CHEN SHUQI (AU)
PRIEBBENOW DANIEL (AU)
JASZEWSKI LEO (AU)
Claims 1. A collection of polycyclic compounds and/or salts thereof, for screening against a polynucleotide target, the collection comprising a plurality of polycyclic compounds which comprise at least 4 fused rings and have the formula A-Het-Cyc-B or A-Het1-Cyc-Het2-B wherein A-Het-Cyc-B is selected from the group consisting of: wherein A is a 5-10-membered carbocyclic or heterocyclic aromatic group; B is a 5-10-membered carbocycle or heterocyclic aromatic group; X is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; Y is NR, -C(O)NR-, -NRC(O)-, -OCH2-, -C(C(O)OC1-4alkyl)-, -C(C(O)N(C1-4alkyl)2)- or -OC(O)-; and R is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; and wherein A-Het1-Cyc-Het2-B is selected from the group consisting of: wherein A is a 5-10-membered carbocyclic or heterocyclic aromatic group; B is a 5-10-membered carbocycle or heterocyclic aromatic group; X is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^ is O, S, NH, NC1-4alkyl, -N=CH-, -N=N- or -OC(O)-; Y is NR, -C(O)NR-, -NRC(O)-; and R is H, C1- 4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1- 4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3. 2. The collection of polycyclic compounds and/or salts as claimed in claim 1, wherein the collection contains compounds from one or more of formulae a) to u), and/or salts thereof: wherein A1 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B1 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X1 is O, S, NH or NC1-4alkyl; and R1 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; wherein A2 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B2 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X2 is O, S, NH or NC1-4alkyl; and R2 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1- 4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; wherein A3 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B3 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X3 is O, S, NH or NC1-4alkyl; and R3 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1- 4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; d) ; wherein A4 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B4 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X4 is O, S, NH or NC1-4alkyl; and R4 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; wherein A5 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B5 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X5 is O, S, NH or NC1-4alkyl; and R5 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; wherein A6 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B6 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R6 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; g) ; wherein A7 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B7 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R7 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; h) ; wherein A8 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B8 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R8 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; wherein A9 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B9 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R9 is H, C1- 4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1- 4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; j) ; wherein A10 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B10 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R10 is H, C1- 4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1- 4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; wherein A11 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and B11 is a 5-10 membered carbocyclic or heterocyclic aromatic group; l) wherein A12 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and B12 is a 5-10 membered carbocyclic or heterocyclic aromatic group; m) wherein A13 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and B13 is a 5-10 membered carbocyclic or heterocyclic aromatic group; n) ; wherein A14 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B14 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and Y14 is OC1-4alkyl or N(C1-4alkyl)2; o) ; wherein A15 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B15 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R15 is H, C1- 4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1- 4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; p) ; wherein A16 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B16 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X16 is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^16 is O, S, NH, NC1-4alkyl, -N=CH-, -N=N- or -OC(O)-; and R16 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; q) ; wherein A17 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B17 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X17 is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^17 is O, S, NH, NC1-4alkyl, -N=CH-, -N=N- or -OC(O)-; and R17 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; ; wherein A18 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B18 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X18 is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^18 is O, S, NH, NC1-4alkyl, -N=CH-, -N=N- or -OC(O)-; and R18 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; s) ; wherein A19 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B19 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X19 is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^19 is O, S, NH, NC1-4alkyl, -N=CH-, -N=N- or -OC(O)-; and R19 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; ; wherein A20 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B20 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X20 is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^20 is O, S, NH, NC1-4alkyl, -N=CH-, -N=N- or -OC(O)-; and R20 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; or membered carbocyclic or heterocyclic aromatic group; B21 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X21 is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^21 is O, S, NH, NC1-4alkyl, -N=CH-, -N=N- or -OC(O)-; and R21 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3. 3. The collection of polycyclic compounds and/or salts as claimed in claim 2, wherein A1-A21 are each independently selected from the group consisting of phenyl, thiophene, pyridine and benzothiophene. 4. The collection of polycyclic compounds and/or salts as claimed as claimed in claim 3, wherein A1-A21 are each independently selected from the group consisting of phenyl and benzothiophene. 5. The collection of polycyclic compounds and/or salts as claimed in any of claims 2 to 4, wherein B1-B21 are each independently selected from the group consisting of phenyl, thiophene and pyridine. 6. The collection of polycyclic compounds and/or salts as claimed in claim 5, wherein B1-B21 are each independently selected from the group consisting of phenyl and thiophene. 7. The collection of polycyclic compounds and/or salts as claimed in any of claims 2 to 6, wherein X1-X5 and X16-X21 are each independently selected from O and S. 8. The collection of polycyclic compounds and/or salts as claimed in any of claims 2 to 7, wherein R1-R21 are each H or C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1- 4alkyl)2, optionally wherein R1-R21 are each C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, optionally wherein R1-R21 are each C1-4alkyl substituted by N(C1- 4alkyl)2. 9. The collection of polycyclic compounds and/or salts as claimed in any of claims 2 to 8, wherein R1-R21 are each phenyl optionally substituted by up to two substituents independently selected from methyl and CF3, optionally wherein R1-R21 are each phenyl substituted by one CF3. 10. The collection of polycyclic compounds and/or salts as claimed in any of claims 2 to 9, wherein the collection contains one or more compounds of the formula p) and/or salts thereof, and wherein A16 is different from B16 and/or X16 is different from X ^16. 11. The collection as claimed in any of claims 1 to 10, wherein the collection comprises: at least 10 compounds and/or salts as defined in any of claims 1 to 10, optionally at least 100 compounds and/or salts as defined in any of claims 1 to 10, optionally at least 250 compounds and/or salts as defined in any of claims 1 to 10, optionally at least 500 compounds and/or salts as defined in any of claims 1 to 10, or optionally at least 1000 compounds and/or salts as defined in any of claims 1 to 10. 12. A polycyclic compound or salt thereof, wherein the polycyclic compound comprises at least 4 fused rings and has the formula A-Het-Cyc-B or A-Het1-Cyc-Het2-B wherein A-Het-Cyc-B is selected from the group consisting of: wherein A is a 5-10-membered carbocyclic or heterocyclic aromatic group; B is a 5-10-membered carbocycle or heterocyclic aromatic group; X is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; Y is NR, -C(O)NR-, -NRC(O)-, -OCH2-, -C(C(O)OC1-4alkyl)-, -C(C(O)N(C1-4alkyl)2)- or -OC(O)-; and R is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; and wherein A-Het1-Cyc-Het2-B is selected from the group consisting of: wherein A is a 5-10-membered carbocyclic or heterocyclic aromatic group; B is a 5-10-membered carbocycle or heterocyclic aromatic group; X is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^ is O, S, NH, NC1-4alkyl, -N=CH-, -N=N- or -OC(O)-; Y is NR, -C(O)NR-, -NRC(O)-; and R is H, C1- 4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1- 4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; and wherein the compound is not , , or . 13. The polycyclic compound or salt as claimed in claim 12, wherein the compound is selected from compounds having one of the following formulae: wherein A1 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B1 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X1 is O, S, NH or NC1-4alkyl; and R1 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1- 4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; wherein A2 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B2 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X2 is O, S, NH or NC1-4alkyl; and R2 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1- 4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; c) ; wherein A3 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B3 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X3 is O, S, NH or NC1-4alkyl; and R3 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1- 4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; d) ; wherein A4 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B4 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X4 is O, S, NH or NC1-4alkyl; and R4 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; e) wherein A5 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B5 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X5 is O, S, NH or NC1-4alkyl; and R5 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; f) ; wherein A6 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B6 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R6 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; wherein A7 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B7 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R7 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; wherein A8 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B8 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R8 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; i) ; wherein A9 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B9 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R9 is H, C1- 4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1- 4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; j) ; wherein A10 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B10 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R10 is H, C1- 4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1- 4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; wherein A11 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and B11 is a 5-10 membered carbocyclic or heterocyclic aromatic group; l) wherein A12 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and B12 is a 5-10 membered carbocyclic or heterocyclic aromatic group; m) ; wherein A13 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and B13 is a 5-10 membered carbocyclic or heterocyclic aromatic group; o) ; wherein A15 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B15 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R15 is H, C1- 4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1- 4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; p) ; wherein A16 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B16 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X16 is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^16 is O, S, NH, NC1-4alkyl, -N=CH-, -N=N- or -OC(O)-; and R16 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; ; wherein A17 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B17 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X17 is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^17 is O, S, NH, NC1-4alkyl, -N=CH-, -N=N- or -OC(O)-; and R17 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; wherein A18 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B18 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X18 is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^18 is O, S, NH, NC1-4alkyl, -N=CH-, -N=N- or -OC(O)-; and R18 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; s) ; wherein A19 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B19 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X19 is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^19 is O, S, NH, NC1-4alkyl, -N=CH-, -N=N- or -OC(O)-; and R19 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; wherein A20 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B20 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X20 is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^20 is O, S, NH, NC1-4alkyl, -N=CH-, -N=N- or -OC(O)-; and R20 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3; or wherein A21 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B21 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X21 is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^21 is O, S, NH, NC1-4alkyl, -N=CH-, -N=N- or -OC(O)-; and R21 is H, C1-4alkyl, phenyl or benzyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, said phenyl being optionally substituted by up to two substituents independently selected from methyl and CF3, and said benzyl being optionally substituted by up to two substituents independently selected from methyl and CF3. 14. The polycyclic compound or salt as claimed in claim 13, wherein A1-A21 are each independently selected from the group consisting of phenyl, thiophene, pyridine and benzothiophene. 15. The polycyclic compound or salt as claimed in claim 14, wherein A1-A21 are each independently selected from the group consisting of phenyl and benzothiophene. 16. The polycyclic compound or salt as claimed in any of claims 13 to 15, wherein B1-B21 are each independently selected from the group consisting of phenyl, thiophene and pyridine. 17. The polycyclic compound or salt as claimed in claim 16, wherein B1-B21 are each independently selected from the group consisting of phenyl and thiophene. 18. The polycyclic compound or salt as claimed in any of claims 13 to 17, wherein X1-X5 and X16- X21 are each independently selected from O and S. 19. The polycyclic compound or salt as claimed in any of claims 13 to 18, wherein R1-R21 are each H or C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2, optionally wherein R1-R21 are each C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1- 4alkyl or N(C1-4alkyl)2, optionally wherein R1-R21 are each C1-4alkyl substituted by N(C1-4alkyl)2. 20. The polycyclic compound or salt as claimed in claim 19, wherein R1-R21 are each phenyl optionally substituted by up to two substituents independently selected from methyl and CF3, optionally wherein R1-R21 are each phenyl substituted by one CF3. 21. The polycyclic compound or salt as claimed in any of claims 13 to 20, wherein the compound is of the formula p), and wherein A16 is different from B16 and/or X16 is different from X ^16. 22. A method of synthesising a polycyclic compound of formula a), as defined in any of claims 13 to 20, comprising: reacting a compound of formula wherein A1, B1 and X1 are as defined in any of claims 13 to 20, Hal1 is halogen; and Hal2 is halogen; with a compound of formula R1-NH2 in the presence of a palladium or copper catalyst, wherein R1 is as defined in any of claims 13 to 20; and optionally forming a salt of the compound. 23. The method as claimed in claim 22, wherein the compound of formula , 22, and X1a is OC1- 4alkyl, SC1-4alkyl, NH2, NHC1-4alkyl or N(C1-4alkyl)2; to a halocyclization reaction. 24. A method of synthesising a polycyclic compound of formula b), or salt thereof, as defined in any of claims 13 to 20, comprising: i) reacting a compound of formula wherein A2, B2 and X2 are as defined in any of claims 13 to 20, Hal1 is halogen; and Hal2 is halogen; with a compound of formula R2-NH2 in the presence of a palladium catalyst and carbon monoxide, wherein R2 is as defined in any of claims 13 to 20; and if the product of step i) is a compound of formula rather than a compound of formula b), ii) contacting the product of step i) with a copper or palladium catalyst to form the compound of formula b); and optionally forming a salt of the compound. 25. The method as claimed in claim 24, wherein the compound of formula , are as 4alkyl, SC1-4alkyl, NH2, NHC1-4alkyl or N(C1-4alkyl)2; to a halocyclization reaction. 26. A method of synthesising a polycyclic compound of formula c), or salt thereof, as defined in any of claims 13 to 20, comprising: i) reacting a compound of formula wherein A3, B3 and X3 are as defined in any of claims 13 to 20, Hal1 is halogen; and Hal2 is halogen; with a compound of formula R3-NH2 in the presence of a palladium catalyst and carbon monoxide, wherein R3 is as defined in any of claims 13 to 20; and if the product of step i) is a compound of formula rather than a compound of formula c), ii) contacting the product of step i) with a copper or palladium catalyst to form the compound of formula c); and optionally forming a salt of the compound. 27. The method as claimed in claim 26, wherein the compound of formula , 4alkyl, SC1-4alkyl, NH2, NHC1-4alkyl or N(C1-4alkyl)2; to a halocyclization reaction. 28. A method of synthesising a polycyclic compound of formula d), or salt thereof, as defined in any of claims 13 to 20, comprising: reacting a compound of formula wherein A4, B4 and X4 are as defined in any of claims 13 to 20, Hal1 is halogen; and Hal2 is halogen; with a compound of formula R4-NH2 in the presence of a copper catalyst, wherein R4 is as defined in any of claims 13 to 20; and optionally forming a salt of the compound. 29. The method as claimed in claim 28, wherein the compound of formula , wherein A4, B4, Hal2 are as defined in claim 28, and X4a is OC1- 4alkyl, SC1-4alkyl, NH2, NHC1-4alkyl or N(C1-4alkyl)2; to a halocyclization reaction. 30. A method of synthesising a polycyclic compound of formula e), or salt thereof, as defined in any of claims 13 to 20, comprising: reacting a compound of formula wherein A5, B5 and X5 are as defined in any of claims 13 to 20, Hal1 is halogen; and Hal2 is halogen; with a compound of formula R5NH2 in the presence of a copper catalyst, wherein R5 is as defined in any of claims 13 to 20; and optionally forming a salt of the compound. 31. The method as claimed in claim 30, wherein the compound of formula produced by subjecting a compound of formula , wherein A5, B5 and Hal2 are as defined in claim 30, and X5a is OC1- 4alkyl, SC1-4alkyl, NH2, NHC1-4alkyl or N(C1-4alkyl)2; to a halocyclization reaction. 32. A method of synthesising a polycyclic compound of formula f), or salt thereof, as defined in any of claims 13 to 20, comprising: reacting a compound of formula wherein A6, B6 and X6 are as defined in any of claims 13 to 20, Hal1 is halogen; and Hal2 is halogen; with a compound of formula R6NH2 in the presence of a copper catalyst, wherein R6 is as defined in any of claims 13 to 20; and optionally forming a salt of the compound. 33. The method as claimed in claim 32, wherein the compound of formula is produced by subjecting a compound of formula , wherein A6, B6 and Hal2 are as defined in claim 32, and RX is OC1-4alkyl or C1-4alkyl; to a halocyclization reaction. 34. A method of synthesising a polycyclic compound of formula g), or salt thereof, as defined in any of claims 13 to 20, comprising: i) reacting a compound of formula wherein A7 and B7 are as defined in any of claims 13 to 20, Hal1 is halogen; and Hal2 is halogen; with a compound of formula R7-NH2 in the presence of a palladium catalyst and carbon monoxide, wherein R7 is as defined in any of claims 13 to 20; and if the product of step i) is a compound of formula rather than a compound of formula g), ii) contacting the product of step i) with a copper or palladium catalyst to form the compound of formula g); and optionally forming a salt of the compound. 35. The method as claimed in claim 34, wherein the compound of formula , are as or C1-4alkyl; to a halocyclization reaction. 36. A method of synthesising a polycyclic compound of formula h), or salt thereof, as defined in any of claims 13 to 20, comprising: i) reacting a compound of formula wherein A8 and B8 are as defined in any of claims 13 to 20, Hal1 is halogen; and Hal2 is halogen; with a compound of formula R8-NH2 in the presence of a palladium catalyst and carbon monoxide, wherein R8 is as defined in any of claims 13 to 20; and if the product of step i) is a compound of formula rather than a compound of formula h), ii) contacting the product of step i) with a copper or palladium catalyst to form the compound of formula h); and optionally forming a salt of the compound. , wherein A8, B8 and Hal2 are as defined in claim 36, and RX is OC1-4alkyl or C1-4alkyl; to a halocyclization reaction. 38. A method of synthesising a polycyclic compound of formula i) or salt thereof, as defined in any of claims 13 to 20, comprising: reacting a compound of formula wherein A9 and B9 are as defined in any of claims 13 to 20, Hal1 is halogen; and Hal2 is halogen; with a compound of formula R9NH2 in the presence of a copper catalyst, wherein R9 is as defined in any of claims 13 to 20; and optionally forming a salt of the compound. 39. The method as claimed in claim 38, wherein the compound of formula , reagent, and then contacting the resulting product with a halide source. 40. A method of synthesising a polycyclic compound of formula j), or salt thereof, as defined in any of claims 13 to 20, comprising: i) reacting a compound of formula wherein A10 and B10 are as defined in any of claims 13 to 20, Hal1 is halogen; and Hal2 is halogen; with a compound of formula R10-NH2 in the presence of a palladium catalyst and carbon monoxide, wherein R10 is as defined in any of claims 13 to 20; and if the product of step i) is a compound of formula rather than a compound of formula j), ii) contacting the product of step i) with a copper or palladium catalyst to form the compound of formula j); and optionally forming a salt of the compound. 41. The method as claimed in claim 40, wherein the compound of formula , dehydrating reagent, and then contacting the resulting product with a halide source. 42. A method of synthesising a polycyclic compound of formula k), or salt thereof, as defined in any of claims 13 to 20, comprising: reacting a compound of formula wherein A11 and B11 are as defined in any of claims 13 to 20, and wherein each R11 is independently C1-4alkyl; with a dehydrating reagent, and then contacting the resulting product with an acid, thereby forming the compound of formula k); and optionally forming a salt of the compound. 43. A method of synthesising a polycyclic compound or salt of formula l) as defined in any of claims 13 to 20, comprising: contacting a compound of formula wherein A12 and B12 are as defined in any of claims 13 to 20, each Ra is independently C1- 4alkyl, or both Ra groups together with their connecting nitrogen form a pyrrolidine, piperidine or homopiperidine group, and X ^ is OC1-4alkyl, NH2, NHC1-4alkyl or N(C1-4alkyl)2; with an acid, thereby forming the compound of formula l); and optionally forming a salt of the compound. 44. A method of synthesising a polycyclic compound of formula m), or salt thereof, as defined in any of claims 13 to 20, comprising: contacting a compound of formula wherein A13 and B13 are as defined in any of claims 13 to 20, each Ra is independently C1- 4alkyl, or both Ra groups together with their connecting nitrogen form a pyrrolidine, piperidine or homopiperidine group; with an acid, thereby forming the compound of formula m); and optionally forming a salt of the compound. 45. A method of synthesizing a polycyclic compound of formula n), or salt thereof, as defined in any of claims 13 to 20, comprising: contacting a compound of formula wherein A14, B14 and Y14 are as defined in any of claims 13 to 20, and each Ra is independently C1-4alkyl, or both Ra groups together with their connecting nitrogen form a pyrrolidine, piperidine or homopiperidine group; with an acid, thereby forming the compound of formula n); and optionally forming a salt of the compound. 46. A method of synthesizing a compound of formula o), or salt thereof, as defined in any of claims 13 to 20, comprising: reacting a compound of formula wherein A15 and B15 are as defined in any of claims 13 to 20, Hal1 is halogen, and Rb is C1- 4alkyl; with R15NH2, wherein R15 is as defined in any of claims 13 to 20, thereby forming the compound of formula o); and optionally forming a salt of the compound. 47. The method as claimed in claim 46, wherein the compound of formula is produced by contacting a compound of formula wherein A15, B15 and Rb are as defined in any of claims 13 to 20, and each Ra is independently C1-4alkyl, or both Ra groups together with their connecting nitrogen form a pyrrolidine, piperidine or homopiperidine group; with an acid and a halide source. 48. A method of identifying a compound having activity against a polynucleotide target or a polynucleotide-protein complex target, comprising: testing a collection of compounds as defined in any of claims 1 to 11 or part thereof, or testing one or more compounds as defined in any of claims 12 to 21 for activity against a polynucleotide target; and identifying whether the compound or compounds have activity against the polynucleotide target. 49. The method as claimed in claim 48, wherein the polynucleotide target is an RNA target, optionally an mRNA target, micro-RNA or a non-coding RNA target. 50. The method as claimed in claim 49, wherein the polynucleotide target is a DNA target. 51. The method as claimed in any of claims 48 to 50, wherein the polynucleotide target is a polynucleotide-protein complex or a functional DNA topology. 52. The method as claimed in any of claims 48 to 51, wherein the polynucleotide target is a DNA complex with a transcription factor, an epigenetic modulator, an RNA-polymerase complex, Z-DNA, or a G-quadruplex. 53. The method as claimed in any of claims 48 to 52, wherein the polynucleotide target is selected from the group consisting of DNA-topoisomerase 1, mRNA encoding SMN2 protein, and G-quadruplex mRNA encoding oncogenic N-Ras protein. 54. The method as claimed in any of claims 48 to 53, wherein the compound is tested for activity using an assay selected from the group consisting of a radiolabelled DNA-cleavage assay, a cell cytoxicity assay, and an affinity assay for polynucleotides and their protein complexes by one or more of surface plasmon resonance assay, fluorometric assay, nuclear magnetic resonance assay and thermal shift assay. 55. Use of a compound as defined in any of claims 13 to 21 as a reference compound in a competition assay for determining activity of a test compound against a polynucleotide target. 56. Use of a compound as claimed in claim 55, wherein a radiolabelled form of the compound as defined in any of claims 13 to 21 is used in the assay. 57. A phenotypic method of identifying a new polynucleotide target for therapy of a disease or disorder, comprising contacting a collection of compounds as defined in any of claims 1 to 11 or part thereof, or contacting one or more compounds as defined in any of claims 13 to 21 with a cell, tissue or animal disease model and monitoring for a change associated with a disease or disorder; and if a change associated with the disease or disorder is identified, determining the biological target to which the compound binds. 58. The phenotypic method as claimed in claim 57, wherein the compound is contacted with a cell. |
Scheme 2. Preparation of 16a,b, 17a,b, 19a,b, 23, 27, 30 and 35 The construction of a series of equivalent pyridyl analogues 40, 41, and 43 was investigated next (Scheme 3, Part A). This approach centered on the halocyclisation of imines 38a,b. The synthesis of 38a,b involved Sonogashira coupling of 2-iodobenzaldehyde 36 with bromoethynylbenzene 33 to give 37 (92%) followed by Schiff base condensation with MeONH 2 (Method A) to give 38a (94%) or t-BuNH 2 (Method B) to give 38b (not isolated). Bromocyclisation of 38a was achieved using the method previously described by Yu et al. 3 employing CuBr 2 in DMA at 100 °C, giving 39a (34%). The yield of this reaction was limited by a competing oxidative-cyclisation to give lactam 39b (44%) as the major by-product. Oxime 38a could not be iodocyclised, though the corresponding t-Bu-aldimine 38b could be by employing ICl in CH 3 CN with a weak base (NaOAc) to give product 42 (51%). UCC of dibromide 39a with DMD gave the heterotetracene 40 (53%). PdCC 1 of dibromide 39a with DMD proved surprisingly regioselective, favoring lactam 41 (44%) as the major product (no regioisomeric lactam could be detected). A possible explanation for this regioselectivity is that under the thermal reaction conditions (80 °C in N-methyl-2-pyrrolidone) nucleophilic aromatic substitution of the bromo group on the isoquinoline precedes Pd-mediated carbonylative ring closure onto the bromophenyl ring. This regioselectivity is reversed in the PdCC 2 of the iodobromo substrate 42 with DMD, giving 43 (45%). In this case, Pd-mediated carboxyamidation with DMD precedes ring closure onto the bromophenyl, in a separate UCC step. In Scheme 3 Part B, alkyne 12a was converted into 3-iodobenzo[b]thiophene-2-carbaldehyde (44) by formylation and iodocyclisation. Iodoaldehyde 44 was then subject to an identical series of reactions to those used in Part A to generate a series of thiopheno-fused systems 48, 49 and 51. 2 Scheme 3: Preparation of 40, 41, 43, 48, 49, and 51. Triazenes can be used to operate as masked diazoniums that could be unmasked by acid in the presence of a nucleophile Nu (tethered or untethered) to give a cinnoline (Scheme 4 Box). 4 In the present disclosure, this chemistry was exploited toward the rapid assembly of a series cinnolines 56a-d from 2- iodoaniline 52 (Scheme 4). Terminal alkyne 53 was prepared in three steps, involving diazotisation and triazene formation, followed by Sonogashira coupling with TMS-acetylene and deprotection. A Cu-free Sonogashira coupling was employed to couple alkyne 53 to iodobenzenes 54a-d, giving tolans 55a-d (42-96%). Treatment of tolans 55a-c with MeSO3H unmasked the diazonium cation and induced electrophilic co-cyclisation to give 56a-c. Treatment of the ester 55d with MeSO3H in the presence of tetraethylammonium chloride gave a chlorocinnoline 57 (unpurified). Reaction of 57 with DMD at elevated temperature afforded 56d 52 through a domino nucleophilic aromatic substitution lactamisation sequence in excellent yield (95%). Scheme 4: Preparation of 56a-d Given the success of the diazonium cyclisations to give cinnolines, the inventors proposed to explore related cyclisation on nitrilium ion 62 to give 63 and 64 (Scheme 5). Sonogashira coupling of 2-iodophenylformamide 58 to alkynes 33 and 59 gave tolans 60a and 60b, respectively (66−67%). Reaction of 60a with Burgess reagent and of 60b with POCl3 and diisopropylethylamine (DIPEA) gave rise to the isonitriles 61a and 61b, respectively. Both isocyanides 61a,b were stable in solution ( 1 H NMR), but reverted to the formamides 60a,b upon attempted extractive work up, consequently, they were not isolated but used directly in the next reaction. Attempted protonation and cyclisation of 61a and 61b to quinolines 63 and 64 respectively, via nitrilium ion 62 failed. Rather, 61a gave the regioisomeric quinoline 67 (21% from 60a) and 61b reverted to the formamide 60b. Bromocyclisation of 61b to give 69 (72%) was achieved upon addition of Et4N.Br without acid, in a process previously described by Mitamura et al. 5 This involves nucleophilic cyclisation of a bromide adduct ion 68 with concomitant protonation by residual diisopropylethylammonium ion (from isonitrile formation). Ring closure of dibromide 69 under UCC and PDCC 2 conditions gave 70 (52%) and 71 (32%), respectively. Scheme 5: Preparation of 67, 70 and 71 Finally, since 19a (Scheme 2) proved to be active as a TOP1 inhibitor (see below), analogue 77 was also prepared (Scheme 6) that bears the additional TOP1 protein binding methoxy and methylenedioxy groups seen in 3 and 4 (Figure 1). Sonogashira coupling of the known aryliodide 72 and arylalkyne 73 afforded tolan 74 (89%). Iodocyclisation of 74 proceeded chemoselectively through the methylsulfide (and not the ester) to give benzo[b]thiophene 75 (94%). The ester was efficiently converted to the amide 76 (92% over 3 steps) and cyclised under Buchwald-Hartwig conditions to furnish the target compound 77 (51%). Scheme 6: Preparation of fully decorated compound 77 Efficient coupling-cyclisation processes for the three benzo[b]thiophene substrates 15a, 18a, and 29 could also be achieved with improved efficiency using the PdCC 3 protocol to give lactams 17a (89% from 15a), 19a (89% from 18a), 30 (89% from 29) (Scheme 7). Substrates 15a and 29 were also reacted with amines to generate a pyrrole ring through BHCC, giving 78 (58% from 15a), 79 (78% from 29), and 80 (47% from 29) (Scheme 7). Scheme 7: Examples of efficient coupling-cyclisation processes using PdCC 3 and BHCC The benzo[b]thiophene substrate can be replaced with other heterocycles, as exemplified for the pyridine 81 which, like other benzene substrates above, also bears ortho halo (iodo) and nucleophilic (NuMe = SMe) groups. Conversion of 81 to alkyne 84 (81% over 2 steps), followed by Sonogashira coupling (gives 85 56%) and bromo-cyclisation bromo-iodo substrate thiophenofused pyridine 86 (100%). Reaction 86 with DMD under PdCC 3 conditions gave the polyfused heterocycle 87 (60%) (Scheme 8). Scheme 8: Exemplification of ortho iodo/SMe pyridine 82 as alternative heterocyclic substrate to benzene furnishing polyfused hetereocycle 87 through a sequence of halocyclization and PdCC. General Procedure A (Sonogashira coupling) for the synthesis of alkynes 13a, 13b, 14a, 14b, 28, 37, 45, 60a, 60b, and 74. The respective 2-iodobenzene was dissolved in Et3N (0.2 M) in a dry round-bottom flask (RBF), followed by addition of CuI (4–6 mol%) and Pd(PPh 3 ) 2 Cl 2 (2–3 mol%). The RBF was then degassed and backfilled with N 2 (g) three times. Finally, a solution of the terminal alkyne (1.2 equiv.) in Et 3 N (1 M) was added dropwise under an N 2 (g) atmosphere. The reaction mixture was stirred at rt−60 °C overnight. On completion, the suspension was filtered through Celite ® and washed with Et 2 O. Washed with H 2 O twice and with brine twice, the organic extract was dried over anhydrous MgSO 4 , filtered and concentrated under reduced pressure. The crude product obtained was purified by flash column chromatography to yield the desired alkyne. General Procedure B (Cu-free Sonogashira coupling) for the synthesis of alkynes 55a-d. 54a-d was dissolved in pyrrolidine (0.5 M), followed by addition of Pd(PPh 3 ) 4 (5 mol%). The RBF was degassed and backfilled with N 2 (g) for three times. Finally, a solution of 53 (1.5 equiv.) in pyrrolidine (3 M) was added dropwise under N 2 (g) atmosphere. The reaction mixture was heated at 60 o C for 4−16 h. On completion, the suspension was filtered through Celite ® and washed with EtOAc. Washed with H 2 O three times, the organic extract was dried over anhydrous MgSO 4 , filtered and concentrated under reduced pressure. The crude product obtained was purified by flash column chromatography (1:1 hexanes:EtOAc) to yield the desired alkynes 55a-d. General Procedure C (Sonogashira Coupling–Desilylation) for the synthesis of alkynes 53, 59, and 73. The respective 2-iodobenzene was dissolved in Et3N (0.2 M) in a dry round-bottom flask (RBF), followed by addition of CuI (4–6 mol%) and Pd(PPh3)2Cl2 (2–3 mol%). The RBF was then degassed and backfilled with N2 three times. Finally, trimethylsilylacetylene (1.2 equiv.) was added dropwise under an N2(g) atmosphere. The reaction mixture was stirred at room temperature (rt) overnight. On completion, the suspension was filtered through Celite ® and extracted with Et2O twice, and washed with H2O twice and with brine twice. The combined organic extracts were dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude product was purified by a silica plug (100% hexanes) to yield the TMS-protected terminal alkyne, which was then dissolved in MeOH/Et2O (2 : 1, 0.2 M), followed by addition of K2CO3 (1−2 equiv.). The reaction mixture was stirred at rt overnight. On completion, the mixture was concentrated to a residue and taken up in Et2O. Washed with H2O twice and with brine twice, the organic extract was dried over anhydrous MgSO4, filtered, and concentrated to yield the desired terminal alkynes, which were directly used in the next step without further purification. General Procedure D (Iodocyclisation) for the synthesis of iodides 15a,b, 22, 29, 34, 44, 75: I2 (1.2 − 3 equiv.) was added to a stirred solution of the respective alkyne substrates in dry CH2Cl2 (0.2 M) under an N2(g) atmosphere. The reaction mixture was stirred at rt for 1 – 18 h. On completion, the reaction mixture was quenched with saturated Na2S2O3 solution and extracted with CH2Cl2 twice. The combined organic extracts were washed with H2O twice and with brine twice, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to yield the desired iodocyclised product. General UCC Procedure for the final ring closure of 15a, 15b, 22, 26, 39a, 47 and 69. In a dry RBF, the respective dihalide was dissolved in dry n-butanol or DMF (0.1−0.2 M). K 3 PO 4 (4 equiv.), ethylene glycol (12 equiv.), 1,1-dimethylethane-1,2-diamine (DMD) (15 equiv.) and CuI (10−40 mol%) were added sequentially into the flask. The RBF was degassed and backfilled with N 2 (g) three times, and the reaction mixture was heated at 80−110 °C. On completion, the reaction mixture was cooled down to rt, quenched with saturated NH 4 Cl solution and extracted with EtOAc twice. The combined organic extracts were washed with H 2 O three times and with brine twice, dried over anhydrous MgSO 4 , filtered, and concentrated under reduced pressure. The crude product obtained was purified by flash column chromatography to yield the desired alkyne. General BHCC Procedure for the final ring closure of 15a, 18a, and 29. In a dry RBF, the respective dihalide was dissolved in dry 1,4-dioxane or toluene (0.1−0.2 M). Cs 3 CO 3 (2-4 equiv.), Pd 2 dba 3 (cat.), and Xantphos (cat.) and an amine (1-15 equiv.) coupling partner. The RBF was degassed and backfilled with N 2 (g) three times, and the reaction mixture was heated to reflux. On completion, the reaction mixture was cooled down to rt, quenched with saturated NH4Cl solution and extracted with EtOAc twice. The combined organic extracts were washed with H2O three times and with brine twice, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude product obtained was purified by flash column chromatography to yield the desired alkyne. General PdCC 1 Procedure for the final ring closure of 15a, 39b and 47. The respective dihalide, Pd(OAc)2 (10 mol%), CuI (10 mol%), PPh3 (1.5 equiv.), DMD (15 equiv.), Et3N (2 equiv.) and dry NMP (0.1−0.15 M) was added to a dry RBF. The RBF was degassed and backfilled with CO(g) for three times, the reaction mixture was then heated at 80 °C for 15−49 h under CO(g) atmosphere. On completion, the reaction mixture was cooled down to rt, quenched with saturated NH4Cl solution and extracted with EtOAc twice. The combined organic extracts were washed with H2O three times and with brine twice, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude product obtained was purified by flash column chromatography to yield the desired final product. General PdCC 2 Procedure as a two-step sequence for the final ring closure of 15b, 18a, 18b, 29, 34, 42, 50 and 79. Step 1: use General PdCC 1 Procedure to form the secondary amide; step 2: use a modified UCC Procedure to close the ring and form final products (use N,N,N',N'-tetramethylethane-1,2-diamine (TMD) in lieu of DMD). General PdCC 3 Procedure for the final ring closure of 15a, 18a, 29, and 86. In a dry RBF, the respective dihalide was dissolved in dry 1,4-dioxane (0.1−0.2 M). Cs3CO3 (2- 4 equiv.), Pd 2 dba 3 (cat.), and Xantphos (cat.) and an amine (1-15 equiv.) coupling partner. The RBF was degassed and backfilled with CO (g) three times and the reaction mixture was heated to 70 o C. Upon complete consumption of the dihalo starting material, the CO atmosphere was replace with N 2 (g) and the reaction mixture heated 120 o C. Upon completion, the reaction was cooled down to rt, quenched with saturated NH 4 Cl solution and extracted with EtOAc twice. The combined organic extracts were washed with H 2 O three times and with brine twice, dried over anhydrous MgSO 4 , filtered, and concentrated under reduced pressure. The crude product obtained was purified by flash column chromatography to yield the desired alkyne. The following materials were prepared according to literature procedures: 12a-b, 7 19, 7 20-22, 2 31-32, 1 33-34, 2 44-45, 2 46b, 2 50, 2 1-((2-iodophenyl)diazenyl) piperidine, 4 58, 8 59 9 . Synthetic Methods (2-((2-Bromophenyl)ethynyl)phenyl)(methyl)sulfane (13a): Compound 13a was synthesised according to General Procedure A. The crude product obtained was purified by flash column chromatography (49:1 hexanes:EtOAc, R f = 0.3) to yield 13a (577 mg, 100%) as a yellow oil. 1 H NMR (400 MHz,CDCl 3 ) δ 7.62 (dt, J = 7.5, 1.2 Hz, 2H), 7.57 – 7.53 (m, 1H), 7.36-7.28 (m, 2H), 7.22 – 7.16 (m, 2H), 7.13 (td, J = 7.5, 1.2 Hz, 1H), 2.52 (s, 3H). 13 C DEPT-Q NMR (101 MHz, CDCl 3 ) δ 142.0 (C), 133.7 (CH), 132.9 (CH), 132.6 (CH), 129.6 (CH), 129.3 (CH), 127.1 (CH), 125.6 (C), 125.5 (C), 124.43 (CH), 124.41 (CH), 121.2 (C), 94.3 (C), 91.5 (C), 15.4 (CH3). LCMS (API-ES) m/z (%): 4.2 min, 304.9. HPLC: PP gradient method, = 7.7 min, 97.9 % purity at 254 nm. HR-ESI (m/z) calcd for C15H12BrS + [M + H] + 302.9838, found 302.9831. The spectroscopic data are consistent with those previously reported in the literature. 1-Bromo-2-((2-methoxyphenyl)ethynyl)benzene (13b): Compound 13b was synthesised according to General Procedure A. The crude product (2.80 g) was purified by flash column chromatography (100% hexanes, Rf = 0 → 4:1 hexanes:EtOAc, Rf = 0.7) to yield the title compound (2.35 g, 96%) as a bright orange oil. 1 H NMR (400 MHz,CDCl3) δ 7.60 (app td, J = 7.8, 1.4, 2H), 7.55 (dd, J = 7.7, 1.6 Hz, 1H), 7.33 (ddd, J = 8.4, 7.5, 1.7 Hz, 1H), 7.30-7.26 (td, J = 7.6, 1.3 Hz, 1H), 7.16 (ddd, J = 8.0, 7.5, 1.7 Hz, 1H), 6.95 (td, J = 7.5, 1.0 Hz, 1H), 6.92 (d, J = 8.4 Hz, 1H), 3.93 (s, 3H). HPLC: PP gradient method, = 7.6 min, 90.8 % purity at 254 nm. HR-APCI calcd for C15H12BrO [M + H] + 287.0066 and 289.0047, found 287.0065 and 289.0044. The spectroscopic data are consistent with those previously reported in the literature. (2-((2-Iodophenyl)ethynyl)phenyl)(methyl)sulfane (14a): Compound 14a was synthesised according to General Procedure A. The crude product obtained (brown oil, 1.38 g) was purified by flash column chromatography (50:1 hexanes:EtOAc, R f = 0.25) to yield 14a (227 mg, 64%) as a light purple oil. 1 H NMR (400 MHz, CDCl 3 ) δ 7.88 (dd, J = 8.0, 0.9 Hz, 1H), 7.58 (td, J = 7.5, 1.7 Hz, 2H), 7.34 (td, J = 7.6, 1.2 Hz, 1H), 7.33 (ddd, J = 8.0, 7.4, 1.5 Hz, 1H), 7.20 (d, J = 7.3 Hz, 1H), 7.13 (td, J = 7.5, 1.2 Hz, 1H), 7.04 – 6.99 (m, 1H), 2.53 (s, 3H). 13 C DEPT-Q NMR (101 MHz, CDCl 3 ) δ 142.0 (C), 138.9 (CH), 133.0 (CH), 132.9 (CH), 130.0 (C), 129.6 (CH), 129.3 (CH), 127.9 (CH), 124.5 (CH), 124.4 (CH), 121.2 (C), 100.7 (C), 97.6 (C), 90.6 (C), 15.4 (CH 3 ). LCMS (APCI) m/z (%): t = 4.8 min, 351.0 (100, M + H + ). HPLC: PP gradient method, = 7.1 min, 95.7 % purity at 254 nm. HR-ESI (m/z) calcd for C 15 H 12 IS + [M + H] + 350.9699, found 350.9695. The spectroscopic data are consistent with those previously reported in the literature. 1-Iodo-2-((2-methoxyphenyl)ethynyl)benzene (14b): Compound 14b was synthesised according to General Procedure A. The crude product obtained (14.12 g, red oil) was purified by flash column chromatography (49:1 hexanes:EtOAc, R f = 0.33) to yield the title product (3.89 g, 91%) as an orange oil. 1 H NMR (401 MHz, CDCl 3 ) δ 7.87 (d, J = 8.3 Hz, 2H), 7.62 – 7.53 (m, 2H), 7.36 – 7.29 (m, 2H), 7.06 – 7.03 (m, 1H), 7.02 – 6.93 (m, 2H), 6.92 (d, J = 8.4 Hz, 1H), 3.93 (s, 3H). LCMS (APCI) m/z (%): t = 4.4 min, 335.0 (100, M + H + ). HPLC: PP gradient method, = 6.7 min, 92.8 % purity at 254 nm. The spectroscopic data are consistent with those previously reported in the literature. 2-(2-Bromophenyl)-3-iodobenzo[b]thiophene (15a): Compound 15a was synthesised according to General Procedure D. 15a (705 mg, 95%) was obtained as a yellow oil and directly used in the next step without further purification. 1 H NMR (400 MHz, CDCl3) δ 7.83 (dd, J = 7.9, 1.1 Hz, 2H), 7.73 (dd, J = 8.2, 0.9 Hz, 1H), 7.50 (ddd, J = 7.2, 4.6, 1.1 Hz, 1H), 7.46-7.41 (m, 3H), 7.35 (ddd, J = 8.0, 6.0, 3.2 Hz, 1H). 13 C DEPT-Q NMR (101 MHz, CDCl3) δ 141.8 (C), 141.0 (C), 139.5 (C), 136.1 (C), 133.2 (CH), 132.7 (CH), 130.9 (CH), 127.4 (CH), 126.2 (CH), 125.9 (CH), 125.6 (CH), 124.7 (C), 122.4 (CH), 83.7 (C). HPLC: PP gradient method, t R = 8.4 min, 92.6 % purity at 254 nm. HR-APCI (m/z) calcd for C 14 H 8 BrIS + [M] + 413.8569, found 413.8561. The spectroscopic data are consistent with those previously reported in the literature. 2-(2-Bromophenyl)-3-iodobenzofuran (15b): Compound 15b was synthesised according to General Procedure D. The crude product obtained was purified by flash column chromatography (9:1 hexanes:CH2Cl2, Rf = 0.33) to yield 15b (2.54 g, 78%) as a light yellow solid. 1 H NMR (400 MHz, CDCl3) δ 7.74 (dd, J = 8.0, 1.2 Hz, 1H), 7.57 (dd, J = 7.6, 1.8 Hz, 1H), 7.52 (dd, J = 7.3, 0.9 Hz, 1H), 7.49 (dd, J = 7.7, 1.4 Hz, 1H), 7.45 (td, J = 7.6, 1.2 Hz, 1H), 7.43-7.34 (m, 3H). LCMS (ESI) m/z (%): t = 4.6 min, 271.0 (100, M-I-) and 272.9 (70, M-I-). HPLC: PP gradient method, tR = 8.2 min, 96.4 % purity at 254 nm. HR-APCI calcd for C14H8BrIO [M] + 397.8798 and 399.8778, found 397.8791 and 399.8771. The spectroscopic data are consistent with those previously reported in the literature. 2-(10H-Benzo[4,5]thieno[3,2-b]indol-10-yl)-N,N-dimethylethan -1-amine (16a): Compound 16a was synthesised according to General UCC Procedure. The crude product (83 mg, yellow solid) obtained was purified by flash column chromatography (99:1 CH2Cl2:MeOH, Rf = 0.3) to yield 16a (25 mg, 29%) as a light yellow oil. 1 H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 8.0 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.78 (d, J = 7.9 Hz, 1H), 7.54 – 7.47 (m, 1H), 7.46 (ddd, J = 8.1, 7.2, 1.1 Hz, 2H), 7.37 (ddd, J = 8.3, 7.2, 1.1 Hz, 2H), 7.23 (ddd, J = 7.9, 7.1, 0.9 Hz, 1H), 4.69 (app d, J = 8.0 Hz, 2H), 2.80 (app d, J = 8.0 Hz, 2H), 2.41 (s, 6H). 13 C DEPT-Q NMR (101 MHz, CDCl3) δ 143.3 (C), 141.5 (C), 137.4 (C), 127.0 (C), 124.8 (CH), 124.5 (CH), 124.0 (CH), 123.2 (CH), 121.9 (C), 119.8 (CH), 119.7 (CH), 119.6 (CH), 115.7 (C), 109.9 (CH), 58.9 (CH2), 46.2 (CH3), 43.8 (CH2). LCMS (ESI) m/z (%): t = 2.6 min, 295.1 (100, M + H + ). HPLC: PP gradient method, tR = 5.2 min, 98.2 % purity at 254 nm. HR-ESI (m/z) calcd for C18H19N2S + [M + H] + 295.1263, found 295.1272. 2-(10H-Benzofuro[3,2-b]indol-10-yl)-N,N-dimethylethan-1-amin e (16b): Compound 16b was synthesised according to General UCC Procedure. The crude product was purified by flash column chromatography (10:5:1 hexanes:CH 2 Cl 2 :Et 3 N, R f = 0.35) to yield 16b (86 mg, 42%) as a transparent oil. 1 H NMR (400 MHz, CDCl 3 ) δ 7.84 (ddd, J = 7.9, 1.2, 0.8 Hz, 1H), 7.78-7.75 (m, 1H), 7.65-7.63 (m, 1H), 7.48 (d, J = 8.4 Hz, 1H), 7.36-7.29 (m, 3H), 7.22 (ddd, J = 8.0, 7.1, 0.9 Hz, 1H), 4.54 (t, J = 7.6 Hz, 2H), 2.81 (t, J = 7.6 Hz, 2H), 2.37 (s, 6H). 13 C DEPT-Q NMR (101 MHz, CDCl3) δ 159.3 (C), 142.5 (C), 139.7 (C), 126.8 (C), 123.9 (CH), 122.8 (CH), 122.6 (CH), 119.7 (CH), 118.9 (C), 117.6 (CH), 117.5 (CH), 113.8 (C), 112.9 (CH), 110.1 (CH), 59.0, 46.1, 44.0. LCMS (ESI) m/z (%): t = 3.1 min, 278.9 (100, M + H + ), 279.9 (20, M + H + ). HPLC: PP gradient method, = 5.5 min, 98.0 % purity at 254 nm. HR-ESI calcd for C18H19N2O [M + H] + 279.1492, found 279.1487. 5-(2-(Dimethylamino)ethyl)benzo[4,5]thieno[3,2-c]quinolin-6( 5H)-one (17a): PdCC 1 : Compound 17a was synthesised according to General PdCC 1 Procedure. The crude product (182 mg) was purified by flash column chromatography (3:1 Et2O:MeOH, Rf = 0.35) to yield 17a (25 mg, 43%) as a yellow oil. 1 H NMR (400 MHz, CDCl3) δ 8.94 (dd, J = 8.0, 1.3 Hz, 1H), 7.88 – 7.82 (m, 2H), 7.60 – 7.42 (m, 4H), 7.30 – 7.24 (m, 1H), 4.60 – 4.52 (m, 2H), 2.72 – 2.64 (m, 2H), 2.42 (s, 6H). 13 C DEPT-Q NMR (101 MHz, CDCl3) δ 158.7 (C), 147.7 (C), 137.9 (C), 137.3 (C), 137.2 (C), 130.5 (CH), 126.2 (CH), 125.8 (CH), 125.7 (CH), 125.4 (CH), 123.5 (C), 122.4 (CH), 122.0 (CH), 118.0 (C), 115.1 (CH), 56.3 (CH2), 46.0 (CH3), 40.7 (CH2). LCMS (ESI) m/z (%): t = 4.7 min, 323.1. HPLC: PP gradient method, = 5.5 min, 90.8 % purity at 254 nm. HR-ESI (m/z) calcd for C 19 H 19 N 2 OS + [M + H] + 323.1213, found 323.1221. PdCC 3 : To a dry RBF, 2-(2-bromophenyl)-3-iodobenzo[b]thiophene (100 mg, 0.241 mmol), Cs2CO3 (235 mg, 0.723 mmol), Pd2dba3 (22.0 mg, 0.0241 mmol), and Xantphos (27.9 mg, 0.0482 mmol) were added and dissolved in anhydrous 1,4-dioxane (1.20 mL). The vessel was subsequently degassed and backfilled with N 2 (g) three times and allowed to stir at room temperature for 10 minutes. N,N- Dimethylethylenediamine (DMD) (0.0389 mL, 0.362 mmol) was then added to the flask before it was subsequently degassed and backfilled with CO (g) three times and allowed to stir under this atmosphere for 4.5 h at 70 o C. After the dehalogenated pyridine starting material had been consumed, the atmosphere of the vessel was reverted back to N 2 (g) and the reaction mixture was allowed to stir at 120 o C for 20 h. Upon completion, the mixture was extracted with EtOAc (3 x 20 mL) and filtered through Celite ®, before being washed with water (3 x 10 mL) and brine (2 x 10 mL). The organic layer was subsequently collected, dried over MgSO 4 , and concentrated under vacuum. The crude product was then purified via flash column chromatography (95% EtOAc/ 5% Et3N/ 1% MeOH, Rf = 0.30) to yield the desired compound (69.0 mg, 88%) as an amber wax. Data in accordance with that above. 2-(2-Bromophenyl)-N-(2-(dimethylamino)ethyl)benzofuran-3-car boxamide: 14b (100 mg, 251 µmol), Pd(OAc)2 (5.6 mg, 25 µmol), PPh3 (98.6 mg, 376 µmol), DMD (331 mg, 3.76 mmol, 0.41 mL), Et3N (51 mg, 501 µmol, 47 µL), CuI (4.8 mg, 25 µmol) and dry NMP (2.5 mL) was added to a 10 mL dry RBF accordingly. The RBF was degassed and backfilled with CO(g) for three times, the reaction mixture was then heated at 80 °C for 18 h. After heating, the mixture was cooled down rt, diluted with saturated NaHCO3 solution (25 mL) and extracted with EtOAc (2 x 15 mL). The combined organic extracts were washed with H2O (2 x 20 mL), and brine (2 x 20 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude product obtained (light yellow oil) was purified by flash column chromatography (100% EtOAc → 9:1 EtOAc:MeOH, Rf = 0.2) to yield 2-(2-bromophenyl)-N-(2-(dimethylamino)ethyl)benzofuran-3-car boxamide (62 mg, 64%) as a colourless oil. 1 H NMR (400 MHz, CDCl3) δ 8.17 – 8.13 (m, 1H), 7.75 (dd, J = 8.0, 1.1 Hz, 1H), 7.58 (dd, J = 7.4, 1.9 Hz, 1H), 7.57 – 7.48 (m, 1H), 7.47 (td, J = 7.5, 1.3 Hz, 1H), 7.44 – 7.34 (m, 3H), 6.40 (br s, 1H), 3.41 (td, J = 6.0, 4.8 Hz, 2H), 2.36 (t, J = 5.9 Hz, 2H), 2.07 (s, 6H). 13 C DEPT-Q NMR (101 MHz, CDCl3) δ 163.1 (C), 154.6 (C), 154.4 (C), 133.5 (CH), 132.7 (CH), 131.8 (CH), 131.4 (C), 127.7 (CH), 126.8 (C), 125.5 (CH), 124.5 (C), 124.1 (CH), 122.4 (CH), 115.2 (C), 111.4 (CH), 57.1 (CH2), 44.8 (CH3), 36.6 (CH2). LCMS (ESI) m/z (%): t = 2.3 min, 657.1 (100, M + H + ) and 389.1 (100, M + H + ). HPLC: PP gradient method, = 5.2 min, 94.8 % purity at 254 nm. HR-ESI (m/z) calcd for C19H20BrN2O2 + [M + H] + 387.0703, found 387.0711. 5-(2-(Dimethylamino)ethyl)benzofuro[3,2-c]quinolin-6(5H)-one (17b): In a dry RBF, 2-(2-bromophenyl)-N-(2-(dimethylamino)ethyl)benzofuran-3-car boxamide (60 mg, 155 µmol) was dissolved in n-butanol (0.8 mL) and K 3 PO 4 (132 mg, 620 µmol, 4.0 equiv.), ethylene glycol (104 µL, 1.86 mmol, 12 equiv.), TMD (288 mg, 2.48 mmol, 0.37 mL), and CuI (11.8 mg, 62 µmol), were added accordingly. The RBF was degassed and backfilled with N2(g) for three times, the reaction mixture was then heated at 90 °C for 15 h. After heating, the reaction mixture was cooled down to rt and diluted with EtOAc (20 mL). The combined organic layer was washed with H2O (2 x 15 mL) and brine (2 x 15 mL), then dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude product (44 mg) obtained was purified by flash column chromatography (10:1 EtOAc:MeOH, Rf = 0.1) to yield 16b (34 mg, 72%) as a transparent oil. 1 H NMR (400 MHz, CDCl3) δ 8.29 (dd, J = 6.0, 2.3 Hz, 1H), 8.20 (dd, J = 7.9, 1.6 Hz, 1H), 7.69 – 7.60 (m, 2H), 7.57 (d, J = 8.4 Hz, 1H), 7.51 – 7.39 (m, 2H), 7.38 (ddd, J = 8.0, 7.1, 1.0 Hz, 1H), 4.59 (br t, J = 7.8 Hz, 2H), 2.69 (br t, J = 7.9 Hz, 2H), 2.43 (s, 6H). 13 C DEPT-Q NMR (101 MHz, CDCl3) δ 159.6 (C), 157.6 (C), 155.6 (C), 138.8 (C), 131.0 (CH), 126.3 (CH), 124.7 (C), 124.6 (CH), 122.7 (CH), 122.5 (CH), 122.4 (CH), 115.2 (CH), 113.2 (C), 111.5 (CH), 110.3 (C), 56.5 (CH2), 46.0 (CH3), 40.7 (CH2). LCMS (ESI) m/z (%): t = 3.06 min, 307.2 (100, M + H + ). HPLC: PP gradient method, = 5.1 min, 99.2 % purity at 254 nm. HR-ESI (m/z) calcd for C19H19N2O2 + [M + H] + 307.1441, found 307.1447. 3-Bromo-2-(2-iodophenyl)benzo[b]thiophene (18a): CuBr 2 (899 mg, 4.03 mmol, 3.0 equiv.) was added to a stirred solution of 14a (470 mg, 1.34 mmol) in dry DCE (7 mL) under N 2 (g) atmosphere. The reaction was heated at 45 ºC for 15 h. On completion, the reaction mixture was quenched with saturated Na 2 S 2 O 3 solution (35 mL), and extracted with CH 2 Cl 2 (2 x 25 mL). The combined organic extracts were washed with H 2 O (2 x 40 mL) and brine (2 x 40 mL), dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The crude product obtained (pale yellow solid, 550 mg) was purified by flash column chromatography (40:1 hexanes:CH 2 Cl 2 , R f = 0.55) to yield 18a (453 mg, 81%) as a white crystal. 1 H NMR (400 MHz, CDCl 3 ) δ 7.99 (dd, J = 8.0, 1.2 Hz, 1H), 7.88 (dd, J = 7.8, 1.3 Hz, 1H), 7.84 (dd, J = 8.0, 1.0 Hz, 1H), 7.51 (ddd, J = 8.0, 7.2, 1.2 Hz, 1H), 7.48 – 7.40 (m, 3H), 7.16 (ddd, J = 8.0, 7.0, 2.1 Hz, 1H). 13 C DEPT-Q NMR (101 MHz, CDCl3) δ 140.6 (C), 139.5 (CH), 138.5 (C), 138.4 (C), 138.0 (C), 131.7 (CH), 130.8 (CH), 128.2 (CH), 125.9 (CH), 125.4 (CH), 123.9 (CH), 122.5 (CH), 108.6 (CH), 100.4 (C). LCMS (ESI) m/z (%): t = 4.9 min, 413.9 (100, M + H + ). HPLC: PP gradient method, tR = 7.4 min, 97.0 % purity at 254 nm. HR-ESI (m/z) calcd for C14H9BrIS + [M + H] + 414.8648, found 414.8634. mp 134–136 °C. 3-Bromo-2-(2-iodophenyl)benzofuran (18b): 14b (407 mg, 1.22 mmol) was dissolved in anhydrous DCE (6.5 mL), followed by addition of N-methylpyrrolidin-2-one hydrotribromide (MPHT) (575 mg, 1.31 mmol). The orange solution was heated at 45 °C over a period of 69 h. On completion, the mixture was cooled down to rt, diluted with saturated Na 2 S 2 O 3 solution (30 mL) and extracted with CH 2 Cl 2 (2 x 25 mL). The combined organic extracts were washed with H 2 O (2 x 50 mL) and brine (2 x 50 mL), dried over anhydrous MgSO 4 , filtered and concentrated under reduced pressure. The crude product obtained (light yellow oil, 630 mg) was purified by flash column chromatography (25:1 hexanes:CH 2 Cl 2 , R f = 0.6) to yield 18b (202 mg, 42%) as a transparent oil. 1 H NMR (401 MHz, CDCl 3 ) δ 8.02 (dd, J = 8.0, 1.2 Hz, 1H), 7.61 (dd, J = 7.7, 1.5 Hz, 1H), 7.59 – 7.50 (m, 2H), 7.48 (td, J = 7.5, 1.2 Hz, 1H), 7.46 – 7.33 (m, 2H), 7.19 (ddd, J = 8.0, 7.3, 1.8 Hz, 1H). 13 C DEPT-Q NMR (101 MHz, CDCl 3 ) δ 153.8 (C), 153.4 (C), 139.9 (CH), 134.8 (C), 132.4 (CH), 131.4 (CH), 128.4 (C), 128.0 (CH), 125.9 (CH), 123.7 (CH), 120.2 (CH), 111.8 (CH), 98.3 (C), 97.0 (C). LCMS (APCI) m/z (%): t = 4.7 min, 399.9 (100, M + H + ). HPLC: PP gradient method, t R = 7.1 min, 99.8 % purity at 254 nm. HR-ESI (m/z) calcd for C 14 H 9 BrIO + [M + H] + 398.8876, found 398.8882. 2-(3-Bromobenzo[b]thiophen-2-yl)-N-(2-(dimethylamino)ethyl)b enzamide: 18a (250 mg, 602 µmol), Pd(OAc)2 (20 mg, 90 µmol), PPh3 (237 mg, 903 µmol), DMD (796 mg, 9.03 mmol, 0.97 mL), Et3N (122 mg, 1.2 mmol, 0.11 mL), CuI (11 mg, 60 µmol) and dry NMP (4.5 mL) was added to a 25 mL dry RBF accordingly. The RBF was degassed and backfilled with CO(g) for three times, the reaction mixture was then heated at 90 °C for 19 h. After heating, the mixture was cooled down to rt, diluted with saturated NH 4 Cl solution (25 mL) and extracted with EtOAc (2 x 25 mL). The combined organic extracts were washed with H 2 O (2 x 25 mL), and brine (2 x 25 mL), dried over anhydrous MgSO 4 , filtered, and concentrated under reduced pressure. The crude product (463 mg, orange oil) obtained was purified by flash column chromatography (9:1 EtOAc:MeOH, R f = 0.2) to yield 2-(3-bromobenzo[b]thiophen-2-yl)-N-(2-(dimethylamino)ethyl)b enzamide (192 mg, 79%) as a transparent oil. 1 H NMR (400 MHz, CDCl 3 ) δ 7.93 – 7.89 (m, 1H), 7.85 (dd, J = 8.0, 1.3 Hz, 1H), 7.82 (dd, J = 8.0, 1.0 Hz, 1H), 7.58 – 7.40 (m, 5H), 6.37 (br s, 1H), 3.23 (td, J = 5.9, 4.7 Hz, 2H), 2.03 (t, J = 5.9 Hz, 2H), 1.70 (s, 6H). 13 C DEPT-Q NMR (101 MHz, CDCl 3 ) δ 167.7 (C), 138.8 (C), 138.4 (C), 137.0 (C), 136.9 (C), 132.0 (CH), 130.4 (C), 130.3 (CH), 129.7 (CH), 129.6 (CH), 125.9 (CH), 125.5 (CH), 123.8 (CH), 122.4 (CH), 108.5 (C), 56.9 (CH 2 ), 44.5 (CH 3 ), 37.4 (CH 2 ). LCMS (ESI) m/z (%): t = 3.1 min, 403.0 (100, M + H + ). HPLC: PP gradient method, = 5.0 min, 98.1 % purity at 254 nm. HR- ESI (m/z) calcd for C19H20N2BrOS + [M + H] + 403.0474, found 403.0482. 6-(2-(Dimethylamino)ethyl)benzo[4,5]thieno[3,2-c]isoquinolin -5(6H)-one (19a): In a dry RBF, 2-(3-bromobenzo[b]thiophen-2-yl)-N-(2-(dimethylamino)ethyl) benzamide (73 mg, 181 µmol) was dissolved in n-butanol (0.9 mL) and K3PO4 (154 mg, 724 µmol), ethylene glycol (121 µL, 2.17 mmol), TMD(337 mg, 2.9 mmol, 0.43 mL), and CuI (14 mg, 72 µmol) were added accordingly. The RBF was degassed and backfilled with N2(g) for three times, the reaction mixture was then heated at 90 °C for 22 h. After heating, the reaction mixture was cooled down to rt and diluted with EtOAc (20 mL). The combined organic extracts were washed with H2O (2 x 15 mL) and brine (2 x 15 mL), then dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude product (47 mg) obtained was purified by flash column chromatography (94:5:1 EtOAc:Et3N:MeOH, Rf = 0.15) to yield 19a (61 mg, 80%) as a light yellow oil. 1 H NMR (400 MHz, CDCl3) δ 8.48 (d, J = 8.0 Hz, 1H), 8.29 (d, J = 8.3 Hz, 1H), 7.85 (d, J = 7.8 Hz, 1H), 7.68 (d, J = 4.5 Hz, 2H), 7.54-7.49 (m, 1H), 7.47 (ddd, J = 8.5, 7.1, 1.4 Hz, 1H), 7.41 (td, J = 7.6, 7.1, 1.1 Hz, 2H), 4.81 (t, J = 8.0 Hz, 2H), 2.81 (t, J = 8.1 Hz, 2H), 2.43 (s, 6H). 13 C DEPT-Q NMR (101 MHz, CDCl3) δ 162.5 (C), 138.6 (C), 133.0 (C), 132.8 (CH), 132.4 (C), 130.8 (C), 129.1 (CH), 127.6 (CH), 125.8 (CH), 125.4 (CH), 124.0 (C), 123.9 (CH), 123.5 (CH), 123.2 (CH), 117.9 (C), 57.0 (CH 2 ), 46.1 (CH 3 ), 43.5 (CH 2 ). LCMS (ESI) m/z (%): t = 3.1 min, 323.1 (100, M + H + ). HPLC: PP gradient method, = 4.9 min, 95.5 % purity at 254 nm. HR-ESI (m/z) calcd for C 19 H 19 N 2 OS + [M + H] + 323.1213, found 323.1220. PdCC 3 : To a dry RBF, 3-bromo-2-(2-iodophenyl)benzo[b]thiophene (100 mg, 0.241 mmol), Cs 2 CO 3 (235 mg, 0.723 mmol), Pd 2 dba 3 (22.0 mg, 0.0241 mmol), and Xantphos (27.9 mg, 0.0482 mmol) were added and dissolved in anhydrous 1,4-dioxane (1.20 mL). The vessel was subsequently degassed and backfilled with N 2 (g) three times and allowed to stir at room temperature for 10 minutes. N,N- Dimethylethylenediamine (0.0389 mL, 0.362 mmol) was then added to the flask before it was subsequently degassed and backfilled with CO (g) three times and allowed to stir under this atmosphere for 4.5 h at 70 o C. After the dehalogenated pyridine starting material has been consumed, the atmosphere of the vessel was reverted back to N 2 (g) and the reaction mixture was allowed to stir at 120 o C for 20 h. Upon completion, the mixture was extracted with EtOAc (3 x 20 mL) and filtered through Celite ®, before being washed with water (3 x 10 mL) and brine (2 x 10 mL). The organic layer was subsequently collected, dried over MgSO 4 , and concentrated under vacuum. The crude product was then purified via flash column chromatography (95% EtOAc/ 5% Et 3 N/ 1% MeOH, R f = 0.30) to yield the desired compound (68.5 mg, 88%) as an amber wax. 1 H NMR (401 MHz, CDCl 3 ) δ 8.48 (dd, J = 8.0, 1.1 Hz, 1H), 8.30 (d, J = 8.4 Hz, 1H), 7.85 (dd, J = 7.9, 1.4 Hz, 1H), 7.76 – 7.62 (m, 2H), 7.58 – 7.32 (m, 3H), 4.82 (t, J = 8.1 Hz, 2H), 2.82 (t, J = 8.2 Hz, 2H), 2.44 (s, 6H). LCMS (APCI) m/z: 323.2 [M+H + ]. 2-(3-Bromobenzofuran-2-yl)-N-(2-(dimethylamino)ethyl)benzami de: 17b (125 mg, 313 µmol), Pd(OAc) 2 (11 mg, 47 µmol), PPh 3 (123 mg, 470 µmol), DMD (414 mg, 4.7 mmol, 0.51 mL), Et 3 N (63 mg, 627 µmol, 57 µL) and dry NMP (2 mL) was added to a 25 mL dry RBF accordingly. The RBF was degassed and backfilled with CO(g) for three times, the reaction mixture was then heated at 90 °C for 20 h. After heating, the mixture was cooled down to rt, diluted with saturated NaHCO 3 solution (25 mL) and extracted with EtOAc (2 x 25 mL). The combined organic extracts were washed with H 2 O (2 x 25 mL), and brine (2 x 25 mL), dried over anhydrous MgSO 4 , filtered, and concentrated under reduced pressure. The crude product (270 mg, orange oil) obtained was purified by flash column chromatography (10:1 EtOAc:MeOH, R f = 0.15) to yield the title product (91 mg, 75%) as a light yellow oil. 1 H NMR (401 MHz, CDCl 3 ) δ 7.85 – 7.77 (m, 1H), 7.79 – 7.71 (m, 1H), 7.61 – 7.51 (m, 3H), 7.49 (dd, J = 7.6, 2.2 Hz, 1H), 7.36 (td, J = 7.3, 1.7 Hz, 1H), 7.33 (td, J = 7.3, 1.3 Hz, 1H), 6.36 (s, 1H), 3.32 (dd, J = 10.7, 5.9 Hz, 2H), 2.10 (t, J = 5.9 Hz, 3H), 1.85 (s, 6H). 13 C DEPT- Q NMR (101 MHz, CDCl 3 ) δ 168.5 (C), 154.0 (C), 150.7 (C), 137.0 (C), 130.9 (CH), 130.12 (CH), 130.11 (CH), 129.3 (CH), 128.8 (C), 126.7 (C), 125.9 (CH), 123.8 (CH), 120.2 (CH), 111.7 (CH), 96.7 (C), 57.2 (CH2), 44.6 (CH3), 37.3 (CH2). LCMS (ESI) m/z (%): t = 3.2 min, 389.1 (100, M + H + ). HPLC: PP gradient method, = 4.84 min, 95.1 % purity at 254 nm. HR-ESI (m/z) calcd for C19H20BrN2O2 [M + H] + 387.0703, found 387.0712. 5-(2-(Dimethylamino)ethyl)benzo[4,5]thieno[3,2-b]quinolin-11 (5H)-one (23): Compound 23 was synthesised according to General UCC Procedure. The crude product (91 mg, bright yellow oil) obtained was purified by flash column chromatography (24:1 EtOAc:Et 3 N, R f = 0.35) to yield 23 (23 mg, 36%) as a pale orange solid. 1 H NMR (400 MHz, CDCl 3 ) δ 8.62 (dd, J = 8.2, 1.8 Hz, 1H), 8.48 (dd, J = 8.3, 1.6 Hz, 1H), 8.00 (dd, J = 7.7, 1.6 Hz, 1H), 7.84 – 7.71 (m, 2H), 7.63 – 7.50 (m, 2H), 7.45 (ddd, J = 7.9, 6.6, 1.2 Hz, 1H), 4.92 (t, J = 8.2 Hz, 2H), 3.05 (br t, J = 7.9 Hz, 2H), 2.50 (s, 6H). 13 C DEPT-Q NMR (101 MHz, CDCl3) δ 173.4 (C), 142.5 (C), 142.0 (C), 141.4 (C), 132.8 (CH), 130.6 (C), 127.9 (CH), 126.8 (CH), 125.3 (CH), 125.1 (CH), 124.8 (CH), 123.5 (C), 123.1 (C), 123.0 (CH), 115.1 (CH), 57.37 (CH2), 48.0 (CH2), 46.2 (CH3). LCMS (ESI) m/z (%): t = 2.7 min, 323.1 (100, M + H + ). HPLC: PP gradient method, = 4.3 min, 96.2 % purity at 254 nm. HR-ESI (m/z) calcd for C19H19N2OS + [M + H] + 323.1213, found 323.1216. mp 177–179 °C. 3-(2-Bromophenyl)-N,N-dimethylpropiolamide (24): n-BuLi (3.15 mL, 7.88 mmol) was added dropwise to a stirred solution of 33 3 (1.09 mL, 8.73 mmol) in dry THF (44 mL) at –78 °C under N 2 (g) atmosphere. The solution was left to stir at –78 °C for 30 min, followed by dropwise addition of dimethylcarbamoyl chloride (0.88 mL, 9.60 mmol). The reaction mixture was then left at stirring at –78 °C for 5 min, then raised to rt. The dark brown suspension was quenched with saturated NH 4 Cl solution and extracted with Et 2 O (2 x 75 mL). The combined organic extracts were washed with H 2 O (2 x 100 mL) and brine (2 x 100 mL), dried over anhydrous MgSO 4 , filtered and concentrated under reduced pressure. The crude product (2.01 g) was obtained as a brown oil and purified by flash column chromatography (2:1 hexanes:EtOAc , R f = 0.3) to yield 24 (1.47 g, 74%) as a pink solid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.62 (dd, J = 7.5, 1.9 Hz, 1H), 7.61 (dd, J = 7.7, 1.5 Hz, 1H), 7.26 (td, J = 7.8, 1.8 Hz, 1H), 3.36 (s, 3H), 3.04 (s, 3H). 13 C DEPT-Q NMR (101 MHz, CDCl 3 ) δ 154.1 (C), 134.5 (CH), 132.5 (CH), 131.1 (CH), 127.2 (CH), 125.9 (C), 122.9 (C), 87.7 (C), 85.4 (C), 38.3 (CH 3 ), 34.1 (CH 3 ). LCMS (ESI) m/z (%): t = 3.6 min, 253.9 (100, M + H + ), 255.9 (80, M + H + ). HPLC: PP gradient method, = 5.6 min, 98.8 % purity at 254 nm. HR-ESI (m/z) calcd for C11H11BrNO + [M + H] + 252.0019, found 252.0022. mp 70–74 °C. 3-(2-Bromophenyl)-1-(2-(methylthio)phenyl)prop-2-yn-1-one (25): n-BuLi (0.64 mL, 1.6 mmol, 2.5 M in hexanes) was added dropwise to a stirred solution of 11a (400 mg, 1.6 mmol) in dry THF (8 mL) at –78 °C under N2(g) atmosphere. The solution was left to stir at –78 °C for 15 min, followed by addition of a solution of 24 (353 mg, 1.4 mmol) in dry THF (2 mL). The reaction was left to stir at –78 °C for 1 h, then raised to rt and quenched with saturated NH 4 Cl solution (40 mL) and extracted with Et 2 O (2 x 25 mL). The combined organic extracts were washed with H 2 O (2 x 40 mL) and brine (2 x 40 mL), dried over anhydrous MgSO 4 , filtered and concentrated under reduced pressure. The crude product (544 mg, brown oil) obtained was purified by flash column chromatography (19:1 hexanes:EtOAc, Rf = 0.25) to yield 25 (330 mg, 71%) as a bright yellow solid. 1 H NMR (400 MHz, CDCl3) δ 8.60 (dd, J = 7.9, 1.5 Hz, 1H), 7.66 (dd, J = 7.7, 1.8 Hz, 1H), 7.62 (dd, J = 7.9, 1.3 Hz, 1H), 7.52 (ddd, J = 8.2, 7.2, 1.6 Hz, 1H), 7.37 – 7.20 (m, 4H), 2.44 (s, 3H). 13 C DEPT-Q NMR (101 MHz, CDCl3) δ 177.4 (C), 145.0 (C), 135.3 (CH), 135.2 (CH), 133.5 (CH), 132.9 (C), 132.8 (CH), 131.8 (CH), 127.4 (CH), 126.7 (C), 124.2 (CH), 123.4 (CH), 122.9 (C), 90.6 (C), 90.3 (C), 15.5 (CH3). LCMS (APCI) m/z (%): t = 3.4 min, 331.0 (25, M + H + ), 354.9 (100, M+Na + ). HPLC: PP gradient method, tR = 7.2 min, 90.8 % purity at 254 nm. HR-ESI (m/z) calcd for C16H12BrOS + [M + H] + 330.9787, found 330.9780. mp 96–100 °C. 2-(2-Bromophenyl)-3-iodo-4H-thiochromen-4-one (26): 25 (140 mg, 423 µmol) was dissolved in anhydrous CH 3 CN (4 mL) in a dry RBF, followed by slow addition of a solution of ICl (103 mg, 634 µmol) in anhydrous CH 3 CN (0.9 mL) to the stirred solution. The reaction was left to stir at rt for 26 h in the dark. On completion, the reaction mixture was quenched with saturated Na2S2O3 solution (30 mL) and extracted with EtOAc (2 x 20 mL). Washed with H2O (2 x 30 mL) and brine (2 x 30 mL), the combined organic extracts were dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The crude product (185 mg) obtained was purified by flash column chromatography (2:1 hexanes:toluene, Rf = 0.2) to yield 26 (97 mg, 52%) as a pale yellow solid. 1 H NMR (400 MHz, CDCl3) δ 8.63 (dd, J = 8.7, 1.5 Hz, 1H), 7.72 (dd, J = 8.0, 1.2 Hz, 1H), 7.71 – 7.57 (m, 3H), 7.48 (td, J = 7.5, 1.2 Hz, 1H), 7.39 (ddd, J = 8.1, 7.5, 1.8 Hz, 1H), 7.32 (dd, J = 7.6, 1.7 Hz, 1H). 13 C DEPT-Q NMR (101 MHz, CDCl3) δ 176.2 (C), 153.2 (C), 141.2 (C), 137.5 (C), 133.6 (CH), 132.2 (CH), 131.5 (CH), 130.24 (CH), 130.16 (CH), 128.7 (CH), 128.1 (CH), 127.5 (C), 125.6 (CH), 122.3 (C), 105.1 (C). LCMS (APCI) m/z (%): t = 3.4 min, 443.9 (25, M + H + ), 466.9 (100, M+Na + ). HPLC: PP gradient method, = 7.0 min, 95.0 % purity at 254 nm. HR-ESI (m/z) calcd for C15H9BrIOS + [M + H] + 442.8597, found 442.8597. mp 200–202 °C. 10-(2-(Dimethylamino)ethyl)thiochromeno[3,2-b]indol-11(10H)- one (27): Compound 27 was synthesised according to General UCC Procedure. The crude product (51 mg) was purified by flash column chromatography (97:3 EtOAc:Et3N, Rf = 0.25) to yield 27 (38 mg, 78%) as a bright yellow oil. 1 H NMR (400 MHz, CDCl3) δ 8.75 (dd, J = 8.1, 1.6 Hz, 1H), 7.86 (dt, J = 8.1, 1.0 Hz, 1H), 7.76 (dd, J = 8.1, 1.3 Hz, 1H), 7.66 – 7.50 (m, 4H), 7.28 (td, J = 8.1, 1.4 Hz, 1H), 5.04 (br t, J = 7.6 Hz, 2H), 2.79 (br t, J = 7.6 Hz, 2H), 2.41 (s, 6H). 13 C DEPT-Q NMR (101 MHz, CDCl3) δ 173.3 (C), 139.6 (C), 136.0 (C), 132.7 (C), 130.7 (CH), 129.0 (CH), 128.1 (CH), 127.7 (C), 126.9 (CH), 126.0 (CH), 123.0 (C), 120.9 (CH), 120.7 (C), 119.4 (C), 110.9 (CH), 59.6 (CH 2 ), 46.1 (CH 3 ), 44.0 (CH2). LCMS (ESI) m/z (%): t = 2.5 min, 323.1 (100, M + H + ). HPLC: PP gradient method, tR = 5.5 min, 97.8 % purity at 254 nm. HR-ESI (m/z) calcd for C19H19N2OS + [M + H] + 323.1213, found 323.1221. 3-Bromo-2-((2-(methylthio)phenyl)ethynyl)thiophene (28): Compound 28 was synthesised according to General Procedure A. The crude product (2.83 g) obtained was purified by flash column chromatography (100% hexanes 17:3 hexanes:EtOAc, R f = 0.45) to yield 28 (1.23 g, 58%) as a light yellow oil. 1 H NMR (400 MHz, CDCl 3 ) δ 7.51 (ddd, J = 7.7, 1.5, 0.4 Hz, 1H), 7.33 (ddd, J = 8.0, 7.4, 1.5 Hz, 1H), 7.25 (d, J = 5.4 Hz, 1H), 7.20 (dd, J = 8.0, 0.9 Hz, 1H), 7.12 (td, J = 7.5, 1.2 Hz, 1H), 7.01 (d, J = 5.4 Hz, 1H), 2.53 (s, 3H). 13 C DEPT-Q NMR (101 MHz, CDCl 3 ) δ 141.8 (C), 132.5 (CH), 130.3 (CH), 129.3 (CH), 127.5 (CH), 124.5 (CH), 124.4 (CH), 120.8 (C), 120.8 (C), 116.3 (C), 94.5 (C), 87.2 (C), 15.3 (CH 3 ). HPLC: PP gradient method, t R = 7.8 min, 97.1 % purity at 254 nm. HR-ESI (m/z) calcd for C 13 H 10 BrS 2 + [M + H] + 308.9402, found 308.9398. 2-(3-Bromothiophen-2-yl)-3-iodobenzo[b]thiophene (29): Compound 29 was synthesised according to General Procedure D. 29 (1.44 g, 97%) was obtained as a grey amorphous solid and directly used in the next step without further purification. 1 H NMR (400 MHz, CDCl3) δ 7.82 (app tdd, J = 7.9, 1.4, 0.7, 2H), 7.51-7.47 (m, 1H), 7.48 (d, J = 5.4 Hz, 1H), 7.44 (ddd, J = 7.8, 7.2, 1.4, 1H), 7.13 (d, J = 5.4 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ 141.1 (C), 140.1 (C), 133.4 (C), 131.0 (CH), 128.4 (CH), 126.6 (CH), 126.3 (CH), 125.7 (CH), 122.3 (CH), 113.5 (C), 86.3 (C). One quaternary carbon is overlapping at 113.5 ppm. HPLC: PP gradient method, t R = 8.5 min, 99.3 % purity at 254 nm. HR-APCI calcd for C 12 H 6 BrIS 2 [M] + 419.8133, found 419.8129. 2-(3-Bromothiophen-2-yl)-N-(2-(dimethylamino)ethyl)benzo[b]t hiophene-3-carboxamide: Compound 29 (100 mg, 0.24 mmol), Pd(OAc) 2 (5.3 mg, 0.024 mmol), PPh 3 (94 mg, 0.36 mmol), DMD (80 µL, 0.71 mmol), Et 3 N (70 µL, 0.47 mmol) and dry DMF (2.5 mL) was added to a Schlenk tube. The tube was degassed and backfilled with CO(g) for three times, the reaction mixture was then heated at 80 ºC for 17 h. On completion, the reaction mixture was cooled down to rt and extracted with EtOAc (2 x 15 mL). The combined organic extracts were washed with H 2 O (3 x 40 mL), saturated NH 4 Cl solution (40 mL) and brine (2 x 40 mL), then dried over anhydrous MgSO 4 , filtered, and concentrated under reduced pressure. The crude product (165 mg) obtained was purified by flash column chromatography (4:1 MeOH:EtOAc, Rf = 0.17). 2-(3-Bromothiophen-2-yl)-N-(2- (dimethylamino)ethyl)benzo[b]thiophene-3-carboxamide (51 mg, 52%) was obtained as a light yellow oil. 1 H NMR (400 MHz, CDCl 3 ) δ 8.31 (dd, J = 7.6, 1.7 Hz, 1H), 7.80 (dd, J = 8.2, 1.0 Hz, 1H), 7.45 (d, J = 5.4 Hz, 1H), 7.46-7.38 (m, 2H), 7.09 (d, J = 5.4, 1H), 6.41 (s, 1H), 3.39 (dd, J = 10.8, 5.9 Hz, 2H), 2.28 (t, J = 6.0 Hz, 2H), 2.05 (s, 6H). 13 C DEPT-Q NMR (101 MHz, CDCl3) δ 163.7 (C), 139.8 (C), 138.2 (C), 133.4 (C), 132.5 (C), 131.3 (CH), 129.5 (C), 128.4 (CH), 125.8 (CH), 125.3 (CH), 125.0 (CH), 121.7 (CH), 113.4 (C), 57.1 (CH2), 44.9 (CH3), 37.0 (CH2). LCMS (ESI) m/z (%): t = 3.9 min, 408.8 (100, M + H + ), 410.9 (80, M + H + ). HPLC: PP gradient method, = 5.42 min, 97.0 % purity at 254 nm. HR-ESI (m/z) calcd for C17H18BrN2OS2 + [M + H] + 409.0038, found 409.0044. 4-(2-(Dimethylamino)ethyl)benzo[4,5]thieno[2,3-d]thieno[3,2- b]pyridin-5(4H)-one (30): In a dry RBF, 2-(3-bromothiophen-2-yl)-N-(2-(dimethylamino)ethyl)benzo[b] thiophene-3- carboxamide (50 mg, 0.12 mmol) was dissolved in n-butanol (0.6 mL) and CuI (9.3 mg, 50 µmol), K 3 PO 4 (104 mg, 0.49 mmol), ethylene glycol (80 µL, 1.47 mmol), and TMD (40 µL, 0.24 mmol) were added sequentially. The RBF was degassed and backfilled with N 2 (g) for three times, the reaction mixture was then heated at 90 °C for 17 h. After heating, the reaction mixture was cooled down to rt and diluted with EtOAc (15 mL). The organic extract was washed with H 2 O (2 x 20 mL) and brine (2 x 20 mL), then dried over anhydrous MgSO 4 , filtered, and concentrated under reduced pressure. The crude product (40 mg) obtained was then purified by flash column chromatography (3:1 EtOAc:MeOH, R f = 0.33). 30 (33 mg, 83%) was obtained as a white solid. 1 H NMR (400 MHz, CDCl3) δ 8.93 (d, J = 8.0 Hz, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.55 (d, J = 5.4 Hz, 1H), 7.52 (t, J = 7.5 Hz, 1H), 7.43 (t, J = 7.5 Hz, 1H), 7.19 (d, J = 5.5 Hz, 1H), 4.49 (t, J = 7.7 Hz, 2H), 2.72 (t, J = 7.7 Hz, 2H), 2.40 (s, 6H). 13 C DEPT- Q NMR (101 MHz, CDCl3) δ 158.5 (C), 143.7 (C), 141.7 (C), 137.0 (C), 128.2 (CH), 125.87 (CH), 125.86 (CH), 125.3 (CH), 122.2 (CH), 120.9 (C), 117.2 (CH), 114.5 (C), 57.0 (CH2), 45.9 (CH3), 43.3 (CH2). One quaternary carbon is overlapping at 137.0 ppm. LCMS (ESI) m/z (%): t = 4.0 min, 328.9 (100, M + H + ). HPLC: PP gradient method, tR = 5.5 min, 95.3 % at 254 nm. HR-ESI (m/z) calcd for C17H17N2OS2 + [M + H] + 329.0777, found 329.0788. PdCC 3 : To a dry RBF, 2-(3-bromothiophen-2-yl)-3-iodobenzo[b]thiophene (100 mg, 0.237 mmol), Cs2CO3 (232 mg, 0.712 mmol), Pd2dba3 (21.8 mg, 0.0238 mmol), and Xantphos (27.5 mg, 0.0475 mmol) were added and dissolved in anhydrous 1,4-dioxane (1.20 mL). The vessel was subsequently degassed and backfilled with N2(g) three times and allowed to stir at room temperature for 10 minutes. N,N-Dimethylethylenediamine (0.0383 mL, 0.356 mmol) was then added to the flask before it was subsequently degassed and backfilled with CO (g) three times and allowed to stir under this atmosphere for 4.5 h at 70 o C. After the dehalogenated pyridine starting material has been consumed, the atmosphere of the vessel was reverted back to N2(g) and the reaction mixture was allowed to stir at 120 o C for 20 h. Upon completion, the mixture was extracted with EtOAc (3 x 20 mL) and filtered through Celite ®, before being washed with water (3 x 10 mL) and brine (2 x 10 mL). The organic layer was subsequently collected, dried over MgSO4, and concentrated under vacuum. The crude product was then purified via flash column chromatography (95% EtOAc/ 5% Et3N/ 1% MeOH, Rf = 0.25) to yield the desired compound (69.0 mg, 45%) as a dark orange wax. Data in accordance with that recorded above. 2-(2-Bromophenyl)-N-(2-(dimethylamino)ethyl)benzo[b]thieno[3 ,2-d]thiophene-3-carboxamide: 34 46 (95 mg, 0.20 mmol), Pd(OAc)2 (4.5 mg, 20 µmol), PPh3 (79 mg, 0.30 mmol), DMD (0.34 mL, 3.2 mmol), Et3N (60 µL, 0.40 mmol) and dry DMF (2.0 mL) were added to a 25 mL dry RBF. The RBF was degassed and backfilled with CO(g) for three times, the reaction mixture was then heated at 80 °C for 17 h. On completion, the reaction mixture was cooled down to rt, diluted with H 2 O (25 mL) and extracted with EtOAc (2 x 20 mL). The combined organic extracts were washed with saturated NH 4 Cl solution (25 mL), H 2 O (3 x 40 mL) and brine (2 x 30 mL). The organic extract was then dried over anhydrous MgSO 4 , filtered, and concentrated under reduced pressure. The crude product (142 mg) obtained was then purified by flash column chromatography (100% EtOAc 7:3 EtOAc:MeOH, Rf = 0.45) to yield 2-(2-bromophenyl)-N-(2-(dimethylamino)ethyl)benzo[b]thieno[3 ,2-d]thiophene-3- carboxamide (56 mg, 60%) as a pale brown amorphous solid. 1 H NMR (400 MHz, CDCl3) δ 8.41 (dd, J = 7.8, 1.5 Hz, 1H), 7.80 (dd, J = 7.8, 1.3 Hz, 1H), 7.69 (dd, J = 8.0, 1.2 Hz, 1H), 7.52 (dd, J = 7.6, 1.7 Hz, 1H), 7.43-7.33 (m, 3H), 7.30 (td, J = 7.7, 1.8 Hz, 1H), 6.39 (s, 1H), 3.35 (dd, J = 11.0, 5.8 Hz, 2H), 2.18 (t, J = 6.0 Hz, 2H), 2.02 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 164.1 (C), 143.6 (C), 143.2 (C), 139.2 (C), 138.4 (C), 134.3 (C), 133.1 (CH), 133.0 (CH), 132.7 (C), 130.7 (CH), 130.5 (C), 127.6 (CH), 125.2 (C), 124.8 (C), 124.8 (CH), 123.7 (CH), 122.9 (CH), 57.0 (CH2), 44.8 (CH3), 37.1 (CH2). LCMS (ESI) m/z (%): t = 4.0 min, 460.8 (100, M + H + ), 462.8 (20, M + H + ). HPLC: PP gradient method, tR = 6.0 min, 99.3 % purity at 254 nm. HR-ESI (m/z) calcd for C21H20BrN2OS2 + [M + H] + 459.0195, found 459.0205. 5-(2-(Dimethylamino)ethyl)benzo[4',5']thieno[3',2':4,5]thien o[3,2-c]quinolin-6(5H)-one (35): In a dry RBF, 2-(2-bromophenyl)-N-(2-(dimethylamino)ethyl)benzo[b]thieno[3 ,2- d]thiophene-3-carboxamide (50 mg, 0.11 mmol) was dissolved in n-butanol (0.55 mL) and CuI (8.3 mg, 40 µmol), K3PO4 (92 mg, 0.44 mmol), ethylene glycol (70 µL, 1.31 mmol), and TMD(30 µL, 0.22 mmol) were added sequentially. The RBF was degassed and backfilled with N2(g) for three times, the reaction mixture was then heated at 90 °C for 20 h. The reaction mixture was cooled down to rt and extracted with EtOAc (2 x 10 mL). The combined organic extracts were washed with H2O (2 x 10 mL) and brine (2 x 10 mL), then dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude product (43 mg) obtained was purified by flash column chromatography (100 % EtOAc → 3:1 EtOAc:MeOH, Rf = 0.33) to yield 35 (39 mg, 95%) as a white solid. 1 H NMR (400 MHz, CDCl3) δ 9.61 (ddd, J = 8.2, 1.2, 0.6 Hz, 1H), 7.81 (app t, J = 7.3 Hz, 2H), 7.54-7.49 (m, 3H), 7.39 (ddd, J = 8.1, 7.1, 1.2 Hz, 1H), 7.29-7.25 (m, 1H), 4.59 (app t, J = 7.8 Hz, 2H), 2.75-2.71 (app t, J = 7.9 Hz, 2H), 2.45 (s, 6H). 13 C DEPT-Q NMR (101 MHz, CDCl3) δ 158.4 (C), 149.3 (C), 143.6 (C), 139.7 (C), 137.5 (C), 136.6 (C), 133.4 (C), 129.7 (CH), 126.6 (CH), 125.1 (CH), 124.9 (CH), 124.85 (C), 124.0 (CH), 122.6 (CH), 122.6 (CH), 118.7 (C), 115.2 (CH), 56.2 (CH2), 46.0 (CH3), 41.2 (CH2). LCMS (API- ES) m/z (%): t = 4.2 min, 378.9 (100, M + H + ). HPLC: PP gradient method, = 6.5 min, 99.8 % purity at 254 nm. HR-ESI (m/z) calcd for C21H19N2OS2 + [M + H] + 379.0933, found 379.0945. 2-((2-Bromophenyl)ethynyl)benzaldehyde (37): Compound 37 was synthesised according to General Procedure A. The crude product (839 mg) obtained was purified by flash column chromatography (3:1 hexanes:CH 2 Cl 2 , R f = 0.25) to yield 37 (678 mg, 92%) as a pale yellow solid. 1 H NMR (400 MHz, CDCl 3 ) δ 10.76 (d, J = 0.8 Hz, 1H), 7.97 (dd, J = 7.8, 1.4 Hz, 1H), 7.70 (dd, J = 7.7, 1.3 Hz, 1H), 7.64 (dd, J = 8.0, 1.2 Hz, 1H), 7.63 – 7.57 (m, 2H), 7.51 – 7.46 (td, J = 7.6, 1.1 Hz, 1H), 7.33 (td, J = 7.6, 1.3 Hz, 1H), 7.23 (td, J = 7.5, 1.7 Hz, 1H). 13 C DEPT- Q NMR (101 MHz, CDCl 3 ) δ 192.1 (CH), 136.3 (C), 133.9 (CH), 133.6 (CH), 133.5 (CH), 132.8 (CH), 130.3 (CH), 129.2 (CH), 127.33 (CH), 127.31 (CH), 126.6 (C), 125.9 (C), 124.8 (C), 94.8 (C), 89.5 (C). LCMS (ESI) m/z (%): t = 3.6 min, 285.0 (100, M + H + ). HPLC: PP gradient method, = 7.04 min, 95.3 % purity at 254 nm. HR-ESI (m/z) calcd for C 15 H 10 BrO + [M + H] + 284.9910, found 284.9907. mp 66– 68 °C. The spectroscopic data are consistent with those previously reported in the literature. (E)-2-((2-Bromophenyl)ethynyl)benzaldehyde O-methyl oxime (38a): O-Methylhydroxylamine hydrochloride (776 mg, 9.29 mmol) was slowly added to a stirred solution of 37 (530 mg, 1.86 mmol) in pyridine (3 mL) and EtOH (6 mL). The reaction mixture was left to stir at rt overnight. On completion, the reaction mixture was diluted with H 2 O (20 mL) and extracted with CH 2 Cl 2 (2 x 25 mL). Washed with H 2 O (2 x 30 mL) and brine (2 x 30 mL), the combined organic extracts were dried over anhydrous MgSO 4 , filtered and concentrated under reduced pressure. The crude product (824 mg) obtained was purified by flash column chromatography (2:1 hexanes:CH 2 Cl 2 , R f = 0.45) to yield 38a (546 mg, 94%) as a clear yellow oil. 1 H NMR (400 MHz, CDCl 3 ) δ 8.81 (s, 1H), 7.98 – 7.90 (m, 1H), 7.63 (dd, J = 8.0, 1.3 Hz, 1H), 7.62 – 7.54 (m, 2H), 7.38 – 7.34 (m, 2H), 7.31 (td, J = 7.6, 1.2 Hz, 1H), 7.20 (ddd, J = 8.0, 7.5, 1.7 Hz, 1H), 4.01 (s, 3H). 13 C DEPT-Q NMR (101 MHz, CDCl 3 ) δ 147.5 (CH), 133.7 (C), 133.4 (CH), 132.73 (CH), 132.66 (CH), 129.8 (CH), 129.5 (CH), 129.0 (CH), 127.2 (CH), 125.9 (C), 125.3 (CH), 125.2 (C), 122.7 (C), 93.4 (C), 91.0 (C), 62.3 (CH 3 ). LCMS (ESI) m/z (%): t = 5.0 min, 314.0 (100, M + H + ). HPLC: PP gradient method, t R = 8.0 min, 96.4 % purity at 254 nm. HR-ESI (m/z) calcd for C 16 H 13 BrNO + [M + H] + 314.0175, found 314.0170. 4-Bromo-3-(2-bromophenyl)isoquinoline (39a) and 4-bromo-3-(2-bromophenyl) isoquinolin-1-ol (39b): CuBr 2 (448 mg, 2.01 mmol, 2 equiv.) was added slowly to a stirred solution of 38a (315 mg, 1.0 mmol) in dry dimethylacetamide (5 mL) under N 2 (g) atmosphere. The reaction was heated at 100 ºC for 17 h. After heating, the mixture was quenched with saturated NH 4 Cl solution (35 mL) and extracted with EtOAc (3 x 30 mL). Washed with H 2 O (2 x 80 mL) and brine (2 x 80 mL), the combined organic extracts were dried over anhydrous MgSO 4 , filtered and concentrated under reduced pressure. The crude product (327 mg, brown oil) obtained was purified by flash column chromatography (3:1 hexanes:CH 2 Cl 2 , R f = 0.1 → 1:1 hexanes:CH 2 Cl 2 , R f = 0.2, 2:3 hexanes:CH 2 Cl 2 , R f = 0.7) to yield 39a (122 mg, 34%) as a clear yellow oil. 1 H NMR (400 MHz, CDCl3) δ 9.26 (s, 1H), 8.32 (dd, J = 8.5, 0.9 Hz, 1H), 8.06 (dt, J = 8.1, 1.0 Hz, 1H), 7.88 (ddd, J = 8.4, 6.9, 1.3 Hz, 1H), 7.78 – 7.68 (m, 2H), 7.50 – 7.38 (m, 2H), 7.32 (ddd, J = 8.1, 7.0, 2.2 Hz, 1H). 13 C DEPT-Q NMR (101 MHz, CDCl 3 ) δ 152.4 (C), 151.2 (CH), 142.0 (C), 135.7 (C), 132.9 (CH), 132.2 (CH), 130.9 (CH), 130.0 (CH), 129.0 (C), 128.5 (CH), 128.0 (CH), 127.5 (CH), 126.9 (CH), 123.1 (C), 121.3 (C), 120.0 (C). LCMS (ESI) m/z (%): t = 5.6 min, 363.8 (100, M + H + ). HPLC: PP gradient method, = 6.6 min, 96.6 % purity at 254 nm. HR- ESI (m/z) calcd for C15H10Br2N + [M + H] + 361.9175, found 361.9176. Byproduct 4-bromo-3-(2-bromophenyl)isoquinolin-1-ol 39b (167 mg, 44%) was also obtained as an off-white solid. 1 H NMR (400 MHz, Methanol-d4) δ 8.88 (br s, 1H), 8.32 (d, J = 8.5 Hz, 1H), 7.99 (d, J = 8.3 Hz, 1H), 7.88 (t, J = 7.5 Hz, 1H), 7.81 (d, J = 8.0 Hz, 2H), 7.59 (s, 1H), 7.48 (t, J = 7.6 Hz, 2H). LCMS (ESI) m/z (%): t = 3.5 min, 377.8 (100, M+H + ). HPLC: PP gradient method, tR = 5.8 min, 98.3 % purity at 254 nm. HR-ESI (m/z) calcd for C15H10Br2NO + [M + H] + 377.9124, found 377.9123. 2-(11H-indolo[3,2-c]isoquinolin-11-yl)-N,N-dimethylethan-1-a mine (40): Compound 40 was synthesised according to General UCC Procedure. The crude product (68 mg, brown oil) obtained was purified by flash column chromatography (99:1 EtOAc:Et3N, Rf = 0.2) to yield 40 (23 mg, 53%) as a light green oil. 1 H NMR (400 MHz, CDCl 3 ) δ 9.12 (s, 1H), 8.48 (d, J = 8.6 Hz, 1H), 8.45 (d, J = 7.8 Hz, 1H), 8.18 (d, J = 8.0 Hz, 1H), 7.83 (ddd, J = 8.5, 6.9, 1.4 Hz, 1H), 7.64 (ddd, J = 8.0, 6.9, 1.0 Hz, 1H), 7.63 – 7.51 (m, 2H), 7.39 (ddd, J = 7.9, 6.4, 1.6 Hz, 1H), 4.86 (br t, J = 8.1 Hz, 2H), 2.87 (br t, J = 8.1 Hz, 2H), 2.44 (s, 6H). 13 C DEPT-Q NMR (101 MHz, CDCl3) δ 145.9 (CH), 140.0 (C), 135.1 (C), 130.1 (CH), 129.7 (CH), 127.7 (C), 127.0 (C), 126.2 (CH), 125.6 (CH), 124.5 (C), 122.9 (C), 120.8 (CH), 120.6 (CH), 120.2 (CH), 109.0 (CH), 58.3 (CH2), 46.2 (CH3), 44.4 (CH2). LCMS (ESI) m/z (%): t = 3.3 min, 290.1 (100, M + H + ). HPLC: PP gradient method, tR = 3.5 min, 96.7 % purity at 254 nm. HR-ESI (m/z) calcd for C19H20N3 + [M + H] + 290.1652, found 290.1659. 5-(2-(Dimethylamino)ethyl)dibenzo[c,h][1,5]naphthyridin-6(5H )-one (41): Compound 41 was synthesised according to General PdCC 1 Procedure. The crude product (111 mg) was purified by flash column chromatography (9:1 EtOAc:MeOH, R f = 0.2) to yield 41 (23 mg, 44%) as a beige oil. 1 H NMR (400 MHz, CDCl 3 ) δ 9.14 (s, 1H), 8.91 (d, J = 8.2 Hz, 1H), 8.52 (d, J = 8.8 Hz, 1H), 8.48 (d, J = 8.0 Hz, 1H), 8.08 (d, J = 8.1 Hz, 1H), 7.85 (ddd, J = 8.3, 7.1, 1.4 Hz, 1H), 7.80 (ddd, J = 8.6, 6.9, 1.5 Hz, 1H), 7.68 (ddd, J = 8.0, 6.0, 1.0 Hz, 2H), 7.66 (ddd, J = 8.2, 7.1, 1.2 Hz, 2H), 4.73 (t, J = 7.3 Hz, 2H), 3.02 (t, J = 7.3 Hz, 2H), 2.33 (s, 6H). 13 C DEPT-Q NMR (101 MHz, CDCl 3 ) δ 164.3 (C), 148.0 (CH), 135.7 (C), 133.1 (CH), 132.3 (C), 130.2 (CH), 130.1 (C), 129.5 (C), 129.2 (CH), 128.9 (CH), 127.9 (CH), 127.5 (CH), 127.1 (C), 126.0 (C), 124.2 (CH), 124.1 (CH), 57.6 (CH 2 ), 48.8 (CH 2 ), 45.8 (CH 3 ). LCMS (ESI) m/z (%): t = 2.6 min, 318.2 (100, M + H + ). HPLC: PP gradient method, t R = 4.9 min, 95.4 % purity at 254 nm. HR-ESI (m/z) calcd for C 20 H 20 N 3 O + [M + H] + 318.1601, found 318.1604. 3-(2-Bromophenyl)-4-iodoisoquinoline (42): In a dry RBF, 37 (350 mg, 1.23 mmol) was dissolved in anhydrous DCE (6 mL), followed by addition of anhydrous MgSO 4 (443 mg, 3.68 mmol) and tert-butylamine (898 mg, 12.27 mmol, 1.29 mL). The reaction mixture was left to stir at 45 ºC for 1 d. After heating, the reaction mixture was cooled down to rt, diluted with CH 2 Cl 2 (20 mL), dried over anhydrous MgSO 4 , filtered and concentrated under reduced pressure to yield 38b (417 mg) as an orange oil.38b was unstable and used in situ in the next step. Rapid analysis of 38b: 1 H NMR (400 MHz, CDCl 3 ) δ 9.00 (s, 1H), 8.14 – 8.09 (m, 1H), 7.64 (dd, J = 8.0, 1.3 Hz, 1H), 7.62 – 7.55 (m, 2H), 7.42 – 7.36 (m, 2H), 7.32 (td, J = 7.6, 1.2 Hz, 1H), 7.21 (ddd, J = 8.1, 7.5, 1.7 Hz, 1H), 1.34 (s, 9H). 13 C DEPT-Q NMR (101 MHz, CDCl 3 ) δ 154.3 (CH), 138.2 (C), 133.5 (CH), 132.8 (CH), 132.6 (CH), 129.9 (CH), 129.8 (CH), 129.2 (CH), 127.3 (CH), 126.2 (CH), 125.5 (C), 125.4 (C), 123.6 (C), 93.1 (C), 91.5 (C), 30.1 (CH3). Oven-dried 4Å powdered molecular sieves was added to 38b (265 mg, 779 µmol) and NaOAc (192 mg, 2.34 mmol) in a dry RBF, followed by addition of dry CH2Cl2 (15 mL) under N2(g) atmosphere. A solution of ICl (253 mg, 1.56 mmol) and in dry CH2Cl2 (7.5 mL) was added slowly over 10 min to the stirred suspension, and reaction was left to stir at 0 °C for 4 h in the dark. The reaction mixture was filtered through Celite ® . Washed with saturated Na2S2O3 solution (2 x 30 mL), H2O (2 x 30 mL) and brine (20 mL), the organic extract was dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The crude product obtained (406 mg, brown oil) was purified by flash column chromatography (19:1 toluene:EtOAc, Rf = 0.2) to yield 42 (164 mg, 51% from 37) as a pale yellow solid. 1 H NMR (400 MHz, CDCl3) δ 9.21 (d, J = 0.7 Hz, 1H), 8.20 (dd, J = 8.5, 0.9 Hz, 1H), 8.00 (dt, J = 8.1, 1.0 Hz, 1H), 7.85 (ddd, J = 8.4, 6.9, 1.3 Hz, 1H), 7.75 – 7.70 (m, 2H), 7.46 (td, J = 7.5, 1.2 Hz, 1H), 7.38 (dd, J = 7.6, 1.9 Hz, 1H), 7.33 (ddd, J = 8.0, 7.3, 1.8 Hz, 1H). 13 C DEPT-Q NMR (101 MHz, CDCl3) δ 157.0 (C), 152.2 (CH), 144.8 (C), 138.3 (C), 132.8 (CH), 132.5 (CH), 132.1 (CH), 130.9 (CH), 130.0 (CH), 128.6 (CH), 128.4 (C), 128.2 (CH), 127.5 (CH), 123.1 (C), 100.0 (C). LCMS (ESI) m/z (%): t = 5.6 min, 411.7 (100, M + H + ). HPLC: PP gradient method, = 6.48 min, 82.6 % purity at 254 nm. HR-ESI (m/z) calcd for C15H10BrIN + [M + H] + 409.9036 and 411.9016, found 409.9043 and 411.9023. mp 164–166 °C. 3-(2-Bromophenyl)-N-(2-(dimethylamino)ethyl)isoquinoline-4-c arboxamide: 42 (75 mg, 183 µmol), Pd(OAc)2 (4.1 mg, 18 µmol), PPh3 (72 mg, 274 µmol), DMD (242 mg, 2.74 mmol, 0.30 mL), Et3N (37 mg, 366 µmol, 33 µL) and dry NMP (1.8 mL) was added to a 10 mL dry RBF accordingly. The RBF was degassed and backfilled with CO(g) for three times, the reaction mixture was then heated at 90 °C for 47 h. After heating, the mixture was cooled down to rt, diluted with saturated NaHCO3 solution (25 mL) and extracted with EtOAc (2 x 15 mL). The combined organic extracts were washed with H2O (2 x 20 mL), and brine (2 x 20 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude product (138 mg) was purified by flash column chromatography (49:1 EtOAc:Et3N, Rf = 0.15) to yield 3-(2-bromophenyl)-N-(2- (dimethylamino)ethyl)isoquinoline-4-carboxamide (53 mg, 73%) as a light yellow oil. 1 H NMR (400 MHz, CDCl 3 δ 9.34 (d, J = 0.9 Hz, 1H), 8.12 (dq, J = 8.5, 0.9 Hz, 1H), 8.05 (dt, J = 8.2, 1.1 Hz, 1H), 7.79 (ddd, J = 8.4, 6.9, 1.4 Hz, 1H), 7.69 (dtd, J = 8.1, 3.5, 1.1 Hz, 2H), 7.46 (dd, J = 7.6, 1.8 Hz, 1H), 7.38 (td, J = 7.5, 1.2 Hz, 1H), 7.29 (ddd, J = 8.0, 7.4, 1.8 Hz, 1H), 6.48 (br s, 1H), 3.37 (t, J = 7.0 Hz, 1H), 3.25 (br q, J = 5.3, 4.7 Hz, 2H), 2.36 (t, J = 8.1 Hz, 1H), 2.06 (s, 6H). 13 C DEPT-Q NMR (101 MHz, CDCl3) δ 167.0 (C), 153.0 (CH), 149.3 (C), 140.7 (C), 133.5 (C), 132.9 (CH), 131.7 (CH), 131.3 (CH), 130.0 (CH), 128.1 (CH), 127.99 (C), 127.96 (CH), 127.62 (C), 127.59 (CH), 125.1 (CH), 123.2 (C), 57.1 (CH2), 45.0 (CH3), 37.1 (CH2). LCMS (ESI) m/z (%): t = 2.0 min, 398.1 (100, M + H + ). HPLC: PP gradient method, tR = 3.3 min, 79.2 % purity at 254 nm. HR-ESI (m/z) calcd for C20H21BrN3O + [M + H] + 398.0863, found 398.0869. 12-(2-(Dimethylamino)ethyl)dibenzo[c,h][1,6]naphthyridin-11( 12H)-one (43): In a dry RBF, 3-(2-bromophenyl)-N-(2-(dimethylamino)ethyl)isoquinoline-4-c arboxamide (34 mg, 85 µmol) was dissolved in n-butanol (0.8 mL) and K3PO4 (72 mg, 341 µmol), ethylene glycol (57 µL, 1.02 mmol), TMD(159 mg, 1.37 mmol, 0.2 mL), and CuI (6.5 mg, 34 µmol), were added accordingly. The RBF was degassed and backfilled with N2(g) for three times, the reaction mixture was then heated at 80 °C for 18 h. After heating, the reaction mixture was cooled down to rt, diluted with water (20 mL) and extracted with EtOAc (3 x 20 mL). Washed with H2O (2 x 15 mL) and brine (2 x 15 mL), the combined organic extracts were dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude product (29 mg) obtained was purified by flash column chromatography (19:1 EtOAc:MeOH, Rf = 0.1) to yield 43 (16.4 mg, 61%) as an off-white solid. 1 H NMR (400 MHz, CDCl3) δ 10.08 (d, J = 9.0 Hz, 1H), 9.50 (d, J = 0.8 Hz, 1H), 9.09 (dd, J = 8.1, 1.6 Hz, 1H), 8.09 (d, J = 8.1 Hz, 1H), 7.94 (ddd, J = 8.6, 7.0, 1.5 Hz, 1H), 7.73 (ddd, J = 8.1, 7.0, 1.1 Hz, 1H), 7.67 (ddd, J = 8.6, 7.1, 1.6 Hz, 1H), 7.53 (d, J = 7.6 Hz, 1H), 7.41 (ddd, J = 8.1, 7.1, 1.0 Hz, 1H), 4.64 (br t, J = 7.9 Hz, 2H), 2.76 (br t, J = 7.9 Hz, 2H), 2.47 (s, 6H). 13 C DEPT-Q NMR (101 MHz, CDCl3) δ 162.4 (C), 157.7 (CH), 147.7 (C), 138.1 (C), 134.5 (C), 132.9 (CH), 131.3 (CH), 128.7 (CH), 128.2 (C), 127.8 (CH), 127.3 (CH), 126.6 (CH), 122.6 (CH), 121.1 (C), 114.1 (CH), 113.2 (C), 56.1 (CH2), 46.0 (CH3), 41.3 (CH2). LCMS (ESI) m/z (%): t = 2.3 min, 318.2 (100, M + H + ). HPLC: PP gradient method, = 5.1 min, 95.8 % purity at 254 nm. HR-ESI (m/z) calcd for C20H20N3O + [M + H] + 318.1601, found 318.1613. 3-((2-Bromophenyl)ethynyl)benzo[b]thiophene-2-carbaldehyde O-methyl oxime (46a): O-Methylhydroxylamine hydrochloride (284 mg, 3.4 mmol) was slowly added to a stirred solution of 45 (232 mg, 680 µmol) in pyridine (3 mL) and EtOH (6 mL). The reaction mixture was left to stir at rt overnight. On completion, the reaction mixture was diluted with H 2 O (25 mL) and extracted with CH 2 Cl 2 (2 x 25 mL). Washed with H 2 O (2 x 25 mL) and brine (2 x 25 mL), the combined organic extracts were dried over anhydrous MgSO 4 , filtered and concentrated under reduced pressure. The crude product (500 mg) obtained was purified by flash column chromatography (10:1 hexanes: EtOAc, R f = 0.45) to yield 46a (247 mg, 99%) as a yellow solid.46a appears as a pair of E/Z isomers in 1 H NMR, 13 C NMR, LCMS and analytical HPLC. 1 H NMR (400 MHz, CDCl 3 ) δ 8.74 (s, 1H), 8.37 (s, 1H), 8.19 – 8.12 (m, 1H), 8.12 – 8.03 (m, 1H), 7.89 – 7.81 (m, 1H), 7.83 – 7.75 (m, 1H), 7.71 – 7.60 (m, 4H), 7.51 – 7.41 (m, 4H), 7.38 – 7.34 (m, 2H), 7.26 – 7.21 (m, 2H), 4.17 (s, 3H), 4.04 (s, 3H). 13 C DEPT-Q NMR (101 MHz, CDCl 3 ) δ 143.7 (CH), 141.2 (C), 140.2(CH), 139.32 (C), 139.29 (C), 138.5 (C), 137.7 (C), 133.7 (C), 133.54 (CH), 133.50 (CH), 132.8 (CH), 132.7 (CH), 130.04 (CH), 130.00 (CH), 127.4 (CH), 127.3(CH), 127.0 (CH), 126.8 (CH), 125.64 (C), 125.63 (C), 125.34 (CH), 125.30 (CH), 125.08 (C), 125.06 (C), 124.1 (CH), 123.7 (CH), 122.6 (CH), 122.4 (CH), 121.0 (C), 119.9 (C), 96.1 (C), 95.8 (C), 86.5 (C), 86.0 (C), 63.0 (CH 3 ), 62.8 (CH 3 ). LCMS (ESI) m/z (%): t = 7.8 min, 371.8 (40, M + H + ). HPLC: PP gradient method, = 8.8 and 8.9 min, 95.1 % purity at 254 nm. HR-ESI (m/z) calcd for C 18 H 13 BrNOS + [M + H] + 369.9896, found 369.9896. 4-Bromo-3-(2-bromophenyl)benzo[4,5]thieno[2,3-c]pyridine (47): CuBr2 (205 mg, 918 µmol) was added slowly to a stirred solution 46a (170 mg, 392 µmol) in DMA (3 mL) under N2(g) atmosphere. The reaction was heated at 100 ºC for 7 h. After heating, the mixture was quenched with saturated NH4Cl solution (15 mL) and extracted with EtOAc (3 x 15 mL). Washed with H2O (2 x 25 mL) and brine (2 x 25 mL), the combined organic extracts were dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The crude product (163 mg) obtained was purified by flash column chromatography (100 % CH2Cl2, Rf = 0.4) to 47 (62 mg, 32%) as a brown foam. 1 H NMR (400 MHz, CDCl3) δ 9.30 (dd, J = 8.3, 1.3 Hz, 1H), 9.15 (s, 1H), 7.99 (dd, J = 8.1, 1.2 Hz, 1H), 7.73 (dd, J = 8.1, 1.2 Hz, 1H), 7.69 (ddd, J = 8.1, 7.2, 1.3 Hz, 1H), 7.60 (ddd, J = 8.3, 7.2, 1.2 Hz, 1H), 7.47 (ddd, J = 7.6, 7.2, 1.1 Hz, 1H), 7.42 (dd, J = 7.9, 2.0 Hz, 1H), 7.34 (ddd, J = 8.1, 7.2, 2.0 Hz, 1H). 13 C DEPT-Q NMR (101 MHz, CDCl 3 ) δ 154.4 (C), 142.7 (CH), 142.0 (C), 141.6 (C), 140.1 (C), 136.8 (C), 134.2 (C), 132.9 (CH), 130.9 (CH), 130.1 (CH), 129.5 (CH), 127.6 (CH), 127.1 (CH), 124.8 (CH), 123.4 (CH), 123.3 (C), 116.2 (C). LCMS (ESI) m/z (%): t = 4.3 min, 417.9 (50, M + H + ) and 419.9 (100, M + H + ). HPLC: PP gradient method, = 7.6 min, 97.1 % purity at 254 nm. HR- ESI (m/z) calcd for C17H10Br2NS + [M + H] + 417.8895, found 417.8903. 2-(12H-Benzo[4',5']thieno[3',2':4,5]pyrido[3,2-b]indol-12-yl )-N,N-dimethylethan-1-amine (48): Compound 48 was synthesised according to General UCC Procedure. The crude product (44 mg) obtained was purified by flash column chromatography (100% EtOAc, R f = 0.2) to yield 48 (13 mg, 35%) as a light yellow oil. 1 H NMR (400 MHz, CDCl 3 ) δ 9.04 (s, 1H), 8.74 – 8.66 (m, 1H), 8.43 (d, J = 7.8 Hz, 1H), 8.05 – 7.98 (m, 1H), 7.67 – 7.55 (m, 4H), 7.41 (ddd, J = 7.9, 6.7, 1.3 Hz, 1H), 4.93 (br t, J = 7.9 Hz, 2H), 2.84 (br t, J = 7.9 Hz, 2H), 2.32 (s, 6H). 13 C DEPT-Q NMR (101 MHz, CDCl3) δ 142.0 (C), 140.9 (C), 139.4 (C), 137.4 (CH), 134.1 (C), 133.1 (C), 131.1 (C), 127.6 (CH), 127.3 (CH), 126.6 (C), 126.2 (CH), 125.0 (CH), 123.9 (C), 123.8 (CH), 121.2 (CH), 120.5 (CH), 110.4 (CH), 58.4 (CH2), 46.0 (CH3), 45.9 (CH2). LCMS (ESI) m/z (%): t = 2.6 min, 346.1 (60, M + H + ). HPLC: PP gradient method, = 4.5 min, 94.2 % purity at 254 nm. HR-ESI (m/z) calcd for C21H20N3S + [M + H] + 346.1372, found 346.1379. 12-(2-(Dimethylamino)ethyl)benzo[c]benzo[4,5]thieno[2,3-h][1 ,5]naphthyridin-13(12H)-one (49): Compound 49 was synthesised according to General PdCC 1 Procedure. The crude product (121 mg) was purified by two flash column chromatography (4:1 EtOAc:CH2Cl2, Rf = 0.25; 3:1 EtOAc:CH2Cl2, Rf = 0.2) to yield 49 (20 mg, 44%) as a light yellow oil. 1 H NMR (400 MHz, CDCl3) δ 9.02 (s, 1H), 8.82 (dd, , J = 8.1, 1.1 Hz, 1H), 8.49 (dd, J = 8.0, 1.4 Hz, 1H), 8.20 (d, J = 7.5 Hz, 1H), 7.97 (dd, J = 6.4, 2.3 Hz, 1H), 7.84 (ddd, J = 8.2, 7.2, 1.4 Hz, 1H), 7.66 (ddd, J = 8.2, 7.2, 1.2 Hz, 1H), 7.61 – 7.54 (m, 2H), 4.68 (br s, 2H), 2.25 (t, J = 6.5 Hz, 2H), 1.88 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 164.6 (C), 141.1 (C), 139.3 (CH), 136.8 (C), 135.4 (C), 135.1 (C), 133.3 (CH), 132.8 (C), 131.0 (C), 130.4 (C), 129.2 (CH), 128.4 (CH), 128.3 (CH), 127.0 (CH), 126.7 (C), 125.0 (CH), 123.8 (CH), 123.5 (CH), 57.2 (CH 2 ), 49.1 (CH 2 ), 45.3 (CH 3 ). LCMS (ESI) m/z (%): t = 3.9 min, 374.0 (100, M + H + ). HPLC: PP gradient method, t R = 5.6 min, 95.5 % purity at 254 nm. HR-ESI (m/z) calcd for C 22 H 20 N 3 OS + [M + H] + 374.1322, found 374.1322. 13-(2-(Dimethylamino)ethyl)benzo[h]benzo[4,5]thieno[2,3-c][1 ,6]naphthyridin-12(13H)-one (51): 50 3 (42 mg, 90 µmol), Pd(OAc)2 (2.0 mg, 9 µmol), PPh3 (35 mg, 135 µmol), DMD (119 mg, 1.35 mmol, 0.15 mL), Et3N (18 mg, 180 µmol, 16 µL) and dry NMP (1 mL) was added to a 10 mL dry RBF. The RBF was degassed and backfilled with CO(g) for three times, the reaction mixture was then heated at 90 °C for 28 h. On completion, the reaction mixture was cooled down to rt, diluted with H2O (15 mL) and extracted with EtOAc (2 x 20 mL). The combined organic extracts were washed with saturated NaHCO3 solution (30 mL), H2O (2 x 30 mL) and brine (2 x 30 mL). Dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure, the crude product (85 mg) was purified by flash column chromatography (49:1 EtOAc:Et3N, Rf = 0.15) to yield the 3-(2-bromophenyl)-N-(2- (dimethylamino)ethyl)benzo[4,5]thieno [2,3-c]pyridine-4-carboxamide (27 mg) as a cloudy white oil containing impurity but was directly used in the next step without further purification. LCMS (ESI) m/z (%): t = 2.3 min, 454.1 (100, M + H + ). HPLC: PP gradient method, tR = 4.41 min, 81 % purity at 254 nm. HR-ESI (m/z) calcd for C22H21BrN3OS + [M + H] + 454.0583, found 454.0585. In a dry RBF, 3-(2-bromophenyl)-N-(2-(dimethylamino)ethyl)benzo[4,5] thieno[2,3- c]pyridine-4-carboxamide (20 mg, 44 µmol) was dissolved in n-butanol (0.4 mL) and K 3 PO 4 (37 mg, 176 µmol), ethylene glycol (30 µL, 528 µmol, 12 equiv.), TMD (0.1 mL), and CuI (3.3 mg, 18 µmol), were added accordingly. The RBF was degassed and backfilled with N2(g) for three times, the reaction mixture was then heated at 80 °C for 15 h. After heating, the reaction mixture was cooled down rt, diluted with H 2 O (15 mL) and extracted with EtOAc (3 x 15 mL). The combined organic extracts were washed with H 2 O (2 x 30 mL) and brine (2 x 30 mL), dried over anhydrous MgSO 4 , filtered, and concentrated under reduced pressure. The crude product (32 mg) obtained was purified by flash column chromatography (19:1 EtOAc:MeOH, R f = 0.2) to yield 51(10 mg, 40% from 50) as an off-white solid. 1 H NMR (400 MHz, CDCl 3 ) δ 9.93 – 9.88 (m, 1H), 9.42 (s, 1H), 9.04 (dd, J = 8.0, 1.6 Hz, 1H), 7.99 – 7.94 (m, 1H), 7.68 – 7.57 (m, 3H), 7.53 (d, J = 8.5 Hz, 1H), 7.40 (ddd, J = 8.1, 7.1, 1.1 Hz, 1H), 4.6 (br t, J = 7.8 Hz, 2H), 2.84 – 2.72 (br t, J = 7.8 Hz, 2H), 2.48 (s, 6H). 13 C DEPT-Q NMR (101 MHz, CDCl 3 ) δ 161.5 (C), 148.7 (CH), 148.1 (C), 142.3 (C), 141.0 (C), 137.7 (C), 136.7 (C), 134.6 (C), 132.1 (CH), 131.1 (CH), 129.1 (CH), 126.5 (CH), 124.8 (CH), 122.8 (CH), 121.5 (C), 117.6 (C), 114.1 (CH), 56.0 (CH 2 ), 46.0 (CH 3 ), 41.6 (CH 2 ). LCMS (ESI) m/z (%): t = 2.5 min, 374.1 (100, M + H + ). HPLC: PP gradient method, = 5.8 min, 98.8 % purity at 254 nm. HR-ESI (m/z) calcd for C 22 H 20 N 3 OS + [M + H] + 374.1322, found 374.1336. mp 186–188 °C. (E)-1-((2-Ethynylphenyl)diazenyl)piperidine (53): Compound 53 was synthesised according to General Procedure C from (E)-1-((2- iodophenyl)diazenyl) piperidine, the synthesis of which has been reported in our previous work. 51 Intermediate 1-((2-((trimethylsilyl)ethynyl)phenyl)diazenyl)piperidine (2.3 g, quant.) was obtained as an orange oil after purified by flash column chromatography (49:1 hexanes:EtOAc, R f = 0.2). 1 H NMR (400 MHz, CDCl3) δ 7.48 (ddd, J = 0.4, 1.5, 7.6 Hz, 1H), 7.42 (dd, J = 0.8, 8.2 Hz, 1H), 7.25 (ddd, J = 1.5, 7.3, 8.2 Hz, 1H), 7.06 (dt, J = 1.2, 7.6 Hz, 1H), 3.85 (br s, 4H), 1.72 (br s, 6H), 0.25 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 152.2, 133.0, 129.0, 124.9, 118.0, 116.7, 103.2, 98.224.3, 0.0. HR- ESI (m/z) calcd for C16H24N3Si + [M + H] + 286.1734, found 286.1725. 53 (1.6 g, 90% from 52) was obtained as a yellow oil. 1 H NMR (400 MHz, CDCl3) δ 7.51 (dd, J = 1.4, 7.7 Hz, 1H), 7.43 (dd, J = 0.8, 8.2 Hz, 1H), 7.29 (ddd, J = 1.5, 7.4, 8.2 Hz, 1H), 7.08 (dt, J = 1.2, 7.5 Hz, 1H), 3.84 (br s, 4H), 3.27 (s, 1H), 1.72 (br s, 6H). 13 C NMR (101 MHz, CDCl3) δ 152.5, 133.6, 129.4, 125.0, 117.1, 116.9, 81.9, 81.0, 24.4. ). LCMS (ESI) m/z: 214.2 [M + H] + . HR-ESI (m/z) calcd for C13H16N3 + [M + H] + 214.1339, found 214.1337. (E)-(2-((2-(Piperidin-1-yldiazenyl)phenyl)ethynyl)phenyl)met hanol (55a): Compound 55a was synthesised according to General Procedure B. The crude product obtained was purified by flash column chromatography (2:1 hexanes:EtOAc, R f = 0.45) to yield 55a (789 mg, 96%) as a pale orange oil. 1 H NMR (400 MHz, CDCl3) δ 7.54 – 7.56 (m, 2H), 7.48 (dd, J = 0.8, 8.2 Hz, 1H), 7.36 – 7.39 (m, 1H), 7.28 – 7.33 (m, 3H), 7.13 (dt, J = 1.2, 7.6 Hz, 1H), 4.85 (d, J = 7.0 Hz, 2H), 3.88 (brs, 2H), 3.12 (t, J = 7.0 Hz, 1H), 1.72 (br s, 6H). 13 C NMR (101 MHz, CDCl3) δ 152.2, 143.0, 132.9, 131.9, 129.3, 128.3, 127.6, 127.5, 125.1, 122.3, 117.5, 117.3, 93.0, 91.1, 64.5, 25.4, 24.2. LCMS (ESI) m/z: 320.1 [M + H] + . HR-ESI (m/z) calcd for C20H22N3O [M + H] + 320.1757, found 320.1757. (E)-N,N-Dimethyl-2-(2-((2-(piperidin-1-yldiazenyl)phenyl)eth ynyl)phenyl)acetamide (55b): Compound 55b was synthesised according to General Procedure B. The crude product obtained was purified by flash column chromatography (1:1 hexanes:EtOAc) to yield 55b (464 mg, 62%) as a brown oil. 1 H NMR (600 MHz, CDCl 3 ) δ 7.54 (t, J = 8.0 Hz, 2H), 7.48 (d, J = 8.2 Hz, 1H), 7.39 (d, J = 7.7 Hz, 1H), 7.26 – 7.30 (m, 2H), 7.23 (t, J = 7.4 Hz, 1H), 7.12 (t, J = 7.4 Hz, 1H), 4.09 (s, 2H), 3.85 (br s, 4H), 2.95 (s, 3H), 2.94 (s, 3H), 1.71 (br s, 6H). HR-ESI (m/z) calcd for C 23 H 26 N 4 ONa + [M + Na] + 397.1999, found 397.1980. (E)-2-((2-(Piperidin-1-yldiazenyl)phenyl)ethynyl)benzamide (55c): Compound 55c was synthesised according to General Procedure B. The crude product obtained was purified by flash column chromatography (1:1 hexanes:EtOAc) to yield 55c (1.03 g, 42%) as a brown oil. 1 H NMR (400 MHz, CDCl3) δ 8.30 (br s, 1H), 8.25 (m, 1H), 7.62 (m, 1H), 7.55 (dd, J = 1.2, 7.7 Hz, 1H), 7.42 – 7.50 (m, 3H), 7.34 (ddd, J = 1.5, 7.3, 8.2 Hz, 1H), 7.15 (dt, J = 1.2, 7.6 Hz, 1H), 5.85 (br s, 1H), 3.84 (br s, 4H), 1.72 (br s, 6H). 13 C NMR (101 MHz, CDCl3) δ 167.6, 152.4, 133.43, 133.38, 132.8, 131.1, 130.9, 130.0, 128.5, 125.3, 120.9, 117.3, 116.8, 95.1, 92.0, 24.2. HR-ESI (m/z) calcd for C20H21N4O + [M + H] + 333.1710, found 333.1711. 12H-Isochromeno[4,3-c]cinnoline (56a): 55a (350 mg, 1.09 mmol) was dissolved in CH2Cl2 (10 mL), followed by addition of HCl (2.74 mL, 1 M in Et2O) solution. The reaction mixture was left to stir at rt for 1 h. On completion, the reaction was quenched by saturated NaHCO3 solution (10 mL), and extracted with CH2Cl2 (2 x 10 mL). The combined organic extracts were dried over MgSO 4 , filtered and concentrated under reduced pressure. The crude product obtained was purified by flash column chromatography (4:1 hexanes:EtOAc, , R f = 0.25) to yield 56a (226 mg, 88%) as a pale orange solid. 1 H NMR (400 MHz, CDCl 3 ) δ 8.62 (d, J = 5.2 Hz, 1H), 8.42 (d, J = 5.7 Hz, 1H), 8.12 (d, J = 5.6 Hz, 1H), 7.76 (t, J = 5.5 Hz, 1H), 7.66 (t, J = 5.3 Hz, 1H), 7.51 (t, J = 5.0 Hz, 1H), 7.41 (t, J = 5.0 Hz, 1H), 7.17 (d, J = 5.0 Hz, 1H), 5.52 (s, 2H). 13 C NMR (101 MHz, CDCl3) δ 151.3, 148.0, 137.5, 130.4, 129.9, 129.61, 129.57, 129.4, 129.2, 128.5, 124.2, 123.0, 120.8, 117.9, 69.1. LCMS (ESI) m/z: 235.1 [M + H] + . HR-ESI (m/z) calcd for C15H11N2O + [M + H] + 235.0866, found 235.0851. mp 165–167 °C. N,N-Dimethyl-11H-indeno[1,2-c]cinnoline-11-carboxamide (56b): 55b (374 mg, 1 mmol) was dissolved in CH2Cl2 (10 mL) at 0 o C, followed by addition of MeSO3H (5 mmol). The reaction mixture was left to stir at rt for 72 h. On completion, the mixture was quenched by saturated NaHCO3 solution (10 mL) and extracted with CH2Cl2 (2 x 10 mL). The combined organic extracts were dried over MgSO4, filtered and concentrated under reduced pressure. The crude product obtained was purified by flash column chromatography (3:1 hexanes:EtOAc) to yield 56b (234 mg, 81%) as a yellow amorphous solid. 1 H NMR (CDCl3, 600 MHz) δ 10.52 (d, J = 8.5 Hz, 1H), 8.56 (d, J = 8.3 Hz, 1H), 8.01 (d, J = 8.6 Hz, 1H), 7.76 – 7.79 (m, 2H), 7.68 – 7.74 (m, 2H), 7.50 (dd, J = 7.2, 8.2 Hz, 1H), 7.37 (s, 1H), 3.16 (s, 6H). 13 C NMR (CDCl3, 150 MHz) δ 172.3, 149.6, 146.4, 132.6, 129.5, 129.2, 128.2, 127.4, 125.84, 125.79, 125.5, 125.4, 124.5, 111.4, 43.4. HR-ESI (m/z) calcd for C 18 H 15 N 3 ONa + [M + Na] + 312.1107, found 312.1094. Isoquinolino[4,3-c]cinnolin-12(11H)-one (56c): 55c (900 mg, 2.71 mmol) was dissolved in CH2Cl2 (10 mL) at 0 °C, followed by addition of MeSO3H (906 mg, 9.22 mmol). The reaction mixture was allowed to warm to rt and left to stir for 72 h. After this time, saturated NaHCO3 solution (15 mL) was added, followed by another 0.5 h stirring and extraction with CH2Cl2 (2 × 15 mL). The combined organic extracts were dried over MgSO4, filtered through a silica plug, and evaporated in vacuo to afford the title compound as a bright yellow solid (524 mg, 78%). 1 H NMR (400 MHz, CDCl3) δ 8.52 – 8.53 (m, 1H), 8.32 – 8.34 (m, 1H), 8.25 – 8.28 (m, 1H), 7.85 – 7.94 (m, 3H), 7.43 – 7.50 (m, 2H). 13 C NMR (100 MHz, CDCl 3 ) δ 173.8, 157.8, 151.3, 135.5, 134.5, 133.6, 131.5, 130.7, 130.4, 129.9, 128.6, 127.2, 123.8, 122.2, 120.6. LCMS (ESI) m/z: 249.1 [M + H] + . HR-ESI (m/z) calcd for C 15 H 9 N 2 O 2 + [M + H] + 249.0659, found 249.0660. mp 273–274 °C. 11-(2-(Dimethylamino)ethyl)isoquinolino[4,3-c]cinnolin-12(11 H)-one (56d): Compound 55d was synthesised according to General Procedure B. The crude product obtained was purified by flash column chromatography (19:1 hexanes:EtOAc → 9:1 hexanes:EtOAc) to yield 55d (1.08 g, 91%) which was directly used in the next step without characterisation. 55d (235 mg, 680 µmol) and tetraethylammonium chloride (224 mg, 1.35 mmol) were dissolved in CH 2 Cl 2 (5 mL) at rt, followed by addition of MeSO 3 H (1 M in CH 2 Cl 2 , 2.03 mL). The reaction mixture was left to stir at rt for 2 h, then quenched with H 2 O (10 mL) and extracted with CH 2 Cl 2 (3 x 5 mL). The combined organic extracts were dried over MgSO 4 , filtered and concentrated under reduced pressure to yield 57. 57 (100 mg, 0.33 mmol) was dissolved in CH 3 CN (2 mL), followed by addition of DMD (148 mg, 1.67 mmol). The reaction mixture was heated at 120 °C in the microwave for 1 h. After heating, the mixture was cooled down to rt, concentrated and purified by flash column chromatography (9:1 CHCl 3 :MeOH, R f = 0.25) to yield 56d (101 mg, 95% from 55d) as a beige amorphous solid. 1 H NMR (400 MHz, CDCl3) δ 9.20 (dd, J = 0.6, 8.2 Hz, 1H), 8.56 – 8.62 (m, 2H), 8.42 (ddd, J = 0.5, 1.3, 8.0 Hz, 1H), 7.76 – 7.91 (m, 3H), 7.69 (ddd, J = 1.2, 7.2, 8.1 Hz, 1H), 4.68 (t, J = 7.2 Hz, 2H), 3.00 (t, J = 7.2 Hz, 2H), 2.36 (s, 6H). 13 C NMR (101 MHz, CDCl 3 ) δ 163.2, 150.1, 133.6, 131.2, 130.4, 129.92, 129.88, 127.8, 123.9, 123.6, 115.8, 57.2, 47.4, 45.9. LCMS (ESI) m/z: 319.1 [M + H] + . HR-ESI (m/z) calcd for C19H19N4O + [M + H] + 319.1553, found 319.1556. mp 179–183 °C. The spectroscopic data are consistent with those previously reported in the literature. 2-((2-Formamidophenyl)ethynyl)-N,N-dimethylbenzamide (60a): Compound 60a was synthesised according to General Procedure A. The crude product (466 mg, brown oil) obtained was purified by flash column chromatography (10:1 CH2Cl2:EtOAc, Rf = 0.2) to yield 60a (337 mg, 67%) an orange oil. 1 H NMR (401 MHz, CDCl 3 ) δ 9.02 (s, 1H), 8.71 (d, J = 2.0 Hz, 1H), 8.55 (dd, J = 8.4, 1.1 Hz, 1H), 7.62 (dd, J = 6.7, 1.8 Hz, 1H), 7.45 (dd, J = 7.8, 1.5 Hz, 2H), 7.46 – 7.34 (m, 4H), 7.37 – 7.27 (m, 2H), 7.06 (td, J = 7.6, 1.2 Hz, 1H), 3.13 (s, 3H), 2.92 (s, 3H). 13 C DEPT- Q NMR (101 MHz, CDCl3) δ 171.1 (C), 160.7 (CH), 140.3 (C), 138.4 (C), 132.2 (CH), 131.1 (CH), 130.1 (CH), 129.5 (CH), 128.4 (CH), 126.3 (CH), 123.4 (CH), 120.9 (C) 119.9 (CH), 111.4 (C), 93.9 (C), 89.2 (C), 39.4 (CH3), 35.4 (CH3). LCMS (ESI) m/z (%): t = 2.8 min, 293.1 (100, M + H + ). HPLC: PP gradient method, = 5.0 min, 97.8 % purity at 254 nm. HR-ESI (m/z) calcd for C18H17N2O2 + [M + H] + 293.1285, found 293.1294. N-(2-((2-Bromophenyl)ethynyl)phenyl)formamide (60b): Compound 60b was synthesised according to General Procedure A. The crude product (1.86 g) obtained was purified by flash column chromatography twice (4:1 hexanes:EtOAc, R f = 0.2; 1:1 hexanes:CH 2 Cl 2 ) to yield 60b (711 mg, 66%) as a grey amorphous solid. 1 H NMR (400 MHz, CDCl 3 ) δ 8.89 (d, J = 11.2 Hz, 1H), 8.51 (d, J = 1.7 Hz, 1H), 8.48 (d, J = 8.0 Hz, 1H), 8.43 (br s, 1H), 8.32 (br s, 1H), 7.66-7.63 (m, 2H), 7.61-7.56 (app td, J = 8.4, 1.6 Hz, 3H), 7.53 (dd, J = 7.7, 1.5 Hz, 1H), 7.41- 7.27 (m, 5H), 7.26-7.20 (m, 2H), 7.16 (d, J = 8.2 Hz, 1H), 7.12 (td, J = 7.6, 1.1 Hz, 1H). This compound appears as a pair of rotamers (ratio = 0.36 : 1) in the 1 H NMR spectrum. LCMS (ESI) m/z (%): t = 3.6 min, 299.8 (60, M + H + ), 301.8 (50, M + H + ). HPLC: PP gradient method, = 6.9 min, 97.9 % purity at 254 nm. HR-ESI (m/z) calcd for C 15 H 11 BrNO + [M + H] + 300.0019, found 300.0008. 5H-Isochromeno[3,4-b]quinolin-5-one 60a (100 mg, 342 µmol) was dissolved in dry CH2Cl2 (5 mL) in a dry RBF. The RBF was degassed and backfilled with N2(g) for three times. Burgess reagent (122.3 mg, 513 µmol) was added under N2(g) atmosphere, the reaction mixture was left to stir at rt for 22 h. After this time, the reaction was heated at reflux for 3 h, then cooled down to rt and diluted with CH2Cl2 (20 mL). Washed with H2O (2 x 20 mL), the organic extract was dried over MgSO4, filtered concentrated to about 5 mL in volume. 61a obtained in the organic phase was directly used without isolation as o-alkynylaryl isocyanides are usually quite unstable. MeSO 3 H (32.9 mg, 0.22 mL, 342 µmol) was added slowly to a stirred solution of 61a in CH 2 Cl 2 (5 mL) under N 2 (g) atmosphere. The reaction mixture was left to stir at rt for 14 h. On completion, the reaction mixture was diluted with H 2 O (25 mL) and extracted with CH 2 Cl 2 (3 x 10 mL). The combined organic extracts were washed dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The crude product (brown oil) was purified by flash column chromatography (7:3 hexanes:EtOAc) to yield 63 (18 mg, 21% from 60a) as a white solid. 1 H NMR (400 MHz, CDCl3) δ 8.87 (s, 1H), 8.44 (dd, J = 8.0, 1.4 Hz, 1H), 8.27 (d, J = 8.0 Hz, 1H), 8.06 (d, J = 8.5 Hz, 1H), 7.96 (d, J = 8.1 Hz, 1H), 7.89 (ddd, J = 8.1, 7.3, 1.4 Hz, 1H), 7.78 (ddd, J = 8.4, 6.9, 1.4 Hz, 1H), 7.65 (ddd, J = 8.1, 7.3, 1.0 Hz, 1H), 7.58 (ddd, J = 7.9, 6.8, 0.9 Hz, 1H). 13 C DEPT-Q NMR (101 MHz, CDCl3) δ 160.6 (C), 155.0 (C), 146.8 (C), 135.3 (CH), 133.5 (C), 132.9 (CH), 131.6 (CH), 131.2 (CH), 130.0 (CH), 128.6 (CH), 128.1 (CH), 126.7 (CH), 126.6 (C), 122.3 (CH), 121.8 (C), 113.9 (C). LCMS (ESI) m/z (%): t = 3.6 min, 248.1 (100, M + H + ). HPLC: PP gradient method, = 5.0 min, 96.1% purity at 254 nm. HR-ESI (m/z) calcd for C16H10NO2 + [M + H] + 248.0706, found 248.0705. The spectroscopic data are consistent with those previously reported in the literature. 2-Bromo-3-(2-bromophenyl)quinoline (69): 60b (200 mg, 0.67 mmol) and DIPEA (0.75 mL, 5.33 mmol,) were dissolved in CH 2 Cl 2 (4.5 mL), followed by dropwise addition of POCl 3 (96 µL) under N 2 (g) atmosphere at –78 °C. The reaction mixture was left to stir at 0 °C for 2 h. On completion, reaction mixture was diluted with CH2Cl2 (15 mL) and washed with saturated NaHCO 3 (aq) solution (2 x 15 mL). The organic extract was dried over anhydrous MgSO 4 , filtered and concentrated to about 5 mL in volume.61b obtained in the organic phase was directly used without isolation as o-alkynylaryl isocyanides are usually quite unstable. 53 TBAB (644 mg, 2.00 mmol) was added slowly to a stirred solution of 61b in CH2Cl2 (12 mL) under N2(g) atmosphere. The reaction mixture was left to stir at rt for 17 h. On completion, the reaction mixture was concentrated under reduced pressure, diluted with H2O (50 mL) and extracted with EtOAc (2 x 50 mL). The combined organic extracts were washed with H2O (2 x 75 mL) and brine (2 x 50 mL), dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The crude product (415 mg) was purified by flash column chromatography (2:1 CH2Cl2:hexanes, Rf = 0.4) to yield 69 (173 mg, 72% from 60b) as an off-white amorphous solid. 1 H NMR (400 MHz, CDCl3) δ 8.13 (d, J = 8.6 Hz, 1H), 8.02 (s, 1H), 7.84 (dd, J = 8.1, 1.2 Hz, 1H), 7.78 (ddd, J = 8.5, 7.0, 1.5 Hz, 1H), 7.72 (dd, J = 8.3, 1.2 Hz, 1H), 7.62 (ddd, J = 8.1, 7.0, 1.2 Hz, 1H), 7.44 (ddd, J = 7.5, 7.0, 1.4 Hz, 1H), 7.36-7.32 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 147.9 (C), 143.0 (C), 140.0 (C), 138.4 (CH), 136.5 (C), 132.9 (CH), 131.4 (CH), 130.8 (CH), 130.2 (CH), 128.6 (CH), 127.9 (CH), 127.6 (CH), 127.5 (CH), 127.0 (C), 124.1 (C). LCMS (ESI) m/z (%): t = 3.7 min, 363.8 (100, M + H + ), 365.8 (50, M + H + ). HPLC: PP gradient method, t R = 7.3 min, 90.4 % purity at 254 nm. HR-ESI (m/z) calcd for C 15 H 10 Br 2 N + [M + H] + 363.9155; found 363.9167. 2-(6H-Indolo[2,3-b]quinolin-6-yl)-N,N-dimethylethan-1-amine (70): Compound 70 was synthesised according to General UCC Procedure.. The crude product (76 mg) obtained was purified by flash column chromatography (4:1 EtOAc:MeOH, Rf = 0.33) to yield 70 (31 mg, 52%) as a light yellow oil. 1 H NMR (400 MHz, CDCl 3 ) δ 8.72 (s, 1H), 8.16 (d, J = 7.7 Hz, 1H), 8.12 (d, J = 8.6 Hz, 1H), 8.01 (d, J = 8.2 Hz, 1H), 7.71 (ddd, J = 8.4, 6.9, 1.5 Hz, 1H), 7.61-7.52 (m, 2H), 7.46 (ddd, J = 8.0, 6.9, 1.1 Hz, 1H), 7.31 (t, J = 8.0 Hz, 1H), 4.72 (t, J = 7.2 Hz, 2H), 2.94 (app br s, 2H), 2.47 (s, 6H). 13 C DEPT-Q NMR (101 MHz, CDCl 3 ) δ 152.6 (C), 147.0 (C), 142.3 (C), 128.9 (CH), 128.6 (CH), 128.2 (CH), 127.9 (CH), 127.4 (CH), 124.4 (C), 123.1 (CH), 121.7 (CH), 120.8 (C), 120.1 (CH), 118.3 (CH), 109.1 (C), 57.2 (CH 2 ), 45.9 (CH 3 ), 39.9 (CH 2 ). LCMS (ESI) m/z (%): t = 3.0 min, 290.1 (100, M + H + ), 291.1 (20, M + H + ). HPLC: PP gradient method, = 5.3 min, 96.6 % purity at 254 nm. HR-ESI (m/z) calcd for C 19 H 19 N 3 + [M + H] + 290.1652, found 290.1656. 3-(2-Bromophenyl)-N-(2-(dimethylamino)ethyl)quinoline-2-carb oxamide: 68 (99 mg, 0.27 mmol), Pd(OAc) 2 (6.1 mg, 27 µmmol), PPh 3 (107 mg, 0.41 mmol), DMD (0.45 mL, 4.1 mmol), Et3N (50 µL, 0.55 mmol) and dry NMP (2 mL) were added to a 25 mL dry RBF. The RBF was degassed and backfilled with CO(g) for three times, and then heated at 80 °C for 40 h. On completion, the reaction mixture was cooled down to rt and extracted with EtOAc (2 x 15 mL). The combined organic extracts were washed with H 2 O (3 x 50 mL), saturated NH 4 Cl solution (2 x 50 mL), and brine (2 x 50 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude product (182 mg) obtained was purified by flash column chromatography (100 % EtOAc, Rf 2:1 EtOAc:MeOH, Rf = 0.4). The title compound (63 mg, 58%) was obtained as a light yellow oil. 1 H NMR (400 MHz, CDCl3) δ 8.37 (br s, 1H), 8.20 (d, J = 8.5 Hz, 1H), 8.06 (s, 1H), 7.87 (d, J = 8.5 Hz, 1H), 7.80 (ddd, J = 8.4, 6.9, 1.4 Hz, 1H), 7.67-7.63 (m, 2H), 7.42 (td, J = 7.5, 1.2 Hz, 1H), 7.36 (dd, J = 7.6, 1.9 Hz, 1H), 7.29 – 7.23 (m, 1H), 3.59-3.51 (m, 2H), 2.60 (t, J = 6.1 Hz, 2H), 2.34 (s, 6H). 13 C DEPT-Q NMR (101 MHz, CDCl 3 ) δ 164.9 (C), 148.8 (C), 146.0 (C), 141.3 (C), 139.2, 134.2 (C), 132.2 (CH), 130.4 (CH), 130.1 (CH), 129.8 (CH), 129.0 (CH), 128.6 (C), 128.4 (CH), 127.7 (CH), 127.3 (CH), 123.5 (C), 58.4 (CH2), 45.5 (CH3), 37.3 (CH2). LCMS (ESI) m/z (%): t = 3.2 min, 399.9 (100, M + H + ), 400.9 (20, M + H + ). HPLC: PP gradient method, = 5.3 min, 92.5 % purity at 254 nm. HR-ESI (m/z) calcd for C20H21BrN3O + [M + H] + 398.0863, found 398.0871. 5-(2-(Dimethylamino)ethyl)dibenzo[b,f][1,7]naphthyridin-6(5H )-one (71): 3-(2-Bromophenyl)-N-(2-(dimethylamino)ethyl)quinoline-2-carb oxamide (34 mg, 85 µmol) was dissolved in n-butanol (0.85 mL) in a dry RBF, and CuI (6.5 mg, 34 µmol), K 3 PO 4 (72 mg, 0.34 mmol), ethylene glycol (57 µL, 1.02 mmol), and TMD(30 µL, 0.17 mmol) were added sequentially. The RBF was degassed and backfilled with N 2 (g) for three times, the reaction mixture was heated at 80 °C for 22 h. After heating, the reaction mixture was cooled down to rt, diluted with H 2 O (15 mL) and extracted with EtOAc (2 x 15 mL). The combined organic extracts were washed with H 2 O (2 x 20 mL) and brine (2 x 20 mL), dried over anhydrous MgSO 4 , filtered, and concentrated under reduced pressure. The crude product (29 mg) obtained was purified by flash column chromatography (100 % EtOAc → 100 % MeOH, R f = 0.5) to yield 69 (15 mg, 56%) as a transparent oil. 1 H NMR (400 MHz, CDCl 3 ) δ 9.05 (s, 1H), 8.45 (d, J = 8.6 Hz, 1H), 8.37 (dd, J = 8.0, 1.4 Hz, 1H), 8.00 (d, J = 8.2 Hz, 1H), 7.80 (ddd, J = 8.5, 6.8, 1.4 Hz, 1H), 7.67 (ddd, J = 8.1, 6.8, 1.1 Hz, 1H), 7.58 (ddd, J = 8.5, 7.2, 1.4 Hz, 1H), 7.49 (d, J = 7.9 Hz, 1H), 7.36 (t, J = 7.6 Hz, 1H), 4.60 (app t, J = 7.6 Hz, 2H), 2.75 (app t, J = 7.8 Hz, 2H), 2.42 (s, 6H). 13 C DEPT-Q NMR (101 MHz, CDCl 3 ) δ 160.2 (C), 148.6 (C), 142.0 (C), 136.9 (C), 131.2 (CH), 130.7 (CH), 130.4 (CH), 130.2 (CH), 129.3 (C), 128.8 (CH), 127.8 (CH), 126.5 (C), 123.9 (CH), 123.0 (CH), 118.5 (C), 115.4 (CH), 56.1 (CH 2 ), 46.1 (CH 3 ), 41.7 (CH 2 ). LCMS (ESI) m/z (%): t = 3.1 min, 318.0 (100, M + H + ), 319.0 (20, M + H + ). HPLC: PP gradient method, = 4.7 min, 94.6 % purity at 254 nm. HR-ESI (m/z) calcd for C 20 H 20 N 3 O + [M + H] + 318.1601, found 318.1610. Methyl 2-ethynyl-4,5-dimethoxybenzoate (73): Compound 73 was synthesised according to General Procedure C. 73 (1.05 g, 93%) was obtained as a brown oil. 1 H NMR (400 MHz, CDCl 3 ) δ 7.41 (s, 1H), 7.00 (s, 1H), 3.89 (s, 3H), 3.88 (s, 3H), 3.87 (s, 3H), 3.31 (s, 1H). 13 C NMR (100 MHz, CDCl 3 ) δ 165.9, 151.5, 148.9, 125.1, 116.6, 116.3, 112.6, 82.3, 80.9, 56.1, 56.0, 52.0. LCMS (ESI) m/z : 221.1 [M + H] + . HR-ESI (m/z) calcd for C12H13O4 + [M + H] + 221.0808, found 221.0808. Methyl 4,5-dimethoxy-2-((6-(methylthio)benzo[d][1,3]dioxol-5-yl)eth ynyl)benzoate (74): 72 (250 mg, 850 µmol) was dissolved in Et3N (2 mL) and DMF (2 mL) in a dry RBF, followed by addition of Pd(PPh3)2Cl2 (18 mg, 26 µmol) and CuI (13 mg, 68 µmol). The RBF was then degassed and backfilled with N2(g) for three times. Finally, 73 (225 mg, 1.02 mmol) was slowly added under N2(g) atmosphere over a period of 2 h. The reaction was left to stir at rt for 16 h. On completion, the reaction mixture was filtered through Celite ® , washed with EtOAc (40 mL), dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The crude product obtained was purified by flash column chromatography (4:1 hexanes:EtOAc) to yield 74 (291 mg, 89%) as a pale oil. 1 H NMR (400 MHz, CDCl3) δ 7.50 (s, 1H), 7.10 (s, 1H), 7.01 (s, 1H), 6.75 (s, 1H), 5.98 (s, 2H), 3.95 (s, 3H), 3.94 (s, 6H), 2.49 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 150.0, 139.1, 128.7, 127.0, 117.6, 96.7, 52.6, 45.6, 24.4. LCMS (ESI) m/z: 387.0 [M + H] + . HR-ESI (m/z) calcd for C20H19O6S + [M + H] + 387.0897, found 387.0901. mp 184.2 − 184.9 °C. Methyl 2-(7-iodothieno[2',3':4,5]benzo[1,2-d][1,3]dioxol-6-yl)-4,5- dimethoxybenzoate (75): Compound 75 was synthesised according to General Procedure D. The crude product obtained was purified by flash column chromatography (3:1 hexanes:EtOAc) to yield 75 (414 mg, 94%) as a pale brown amorphous solid. 1 H NMR (400 MHz, CDCl3) δ 7.56 (s, 1H), 7.18 (s, 1H), 7.16 (s, 1H), 6.04 (s, 1H), 3.99 (s, 3H), 3.92 (s, 3H), 3.65 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 166.4, 151.3, 149.0, 147.5, 147.3, 140.6, 135.9, 132.6, 129.6, 123.6, 114.8, 113.0, 105.0, 101.6, 101.2, 81.4, 56.22, 56.16, 52.2. LCMS (ESI) m/z: 498.9 [M + H] + . HR-ESI (m/z) calcd for C19H16O6SI + [M + H] + 498.9707, found 498.9699. N-(2-(Dimethylamino)ethyl)-2-(7-iodothieno[2',3':4,5]benzo[1 ,2-d][1,3]dioxol-6-yl)-4,5- dimethoxybenzamide (76): 75 (200 mg, 0.40 mmol) was dissolved in DMSO (8 mL), followed by addition of KOH (2 M, 4 mL). The reaction mixture was left to stir at rt for 16 h. After stirring, the solution was acidified to pH 3 (using 1M HCl) and extracted with EtOAc (3 x 10 mL). The combined organic extracts were dried over anhydrous MgSO 4 and concentrated under reduced pressure to afford the carboxylic acid. The acid was dissolved in dry CH2Cl2 (10 mL) and cooled to 0 °C, followed by addition of DMF (2 drops) and oxalyl chloride (102 mg, 0.80 mmol). The solution was left to stir at rt for 3 h. After this time the reaction mixture was concentrated under reduced pressure, then redissolved in dry CH2Cl2 (10 mL) followed by addition of N,N-dimethylethylenediamine (106 mg, 1.2 mmol). The reaction mixture was left to stir at rt for 2 h. On completion, the mixture was quenched with H2O (20 mL) and extracted with CH2Cl2 (2 x 15 mL). The combined organic extracts were dried over anhydrous MgSO4, filtered and concentrated under reduced pressure to afford 76 as a pale brown amorphous solid (205 mg, 92%). 1 H NMR (400 MHz, CDCl3) δ 7.49 (s, 1H), 7.19 (s, 1H), 7.15 (s, 1H), 6.77 (s, 1H), 6.29 (br s, 1H), 6.04 (s, 2H), 3.95 (s, 3H), 3.88 (s, 3H), 3.15 – 3.19 (m, 2H), 1.98 (t, J = 5.9 Hz, 2H), 1.65 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 165.8, 148.9, 148.5, 146.7, 146.7, 138.3, 135.2, 132.3, 128.0, 127.2, 123.9, 113.3, 111.3, 104.1, 100.7, 100.2, 82.1, 55.6, 55.2, 55.1, 43.4, 36.3. LCMS (ESI) m/z: 555.1 [M + H] + . HR-ESI (m/z) calcd for C22H24N2O5SI + [M + H] + 555.0445, found 555.0448. 6-(2-(Dimethylamino)ethyl)-2,3-dimethoxy-[1,3]dioxolo[4'',5' ':4',5']benzo[1',2':4,5] thieno[3,2- c]isoquinolin-5(6H)-one (77): A sealed tube containing 76 (200 mg, 360 µmol), Pd 2 (dba) 3 (8 mg, 8.7 µmol), Xantphos (10 mg, 17 µmol) and Cs 2 CO 3 (353 mg, 1.1 mmol) in 1,4-dioxane (3 mL) was heated to 120 o C for 16 h. After heating, the reaction mixture was cooled to rt, filtered and concentrated under reduced pressure. The crude mixture was purified by flash column chromatography (1:9 MeOH:CHCl 3 ) to yield 77 as a pale brown solid (78 mg, 51%). 1 H NMR (400 MHz, CDCl 3 ) δ 7.80 (s, 1H), 7.75 (s, 1H), 7.17 (s, 1H), 6.85 (s, 1H), 6.07 (s, 2H), 4.47 (t, J = 8.0 Hz, 2H), 4.03 (s, 3H), 4.00 (s, 3H), 2.79 (t, J = 8.0 Hz, 2H), 2.42 (s, 6H). 13 C NMR (101 MHz, CDCl 3 ) δ 161.7, 153.7, 149.3, 147.6, 147.0, 132.1, 132.0, 127.7, 124.8, 117.1, 116.3, 108.9, 102.8, 102.6, 102.4, 101.9, 57.1, 56.23, 56.17, 45.9, 43.2. LCMS (ESI) m/z: 427.0 [M + H] + . HR-ESI (m/z) calcd for C22H23N2O5S + [M + H] + 427.1322, found 427.1328. mp 263.8 − 266.9 °C. 10-(4-(Trifluoromethyl)phenyl)-10H-benzo[4,5]thieno[3,2-b]in dole (78) To a dry RBF, 2-(2-bromophenyl)-3-iodobenzo[b]thiophene (100 mg, 0.241 mmol) was added along with caesium carbonate (314 mg, 0.964 mmol), Pd 2 dba 3 (44.1 mg, 0.0482 mmol), and Xantphos (55.8 mg, 0.0964 mmol) under nitrogen, and subsequently dissolved in anhydrous toluene or dioxane (8 mL). Following addition of 4-trifluoromethylaniline (0.0432 mL, 0.344 mmol), the vessel was degassed and backfilled with N 2 (g) three times before being stirred at reflux for 40 h. Upon completion, the reaction mixture was extracted with DCM (3 x 20 mL) and filtered through Celite ® before being washed with water (3 x 20 mL) and brine (2 x 20 mL). The organic layer was collected, dried over MgSO4, and concentrated under vacuum. The crude material was then purified via column chromatography (95% PET spirits / 5% DCM, Rf = 0.30) to yield the desired compound (51.2 mg, 58%) as a powdery white solid. 1 H NMR (401 MHz, CDCl3) δ 7.97 – 7.89 (m, 3H), 7.88 – 7.83 (m, 1H), 7.75 (d, J = 8.2 Hz, 2H), 7.45 – 7.39 (m, 1H), 7.38 – 7.27 (m, 5H). 13 C NMR (101 MHz, CDCl3) δ 143.34, 142.28, 141.30, 136.98, 130.14 (q, J = 32.9 Hz), 127.81, 127.09 (q, J = 3.7 Hz), 126.63, 124.66, 124.39, 124.27, 124.08, 124.045 (q, J = 1,080 Hz), 122.65, 121.25, 120.53, 119.74, 118.36, 110.83. LCMS (APCI) m/z: 367.1 [M + ]. 4-(4-(Trifluoromethyl)phenyl)-4H-benzo[4,5]thieno[3,2-b]thie no[2,3-d]pyrrole (79) To a dry microwave tube, 2-(3-bromothiophen-2-yl)-3-iodobenzo[b]thiophene (100 mg, 0.237 mmol) was added along with caesium carbonate (232 mg, 0.712 mmol), Pd2dba3 (21.8 mg, 0.0238 mmol), and Xantphos (27.5 mg, 0.0475 mmol) under nitrogen, and subsequently dissolved in anhydrous 1,4-dioxane (1.19 mL). Following addition of 4-trifluoromethylaniline (0.0257 mL, 0.356 mmol), the vessel was degassed and backfilled with N 2 (g) three times before being stirred in the microwave at 140 degrees Celsius for 3 h (200 W). Upon completion, the reaction mixture was extracted with EtOAc (3 x 30 mL) and filtered through Celite ® before being washed with water (3 x 20 mL) and brine (2 x 20 mL). The organic layer was collected, dried over MgSO4, and concentrated under vacuum. The crude material was then purified via column chromatography (95% PET spirits/ 5% DCM, Rf = 0.30) to yield the desired compound (62.4 mg, 70%) as a powdery white solid. 1 H NMR (401 MHz, CDCl3) δ 7.90 – 7.78 (m, 3H), 7.78 – 7.64 (m, 2H), 7.43 – 7.35 (m, 1H), 7.30 – 7.15 (m, 3H), 7.01 (d, J = 5.3 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ 145.41, 141.82, 141.32, 135.80, 129.20 (qd, J = 33.0, 0.0 Hz), 126.99, 126.75 (q, J = 3.8 Hz), 125.35, 125.03, 124.19, 123.97, 123.71 (q, J = 272.1 Hz), 123.21, 119.28, 117.49, 117.20, 111.37. LCMS (APCI) m/z: 374.1 [M+H + ]. 2-(4H-Benzo[4,5]thieno[3,2-b]thieno[2,3-d]pyrrol-4-yl)-N,N-d imethylethan-1-amine (80) To a dry microwave tube, 2-(3-bromothiophen-2-yl)-3-iodobenzo[b]thiophene (100 mg, 0.237 mmol) was added along with caesium carbonate (232 mg, 0.712 mmol), Pd2dba3 (21.8 mg, 0.0238 mmol), and Xantphos (27.5 mg, 0.0475 mmol) under nitrogen, and subsequently dissolved in anhydrous 1,4-dioxane (1.19 mL). Following addition of N,N-dimethylethylenediamine (0.0383 mL, 0.356 mmol), the vessel was degassed and backfilled with N2(g) three times before being stirred in the microwave at 140 degrees Celsius for 3 h (200 W). Upon completion, the reaction mixture was extracted with EtOAc (3 x 30 mL) and filtered through Celite ® before being washed with water (3 x 20 mL) and brine (2 x 20 mL). The organic layer was collected, dried over MgSO4, and concentrated under vacuum. The crude material was then purified via column chromatography (95% EtOAc/ 5% Et3N/ 1% MeOH, Rf = 0.25) to yield the desired compound (33.60 mg, 47%) as an amber wax. 1 H NMR (401 MHz, CDCl3) δ 7.88 (dt, J = 8.1, 1.0 Hz, 1H), 7.85 (dt, J = 8.0, 0.9 Hz, 1H), 7.41 (ddd, J = 8.2, 7.2, 1.1 Hz, 1H), 7.28 (td, J = 7.6, 1.1 Hz, 2H), 7.21 (d, J = 5.3 Hz, 1H), 7.08 (d, J = 5.3 Hz, 1H), 4.61 (a pp. t, J = 7.6 Hz, 2H), 2.81 (app. t, J = 7.8 Hz, 2H), 2.37 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 145.80, 141.54, 136.79, 127.69, 124.58, 124.53, 124.33, 122.98, 118.64, 115.52, 114.64, 110.83, 59.48, 46.25, 46.10. 3-Iodo-2-(methylthio)pyridine (82): In a dry RBF, 2-fluoro-3-iodopyridine (3.57 g, 16.0 mmol) was dissolved in DMF to form a 0.2 M solution (80 mL), proceeded by addition of three equivalents of NaSMe (3.36 g, 48.0 mmol). The solution was degassed and backfilled with N 2 (g) three times and stirred at 30 degrees Celsius for 1 h. Upon completion, the product was extracted with 120 mL of EtOAc, and washed with water (3 x 80 mL) and brine (2 x 80 mL). The organic layer was collected, dried over MgSO4, and concentrated under vacuum to yield the crude product (3.20 g, 80 %) as a pale-yellow crystal. 1 H NMR (401 MHz, CDCl3) δ 8.43 (dd, J = 4.7, 1.6 Hz, 1H), 7.93 (dd, J = 7.7, 1.6 Hz, 1H), 6.73 (dd, J = 7.7, 4.7 Hz, 1H), 2.53 (s, 3H). LCMS (APCI) m/z: 252.0 [M+H + ]. Data in accordance with that previously reported. 2-(Methylthio)-3-((trimethylsilyl)ethynyl)pyridine (83): In a dry RBF under N 2 (g) atmosphere, 3-iodo-2-(methylthio)pyridine (3.00 g, 12.0 mmol) was added and dissolved in DIPA to make a 0.2 M solution (60 mL). The vessel was placed in an ice bath and subsequently purged and backfilled with N 2 (g) three times. Pd 2 (PPh 3 ) 2 Cl 2 (168 mg, 0.239 mmol) and CuI (137 mg, 0.717 mmol) were then added to the mixture before the vessel was again purged and backfilled with N 2 (g) three times. The flask was then taken out of the ice bath and stirred at room temperature; TMS-acetylene (2.35 g, 23.9 mmol) was slowly added to the flask over 1h, and the reaction mixture was allowed to stir overnight. The resulting solution was extracted with Et 2 O (2 x 50 mL) and filtered through Celite® before being washed with water (3 x 30 mL) and brine (2 x 30 mL); the organic layer was subsequently dried over MgSO 4 and concentrated to give the desired compound (2.23 g, 84%) as a dark brown oil. The crude mixture was used in subsequent reactions without further purification. 1 H NMR (401 MHz, CDCl3) δ 8.37 (dd, J = 4.9, 1.8 Hz, 1H), 7.57 (dd, J = 7.6, 1.8 Hz, 1H), 6.92 (dd, J = 7.6, 4.9 Hz, 1H), 2.56 (s, 3H), 0.29 (s, 9H). LCMS (APCI) m/z: 222.2 [M+H + ]. Data in accordance with that previously reported. 3-Ethynyl-2-(methylthio)pyridine In a clean RBF, 2-(methylthio)-3-((trimethylsilyl)ethynyl)pyridine (2.03 g, 9.18 mmol) was dissolved in a 1:1 solution of MeOH/Et 2 O to a concentration of 0.2 M. K 2 CO 3 (2.54 g, 18.36 mmol) was then added, with the resulting mixture stirred at room temperature overnight. Upon completion the reaction mixture was concentrated under vacuum, extracted three times with 50 mL of Et 2 O and filtered through Celite. The extract was washed with water (3 x 30 mL) and brine (2 x 30 mL), with the aqueous layer collected and dried over MgSO 4 , before being filtered and concentrated under vacuum to give the final product (1.33 g, 97%) as a dark brown oil. The product was used in subsequent reactions without further purification. 1 H NMR (401 MHz, CDCl 3 ) δ 8.42 (dd, J = 4.9, 1.8 Hz, 1H), 7.62 (dd, J = 7.6, 1.8 Hz, 1H), 6.96 (dd, J = 7.6, 4.9 Hz, 1H), 3.58 (s, 1H), 2.58 (s, 4H). LCMS (APCI) m/z: 150.1 [M+H + ]. Data in accordance with that previously reported. 3-((2-Iodophenyl)ethynyl)-2-(methylthio)pyridine (85): To a small dry RBF, 3-ethynyl-2-(methylthio)pyridine (1.33 g, 8.94 mmol) was dissolved in DIPA to make a 0.5 M solution. The vessel was kept in an ice bath and degassed and backfilled with nitrogen three times before being put aside. To another double-necked RBF, 1,2-diiodobenzene (5.90 g, 17.9 mmol) was dissolved in DIPA to make a 0.7 M solution, which was subsequently cooled down in an ice bath before being degassed and backfilled with N 2 (g) three times. CuI (102 mg, 0.536 mmol) and Pd(PPh 3 ) 2 Cl 2 (125 mg, 0.179 mmol) were then added to the RBF and the vessel was once again degassed and backfilled with N 2 (g) three times. The mixture was then brought to a stir at 60 degrees Celsius before the previously prepared solution containing the respective alkyne was added drop-wise over a period of 5 hours; the reaction was then stirred overnight. Upon completion, the mixture was extracted with Et 2 O (3 x 50 mL) and filtered through Celite ® before being washed with water (3 x 40 mL) and brine (2 x 40 mL). The organic layer was collected and dried over MgSO 4 , and then filtered and concentrated under vacuum. The crude product obtained was then purified via flash column chromatography (100% petroleum spirit → 95% petroleum spirit/5% EtOAc) to yield the desired compound (1.77 g, 56%) as light-yellow crystals. 1 H NMR (401 MHz, CDCl3) δ 8.42 (dd, J = 4.9, 1.8 Hz, 1H), 7.92 – 7.85 (m, 1H), 7.72 (dd, J = 7.6, 1.8 Hz, 1H), 7.62 – 7.57 (m, 1H), 7.35 (td, J = 7.6, 1.2 Hz, 1H), 7.04 (ddd, J = 8.0, 7.5, 1.7 Hz, 1H), 6.99 (dd, J = 7.6, 4.9 Hz, 1H), 2.60 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 162.01, 148.36, 138.90, 138.86, 132.99, 129.86, 129.40, 127.85, 118.27, 117.41, 100.49, 99.79, 88.12, 77.24, 13.21. LCMS (APCI) m/z: 352.0 [M+H + ]. 3-Bromo-2-(2-iodophenyl)thieno[2,3-b]pyridine (86): To a small RBF, 3-((2-iodophenyl)ethynyl)-2-(methylthio)pyridine (500 mg, 1.42 mmol) was added along with CuBr 2 (636 mg, 2.85 mmol) before being dissolved in dry DCE (7 mL) to make a 0.2 M solution. The vessel was subsequently degassed and backfilled with N 2 (g) three times, and the reaction was stirred at 60 degrees Celsius overnight. Upon completion, the reaction was quenched with 5 mL of Na2S2O3, extracted with DCM (3 x 30 mL), and washed with water (2 x 20 mL) and brine (2 x 20 mL). The organic layer was collected, dried over MgSO4 and filtered before being concentrated under vacuum to generate the desired compound (604 mg, quant.) as a pale-yellow crystal. 1 H NMR (401 MHz, CDCl3) δ 8.65 (s, 1H), 8.11 (d, J = 8.1 Hz, 1H), 8.00 (dd, J = 8.0, 1.1 Hz, 1H), 7.45 (dtd, J = 14.2, 7.6, 1.6 Hz, 3H), 7.17 (ddd, J = 8.0, 7.1, 2.0 Hz, 1H). LCMS (APCI) m/z: 415.9 [M+H + ]. 6-(2-(Dimethylamino)ethyl)pyrido[3',2':4,5]thieno[3,2-c]isoq uinolin-5(6H)-one (87): To a dry RBF, 3-bromo-2-(2-iodophenyl)thieno[3,2-b]pyridine (100 mg, 0.240 mmol), Cs 2 CO 3 (235 mg, 0.721 mmol), Pd 2 dba 3 (22.0 mg, 0.0240 mmol), and Xantphos (27.8 mg, 0.0481 mmol) were added and dissolved in anhydrous 1,4-dioxane (1.20 mL). The vessel was subsequently degassed and backfilled with N 2 (g) three times and allowed to stir at room temperature for 10 minutes. N,N-Dimethylethylenediamine (0.0388 mL, 0.361 mmol) was then added to the flask before it was subsequently degassed and backfilled with CO (g) three times and allowed to stir under this atmosphere for 4.5 h at 70 o C. After the dehalogenated pyridine starting material has been consumed, the atmosphere of the vessel was reverted back to N2(g) and the reaction mixture was allowed to stir at 120 o C for 20 h. Upon completion, the mixture was extracted with EtOAc (3 x 20 mL) and filtered through Celite ®, before being washed with water (3 x 10 mL) and brine (2 x 10 mL). The organic layer was subsequently collected, dried over MgSO4, and concentrated under vacuum. The crude product was then purified via flash column chromatography (95% EtOAc/ 5% Et3N/ 1% MeOH, Rf = 0.30) to yield the desired compound (47.0 mg, 60%) as an dark amber wax. 1 H NMR (401 MHz, CDCl3) δ 8.70 – 8.55 (m, 2H), 8.50 (d, J = 7.9 Hz, 1H), 7.83 – 7.67 (m, 2H), 7.57 (ddd, J = 8.2, 6.5, 1.8 Hz, 1H), 7.43 (dd, J = 8.4, 4.6 Hz, 1H), 4.84 – 4.70 (t, J = 8 Hz, 2H), 2.85 – 2.73 (t, J = 8 Hz, 2H), 2.42 (s, 7H). 13 C NMR (101 MHz, CDCl3) δ 162.48, 160.46, 147.95, 133.45, 132.54, 131.53, 130.97, 129.54, 128.56, 125.38, 124.84, 123.90, 120.46, 117.77, 57.15, 46.38, 43.85. LCMS (APCI) m/z: 324.2 [M+H + ]. Topoisomerase I inhibitory activity TOP1 plays a key role modifying and maintaining DNA topology during cellular replication and transcription. TOP1 inhibitors, such as 1-4 (Figure 1), exert their cytotoxic effect on cancer cells by binding to TOP1/DNA cleavage complexes (TOP1cc), forming stable ternary complexes that collide with replication forks leading to DNA damage and apoptosis. TOP1 inhibitors also influence transcription, for example, in hypoxic cancer cells compounds 1 and 2 selectively suppress the expression of hypoxia inducible factor HIF-1α, which is a driver of tumour progression. In this scenario, inhibition of TOP1 increases in the transcription of micro-RNAs, miR-17-5p and miR-155, that promote selective degradation of HIF-1α mRNA. Many of the scaffolds generated in the present disclosure are reminiscent of DNA intercalators that inhibit TOP1, such as 2-4 (Figure 1). To further bias these scaffolds to interact with TOP1cc the inventors have included the N,N-dimethylaminoethylene group in ARC111 (compound 3, Figure 1) to many of the synthesised compounds. Top1-mediated DNA cleavage assay Selected scaffolds were tested for TOP1 inhibition at 100, 10, 1, and 0.1 µM in a TOP1-mediated DNA cleavage assay, which was performed as previously reported. 6 This assay uses 3’-radiolabeled DNA substrates to identify compounds that stabilise TOP1ccs. A representative polyacrylamide gel of the TOP1-mediated DNA cleavage assay conducted on compounds 77, 56d and 19a can be seen in Figures 3A-B. From these data it can be seen that 19a and 56d showed significant TOP1 inhibition in a dose-dependent manner. PC3 cell viability determination TOP1 inhibitors 77, 56d and 19a were also tested for cytotoxicity towards prostate cancer PC3 cells. Dose response curves for representative compounds 77 (IC50 = 0.23 µM), 56d (IC50 = 4.44 µM) and 19a (IC50 = 1.99 µM) can be seen in Figures 4A-C. PC3 cell viability assay Routine cell culture: PC3 prostate cancer cell lines were cultured in DMEM (containing 10% fetal calf serum and penicillin-streptomycin). Cells were grown at 37 °C with 5 % CO 2 and passaged when 80-90% confluent 4 times before use. Cells were harvested by trypsin treatment (5 min) then quenched with an equal volume of serum containing media and the cell suspension then centrifuged at 200 xg for 5 min and the pellet resuspended in 5 mL of media. Cells were exposed to Trypan blue (excludes dead cells) and counted with a haemocytometer. Before treatment with drug compounds, cells were plated at 2,500 cells/well in 96 well plates and incubated at 37 °C with 5 % CO 2 in a humidified incubator for 24 h. Drug stock solutions (50 or 10 mM) were diluted x 1000 in media to a final concentration of either 50 µM or 10 µM with a DMSO vehicle concentration of 0.1%. Compounds were then serially diluted in media (containing 0.1% DMSO) to give 8 final concentrations, all at 0.1% DMSO. Cell culture supernatants were aspirated and replaced with drug containing media. Drug treatments were performed in duplicate wells, while potential plate layout-specific variation in cell growth was accounted for by addition of a vehicle control (0.1% DMSO). An untreated control (media only) was included in each assay. Cells were then incubated with drug compounds at 37 °C with 5 % CO2 in a humidified incubator for 72 h prior to assay. Cell media were diluted with CellTitre AQueous One Solution to produce a final concentration of 317 µg/mL. Cell culture supernatants were then aspirated from wells and replaced with 100 µL of CellTitre solution. Triplicate cell-free control wells containing only CellTitre solution were also included in each assay. Cells were then incubated at 37 °C with 5 % CO2 in a humidified incubator for 1 h at which time absorbance was read at 490 nm with a microplate reader. When analysing data, background absorbance (taken from cell-free control wells) was subtracted from each reading. To determine percentage inhibition of cell viability, absorbance readings for each drug treatment were expressed as a fraction of the vehicle control (0.1% DMSO) readings. For each drug concentration the mean (± SEM) is calculated and a sigmoidal curved is fitted to the data and used to calculate the IC50 of each compound. Observations from Top1-mediated DNA cleavage and PC3 cell viability assays The results from the above-mentioned Top1-mediated DNA cleavage and PC3 cell viability assays demonstrate that introduction of the methylenedioxy and methoxy groups seen in 3 to scaffold 19a gives 77, which is approximately 10-fold more potent than 19a in terms of TOP1 inhibitory activity and PC3 cytotoxicity. Conclusion A scaffold-divergent synthesis strategy for the generation of a sp 2 -rich polynucleotide-biased fragment library has been devised based on the electrophilic cyclisation of alkynes. 10 Scaffold modifications include the use of intermolecular and intramolecular electrophiles and variations in the nature of the second (dihalide) ring closure. The iterative use of halocyclisation further extends the range heteroacene scaffolds that can be accessed. The methods are also applicable to the generation of more substituted systems for further library diversification and/or lead optimisation. The polynucleotide-biased fragment library of scaffolds generated in the present disclosure has proven useful in identifying novel TOP1 inhibitors that target the TOP1cc and may be further useful for additional target and phenotypic screening. The present disclosure also includes the following numbered items: 1. A collection of polycyclic compounds and/or salts thereof, for screening against a polynucleotide target, the collection comprising a plurality of polycyclic compounds which comprise at least 4 fused rings and have the formula A-Het-Cyc-B or A-Het1-Cyc-Het2-B wherein A-Het-Cyc-B is selected from the group consisting of: wherein A is a 5-10-membered carbocyclic or heterocyclic aromatic group; B is a 5-10-membered carbocycle or heterocyclic aromatic group; X is O, S, NH, NC 1-4 alkyl, -CH=N-, -N=N- or -C(O)O-; Y is NR, -C(O)NR-, -NRC(O)-, -OCH 2 -, -C(C(O)OC 1-4 alkyl)-, -C(C(O)N(C 1-4 alkyl) 2 )- or -OC(O)-; and R is H or C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2; and wherein A-Het1-Cyc-Het2-B is selected from the group consisting of: wherein A is a 5-10-membered carbocyclic or heterocyclic aromatic group; B is a 5-10-membered carbocycle or heterocyclic aromatic group; X is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^ is O, S, NH, NC 1-4 alkyl, -N=CH-, -N=N- or -OC(O)-; Y is NR, -C(O)NR-, -NRC(O)-; and R is H or C 1- 4 alkyl, said C 1-4 alkyl being optionally substituted by NH 2 , NHC 1-4 alkyl or N(C 1-4 alkyl) 2 . 2. The collection of polycyclic compounds and/or salts according to item 1, wherein the collection contains compounds from one or more of formulae a) to u), and/or salts thereof: a) ; wherein A1 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B1 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 1 is O, S, NH or NC1-4alkyl; and R 1 is hydrogen or C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2; wherein A2 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B2 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 2 is O, S, NH or NC 1-4 alkyl; and R 2 is hydrogen or C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C 1-4 alkyl) 2 ; wherein A3 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B3 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 3 is O, S, NH or NC1-4alkyl; and R 3 is hydrogen or C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2; d) ; wherein A4 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B4 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 4 is O, S, NH or NC 1-4 alkyl; and R 4 is hydrogen or C 1-4 alkyl, said C 1-4 alkyl being optionally substituted by NH 2 , NHC 1- 4 alkyl or N(C 1-4 alkyl) 2 ; e) ; wherein A5 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B5 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 5 is O, S, NH or NC 1-4 alkyl; and R 5 is hydrogen or C 1-4 alkyl, said C 1-4 alkyl being optionally substituted by NH 2 , NHC 1- 4 alkyl or N(C 1-4 alkyl) 2 ; wherein A6 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B6 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R 6 is hydrogen or C1- 4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2; wherein A7 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B7 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R 7 is hydrogen or C1- 4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2; h) ; wherein A8 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B8 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R 8 is hydrogen or C1- 4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2; i) ; wherein A9 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B9 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R 9 is hydrogen or C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2; wherein A10 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B10 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R 10 is hydrogen or C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2; wherein A11 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and B11 is a 5-10 membered carbocyclic or heterocyclic aromatic group; wherein A12 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and B12 is a 5-10 membered carbocyclic or heterocyclic aromatic group; m) wherein A13 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and B13 is a 5-10 membered carbocyclic or heterocyclic aromatic group; n) ; wherein A14 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B14 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and Y 14 is OC 1-4 alkyl or N(C 1-4 alkyl) 2 ; o) ; wherein A15 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B15 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R 15 is hydrogen or C 1-4 alkyl, said C 1-4 alkyl being optionally substituted by NH 2 , NHC 1-4 alkyl or N(C 1-4 alkyl) 2 ; p) ; wherein A16 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B16 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 16 is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^ 16 is O, S, NH, NC1-4alkyl, -N=CH-, -N=N- or -OC(O)-; and R 16 is hydrogen or C 1-4 alkyl, said C 1-4 alkyl being optionally substituted by NH 2 , NHC 1- 4 alkyl or N(C 1-4 alkyl) 2 ; q) ; wherein A17 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B17 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 17 is O, S, NH, NC 1-4 alkyl, -CH=N-, -N=N- or -C(O)O-; X ^ 17 is O, S, NH, NC 1-4 alkyl, -N=CH-, -N=N- or -OC(O)-; and R 17 is hydrogen or C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1- 4alkyl or N(C1-4alkyl)2; r) ; wherein A18 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B18 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 18 is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^ 18 is O, S, NH, NC1-4alkyl, -N=CH-, -N=N- or -OC(O)-; and R 18 is hydrogen or C 1-4 alkyl, said C 1-4 alkyl being optionally substituted by NH 2 , NHC 1- 4 alkyl or N(C 1-4 alkyl) 2 ; s) ; wherein A19 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B19 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 19 is O, S, NH, NC 1-4 alkyl, -CH=N-, -N=N- or -C(O)O-; X ^ 19 is O, S, NH, NC 1-4 alkyl, -N=CH-, -N=N- or -OC(O)-; and R 19 is hydrogen or C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1- 4alkyl or N(C1-4alkyl)2; t) ; wherein A20 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B20 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 20 is O, S, NH, NC 1-4 alkyl, -CH=N-, -N=N- or -C(O)O-; X ^ 20 is O, S, NH, NC 1-4 alkyl, -N=CH-, -N=N- or -OC(O)-; and R 20 is hydrogen or C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1- 4alkyl or N(C1-4alkyl)2; or wherein A21 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B21 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 21 is O, S, NH, NC 1-4 alkyl, -CH=N-, -N=N- or -C(O)O-; X ^ 21 is O, S, NH, NC 1-4 alkyl, -N=CH-, -N=N- or -OC(O)-; and R 21 is hydrogen or C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1- 4alkyl or N(C1-4alkyl)2. 3. The collection of polycyclic compounds and/or salts according to item 2, wherein A1-A21 are each independently selected from the group consisting of phenyl, thiophene, pyridine and benzothiophene. 4. The collection of polycyclic compounds and/or salts according to item 3, wherein A1-A21 are each independently selected from the group consisting of phenyl and benzothiophene. 5. The collection of polycyclic compounds and/or salts according to any of items 2 to 4, wherein B1-B21 are each independently selected from the group consisting of phenyl, thiophene and pyridine. 6. The collection of polycyclic compounds and/or salts according to item 5, wherein B1-B21 are each independently selected from the group consisting of phenyl and thiophene. 7. The collection of polycyclic compounds and/or salts according to any of items 2 to 6, wherein X 1 -X 5 and X 16 -X 21 are each independently selected from O and S. 8. The collection of polycyclic compounds and/or salts according to any of items 2 to 7, wherein R 1 -R 21 are each C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1- 4alkyl)2. 9. The collection of polycyclic compounds and/or salts according to any of items 2 to 8, wherein R 1 -R 21 are each C1-4alkyl substituted by N(C1-4alkyl)2. 10. The collection of polycyclic compounds and/or salts according to any of items 2 to 9, wherein the collection contains one or more compounds of the formula p) and/or salts thereof, and wherein A16 is different from B16 and/or X 16 is different from X ^ 16 . 11. The collection as claimed according to any of items 1 to 10, wherein the collection comprises: at least 10 compounds and/or salts as defined in any of items 1 to 10, optionally at least 100 compounds and/or salts as defined in any of items 1 to 10, optionally at least 250 compounds and/or salts as defined in any of claims 1 to 10, optionally at least 500 compounds and/or salts as defined in any of items 1 to 10, or optionally at least 1000 compounds and/or salts as defined in any of items 1 to 10. 12. A polycyclic compound or salt thereof, wherein the polycyclic compound comprises at least 4 fused rings and has the formula A-Het-Cyc-B or A-Het1-Cyc-Het2-B wherein A-Het-Cyc-B is selected from the group consisting of: , , and ; wherein A is a 5-10-membered carbocyclic or heterocyclic aromatic group; B is a 5-10-membered carbocycle or heterocyclic aromatic group; X is O, S, NH, NC 1-4 alkyl, -CH=N-, -N=N- or -C(O)O-; Y is NR, -C(O)NR-, -NRC(O)-, -OCH 2 -, -C(C(O)OC 1-4 alkyl)-, -C(C(O)N(C 1-4 alkyl) 2 )- or -OC(O)-; and R is H or C 1-4 alkyl, said C 1-4 alkyl being optionally substituted by NH 2 , NHC 1-4 alkyl or N(C 1-4 alkyl) 2 ; and wherein A-Het1-Cyc-Het2-B is selected from the group consisting of: wherein A is a 5-10-membered carbocyclic or heterocyclic aromatic group; B is a 5-10-membered carbocycle or heterocyclic aromatic group; X is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^ is O, S, NH, NC1-4alkyl, -N=CH-, -N=N- or -OC(O)-; Y is NR, -C(O)NR-, -NRC(O)-; and R is H or C1- 4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2; 13. The polycyclic compound or salt according to item 12, wherein the compound is selected from compounds having one of the following formulae: wherein A1 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B1 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 1 is O, S, NH or NC1-4alkyl; and R 1 is hydrogen or C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2; wherein A2 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B2 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 2 is O, S, NH or NC 1-4 alkyl; and R 2 is hydrogen or C 1-4 alkyl, said C 1-4 alkyl being optionally substituted by NH 2 , NHC 1-4 alkyl or N(C 1-4 alkyl) 2 ; wherein A3 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B3 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 3 is O, S, NH or NC1-4alkyl; and R 3 is hydrogen or C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2; d) ; wherein A4 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B4 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 4 is O, S, NH or NC 1-4 alkyl; and R 4 is hydrogen or C 1-4 alkyl, said C 1-4 alkyl being optionally substituted by NH 2 , NHC 1- 4 alkyl or N(C 1-4 alkyl) 2 ; e) ; wherein A5 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B5 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 5 is O, S, NH or NC 1-4 alkyl; and R 5 is hydrogen or C 1-4 alkyl, said C 1-4 alkyl being optionally substituted by NH 2 , NHC 1- 4 alkyl or N(C 1-4 alkyl) 2 ; wherein A6 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B6 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R 6 is hydrogen or C1- 4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2; wherein A7 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B7 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R 7 is hydrogen or C1- 4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2; h) ; wherein A8 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B8 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R 8 is hydrogen or C1- 4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2; i) ; wherein A9 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B9 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R 9 is hydrogen or C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2; wherein A10 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B10 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R 10 is hydrogen or C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1-4alkyl)2; wherein A11 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and B11 is a 5-10 membered carbocyclic or heterocyclic aromatic group; wherein A12 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and B12 is a 5-10 membered carbocyclic or heterocyclic aromatic group; m) wherein A13 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and B13 is a 5-10 membered carbocyclic or heterocyclic aromatic group; n) ; wherein A14 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B14 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and Y 14 is OC 1-4 alkyl or N(C 1-4 alkyl) 2 ; or o) ; wherein A15 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B15 is a 5-10 membered carbocyclic or heterocyclic aromatic group; and R 15 is hydrogen or C 1-4 alkyl, said C 1-4 alkyl being optionally substituted by NH 2 , NHC 1-4 alkyl or N(C 1-4 alkyl) 2 ; p) ; wherein A16 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B16 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 16 is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^ 16 is O, S, NH, NC1-4alkyl, -N=CH-, -N=N- or -OC(O)-; and R 16 is hydrogen or C 1-4 alkyl, said C 1-4 alkyl being optionally substituted by NH 2 , NHC 1- 4 alkyl or N(C 1-4 alkyl) 2 ; ; wherein A17 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B17 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 17 is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^ 17 is O, S, NH, NC1-4alkyl, -N=CH-, -N=N- or -OC(O)-; and R 17 is hydrogen or C 1-4 alkyl, said C 1-4 alkyl being optionally substituted by NH 2 , NHC 1- 4 alkyl or N(C 1-4 alkyl) 2 ; wherein A18 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B18 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 18 is O, S, NH, NC 1-4 alkyl, -CH=N-, -N=N- or -C(O)O-; X ^ 18 is O, S, NH, NC 1-4 alkyl, -N=CH-, -N=N- or -OC(O)-; and R 18 is hydrogen or C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1- 4alkyl)2; s) ; wherein A19 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B19 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 19 is O, S, NH, NC1-4alkyl, -CH=N-, -N=N- or -C(O)O-; X ^ 19 is O, S, NH, NC1-4alkyl, -N=CH-, -N=N- or -OC(O)-; and R 19 is hydrogen or C 1-4 alkyl, said C 1-4 alkyl being optionally substituted by NH 2 , NHC 1- 4 alkyl or N(C 1-4 alkyl) 2 ; wherein A20 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B20 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 20 is O, S, NH, NC 1-4 alkyl, -CH=N-, -N=N- or -C(O)O-; X ^ 20 is O, S, NH, NC 1-4 alkyl, -N=CH-, -N=N- or -OC(O)-; and R 20 is hydrogen or C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1-4alkyl or N(C1- 4alkyl)2; or u) ; wherein A21 is a 5-10 membered carbocyclic or heterocyclic aromatic group; B21 is a 5-10 membered carbocyclic or heterocyclic aromatic group; X 21 is O, S, NH, NC 1-4 alkyl, -CH=N-, -N=N- or -C(O)O-; X ^ 21 is O, S, NH, NC 1-4 alkyl, -N=CH-, -N=N- or -OC(O)-; and R 21 is hydrogen or C1-4alkyl, said C1-4 alkyl being optionally substituted by NH2, NHC1- 4alkyl or N(C1-4alkyl)2. 14. The polycyclic compound or salt according to item 13, wherein A1-A21 are each independently selected from the group consisting of phenyl, thiophene, pyridine and benzothiophene. 15. The polycyclic compound or salt according to item 14, wherein A1-A21 are each independently selected from the group consisting of phenyl and benzothiophene. 16. The polycyclic compound or salt according to any of items 13 to 15, wherein B1-B21 are each independently selected from the group consisting of phenyl, thiophene and pyridine. 17. The polycyclic compound or salt according to item 16, wherein B1-B21 are each independently selected from the group consisting of phenyl and thiophene. 18. The polycyclic compound or salt according to any of items 13 to 17, wherein X 1 -X 5 and X 16 - X 21 are each independently selected from O and S. 19. The polycyclic compound or salt according to any of items 13 to 18, wherein R 1 -R 21 are each C 1-4 alkyl, said C 1-4 alkyl being optionally substituted by NH 2 , NHC 1-4 alkyl or N(C 1-4 alkyl) 2 . 20. The polycyclic compound or salt according to item 19, wherein R 1 -R 21 are each C 1-4 alkyl substituted by N(C 1-4 alkyl) 2 . 21. The polycyclic compound or salt according to any of items 13 to 20, wherein the compound is of the formula p), and wherein A16 is different from B16 and/or X 16 is different from X ^ 16 . 22. A method of synthesising a polycyclic compound of formula a), as defined in any of items 13 to 20, comprising: reacting a compound of formula wherein A1, B1 and X 1 are as defined in any of claims 13 to 20, Hal 1 is halogen; and Hal 2 is halogen; with a compound of formula R 1 -NH2 in the presence of a copper catalyst, wherein R 1 is as defined in any of items 13 to 20; and optionally forming a salt of the compound. 23. The method according to item 22, wherein the compound of formula , 22, and X 1a is OC1- 4alkyl, SC1-4alkyl, NH2, NHC1-4alkyl or N(C1-4alkyl)2; to a halocyclization reaction. 24. A method of synthesising a polycyclic compound of formula b), or salt thereof, as defined in any of items 13 to 20, comprising: i) reacting a compound of formula wherein A2, B2 and X 2 are as defined in any of items 13 to 20, Hal 1 is halogen; and Hal 2 is halogen; with a compound of formula R 2 -NH2 in the presence of a palladium catalyst and carbon monoxide, wherein R 2 is as defined in any of items 13 to 20; and if the product of step i) is a compound of formula rather than a compound of formula b), ii) contacting the product of step i) with a copper or palladium catalyst to form the compound of formula b); and optionally forming a salt of the compound. 25. The method according to item 24, wherein the compound of formula , are as 4alkyl, SC1-4alkyl, NH2, NHC1-4alkyl or N(C1-4alkyl)2; to a halocyclization reaction. 26. A method of synthesising a polycyclic compound of formula c), or salt thereof, as defined in any of items 13 to 20, comprising: i) reacting a compound of formula wherein A3, B3 and X 3 are as defined in any of items 13 to 20, Hal 1 is halogen; and Hal 2 is halogen; with a compound of formula R 3 -NH 2 in the presence of a palladium catalyst and carbon monoxide, wherein R 3 is as defined in any of items 13 to 20; and if the product of step i) is a compound of formula rather than a compound of formula c), ii) contacting the product of step i) with a copper or palladium catalyst to form the compound of formula c); and optionally forming a salt of the compound. 27. The method according to item 26, wherein the compound of formula , 4alkyl, SC1-4alkyl, NH2, NHC1-4alkyl or N(C1-4alkyl)2; to a halocyclization reaction. 28. A method of synthesising a polycyclic compound of formula d), or salt thereof, as defined in any of items 13 to 20, comprising: reacting a compound of formula wherein A4, B4 and X 4 are as defined in any of items 13 to 20, Hal 1 is halogen; and Hal 2 is halogen; with a compound of formula R 4 -NH2 in the presence of a copper catalyst, wherein R 4 is as defined in any of items 13 to 20; and optionally forming a salt of the compound. 29. The method according to item 28, wherein the compound of formula , wherein A4, B4, Hal 2 are as defined in item 28, and X 4a is OC 1- 4alkyl, SC1-4alkyl, NH2, NHC1-4alkyl or N(C1-4alkyl)2; to a halocyclization reaction. 30. A method of synthesising a polycyclic compound of formula e), or salt thereof, as defined in any of items 13 to 20, comprising: reacting a compound of formula wherein A5, B5 and X 5 are as defined in any of items 13 to 20, Hal 1 is halogen; and Hal 2 is halogen; with a compound of formula R 5 NH2 in the presence of a copper catalyst, wherein R 5 is as defined in any of items 13 to 20; and optionally forming a salt of the compound. 31. The method according to item 30, wherein the compound of formula produced by subjecting a compound of formula , wherein A5, B5 and Hal 2 are as defined in item 30, and X 5a is OC1- 4 alkyl, SC 1-4 alkyl, NH 2 , NHC 1-4 alkyl or N(C 1-4 alkyl) 2 ; to a halocyclization reaction. 32. A method of synthesising a polycyclic compound of formula f), or salt thereof, as defined in any of items 13 to 20, comprising: reacting a compound of formula wherein A6, B6 and X 6 are as defined in any of items 13 to 20, Hal 1 is halogen; and Hal 2 is halogen; with a compound of formula R 6 NH 2 in the presence of a copper catalyst, wherein R 6 is as defined in any of items 13 to 20; and optionally forming a salt of the compound. 33. The method according to item 32, wherein the compound of formula is produced by subjecting a compound of formula , wherein A6, B6 and Hal 2 are as defined in item 32, and R X is OC1-4alkyl or C1-4alkyl; to a halocyclization reaction. 34. A method of synthesising a polycyclic compound of formula g), or salt thereof, as defined in any of items 13 to 20, comprising: i) reacting a compound of formula wherein A7 and B7 are as defined in any of items 13 to 20, Hal 1 is halogen; and Hal 2 is halogen; with a compound of formula R 7 -NH 2 in the presence of a palladium catalyst and carbon monoxide, wherein R 7 is as defined in any of items 13 to 20; and if the product of step i) is a compound of formula rather than a compound of formula g), ii) contacting the product of step i) with a copper or palladium catalyst to form the compound of formula g); and optionally forming a salt of the compound. , are as or C 1-4 alkyl; to a halocyclization reaction. 36. A method of synthesising a polycyclic compound of formula h), or salt thereof, as defined in any of items 13 to 20, comprising: i) reacting a compound of formula wherein A8 and B8 are as defined in any of items 13 to 20, Hal 1 is halogen; and Hal 2 is halogen; with a compound of formula R 8 -NH 2 in the presence of a palladium catalyst and carbon monoxide, wherein R 8 is as defined in any of items 13 to 20; and if the product of step i) is a compound of formula rather than a compound of formula h), ii) contacting the product of step i) with a copper or palladium catalyst to form the compound of formula h); and optionally forming a salt of the compound. The method according to item 36, wherein the compound of formula is produced by subjecting a compound of formula , wherein A8, B8 and Hal 2 are as defined in item 36, and R X is OC1-4alkyl or C1-4alkyl; to a halocyclization reaction. 38. A method of synthesising a polycyclic compound of formula i) or salt thereof, as defined in any of items 13 to 20, comprising: reacting a compound of formula wherein A9 and B9 are as defined in any of items 13 to 20, Hal 1 is halogen; and Hal 2 is halogen; with a compound of formula R 9 NH2 in the presence of a copper catalyst, wherein R 9 is as defined in any of items 13 to 20; and optionally forming a salt of the compound. 39. The method according to item 38, wherein the compound of formula , reagent, and then contacting the resulting product with a halide source. 40. A method of synthesising a polycyclic compound of formula j), or salt thereof, as defined in any of items 13 to 20, comprising: i) reacting a compound of formula wherein A10 and B10 are as defined in any of items 13 to 20, Hal 1 is halogen; and Hal 2 is halogen; with a compound of formula R 10 -NH 2 in the presence of a palladium catalyst and carbon monoxide, wherein R 10 is as defined in any of items 13 to 20; and if the product of step i) is a compound of formula rather than a compound of formula j), ii) contacting the product of step i) with a copper or palladium catalyst to form the compound of formula j); and optionally forming a salt of the compound. 41. The method according to item 40, wherein the compound of formula , dehydrating reagent, and then contacting the resulting product with a halide source. 42. A method of synthesising a polycyclic compound of formula k), or salt thereof, as defined in any of items 13 to 20, comprising: reacting a compound of formula wherein A11 and B11 are as defined in any of items 13 to 20, and wherein each R 11 is independently C1-4alkyl; with a dehydrating reagent, and then contacting the resulting product with an acid, thereby forming the compound of formula k); and optionally forming a salt of the compound. 43. A method of synthesising a polycyclic compound or salt of formula l) as defined in any of items 13 to 20, comprising: contacting a compound of formula wherein A12 and B12 are as defined in any of items 13 to 20, each R a is independently C1-4alkyl, or both R a groups together with their connecting nitrogen form a pyrrolidine, piperidine or homopiperidine group, and X ^ is OC 1-4 alkyl, NH 2 , NHC 1-4 alkyl or N(C 1-4 alkyl) 2 ; with an acid, thereby forming the compound of formula l); and optionally forming a salt of the compound. 44. A method of synthesising a polycyclic compound of formula m), or salt thereof, as defined in any of items 13 to 20, comprising: contacting a compound of formula wherein A13 and B13 are as defined in any of items 13 to 20, each R a is independently C1-4alkyl, or both R a groups together with their connecting nitrogen form a pyrrolidine, piperidine or homopiperidine group; with an acid, thereby forming the compound of formula m); and optionally forming a salt of the compound. 45. A method of synthesizing a polycyclic compound of formula n), or salt thereof, as defined in any of items 13 to 20, comprising: contacting a compound of formula wherein A14, B14 and Y 14 are as defined in any of items 13 to 20, and each R a is independently C1-4alkyl, or both R a groups together with their connecting nitrogen form a pyrrolidine, piperidine or homopiperidine group; with an acid, thereby forming the compound of formula n); and optionally forming a salt of the compound. 46. A method of synthesizing a compound of formula o), or salt thereof, as defined in any of items 13 to 20, comprising: reacting a compound of formula wherein A15 and B15 are as defined in any of items 13 to 20, Hal 1 is halogen, and R b is C1- 4alkyl; with R 15 NH2, wherein R 15 is as defined in any of items 13 to 20, thereby forming the compound of formula o); and optionally forming a salt of the compound. 47. The method according to item 46, wherein the compound of formula is produced by contacting a compound of formula wherein A15, B15 and R b are as defined in any of items 13 to 20, and each R a is independently C1-4alkyl, or both R a groups together with their connecting nitrogen form a pyrrolidine, piperidine or homopiperidine group; with an acid and a halide source. 48. A method of identifying a compound having activity against a polynucleotide target or a polynucleotide-protein complex target, comprising: testing a collection of compounds as defined in any of items 1 to 11 or part thereof, or testing one or more compounds as defined in any of items 12 to 21 for activity against a polynucleotide target; and identifying whether the compound or compounds have activity against the polynucleotide target. 49. The method as according to item 48, wherein the polynucleotide target is an RNA target, optionally an mRNA target, micro-RNA or a non-coding RNA target. 50. The method according to item 49, wherein the polynucleotide target is a DNA target. 51. The method according to any of items 48 to 50, wherein the polynucleotide target is a polynucleotide-protein complex or a functional DNA topology. 52. The method according to any of items 48 to 51, wherein the polynucleotide target is a DNA complex with a transcription factor, an epigenetic modulator, an RNA-polymerase complex, Z-DNA, or a G-quadruplex. 53. The method according to any of items 48 to 52, wherein the polynucleotide target is selected from the group consisting of DNA-topoisomerase 1, mRNA encoding SMN2 protein, and G-quadruplex mRNA encoding oncogenic N-Ras protein. 54. The method according to any of items 48 to 53, wherein the compound is tested for activity using an assay selected from the group consisting of a radiolabelled DNA-cleavage assay, a cell cytoxicity assay, and an affinity assay for polynucleotides and their protein complexes by one or more of surface plasmon resonance assay, fluorometric assay, nuclear magnetic resonance assay and thermal shift assay. 55. Use of a compound as defined in any of items 13 to 21 as a reference compound in a competition assay for determining activity of a test compound against a polynucleotide target. 56. Use of a compound according to item 55, wherein a radiolabelled form of the compound as defined in any of items 13 to 21 is used in the assay. 57. A phenotypic method of identifying a new polynucleotide target for therapy of a disease or disorder, comprising contacting a collection of compounds as defined in any of items 1 to 11 or part thereof, or contacting one or more compounds as defined in any of items 13 to 21 with a cell, tissue or animal disease model and monitoring for a change associated with a disease or disorder; and if a change associated with the disease or disorder is identified, determining the biological target to which the compound binds. 58. The phenotypic method according to item 57, wherein the compound is contacted with a cell. 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