| 主权项 |
1. A method of treating a disease or condition, wherein the disease or condition is impaired visual acuity, diabetic retinopathy, diabetic macular oedema, hereditary angioedema, diabetes, pancreatitis, cerebral hemorrhage, nephropathy, cardiomyopathy, neuropathy, inflammatory bowel disease, arthritis, inflammation, septic shock, hypotension, cancer, adult respiratory distress syndrome, disseminated intravascular coagulation, cardiopulmonary bypass surgery, or post-operative bleeding from surgery, said method comprising administering a therapeutically effective amount of a compound of Formula (I) to a subject in need thereof: wherein:
R1 is H, alkyl, —COalkyl, —COaryl, —COheteroaryl, —CO2alkyl, —(CH2)aOH, —(CH2)bCOOR10, —(CH2)cCONH2, —SO2alkyl, —SO2aryl, —SO2(CH2)hR13, —CO(CH2)iR14, —COcycloalkyl, —COCH═CHR15, —CO(CH2)jNHCO(CH2)kR16, or —CONR17R18;R2 is H, or alkyl;R3 is H, alkyl, —(CH2)daryl, —(CH2)eheteroaryl, —(CH2)fcycloalkyl, —(CH2)gheterocycloalkyl, —CH(cycloalkyl)2, —CH(heterocycloalkyl)2, or —(CH2)laryl-O—(CH2)m-aryl;R4 and R6 are independently H or alkyl;R5 is H, alkyl, alkoxy, or OH;or R4 and R5, together with the atoms to which they are attached, may join to form a 5- or 6-membered azacycloalkyl structure;R7 and R8 are independently H, alkyl, alkoxy, CN, halo, or CF3;R9 is aryl or heteroaryl;R10 is H or alkyl;a, b, c, d, e, f, g, h, i, j, l and m are independently 1, 2 or 3;k is 0, 1, 2 or 3;*1 and *2 denote chiral centres;alkyl is a linear saturated hydrocarbon having up to 10 carbon atoms (C1-C10) or a branched saturated hydrocarbon of between 3 and 10 carbon atoms (C3-C10); alkyl may optionally be substituted with 1 or 2 substituents independently selected from (C3-C10)cycloalkyl, (C1-C6)alkoxy, OH, CN, CF3, COOR11, fluoro and NR11R12;cycloalkyl is a mono- or bi-cyclic saturated hydrocarbon of between 3 and 10 carbon atoms optionally fused to an aryl group;heterocycloalkyl is a C-linked or N-linked 3 to 10 membered saturated, mono- or bi-cyclic ring, wherein said heterocycloalkyl ring contains, where possible, 1, 2 or 3 heteroatoms independently selected from N, NR11 and O;alkoxy is a linear O-linked hydrocarbon of between 1 and 6 carbon atoms (C1-C6) or a branched O-linked hydrocarbon of between 3 and 6 carbon atoms (C3-C6) in either case optionally be substituted with 1 or 2 substituents independently selected from (C3-C10)cycloalkyl, OH, CN, CF3, COOR11, fluoro and NR11R12;aryl is phenyl, biphenyl or naphthyl optionally substituted with up to 5 substituents independently selected from alkyl, alkoxy, OH, halo, CN, COOR11, CF3 and NR11R12;heteroaryl is a 5, 6, 9 or 10 membered mono- or bi-cyclic aromatic ring, containing, where possible, 1, 2 or 3 ring members independently selected from N, NR11, S and O; optionally substituted with 1, 2 or 3 substituents independently selected from alkyl, alkoxy, OH, halo, CN, COOR11, CF3, NR11R12 and NHR19;R11 and R12 are independently H, or alkyl;R13 is aryl or heteroaryl;R14 is aryl, heteroaryl, cycloalkyl or heterocycloalkyl;R15 is H, alkyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl;R16 is H, aryl or heteroaryl;R17 is H, alkyl, aryl, heteroaryl or heterocycloalkyl;R18 is —(CH2)mR21, where m is 0, 1, 2 or 3 and R21 is H, aryl or heteroaryl;R19 —COalkyl, —COaryl or —COheteroaryl;or a tautomer, isomer, stereoisomer or racemic and scalemic mixture thereof, or a pharmaceutically acceptable salt or solvate thereof. |
