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US 8,673,898 B2Granted
Aminodiazepines as toll-like receptor modulators
AssigneeArray BioPharma Inc.
InventorsGeorge A. Doherty, Zachary Jones
Life of this patent
Estimating the term…
Abstract
Provided are compositions and methods useful for modulation signaling through the Toll-like receptor TLR8. The compositions and methods have use in the treatment of autoimmunity, inflammation allergy, asthma, graft rejection, graft versus host disease, infection, sepsis, cancer and immunodeficiency.
Claims20
A method of treating cancer, comprising administering to a mammal in need thereof an effective amount of a compound of the Formula
- and tautomers and pharmaceutically acceptable salts thereof, wherein:
- said cancer is selected from biliary tract cancer, brain cancer, breast cancer, cervical cancer, choriocarcinoma, colon cancer, endometrial cancer, esophageal cancer, gastric cancer, intraepithelial neoplasms, leukemia, lymphoma, liver cancer, lung cancer, melanoma, neuroblastomas, oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, renal cancer, sarcomas, skin cancer, testicular cancer, thyroid cancer, other carcinomas and sarcomas;
- Z is H, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR6 or NR6R7, wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, F, Cl, Br, I, CN, OR6, NR6R7, C(═O)R6, C(═O)OR6, OC(═O)R6, C(═O)NR6R7, (C1-C6 alkyl)amino, CH3OCH2O—, R6OC(═O)CH═CH2—, NR6SO2R7, SR6 and SO2R6;
- R1, R2, R3 and R4 are independently selected from H, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl and heteroaryl, wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, F, Cl, Br, I, CN, OR6, NR6R7, C(═O)R6, C(═O)OR6, OC(═O)R6, C(═O)NR6R7, (C1-C6 alkyl)amino, CH3OCH2O—, R6OC(═O)CH═CH2—, NR6SO2R7, SR6 and SO2R6,
- or R1 and R2 together with the atom to which they are attached form a saturated or partially unsaturated carbocyclic ring, wherein said carbocyclic ring is optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, F, Cl, Br, I, CN, OR6, NR6R7, C(═O)R6, C(═O)OR6, OC(═O)R6, C(═O)NR6R7, (C1-C6 alkyl)amino, CH3OCH2O—, R6OC(═O)CH═CH2—, NR6SO2R7, SR6 and SO2R6,
- or R3 and R4 together are oxo;
- each R5 is independently selected from H, F, Cl, Br, I, OMe, CH3, CH2F, CHF2, CF3 and CF2CF3;
- R6 and R7 are independently selected from H or alkyl;
- and
- n is 0, 1, 2, 3 or 4;
- such that said cancer is treated.
8 more elements
A method of treating allergy, comprising administering to a mammal in need thereof an effective amount of a compound of the Formula
- and tautomers and pharmaceutically acceptable salts thereof, wherein:
- Z is H, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR6 or NR6R7, wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, F, Cl, Br, I, CN, OR6, NR6R7, C(═O)R6, C(═O)OR6, OC(═O)R6, C(═O)NR6R7, (C1-C6 alkyl)amino, CH3OCH2O—, R6OC(═O)CH═CH2—, NR6SO2R7, SR6 and SO2R6;
- R1, R2, R3 and R4 are independently selected from H, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl and heteroaryl, wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, F, Cl, Br, I, CN, OR6, NR6R7, C(═O)R6, C(═O)OR6, OC(═O)R6, C(═O)NR6R7, (C1-C6 alkyl)amino, CH3OCH2O—, R6OC(═O)CH═CH2—, NR6SO2R7, SR6 and SO2R6,
- or R1 and R2 together with the atom to which they are attached form a saturated or partially unsaturated carbocyclic ring, wherein said carbocyclic ring is optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, F, Cl, Br, I, CN, OR6, NR6R7, C(═O)R6, C(═O)OR6, OC(═O)R6, C(═O)NR6R7, (C1-C6 alkyl)amino, CH3OCH2O—, R6OC(═O)CH═CH2—, NR6SO2R7, SR6 and SO2R6,
- or R3 and R4 together are oxo;
- each R5 is independently selected from H, F, Cl, Br, I, OMe, CH3, CH2F, CHF2, CF3 and CF2CF3;
- R6 and R7 are independently selected from H or alkyl;
- and
- n is 0, 1, 2, 3 or 4,
- such that said allergy is treated.
7 more elements
Dependencies are inferred from the claim text.