Back to results
US 7,071,205 B2Granted
5-cycloalkenyl 5H-chromeno[3,4-f]quinoline derivatives as selective progesterone receptor modulator compounds
AssigneeLigand Pharmaceuticals Incorporated
InventorsLin Zhi, Cornelis Arjan Van Oeveren, Bijan Pedram, Donald S. Karanewsky
Life of this patent
Estimating the term…
Abstract
The present invention is directed to compounds, pharmaceutical compositions, and methods for modulating processes mediated by Progesterone Receptor. Also provided are methods of making such compounds and pharmaceutical compositions.
Claims29
A compound of the formula:
- wherein:
- R1 is selected from the group of hydrogen, C1–C4 alkyl, C1–C4 haloalkyl, C1–C4 heteroalkyl, COR11, CO2R11, SO2R11, and CONR11R12;
- R2 and R3 each independently is selected from the group of hydrogen, C1–C6 alkyl, and C1–C6 haloalkyl;
- or
- R2 and R3 taken together form a cycloalkyl ring of from three to twelve carbons;
- R4 through R7 each independently is selected from the group of hydrogen, F, Cl, Br, CN, OR11, C1–C4 alkyl, C1–C4 haloalkyl, and C1–C4 heteroalkyl;
- or
- R5 and R7 taken together form a bond;
- or
- R6 and R7 taken together are selected from the group of methylidene, mono-substituted methylidene, di-substituted methylidene and carbonyl;
- R8 through R10 each independently is selected from the group of hydrogen, F, Cl, Br, I, NO2, CN, OR11, NR11R12, SR11, COR11, CO2R11, CONR11R12, C1–C8 alkyl, C1–C8 heteroalkyl, C1–C8 haloalkyl, allyl, C2–C8 alkenyl and C2–C8 alkynyl;
- R11 and R12 each is independently selected from the group of hydrogen, C1–C4 alkyl, C1–C4 heteroalkyl, and C1–C4 haloalkyl;
- R13 is hydrogen;
- R14 through R20 each independently is selected from the group of hydrogen, F, Cl, Br, OR11, C1–C4 alkyl, C1–C4 haloalkyl, and C1–C4 heteroalkyl;
- or
- R14 and R15 taken together are selected from the group of methylidene, carbonyl and thiocarbonyl;
- or
- R16 and R17 taken together are selected from the group of methylidene, mono-substituted methylidene, di-substituted methylidene, carbonyl and thiocarbonyl;
- or
- R14 and R16 taken together form a bond or “—O—” bridge;
- or
- R16 and R18 taken together form a bond when n is 1;
- or
- R16 and R19 taken together form a bond when n is 0;
- R21 is hydrogen;
- or
- R21 and R20 taken together form a bond;
- n is 0, 1, 2, or 3;
- or a pharmaceutically acceptable salt thereof.
26 more elements
A compound of the formula:
- wherein:
- R1 is selected from the group of hydrogen, C1–C4 alkyl, C1–C4 haloalkyl, C1–C4 heteroalkyl, COR11, CO2R11, SO2R11, and CONR11R12;
- R2 and R3 each independently is selected from the group of hydrogen, C1–C6 alkyl, and C1–C6 haloalkyl;
- or
- R2 and R3 taken together form a cycloalkyl ring of from three to twelve carbons;
- R4 through R7 each independently is selected from the group of hydrogen, F, Cl, Br, CN, OR11, C1–C4 alkyl, C1–C4 haloalkyl, and C1–C4 heteroalkyl;
- or
- R5 and R7 taken together form a bond;
- or
- R6 and R7 taken together are selected from the group of methylidene, mono-substituted methylidene, di-substituted methylidene and carbonyl;
- R8 through R10 each independently is selected from the group of hydrogen, F, Cl, Br, I, NO2, CN, OR11, NR11R12, SR11, COR11, CO2R11, CONR11R12, C1–C8 alkyl, C1–C8 heteroalkyl, C1–C8 haloalkyl, allyl, C2–C8 alkenyl and C2–C8 alkynyl;
- R11 and R12 each is independently selected from the group of hydrogen, C1–C4 alkyl, C1–C4 heteroalkyl, and C1–C4 haloalkyl;
- R13 is hydrogen;
- or
- R13 and R14 taken together form a bond;
- R14 through R20 each independently is selected from the group of hydrogen, F, Cl, Br, OR11, C1–C4 alkyl, C1–C4 haloalkyl, and C1–C4 heteroalkyl;
- or
- R14 and R15 taken together are selected from the group of methylidene, carbonyl and thiocarbonyl;
- or
- R16 and R17 taken together are selected from the group of methylidene, mono-substituted methylidene, di-substituted methylidene, carbonyl and thiocarbonyl;
- or
- R14 and R16 taken together form a bond or “—O—” bridge;
- R16 and R19 taken together form a bond when n is 0;
- R21 is hydrogen;
- or
- R21 and R20 taken together form a bond;
- n is 0, 1, 2, or 3;
- or a pharmaceutically acceptable salt thereof.
25 more elements
A compound of the formula:
- wherein:
- R1 is selected from the group of hydrogen, C1–C4 alkyl, C1–C4 haloalkyl, C1–C4 heteroalkyl, COR11, CO2R11, SO2R11, and CONR11R12;
- R2 and R3 each independently is selected from the group of hydrogen, C1–C6 alkyl, and C1–C6 haloalkyl;
- or
- R2 and R3 taken together form a cycloalkyl ring of from three to twelve carbons;
- R4 through R7 each independently is selected from the group of hydrogen, F, Cl, Br, CN, OR11, C1–C4 alkyl, C1–C4 haloalkyl, and C1–C4 heteroalkyl;
- or
- R5 and R7 taken together form a bond;
- or
- R6 and R7 taken together are selected from the group of methylidene, mono-substituted methylidene, di-substituted methylidene and carbonyl;
- R8 through R10 each independently is selected from the group of hydrogen, F, Cl, Br, I, NO2, CN, OR11, NR11R12, SR11, COR11, CO2R11, CONR11R12, C1–C8 alkyl, C1–C8 heteroalkyl, C1–C8 haloalkyl, allyl, C2–C8 alkenyl and C2–C8 alkynyl;
- R11 and R12 each is independently selected from the group of hydrogen, C1–C4 alkyl, C1–C4 heteroalkyl, and C1–C4 haloalkyl;
- R13 is hydrogen;
- or
- R13 and R14 taken together form a bond;
- R14 through R20 each independently is selected from the group of hydrogen, F, Cl, Br, OR11, C1–C4 alkyl, C1–C4 haloalkyl, and C1–C4 heteroalkyl;
- or
- R14 and R15 taken together are selected from the group of methylidene, carbonyl and thiocarbonyl;
- or
- R16 and R17 taken together are selected from the group of methylidene, mono-substituted methylidene, di-substituted methylidene, carbonyl and thiocarbonyl;
- or
- R14 and R16 taken together form a bond or “—O—” bridge;
- or
- R16 and R18 taken together form a bond when n is 1;
- or
- R16 and R19 taken together form a bond when n is 0;
- R21 is hydrogen;
- n is 0, 1, 2, or 3;
- or a pharmaceutically acceptable salt thereof.
26 more elements
A compound of the formula:
- wherein:
- R1 is selected from the group of hydrogen, C1–C4 alkyl, C1–C4 haloalkyl, C1–C4 heteroalkyl, COR11, CO2R11, SO2R11, and CONR11R12;
- R2 and R3 each independently is selected from the group of hydrogen, C1–C6 alkyl, and C1–C6 haloalkyl;
- or
- R2 and R3 taken together form a cycloalkyl ring of from three to twelve carbons;
- R4 through R7 each independently is selected from the group of hydrogen, F, Cl, Br, CN, OR11, C1–C4 alkyl, C1–C4 haloalkyl, and C1–C4 heteroalkyl;
- or
- R5 and R7 taken together form a bond;
- or
- R6 and R7 taken together are selected from the group of methylidene, mono-substituted methylidene, di-substituted methylidene and carbonyl;
- R8 through R10 each independently is selected from the group of hydrogen, F, Cl, Br, I, NO2, CN, OR11, NR11R12, SR11, COR11, CO2R11, CONR11R12, C1–C8 alkyl, C1–C8 heteroalkyl, C1–C8 haloalkyl, allyl, C2–C8 alkenyl and C2–C8 alkynyl;
- R11 and R12 each is independently selected from the group of hydrogen, C1–C4 alkyl, C1–C4 heteroalkyl, and C1–C4 haloalkyl;
- R13 is hydrogen;
- R14 and R16 taken together form a bond or “—O—” bridge;
- R15, R17, R18, R19, R20 each independently is selected from the group of hydrogen, F, Cl, C1–C4 alkyl, and C1–C4 haloalkyl.
- R21 is hydrogen;
- and
- n is 0, 1, 2, or 3;
- or a pharmaceutically acceptable salt thereof.
16 more elements
A compound of the formula:
- wherein:
- R1 is selected from the group of hydrogen, C1–C4 alkyl, C1–C4 haloalkyl, C1–C4 heteroalkyl, COR11, CO2R11, SO2R11, and CONR11R12;
- R2 and R3 each independently is selected from the group of hydrogen, C1–C6 alkyl, and C1–C6 haloalkyl;
- or
- R2 and R3 taken together form a cycloalkyl ring of from three to twelve carbons;
- R4 through R7 each independently is selected from the group of hydrogen, F, Cl, Br, CN, OR11, C1–C4 alkyl, C1–C4 haloalkyl, and C1–C4 heteroalkyl;
- or
- R5 and R7 taken together form a bond;
- or
- R6 and R7 taken together are selected from the group of methylidene, mono-substituted methylidene, di-substituted methylidene and carbonyl;
- R8 through R10 each independently is selected from the group of hydrogen, F, Cl, Br, I, NO2, CN, OR11, NR11R12, SR11, COR11, CO2R11, CONR11R12, C1–C8 alkyl, C1–C8 heteroalkyl, C1–C8 haloalkyl, allyl, C2–C8 alkenyl and C2–C8 alkynyl;
- R11 and R12 each is independently selected from the group of hydrogen, C1–C4 alkyl, C1–C4 heteroalkyl, and C1–C4 haloalkyl;
- R13 is hydrogen;
- R14, R15, R18, R19, R20 each independently is selected from the group of hydrogen, F, Cl, C1–C4 alkyl, and C1–C4 haloalkyl.
- R16 and R17 taken together are selected from the group of methylidene, mono-substituted methylidene, and di-substituted methylidene;
- R21 is hydrogen;
- or
- R21 and R20 taken together form a bond;
- n is 0, 1, 2, or 3;
- or a pharmaceutically acceptable salt thereof.
17 more elements
A compound of the formula:
- wherein:
- R1 is selected from the group of hydrogen, C1–C4 alkyl, C1–C4 haloalkyl, C1–C4 heteroalkyl, COR11, CO2R11, SO2R11, and CONR11R12;
- R2 and R3 each independently is selected from the group of hydrogen, C1–C6 alkyl, and C1–C6 haloalkyl;
- or
- R2 and R3 taken together form a cycloalkyl ring of from three to twelve carbons;
- R4 through R7 each independently is selected from the group of hydrogen, F, Cl, Br, CN, OR11, C1–C4 alkyl, C1–C4 haloalkyl, and C1–C4 heteroalkyl;
- or
- R5 and R7 taken together form a bond;
- or
- R6 and R7 taken together are selected from the group of methylidene, mono-substituted methylidene, di-substituted methylidene and carbonyl;
- R8 through R10 each independently is selected from the group of hydrogen, F, Cl, Br, I, NO2, CN, OR11, NR11R12, SR11, COR11, CO2R11, CONR11R12, C1–C8 alkyl, C1–C8 heteroalkyl, C1–C8 haloalkyl, allyl, C2–C8 alkenyl and C2–C8 alkynyl;
- R11 and R12 each is independently selected from the group of hydrogen, C1–C4 alkyl, C1–C4 heteroalkyl, and C1–C4 haloalkyl;
- R13 is hydrogen;
- R14, R15, R17, R20 each independently is selected from the group of hydrogen, F, Cl, C1–C4 alkyl, and C1–C4 haloalkyl R16 and R18 taken together form a bond when n is 1;
- R16 and R19 taken together form a bond when n is 0;
- R21 is hydrogen;
- and
- n is 0, 1, 2, or 3;
- or a pharmaceutically acceptable salt thereof.
16 more elements
A compound selected from the group of:
- (±)-(5l, 1′l)-5-(3-methyl-2-cyclohexenyl)-9-fluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 24);
- (±)-(5l, 1′u)-5-(3-methyl-2-cyclohexenyl)-9-fluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 25);
- (+)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-9-fluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 27);
- (−)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-9-fluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 28);
- (±)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-9-hydroxy-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 29);
- (±)-(5l,1′u)-5-(3-methyl-2-cyclohexenyl)-9-hydroxy-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 30);
- (+)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-9-hydroxy-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 32);
- (−)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-9-hydroxy-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 33);
- (±)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 34);
- (±)-(5l,1′u)-5-(3-methyl-2-cyclohexenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 35);
- (+)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 37);
- (−)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 38);
- (±)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-9-methoxy-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 39);
- (±)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-9-fluoro-1,2-dihydro-2,2-dimethyl-5H-chromeno[3,4-f]quinoline (compound 41);
- (±)-(5l,1′u)-5-(3-methyl-2-cyclohexenyl)-9-fluoro-1,2-dihydro-2,2-dimethyl-5H-chromeno[3,4-f]quinoline (compound 42);
- (±)-(5l,1′l)-5-(3-methyl-2-cyclopentenyl)-9-fluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 44);
- (±)-(5l,1′u)-5-(3-methyl-2-cyclopentenyl)-9-fluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 45);
- (±)-(5l,1′l)-5-(3,5,5-trimethyl-2-cyclohexenyl)-9-fluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 47);
- (±)-(5l,1′u)-5-(3,5,5-trimethyl-2-cyclohexenyl)-9-fluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 48);
- (±)-(5l,1′l)-5-(3-methyl-2-cyclopentenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 50);
- (±)-(5l,1′u)-5-(3-methyl-2-cyclopentenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 51);
- (±)-5-(3-methyl-3-cyclopentenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 52);
- (±)-5-(2-cyclopenta-1,3-dienyl)-9-fluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 53);
- (±)-(5l1′)-5-(3-ethyl-2-cyclohexenyl)-9-fluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 55);
- (±)-(5l,1′u)-5-(3-ethyl-2-cyclohexenyl)-9-fluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 56);
- (±)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-7-fluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 58);
- (±)-(5l,1′u)-5-(3-methyl-2-cyclohexenyl)-7-fluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 59);
- (±)-(5l,1′l)-5-(3-ethyl-2-cyclohexenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 61);
- (±)-(5l,1′l)-5-(3-ethylidenecyclohexyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 62);
- (±)-(5l,1′l)-5-(3-methyl-3-cyclohexenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 63);
- (±)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-9-fluoro-1,2-dihydro-8-methoxy-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 64);
- (±)-(5l,1′u)-5-(3-methyl-2-cyclohexenyl)-9-fluoro-1,2-dihydro-8-methoxy-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 65);
- (±)-(5l,1′l)-5-(2-cyclopentenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 67);
- (±)-(5l,1′u)-5-(2-cyclopentenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 68);
- (±)-5-(1-cyclopentenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 69);
- (±)-(5l,1′l)-5-(2,3-dimethyl-2-cyclopentenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 71);
- (+)-(5l,1′l)-5-(2,3-dimethyl-2-cyclopentenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 73);
- (−)-(5l,1′l)-5-(2,3-dimethyl-2-cyclopentenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 74);
- (±)-(5l,1′l)-5-(2-cyclohexenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 75);
- (±)-(5l,1′u)-5-(2-cyclohexenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 76);
- (±)-(5l,1′l)-5-(2-cyclohexenyl)-7,9-difluoro-1,2,3,4-tetrahydro-2,2-dimethyl-4-methylidene-5H-chromeno[3,4-f]quinoline (compound 77);
- (±)-(5l,1′l)-5-(2-methylidenecyclohexyl)-9-fluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 79);
- (±)-(5l,1′u)-5-(2-methylidenecyclohexyl)-9-fluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 80);
- (±)-(5l,1′l)-5-(2-oxocyclohexyl)-9-fluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 81);
- (±)-(5l,1′u)-5-(2-oxocyclohexyl)-9-fluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 82);
- (±)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-9-methoxy-1,2-dihydro-1,2,2,4-tetramethyl-5H-chromeno[3,4-f]quinoline (compound 83);
- (±)-5-(2-cyclohexenyl)-9-fluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]-quinoline (compound 84);
- (±)-(5l,1′l)-5-(2,3-dimethyl-2-cyclohexenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 85);
- (±)-5-(3-methylidene-cyclohexyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 87);
- (±)-(5l,1′u)-5-(3-ethylidenecyclohexyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 88);
- (±)-(5l,1′l)-5-(2-cycloheptenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (Compound 89);
- (±)-(5l,1′l)-5-(2-cyclooctenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (Compound 91);
- (±)-(5l,1′u)-5-(2-cyclooctenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (Compound 92);
- (±)-(5l,1′l)-5-(2,3-epoxy-3-methylcyclohexyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (Compound 94);
- (±)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-7,9-difluoro-1,2,3,4-tetrahydro-2,2-dimethyl-4-methylene-5H-chromeno[3,4-f]quinolin-3-ol (Compound 95);
- (±)-(5l,1′l)-5-(2,3-epoxy-2,3-dimethylcyclopentyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (Compound 96);
- (±)-(5l,1′u)-5-(2,3-epoxy-3-methylcyclohexyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (Compound 97);
- and
- (±)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-7,9-difluoro-1,2,3,4-tetrahydro-2,2-dimethyl-5H-chromeno[3,4-f]quinolin-4-one (Compound 98).
56 more elements
A compound selected from the group of:
- (±)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-9-fluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 24);
- (−)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-9-fluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 28);
- (−)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-9-hydroxy-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 33);
- (±)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 34);
- (±)-(5l,1′u)-5-(3-methyl-2-cyclohexenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 35);
- (−)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 38);
- (±)-(5l,1′l)-5-(3-methyl-2-cyclopentenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 50);
- (±)-(5l,1′u)-5-(3-methyl-2-cyclopentenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 51);
- (±)-(5l,1′l)-5-(2,3-dimethyl-2-cyclopentenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 71);
- (−)-(5l,1′l)-5-(2,3-dimethyl-2-cyclopentenyl)-7,9-difluoro-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (compound 74);
- and
- (±)-(5l,1′l)-5-(3-methyl-2-cyclohexenyl)-7,9-difluoro-1,2,3,4-tetrahydro-2,2-dimethyl-5H-chromeno[3,4-f]quinolin-4-one (Compound 98).
9 more elements
A compound of the formula:
- wherein:
- R2 and R3 each independently is selected from the group of hydrogen, C1–C4 alkyl, and C1–C4 haloalkyl;
- R6 is selected from the group of hydrogen, F, Cl, Br, CN, OR11, C1–C4 alkyl, and C1–C4 haloalkyl;
- R8 and R10 each independently is selected from the group consisting of hydrogen, F, Cl, Br, CN, OR11, NR11R12, SR11, COR11, C1–C4 alkyl, C1–C4 heteroalkyl, C1–C4 haloalkyl, allyl, and C2–C4 alkenyl;
- R11 and R12 each is independently selected from the group of hydrogen, C1–C4 alkyl, C1–C4 heteroalkyl, and C1–C4 haloalkyl;
- R14, R15, R18, R22, R23, R24 each independently is selected from the group of hydrogen, F, Cl, OR11, C1–C4 alkyl, C1–C4 haloalkyl, and C1–C4 heteroalkyl;
- R22, R23, R24 together consists of not more than 3 carbon atoms;
- R16 taken together with one of R14, R18, and R22 form a bond or “—O—” bridge;
- n is 0, 1, 2, or 3;
- or a pharmaceutically acceptable salt thereof.
7 more elements
A compound of the formula:
- wherein:
- R2 and R3 each independently is selected from the group of C1–C4 alkyl;
- R6 is selected from the group of F, Cl, Br, C1–C4 alkyl, and C1–C4 haloalkyl;
- R8 and R10 each independently is selected from the group of hydrogen, F, Cl, Br, CN, OR11, C1–C4 alkyl, and C1–C4 haloalkyl;
- R11 and R12 each is independently selected from the group of hydrogen, C1–C4 alkyl;
- R14, R15, R18, R22, R23, R24 each independently is selected from the group of hydrogen, F, C1–C4 alkyl;
- R16 taken together with one of R14, R18, and R22 form a bond or “—O—” bridge;
- R22, R23, R24 together consists of not more than 3 carbon atoms;
- and
- n is 0, 1, or 2;
- or a pharmaceutically acceptable salt thereof.
8 more elements
A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a compound of formula:
- wherein:
- R1 is selected from the group of hydrogen, C1–C4 alkyl, C1–C4 haloalkyl, C1–C4 heteroalkyl, COR11, CO2R11, SO2R11, and CONR11R12;
- R2 and R3 each independently is selected from the group of hydrogen, C1–C6 alkyl, and C1–C6 haloalkyl;
- or
- R2 and R3 taken together form a cycloalkyl ring of from three to twelve carbons;
- R4 through R7 each independently is selected from the group of hydrogen, F, Cl, Br, CN, OR11, C1–C4 alkyl, C1–C4 haloalkyl, and C1–C4 heteroalkyl;
- or
- R5 and R7 taken together form a bond;
- or
- R6 and R7 taken together are selected from the group of methylidene, mono-substituted methylidene, di-substituted methylidene and carbonyl;
- R8 through R10 each independently is selected from the group of hydrogen, F, Cl, Br, I, NO2, CN, OR11, NR11R12, SR11, COR11, CO2R11, CONR11R12, C1–C8 alkyl, C1–C8 heteroalkyl, C1–C8 haloalkyl, allyl, C2–C8 alkenyl and C2–C8 alkynyl;
- R11 and R12 each is independently selected from the group of hydrogen, C1–C4 alkyl, C1–C4 heteroalkyl, and C1–C4 haloalkyl;
- R13 is hydrogen;
- R14 and R16 taken together form a bond or “—O—” bridge;
- R15, R17, R18, R19, R20 each independently is selected from the group of hydrogen, F, Cl, C1–C4 alkyl, and C1–C4 haloalkyl;
- R21 is hydrogen;
- or
- R21 and R20 taken together form a bond;
- and
- n is 0, 1, 2, or 3;
- or a pharmaceutically acceptable salt thereof.
18 more elements
A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a compound of formula:
- wherein:
- R1 is selected from the group of hydrogen, C1–C4 alkyl, C1–C4 haloalkyl, C1–C4 heteroalkyl, COR11, CO2R11, SO2R11, and CONR11R12;
- R2 and R3 each independently is selected from the group of hydrogen, C1–C6 alkyl, and C1–C6 haloalkyl;
- or
- R2 and R3 taken together form a cycloalkyl ring of from three to twelve carbons;
- R4 through R7 each independently is selected from the group of hydrogen, F, Cl, Br, CN, OR11, C1–C4 alkyl, C1–C4 haloalkyl, and C1–C4 heteroalkyl;
- or
- R5 and R7 taken together form a bond;
- or
- R6 and R7 taken together are selected from the group of methylidene, mono-substituted methylidene, di-substituted methylidene and carbonyl;
- R8 through R10 each independently is selected from the group of hydrogen, F, Cl, Br, I, NO2, CN, OR11, NR11R12, SR11, COR11, CO2R11, CONR11R12, C1–C8 alkyl, C1–C8 heteroalkyl, C1–C8 haloalkyl, allyl, C2–C8 alkenyl and C2–C8 alkynyl;
- R11 and R12 each is independently selected from the group of hydrogen, C1–C4 alkyl, C1–C4 heteroalkyl, and C1–C4 haloalkyl;
- R13 is hydrogen;
- R14, R15, R18, R19, R20 each independently is selected from the group of hydrogen, F, Cl, C1–C4 alkyl, and C1–C4 haloalkyl;
- R16 and R17 taken together are selected from the group of methylidene, mono-substituted methylidene, and di-substituted methylidene;
- R21 is hydrogen;
- or
- R21 and R20 taken together form a bond;
- and
- n is 0, 1, 2, or 3;
- or a pharmaceutically acceptable salt thereof.
18 more elements
A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a compound of formula:
- wherein:
- R1 is selected from the group of hydrogen, C1–C4 alkyl, C1–C4 haloalkyl, C1–C4 heteroalkyl, COR11, CO2R11, SO2R11, and CONR11R12;
- R2 and R3 each independently is selected from the group of hydrogen, C1–C6 alkyl, and C1–C6 haloalkyl;
- or
- R2 and R3 taken together form a cycloalkyl ring of from three to twelve carbons;
- R4 through R7 each independently is selected from the group of hydrogen, F, Cl, Br, CN, OR11, C1–C4 alkyl, C1–C4 haloalkyl, and C1–C4 heteroalkyl;
- or
- R5 and R7 taken together form a bond;
- or
- R6 and R7 taken together are selected from the group of methylidene, mono-substituted methylidene, di-substituted methylidene and carbonyl;
- R8 through R10 each independently is selected from the group of hydrogen, F, Cl, Br, I, NO2, CN, OR11, NR11R12, SR11, COR11, CO2R11, CONR11R12, C1–C8 alkyl, C1–C8 heteroalkyl, C1–C8 haloalkyl, allyl, C2–C8 alkenyl and C2–C8 alkynyl;
- R11 and R12 each is independently selected from the group of hydrogen, C1–C4 alkyl, C1–C4 heteroalkyl, and C1–C4 haloalkyl;
- R13 is hydrogen;
- R14, R15, R17, R20 each independently is selected from the group of hydrogen, F, Cl, C1–C4 alkyl, and C1–C4 haloalkyl;
- R16 and R18 taken together form a bond when n is 1;
- or
- R16 and R19 taken together form a bond when n is 0;
- R21 is hydrogen;
- and
- n is 0, 1, 2, or 3;
- or a pharmaceutically acceptable salt thereof.
18 more elements
Dependencies are inferred from the claim text.