Patent ID: 11896589
Assignee: MYCURAL THERAPEUTICS AB
Field: Pharmaceuticals (Chemistry)
Classification: CPC A  C | IPC A  C

Claim 0:
1. A method of treating a cancer characterised by increased MYC activity comprising administering to a patient in need thereof a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt and/or detectably labelled derivative thereof, wherein the compound is represented by formula I:, , wherein:
R1 represents aryl optionally substituted by one or more groups independently selected from G1c, and heteroaryl optionally substituted by one or more groups independently selected from G1d;
R2 and R3 each represent H;
m represents 0, 1, 2, 3 or 4;
n represents 0, 1, 2 or 3;
each X independently represents —OR12 or H;
each Y independently represents halo, Ra3, —CN, -Aa2-C(O)Rb3, -Ab2-C(O)N(Rc3)Rd3, -Ac2-C(O)ORe3, -Ad2-S(O)pRf3, -Ae2-S(O)pN(Rg3)Rh3, -Af2-S(O)pORi3, —N(Rj3)Rk3, —ORl3 or —SRm3;
each Aa2, Ab2, Ac2, Ad2, Ae2, and Af2 independently represents a single bond, —N(Rn3)— or —O—;
each G1c and G1d independently represents halo, Ra4, —CN, -Aa3-C(Qa2)Rb4, -Ab3-C(Qb2)N(Rc4)Rd4, -Ac3-C(Qc2)ORe4, -Ad3-S(O)pRf4, -Ae3-S(O)pN(Rg4)Rh4, -Af3-S(O)pORi4, —N3, —N(Rj4)Rk4, —N(H)CN, —NO2, —ONO2, —ORl4, —SRm4—B(ORn4)2, —P(O)(N(Ro4)Rp4)2, —P(O)(N(Ro4)Rp4)(ORq4), —P(O)(ORr4)2, or =Qd2;
each Aa3, Ab3, Ac3, Ad3, Ae3, and Af3 independently represents a single bond, —C(O)N(Rs4)—, —N(Rt4)— or —O—;
each Qa2, Qb2, Qc2, and Qd2 independently represents ═O, ═S, ═C(H)NO2, ═N(CN), ═NRu4, ═NN(Rv4)Rw4, ═N(ORx4), or ═NS(O)pN(Rv4)Rw4;
each R12 independently represents H, C1-12 alkyl, C2-12 alkenyl or C2-12 alkynyl each optionally substituted by one or more groups independently selected from G3a and heterocyclyl optionally substituted by one or more groups independently selected from G3b;
each Ra3 and Rf3 independently represents C1-6 alkyl optionally substituted by one or more F;
each Rb3, Rc3, Rd3, Re3, Rg3, Rh3, Ri3, Rj3, Rk3, Rl3, Rm3 and Rn3 independently represents H or C1-6 alkyl optionally substituted by one or more F, or alternatively
any of Rc3 and Rcd, Rfg and Rh3 and/or Rj3 and Rk3, are linked together to form, together with the nitrogen atom to which they are attached, a 3- to 6-membered ring, which ring optionally contains one further heteroatom and which ring optionally is substituted by one or more groups independently selected from F, C1-3 alkyl optionally substituted by one or more F, and ═O;
each Ra4 and Rf4 independently represents C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl each optionally substituted by one or more groups independently selected from G4a, heterocyclyl optionally substituted by one or more groups independently selected from G4b, aryl optionally substituted by one or more groups independently selected from G4, and heteroaryl optionally substituted by one or more groups independently selected from G4d;
each Rb4, Rc4, Rd4, Re4, Rg4, Rh4, Ri4, Rj4, Rk4, Rl4, Rm4, Rn4, Ro4, Rp4, Rq4, Rr4, Rs4, Rt4, Ru4, Rv4, Rw4 and Rx4 independently represents H or C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl each optionally substituted by one or more groups independently selected from G4a, heterocyclyl optionally substituted by one or more groups independently selected from G4b, aryl optionally substituted by one or more groups independently selected from G4c, and heteroaryl optionally substituted by one or more groups independently selected from G4d, or alternatively
any of Rc4 and Rd4, Rg4 and Rh4, Rj4 and Rk4, Ro4 and Rp4 and/or Rv4 and Rw4 are linked together to form, together with the nitrogen atom to which they are attached, a 3- to 6-membered ring, which ring optionally contains one further heteroatom and which ring optionally is substituted by one or more groups independently selected from halo, C1-3 alkyl, C2-3 alkenyl and C2-3 alkynyl each optionally substituted by one or more halo, and ═O, or alternatively
two Rn4 are linked together to form, along with the boron, and the oxygen atoms to which they are attached, a 5- to 8-membered heterocyclic ring, which ring optionally contains one or more further heteroatoms and which ring optionally is substituted by one or more groups independently selected from halo, C1-3alkyl optionally substituted by one or more halo, and ═O, or alternatively
two Rr4 are linked together to form, along with the phosphorus, and the oxygen atoms to which they are attached, a 5- to 8-membered heterocyclic ring, which ring optionally contains one or more further heteroatoms and which ring optionally is substituted by one or more groups independently selected from halo, C1-3 alkyl optionally substituted by one or more halo, and ═O;
each Rv6 and Rx6 idenpendently represents H or C1-6 alkyl optionally substituted by one or more F;
each G3a and G3b independently represents halo, Ra6, -CN, -Aa5-C(Qa4)Rb6, -Ab5-C(Qb4)N(Rc6)Rd6, -Ac5-C(Qc4)ORe6, -Ad5-S(O)pRf6, -Ae5-S(O)pN(Rg6)Rh6, -Af5-S(O)pORi6, -N3, -N(Rk6, -N(H)CN, -NO2, -ONO2, -OR16, -SRm6-B(ORn6)2, -P(O)(N(Ro6)RP6)2, -P(O)(N(Ro6)Rp6)(ORq6), -P(O)(ORr6)2, or =Qd4;
each Aa5, Ab5, Ac5, Ad5, Ae5, and Af5 independently represents a single bond, -C(O)N(Rs6)-, -N(Rt6)—or -O-;
each Qa4, Qb4, Qc4, and Qd4 independently represents =0, =S, =C(H)NO2, =N(CN), =NRu6, =NN(Rv6)Rw6, =N(ORx6), or =NS(O)pN(Rv6)Rw6;
each Rv6 and Rx6 independently represents H or C1-6 alkyl optionally substituted by one or more F;
each Ra6 and Rf6 independently represents C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, each optionally substituted by one or more groups independently selected from G5a, heterocyclyl optionally subtituted by one or more groups independently selected from G5b, aryl optionally substituted by one or more groups independently selected from G5c, and heteroaryl optionally substituted by one or more groups independently selected from G5d;
each Rb6, Rc6, Rd6, Re6, Rg6, Rh6, Ri6, Rj6, Rk6, Rl6, Rm6, Rn6, Ro6, Rp6, Rq6, Rr6, Rs6, Rt6, Ru6, Rv6, Rw6 and Rx6, independently represents H or independently represents C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, each optionally substituted by one or more groups independently selected from G5a, heterocyclyl optionally substituted by one or more groups independently selected from G5b, aryl optionally substituted by one or more groups independently selected from G5c, and heteroaryl optionally substituted by one or more groups independently selected from G5d, or alternatively any of Rc6 and Rd6, Rg6 and Rh6, Rj6 and Rk6, Ro6 and Rp6 and/or Rv6 and Rw6, are linked together to form, together with the nitrogen atom to which they are attached, a 3- to 6-membered ring, which ring optionally contains one further heteroatom and which ring optionally is substituted by one or more groups independently selected from F, C1-3 alkyl optionally substituted by one or more F, and ═O;
each G4a, G4b, G4c and G4d independently represents halo, Ra7, —CN, -Aa6-C(Qa5)Rb7, -Ab6-C(Qb5)N(Rc7)Rd7, -Ac6-C(Qc5)ORe7, -Ad6-S(O)pRf7, -Ae6-S(O)pN(Rg7)Rh7, -Af6-S(O)pORi7, —N3, —N(Rj7)Rk7, —N(H)CN, —NO2, —ONO2, —ORl7, —SRm7—B(ORn7)2, —P(O)(N(Ro7)Rp7)2, —P(O)(N(Ro7)Rp7)(ORq7) —P(O)(ORr7)2 or =Qd5;
each Aa6, Ab6, Ac6, Ad6, Ae5, and Af6 independently represents a single bond, —C(O)N(Rs7)—, —N(Rt7) or —O—;
each Qa5, Qb5, Qc5, and Qd5 independently represents ═O, ═S, ═C(H)NO2, ═N(CN), ═NRu7, ═NN(Rv7)Rw7 or ═N(ORx7), or ═NS(O)pN(Rv7)Rw7;
each Ra7 and Rf7 independently represents C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, each optionally substituted by one or more groups independently selected from G6a, heterocyclyl optionally substituted by one or more groups independently selected from G6b, aryl optionally substituted by one or more groups independently selected from G6c, and heteroaryl optionally substituted by one or more groups independently selected from G6d;
each Rb7, Rc7, Rd7, Re7, Rg7, Rh7, Ri7, Rj7, Rk7, Rl7, Rm7, Rn7, Ro7, Rp7, Rq7, Rr7, Rs7, Rt7, Ru7, Rv7, Rw7 and and Rx7 independently represents H or C1-6 alkyl, C2-6 alkenyl or C2-6, alkynyl, each optionally substituted by one or more groups independently selected from G6a, heterocyclyl optionally substituted by one or more groups independently selected from G6b, aryl optionally substituted by one or more groups independently selected from G6C, and heteroaryl optionally substituted by one or more groups independently selected from G6d, or alternatively
any of Rc7 and Rd7, Rg7 and , Rh7, Rj7 and Rk7, Rn7 and Ro7 and/or Rv7, Rw7, are linked together to form, together with the nitrogen atom to which they are attached, a 3- to 6-membered ring, which ring optionally contains one further heteroatom and which ring optionally is substituted by one or more groups independently selected from F, C1-3 alkyl optionally substituted by one or more F, and ═O;
each G5a, G5b, G5c and G5d independently represents halo, Ra8, —CN, -Aa7-C(Qa6)Rb8, -Ab7-C(Qb6)N(Rc8)Rd8, -Ac7-C(Qc6)ORe8, -Ad7-S(O)pRf8, -Ae7-S(O)pN(Rg8)Rh8, -Af7-S(O)pORi8, —N3, —N(Rj8)Rk8, —N(H)CN, —NO2, —ONO2, —ORl8, —SRm8—B(ORn8)2, —P(O)(N(Ro8)Rp8)2, —P(O)(N(Ro8)Rp8)(ORq8) —P(O)(ORr8)2 or =Qd6;
each Aa7, Ab7, Ac7, Ad7, Ae7, and to Af7 independently represents a single bond, —C(O)N(Rs8)—, —N(Rt8)— or —O—;
each Qa6, Qb6, Qc6, and Qd6 independently represents ═O, ═S, ═C(H)NO2, ═N(CN), ═NRu8, ═NN(Rv8)Rw8, ═N(ORx8), or ═NS(O)pN(Rv8)Rw8;
each G6a, G6b, G6c and G6d independently represents halo, Ra9, —CN, -Aa8-C(Qa7)Rb9, -Ab8-C(Qb7)N(Rc9)Rd9, -Ac8-C(Qc7)ORe9, -Ad8-S(O)pRf9, -Ae8-S(O)pN(Rg9)Rh9, -Af8-S(O)pORi9, —N3, —N(Rj9)Rk9, —N(H)CN, —NO2, —ONO2, —ORl9, —SRm9—B(ORn9)2, —P(O)(N(Ro9)Rp9)2, —P(O)(N(Ro9)Rp9)(ORq9) or —P(O)(ORr9)2 or =Qd7;
each Aa8, Ab8, Ac8, Ad8, Ae8, and Af8 independently represents a single bond, —C(O)N(Rs9)—, —N(Rt9)— or —O—;
each Qa7, Qb7, Qc7, and Qd7 independently represents ═O, ═S, ═C(H)NO2, ═N(CN), ═NRu9, ═NN(Rv9)Rw9, ═N(ORx9), or ═NS(O)pN(Rv9)Rw9;
each Ra8 and Rf8 independently represents H or C1-6 alkyl optionally substituted by one or more F;
each Rb8, Rc8, Rd8, Re8, Rg8, Rh8, Ri8, Rj8, Rk8, Rl8, Rm8, Rn8, Ro8, Rp8, Rq8, Rr8, Rs8, Rt8, Ru8, Rv8, Rw8 and Rx8 independently represents H or C1-6 alkyl optionally substituted by one or more F, or alternatively
any of Rc8 and Rd8, Rg8 and Rh8, Rj8 and Rk8, Rn8 and Ro8 and/or Rv8 and Rw8, are linked together to form, together with the nitrogen atom to which they are attached, a 3- to 6-membered ring, which ring optionally contains one further heteroatom and which ring optionally is substituted by one or more groups independently selected from F, C1-3 alkyl optionally substituted by one or more F, and ═O;
each Ra9 and Rf9 independently represents H or C1-6 alkyl optionally substituted by one or more F;
each Rb9, Rc9, Rd9, Re9, Rg9, Rh9, Ri9, Rj9, Rk9, Rl9, Rm9, Rn9, Ro9, Rp9, Rq9, Rr9, Rs9, Rt9, Ru9, Rv9, Rw9 and Rx9 independently represents H or C1-6 alkyl optionally substituted by one or more F, or alternatively
any of Rc9 and Rdg, Rg9 and Rh9, Rj9 and Rk9, Rn9 and Ro9 and/or Rv9 and Rw9, are linked together to form, together with the nitrogen atom to which they are attached, a 3- to 6-membered ring, which ring optionally contains one further heteroatom and which ring optionally is substituted by one or more groups independently selected from F, C1-3 alkyl optionally substituted by one or more F, and ═O; and
each p independently represents 1 or 2,
wherein a cancer is characterised by increased MYC activity when:
(1) there is an at least 50% increase in the copy number of a MYC gene in a cancer cell from the patient compared to a corresponding non-cancerous cell from the patient; or
(2) there is an at least 50% increase in MYC mRNA or protein levels in a cancer cell from the patient compared to a corresponding non-cancerous cell from the patient; or
(3) there is an at least 50% increase in activity of a MYC pathway in a cancer cell from the patient compared to a corresponding non-cancerous cell from the patient, and

wherein the cancer characterised by increased MYC activity is selected from Burkitt's lymphoma, ovarian cancer, basel-like breast cancer, esophageal squamous cell carcinoma, colon cancer, endometrial cancer, neuroblastoma, small cell lung carcinoma, medulloblastoma, pancreatic cancer, head and neck cancer, prostate cancer, and hepatocellular carcinomas.