use according to claim 39 , wherein the cancer is lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, colon cancer, breast 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, 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, prostate cancer, chronic or acute leukemia, lymphocytic lymphomas, cancer of the bladder, cancer of the kidney or ureter, renal cell carcinoma, carcinoma of the renal pelvis, neoplasms of the central nervous system (CNS), primary CNS lymphoma, spinal axis tumors, brain stem glioma, or pituitary adenoma.
41 . A method of upregulating the activity of STING in a mammal, comprising the step of administering to said mammal an effective amount of a compound or salt according to any one of 1 and 26.
42 . A method of increasing interferon-beta levels in a mammal, comprising the step of administering to said mammal an effective amount of a compound or salt according to any one of 1 and 26.Cited by (0)
No later patents cite this yet.
References (0)
No backward citations on record.