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US 7,745,435 B2Granted
Triheterocyclic compounds and compositions thereof
AssigneeGemix X Pharmaceuticals Canada Inc.
InventorsGiorgio Attardo, Jean-Francois Lavallee, Elise Rioux, Sasmita Tripathy, Terrence W. Doyle
Life of this patent
Estimating the term…
Abstract
The present invention relates to novel Triheterocyclic Compounds, compositions comprising a Triheterocyclic Compound, and methods useful for treating or preventing cancer or a neoplastic disorder comprising administering a Triheterocyclic Compound. The compounds, compositions, and methods of the invention are also useful for inhibiting the growth of a cancer cell or neoplastic cell, treating or preventing a viral infection, or inhibiting the replication and/or infectivity of a virus.
Claims27
A compound of the Formula
- or a pharmaceutically acceptable salt thereof wherein
- Q1 is —N(R1)—;
- Q2 is —C(R3)—;
- Q3 is —C(R5)—;
- Q4 is —C(R9)—;
- R1 is —Ym(Ra), wherein —Ra is —H, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, -phenyl , -naphthyl, -3- to 9-membered heterocycle, —OR14, —O(CH2)OR14, —C(O)R14, —C(O)(CH2)n—R14, —O—C(O)OR14, —O—C(O)NHR14, —O—C(O)N(R14)2, —C(O)NHR14, —S—R14, —SOR14, —S(O)2R14, —NHC(O)R14, —NHSR14, —NHSOR14, —NHS(O)2R14, O—C(S)R14, O—C(S)OR14, O—C(S)NHR14, O—C(S)N(R14)2, —C(S)OR14, —C(S)NHR14, —C(S)N(R14)2, —NHC(S)R14, —NR14C(S)R14, —NHC(S)NHR14, —NHC(S)N(R14)2, —NR14C(S)NHR14, or —NR14C(S)N(R14)2;
- R2 is —H, —C1-C8 alkyl or —OH;
- R3 is —C1-C8 alkyl;
- R4 is —Ym(Rb), wherein Rb is —H, halogen, —NH2, —CN, —NO2, —SH, —N3, —C1-C8 alkyl, —O—(C1-C8 alkyl), —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, -phenyl , -naphthyl, -3- to 9-membered heterocycle, —OR14, —O(CH2)nOR14, —C(O)R14, —O—C(O)R14, —C(O)(CH2)n—R14,—O—C(O)OR14, —O—C(O)NHR14,—O—C(O)N(R14)2, —C(O)N(R14)2, —C(O)OR14, —C(O)NHR14, —S—R14, —SOR14, —S(O)2R14, —NHC(O)R14, —NHSR14, —NHSOR14, —NHS(O)2R14, O—C(S)R14, O—C(S)OR14, O—C(S)NHR14, O—C(S)N(R14)2, —C(S)OR14, —C(S)NHR14, —C(S)N(R14)2, —NHC(S)R14, —NR14C(S)R14, —NHC(S)NHR14, —NHC(S)N(R14)2, —NR14C(S)NHR14, or —NR14C(S)N(R14)2;
- R5 is —C1-C8 alkyl;
- R6 is —H;
- R7 is —Ym—(Rc), wherein —Rc is —C1-C8 alkyl, —O—(C1-C8 alkyl), —O-benzyl, —NH2, —NH(C1-C5 alkyl), —N(C1-C5 alkyl)2, —NH(phenyl), —N(phenyl)2, —NH(naphthyl), —N(naphthyl)2, —CN, —NO2, —N3, —C2-C8 alkynyl, —OR14, —O(CH2)nOR14, —C(O)R14, —O—C(O)R14, —C(O)(CH2)n—R14,—O—C(O)OR14, —O—C(O)NHR14, —O—C(O)N(R14)2, —C(O)N(R14)2, —C(O)OR14, —C(O)NHR14, —S—R14, —SOR14, —S(O)2R14, —NHC(O)R14, —NHSR14, —NHSOR14, —NHS(O)2R14, O—C(S)R14, O—C(S)OR14, O—C(S)NHR14, O—C(S)N(R14)2, —C(S)OR14, —C(S)NHR14, —C(S)N(R14)2, —NHC(S)R14, —NR14C(S)R14, —NHC(S)NHR14, —NHC(S)N(R14)2, —NR14C(S)NHR14, or —NR14C(S)N(R14)2;
- R8 is —Ym(Rd), wherein —Rd is —H, —OH, halogen, amino, —NH(C1-C5 alkyl), —N(C1-C5 alkyl)2, —NH(phenyl), —N(phenyl)2, —NH(naphthyl), —N(naphthyl)2, —CN, —NO2, —N3, —C1-C8 alkyl, —(C1-C8 alkyl)-OH, —O—(C1-C8 alkyl), —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, -phenyl , -naphthyl, -3- to 9-membered heterocycle, —OR14, —O(CH2)nOR14, —C(O)R14, —O—C(O)R14, —C(O)(CH2), —R14,—O—C(O)OR14, —O—C(O)NHR14, —O—C(O)N(R14)2, —C(O)N(R14)2, —C(O)OR14, —C(O)NHR14, —S—R14, —SOR14, —S(O)2R14, —NHC(O)R14, —NHSR14, NHSOR14, —NHS(O)2R14, O—C(S)R14, O—C(S)OR14, O—C(S)NHR14, O—C(S)N(R14)2, —C(S)OR14, —C(S)NHR14, —C(S)N(R14)2, —NHC(S)R14, —NR14C(S)R14, —NHC(S)NHR14, —NHC(S)N(R14)2, —NR14C(S)NHR14, or —NR14C(S)N(R14)2;
- R9 is —Ym(Re), wherein —Re is —H, —NH2, C1-C8 alkyl, —NH(C1-C5 alkyl), —N(C1-C5 alkyl)2, —NH(phenyl), —N(phenyl)2, —NH(naphthyl), —N(naphthyl)2, —C(O)N(C1-C5 alkyl)2, —NHC(O)(C1-C5 alkyl), —NHC(═NH2+)NH2, —CN, —NO2, N3, -3- to 9-membered heterocycle, —OR14, —O(CH2)nOR14, —O—C(O)R14, —C(O)(CH2)n—R14,—O—C(O)OR14, —O—C(O)NHR14, —C(O)N(R14)2, —C(O)NHR14, -S-R14, —SOR14, —S(O)2R14, —NHC(O)R14, —NHSR14, —NHSOR14, —NHS(O)2R14, O—C(S)R14, O—C(S)OR14, O—C(S)NHR14, O—C(S)N(R14)2, —C(S)OR14, —C(S)NHR14, —C(S)N(R14)2, —NHC(S)R14, —NR14C(S)R14, —NHC(S)NHR14, —NHC(S)N(R14)2, —NR14C(S)NHR14, —NR14C(S)N(R14)2;
- R10, R11, R12, and R13 are independently —Ym(Re), wherein —Re is —H, halogen, —NH2, C1-C8 alkyl, —NH(C1-C5 alkyl), —N(C1-C5 alkyl)2, —NH(phenyl), —N(phenyl)2, —NH(naphthyl), —N(naphthyl)2, —C(O)NH(C1-C5 alkyl), —C(O)N(C1-C5 alkyl)2, —NHC(O)(C1-C5 alkyl), —NHC(═NH2+)NH2, —CN, —NO2, N3, -3- to 9-membered heterocycle, —OR14, —O(CH2)nOR14, —C(O)R14, —O—C(O)R14, —C(O)(CH2)n—R14, —O—C(O)OR14, —O—C(O)NHR14, —O—C(O)N(R14)2, —C(O)N(R14)2, —C(O)OR14, —C(O)NHR14, —S—R14, —SOR14, —S(O)2R14, —NHC(O)R14, —NHSR14, —NHSOR14, —NHS(O)2R14, O—C(S)R14, O—C(S)OR14, O—C(S)NHR14, O—C(S)N(R14)2, —C(S)OR14, —C(S)NHR14, —C(S)N(R14)2, —NHC(S)R14, —NR14C(S)R14, —NHC(S)NHR14, —NHC(S)N(R14)2, —NR14C(S)NHR14, —NR14C(S)N(R14)2, with the proviso that neither R10 nor R12 is —OH;
- each R14 is independently —H, —C1-C8 alkyl, —C3-C12 cycloalkyl, -phenyl , -naphthyl, -3- to 9-membered heterocycle, —C2-C8 alkenyl, or —C2-C8 alkynyl;
- each Y is independently —C1-C8 alkylene-, —C2-C8 alkenylene- or —C2-C8 alkynylene-;
- each m is independently 0 or 1;
- and
- each n is independently an integer ranging from 0 to 6.
17 more elements
A composition comprising a pharmaceutically acceptable carrier or vehicle and an effective amount of a compound of the Formula
- or a pharmaceutically acceptable salt thereof wherein
- Q1 is —N(R1)—;
- Q2 is —C(R3)—;
- Q3 is —C(R5)—;
- Q4 is —C(R9)—;
- R1 is —Ym(Ra), wherein —Ra is —H, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, -phenyl , -naphthyl, -3- to 9-membered heterocycle, —OR14, —O(CH2)nOR14, —C(O)R14, —C(O)(CH2)n—R14,—O—C(O)OR14, —O—C(O)NHR14, —O—C(O)N(R14)2, —C(O)NHR14, —S—R14, —SOR14, —S(O)2R14, —NHC(O)R14, —NHSR14, —NHSOR14, —NHS(O)2R14, O—C(S)R14, O—C(S)OR14, O—C(S)NHR14, O—C(S)N(R14)2, —C(S)OR14, —C(S)NHR14, —C(S)N(R14)2, —NHC(S)R14, —NR14C(S)R14, —NHC(S)NHR14, —NHC(S)N(R14)2, —NR14C(S)NHR14, or —NR14C(S)N(R14)2;
- R2 is —H, —C1-C8 alkyl or —OH;
- R3 is —C1-C8 alkyl;
- R4 is —Ym(Rb), wherein Rb is —H, halogen, —NH2, —CN, —NO2, —SH, —N3, —C1-C8 alkyl, —O—(C1-C8 alkyl), —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, -phenyl , -naphthyl, -3- to 9-membered heterocycle, —OR14, —O(CH2)nOR14, —C(O)R14, —O—C(O)R14, —C(O)(CH2)n—R14,—O—C(O)OR14, —O—C(O)NHR14,—O—C(O)N(R14)2, —C(O)N(R14)2, —C(O)OR14, —C(O)NHR14, —S—R14, —SOR14, —S(O)2R14, —NHC(O)R14, —NHSR14, —NHSOR14, —NHS(O)2R14, O—C(S)R14, O—C(S)OR14, O—C(S)NHR14, O—C(S)N(R14)2, —C(S)OR14, —C(S)NHR14, —C(S)N(R14)2, —NHC(S)R14, —NR14C(S)R14, —NHC(S)NHR14, —NHC(S)N(R14)2, —NR14C(S)NHR14, or —NR14C(S)N(R14)2;
- R5 is —C1-C8 alkyl;
- R6 is —H;
- R7 is —Ym—(Rc), wherein —Rc is —C1-C8 alkyl, —O—(C1-C8 alkyl), —O-benzyl, —NH2, —NH(C1-C5 alkyl), —N(C1-C5 alkyl)2, —NH(phenyl), —N(phenyl)2, —NH(naphthyl), —N(naphthyl)2, —CN, —NO2, —N3, —C2-C8 alkynyl, —OR14, —O(CH2)nOR14, —C(O)R14, —O—C(O)R14, —C(O)(CH2)n—R14,—O—C(O)OR14, —O—C(O)NHR14,—O—C(O)N(R14)2, —C(O)N(R14)2, —C(O)OR14, —C(O)NHR14, —S—R14, —SOR14, —S(O)2R14, —NHC(O)R14, —NHSR14, —NHSOR14, —NHS(O)2R14, O—C(S)R14, O—C(S)OR14, O—C(S)NHR14, O—C(S)N(R14)2, —C(S)OR14, —C(S)NHR14, —C(S)N(R14)2, —NHC(S)R14, —NR14C(S)R14, —NHC(S)NHR14, —NHC(S)N(R14)2, —NR14C(S)NHR14, or —NR14C(S)N(R14)2;
- R8 is —Ym(Rd), wherein —Rd is —H, —OH, halogen, amino, —NH(C1-C5 alkyl), —N(C1-C5 alkyl)2, —NH(phenyl), —N(phenyl)2, —NH(naphthyl), —N(naphthyl)2, —CN, —NO2, —N3, —C1-C8 alkyl, —(C1-C8 alkyl)-OH, —O—(C1-C8 alkyl), —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, -phenyl , -naphthyl, -3- to 9-membered heterocycle, —OR14, —O(CH2)nOR14, —C(O)R14, —O—C(O)R14, —C(O)(CH2), —R14,—O—C(O)OR14, —O—C(O)NHR14, —O—C(O)N(R14)2, —C(O)N(R14)2, —C(O)OR14, —C(O)NHR14, —S—R14, —SOR14, —S(O)2R14, —NHC(O)R14, —NHSR14, NHSOR14, —NHS(O)2R14, O—C(S)R14, O—C(S)OR14, O—C(S)NHR14, O—C(S)N(R14)2, —C(S)OR14, —C(S)NHR14, —C(S)N(R14)2, —NHC(S)R14, —NR14C(S)R14, —NHC(S)NHR14, —NHC(S)N(R14)2, —NR14C(S)NHR14, or —NR14C(S)N(R14)2;
- R9 is —Ym(Re), wherein —Re is —H, —NH2, C1-C8 alkyl, —NH(C1-C5 alkyl), —N(C1-C5 alkyl)2, —NH(phenyl), —N(phenyl)2, —NH(naphthyl), —N(naphthyl)2, —C(O)N(C1-C5 alkyl)2, —NHC(O)(C1-C5 alkyl), —NHC(═NH2+)NH2, —CN, —NO2, N3, -3- to 9-membered heterocycle, —OR14, —O(CH2)nOR14, —O—C(O)R14, —C(O)(CH2)n—R14,—O—C(O)OR14, —O—C(O)NHR14, —C(O)N(R14)2, —C(O)NHR14, —S—R14, —SOR14, —S(O)2R14, —NHC(O)R14, —NHSR14, —NHSOR14, —NHS(O)2R14, O—C(S)R14, O—C(S)OR14, O—C(S)NHR14, O—C(S)N(R14)2, —C(S)OR14, —C(S)NHR14, —C(S)N(R14)2, —NHC(S)R14, —NR14C(S)R14, —NHC(S)NHR14, —NHC(S)N(R14)2, —NR14C(S)NHR14, —NR14C(S)N(R14)2;
- R10, R11, R12, and R13 are independently —Ym(Re), wherein —Re is —H, halogen, —NH2, C1-C8 alkyl, —NH(C1-C5 alkyl), —N(C1-C5 alkyl)2, —NH(phenyl), —N(phenyl)2, —NH(naphthyl), —N(naphthyl)2, —C(O)NH(C1-C5 alkyl), —C(O)N(C1-C5 alkyl)2, —NHC(O)(C1-C5 alkyl), —NHC(═NH2+)NH2, —CN, —NO2, N3, -3- to 9-membered heterocycle, —OR14, —O(CH2)nOR14, —C(O)R14, —O—C(O)R14, —C(O)(CH2)n—R14, —O—C(O)OR14, —O—C(O)NHR14,—O—C(O)N(R14)2, —C(O)N(R14)2, —C(O)OR14, —C(O)NHR14, —S—R14, —SOR14, —S(O)2R14, —NHC(O)R14, —NHSR14, —NHSOR14, —NHS(O)2R14, O—C(S)R14, O—C(S)OR14, O—C(S)NHR14, O—C(S)N(R14)2, —C(S)OR14, —C(S)NHR14, —C(S)N(R14)2, —NHC(S)R14, —NR14C(S)R14, —NHC(S)NHR14, —NHC(S)N(R14)2, —NR14C(S)NHR14, —NR14C(S)N(R14)2, with the proviso that neither R10 nor R12 is —OH;
- each R14 is independently —H, —C1-C8 alkyl, —C3-C12 cycloalkyl, -phenyl , -naphthyl, -3- to 9-membered heterocycle, —C2-C8 alkenyl, or —C2-C8 alkynyl;
- each Y is independently —C1-C8 alkylene-, —C2-C8 alkenylene- or —C2-C8 alkynylene-;
- each m is independently 0 or 1;
- and
- each n is independently an integer ranging from 0 to 6.
17 more elements
A compound being:
- 2-[4-methoxy-5-(3-methoxy-1H-pyrrol-2-ylmethylene)-5H-pyrrol-2-yl]-1H-indole;
- 2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-methoxy-5H-pyrrol-2-yl]-5,6-dimethoxy-indole-1-carboxylic acid tert-butyl ester;
- {5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-2-[3-isopropylamino-methyl)-1H-indol-2-yl]-4-methoxy-5H-pyrrol-3-yl}-methanol;
- {2-[5-(3,5-dimethyl,-1H-pyrrol-2-ylmethylene)-4-methoxy-5H-pyrrol-2-yl]-1H-indol-3-yl}thiophen-3-yl-methanone;
- [2-(3-allylaminomethyl-1H-indol-2-yl)-5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-methoxy-5H-pyrrol-3-yl]-methanol;
- {2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-methoxy-5H-pyrrol-2-yl]-1H-indol-3-yl}-methanol;
- 2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-methoxy-5H-pyrrol-2-yl]-indole-1-carboxylic acid 2,3-dihydroxy-propyl ester;
- 2-[5-[(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-methoxy-5H-pyrrol-2-yl]-indole-1-carboxylic acid tert-butyl ester;
- (Z)-ethyl 2-(2-(2-((3,5-dimethyl-1H-pyrrol-2-yl)methylene)-3-methoxy-2H-pyrrol-5-yl)-1H-indol-3-yloxy)acetate;
- or
- 6-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-methoxy-5H-pyrrol-2-yl]-5H-[1,3]dioxolo[4,5-f]indole, or
- a pharmaceutically acceptable salt thereof.
9 more elements
Dependencies are inferred from the claim text.