WO2015095449A1 - Procédés pour la modulation de la quantité de produits de la transcription d'arn - Google Patents

Procédés pour la modulation de la quantité de produits de la transcription d'arn Download PDF

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Publication number
WO2015095449A1
WO2015095449A1 PCT/US2014/071032 US2014071032W WO2015095449A1 WO 2015095449 A1 WO2015095449 A1 WO 2015095449A1 US 2014071032 W US2014071032 W US 2014071032W WO 2015095449 A1 WO2015095449 A1 WO 2015095449A1
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chromen
pyrazin
amino
pyridin
alkyl
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PCT/US2014/071032
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English (en)
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Nikolai Naryshkin
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Ptc Therapeutics, Inc.
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Publication of WO2015095449A1 publication Critical patent/WO2015095449A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A61K31/423—Oxazoles condensed with carbocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/428—Thiazoles condensed with carbocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings

Definitions

  • Described herein are methods for modulating the amount of a gene product and compounds for use in such methods. More particularly, described herein are methods for modulating the amount of an RNA transcript or protein product as the result of gene expression and compounds for use in such methods.
  • RNA transcripts e.g., an RNA transcript or protein
  • the resulting aberrant amounts of RNA transcripts may lead to disease due to corresponding changes in protein expression.
  • Changes in the amount of a particular RNA transcript may be the result of several factors.
  • changes in the amount of RNA transcripts may be due to an aberrant level of transcription of a particular gene, such as by the perturbation of a transcription factor or a portion of the transcription process, resulting in a change in the expression level of a particular RNA transcript.
  • changes in the splicing of particular RNA transcripts can change the levels of a particular RNA transcript.
  • Changes to the stability of a particular RNA transcript or to components that maintain RNA transcript stability, such as the process of poly-A tail incorporation or an effect on certain factors or proteins that bind to and stabilize RNA transcripts may lead to changes in the levels of a particular RNA transcript.
  • the level of translation of particular RNA transcripts can affect the amount of those transcripts, affecting or upregulating RNA transcript decay processes.
  • RNA transport or RNA sequestration may also lead to changes in functional levels of RNA transcripts, and may have an effect on the stability, further processing, or translation of the RNA transcripts.
  • diseases associated with changes to RNA transcript amount are treated with a focus on the aberrant protein expression.
  • the processes responsible for the aberrant changes in RNA levels such as components of the splicing process or associated transcription factors or associated stability factors, could be targeted by treatment with a small molecule, it would be possible to restore protein expression levels such that the unwanted effects of the expression of aberrant levels of RNA transcripts or associated proteins. Therefore, there is a need for methods of modulating the amount of RNA transcripts encoded by certain genes as a way to prevent or treat diseases associated with aberrant expression of the RNA transcripts or associated proteins.
  • RNA transcripts e.g., rRNA, tRNA, miRNA, siRNA, IncRNA, pre-mRNA, or mRNA transcripts
  • methods for modulating the amount of one or more RNA transcripts comprising contacting a cell with a compound of Formula (I)
  • provided herein are methods for modulating the amount of one, two, three or more RNA transcripts of a gene, by way of nonlimiting example, disclosed in Table 1, infra, comprising contacting a cell with a compound of Formula (I) or a form thereof.
  • methods for modulating one, two, three or more RNA transcripts of one, two, three or more genes by way of nonlimiting example, disclosed in Table 1, infra, comprising contacting a cell with a compound of Formula (I) or a form thereof.
  • RNA transcripts of a gene comprising contacting a cell with a compound of Formula (I) or a form thereof.
  • methods for modulating one, two, three or more RNA transcripts of one, two, three or more genes comprising contacting a cell with a compound of Formula (I) or a form thereof.
  • the cell is contacted with the compound of Formula (I) or a form thereof in a cell culture.
  • the cell is contacted with the compound of Formula (I) or a form thereof in a subject ⁇ e.g., a non- human animal subject or a human subject).
  • a compound of Formula (I) is a compound of Formula (la) or Formula (lb) described infra.
  • a compound of Formula (I) is a compound selected from a compound described herein.
  • RNA transcripts of a gene comprising administering to a patient in need thereof a compound of Formula (I) or a form thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a form thereof and a pharmaceutically acceptable carrier, excipient or diluent.
  • RNA transcripts of a gene by way of nonlimiting example, disclosed in Table 1, infra, comprising administering to a patient in need thereof a compound of Formula (I) or a form thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a form thereof and a pharmaceutically acceptable carrier, excipient or diluent.
  • RNA transcripts of one, two, three or more genes disclosed in Table 1, infra comprising administering to a patient in need thereof a compound of Formula (I) or a form thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a form thereof, and a pharmaceutically acceptable carrier, excipient or diluent.
  • a compound of Formula (I) is a compound of Formula (la) or Formula (lb) described infra.
  • a compound of Formula (I) is a compound selected from a compound described herein.
  • RNA transcripts of a gene by way of nonlimiting example, disclosed in Table 2, infra, comprising administering to a patient in need thereof a compound of Formula (I) or a form thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a form thereof and a pharmaceutically acceptable carrier, excipient or diluent.
  • RNA transcripts of one, two, three or more genes disclosed in Table 2, infra comprising administering to a patient in need thereof a compound of Formula (I) or a form thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a form thereof, and a pharmaceutically acceptable carrier, excipient or diluent.
  • a compound of Formula (I) is a compound of Formula (la) or Formula (lb) described infra.
  • a compound of Formula (I) is a compound selected from a compound described herein.
  • kits for preventing and/or treating a disease associated with the aberrant expression of a gene product comprising administering to a patient in need thereof a compound of Formula (I) or a form thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a form thereof and a pharmaceutically acceptable carrier, excipient or diluent.
  • RNA transcript or protein a gene product ⁇ e.g., an RNA transcript or protein
  • a gene product e.g., an RNA transcript or protein
  • Table 1 infra
  • administering to a patient in need thereof a compound of Formula (I) or a form thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a form thereof and a pharmaceutically acceptable carrier, excipient or diluent.
  • RNA transcript or protein a gene product ⁇ e.g., an RNA transcript or protein
  • a pharmaceutical composition comprising a compound of Formula (I) or a form thereof and a pharmaceutically acceptable carrier, excipient or diluent.
  • a compound of Formula (I) is a compound of Formula (la) or Formula (lb) described infra.
  • a compound of Formula (I) is a compound selected from a compound described herein.
  • RNA isoforms encoded by a gene are beneficial to the prevention and/or treatment of the disease, comprising
  • RNA isoforms encoded by gene by way of nonlimiting example, disclosed in Table 1 , infra, is beneficial to the prevention and/or treatment of the disease, comprising administering to a patient in need thereof a compound of Formula (I) or a form thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a form thereof and a pharmaceutically acceptable carrier, excipient or diluent.
  • RNA isoforms encoded by a gene by way of nonlimiting example, disclosed in Table 1, infra, is beneficial to the prevention and/or treatment of the disease, comprising administering to a patient in need thereof a compound of Formula (I) or a form thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a form thereof and a pharmaceutically acceptable carrier, excipient or diluent.
  • a compound of Formula (I) is a compound of Formula (la) or Formula (lb) described infra.
  • a compound of Formula (I) is a compound selected from a compound described herein.
  • RNA isoforms encoded by a gene by way of nonlimiting example, disclosed in Table 2, infra, is beneficial to the prevention and/or treatment of the disease, comprising administering to a patient in need thereof a compound of Formula (I) or a form thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a form thereof and a pharmaceutically acceptable carrier, excipient or diluent.
  • RNA isoforms encoded by a gene by way of nonlimiting example, disclosed in Table 2, infra, is beneficial to the prevention and/or treatment of the disease, comprising administering to a patient in need thereof a compound of Formula (I) or a form thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a form thereof and a pharmaceutically acceptable carrier, excipient or diluent.
  • a compound of Formula (I) is a compound of Formula (la) or Formula (lb) described infra.
  • a compound of Formula (I) is a compound selected from a compound described herein.
  • kits for preventing and/or treating a disease in which a change in the level of expression of one, two, three or more protein isoforms encoded by a gene is beneficial to the prevention and/or treatment of the disease comprising administering to a patient in need thereof a compound of Formula (I) or a form thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a form thereof and a pharmaceutically acceptable carrier, excipient or diluent.
  • provided herein are methods for preventing and/or treating a disease in which the increase in the expression one, two, three or more protein isoforms encoded by a gene, by way of nonlimiting example, disclosed in Table 1, infra, is beneficial to the prevention and/or treatment of the disease, comprising administering to a patient in need thereof a compound of Formula (I) or a form thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a form thereof and a pharmaceutically acceptable carrier, excipient or diluent.
  • a disease in which the decrease in the expression one, two, three or more protein isoforms encoded by a gene by way of nonlimiting example, disclosed in Table 1, infra, is beneficial to the prevention and/or treatment of the disease, comprising administering to a patient in need thereof a compound of Formula (I) or a form thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a form thereof and a pharmaceutically acceptable carrier, excipient or diluent.
  • a compound of Formula (I) is a compound of Formula (la) or Formula (lb) described infra.
  • a compound of Formula (I) is a compound selected from a compound described herein.
  • kits for preventing and/or treating a disease in which the increase in the expression one, two, three or more protein isoforms encoded by a gene by way of nonlimiting example, disclosed in Table 2, infra, is beneficial to the prevention and/or treatment of the disease, comprising administering to a patient in need thereof a compound of Formula (I) or a form thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a form thereof and a pharmaceutically acceptable carrier, excipient or diluent.
  • a disease in which the decrease in the expression one, two, three or more protein isoforms encoded by a gene by way of nonlimiting example, disclosed in Table 2, infra, is beneficial to the prevention and/or treatment of the disease, comprising administering to a patient in need thereof a compound of Formula (I) or a form thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a form thereof and a pharmaceutically acceptable carrier, excipient or diluent.
  • a compound of Formula (I) is a compound of Formula (la) or Formula (lb) described infra.
  • a compound of Formula (I) is a compound selected from a compound described herein.
  • RNA transcripts of one or more of genes comprising contacting a cell with a compound of Formula (I) or a form thereof.
  • a compound of Formula (I) or a form thereof modulates the amount of one or more of the RNA transcripts of one or more of the genes, by way of nonlimiting example, in Table 1, infra.
  • a compound of Formula (I) or a form thereof modulates the amount of one or more of the RNA transcripts of one or more of the genes, by way of nonlimiting example, in Table 2, infra.
  • RNA transcripts of a gene(s) comprising administering to a patient in need thereof a compound of Formula (I) or a form thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a form thereof and a pharmaceutically acceptable carrier, excipient or diluent.
  • a compound of Formula (I) or a form thereof modulates the amount of one, two, three or more of the RNA transcripts of one, two, three or more of the genes, by way of nonlimiting example, in Table 1, infra.
  • a compound of Formula (I) or a form thereof modulates the amount of one, two, three or more of the RNA transcripts of one, two, three or more of the genes, by way of nonlimiting example, in Table 2, infra.
  • a disease associated with the aberrant expression of a gene comprising administering to a patient in need thereof a compound of Formula (I) or a form thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a form thereof and a pharmaceutically acceptable carrier, excipient or diluent.
  • the disease is associated with the aberrant expression of a gene, by way of nonlimiting example, in Table 1, infra.
  • the disease is associated with the aberrant expression of a gene, by way of nonlimiting example, in Table 2, infra.
  • the disease is not associated with the aberrant expression of the SMN2 gene.
  • RNA isoforms of a gene(s) are beneficial to the prevention and/or treatment of the disease, comprising administering to a patient in need thereof a compound of Formula (I) or a form thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a form thereof and a pharmaceutically acceptable carrier, excipient or diluent.
  • an increase in the level of expression of one, two, three or more RNA isoforms of one, two, three or more genes, by way of nonlimiting example, in Table 1, infra is beneficial to prevent and/or treat a disease.
  • a decrease in the level of expression of one, two, three or more RNA isoforms of one, two or more genes, by way of nonlimiting example, in Table 1, infra is beneficial to prevent and/or treat a disease.
  • an increase in the level of expression of one, two, three or more RNA isoforms of one, two, three or more genes, by way of nonlimiting example, in Table 2, infra is beneficial to prevent and/or treat a disease.
  • a decrease in the level of expression of one, two, three or more RNA isoforms of one, two or more genes, by way of nonlimiting example, in Table 2, infra is beneficial to prevent and/or treat a disease.
  • kits for preventing and/or treating a disease in which a change in the level of expression of one, two, three or more protein isoforms of a gene(s) is beneficial to the prevention and/or treatment of the disease comprising administering to a patient in need thereof a compound of Formula (I) or a form thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a form thereof and a pharmaceutically acceptable carrier, excipient or diluent.
  • an increase in the level of expression of one, two, three or more protein isoforms of one, two, three or more genes is beneficial to prevent and/or treat a disease.
  • a decrease in the level of expression of one, two, three or more protein isoforms of one, two or more genes, by way of nonlimiting example, in Table 1, infra, is beneficial to prevent and/or treat a disease.
  • an increase in the level of expression of one, two, three or more protein isoforms of one, two, three or more genes, by way of nonlimiting example, in Table 2, infra is beneficial to prevent and/or treat a disease.
  • a decrease in the level of expression of one, two, three or more protein isoforms of one, two or more genes, by way of nonlimiting example, in Table 2, infra is beneficial to prevent and/or treat a disease.
  • wi and w 2 are C-Ri or C-R 2 ; wherein, one of wi and w 2 is C-Ri and the other is C-R 2 , provided that, when wi is C-Ri, then w 2 is C-R 2 ; or, when wi is C-R 2 , then w 2 is C-Ri;
  • Ri is Ci_ 8 alkyl, amino, Ci_ 8 alkyl-amino, (Ci_ 8 alkyl) 2 -amino,
  • Ci_8alkoxy-Ci_8alkyl-amino Ci_8alkoxy-Ci_8alkyl-amino, (Ci_8alkoxy-Ci_8alkyl) 2 -amino,
  • Ci_8alkyl-amino-C i.salkyl-amino (C i.galkyl-amino-C i_8alkyl) 2 -amino,
  • Ci_ 8 alkyl-amino-C 2 - 8 alkynyl Ci_ 8 alkyl-amino-C 2 - 8 alkynyl, (Ci_ 8 alkyl) 2 -amino-C 2 - 8 alkynyl,
  • heterocyclyl-Ci_salkyl heterocyclyl-Ci_ 8 alkoxy, heterocyclyl-amino,
  • heterocyclyl (Ci_8alkyl)amino
  • heterocyclyl-amino-Ci_8alkyl heterocyclyl-Ci_8alkyl-amino
  • heterocyclyl-Ci_8alkyl 2 -amino
  • heterocyclyl-Ci_8alkyl (heterocyclyl-Ci_8alkyl)(Ci_8alkyl)amino
  • heterocyclyl-Ci_ 8 alkyl-amino-Ci_ 8 alkyl (heterocyclyl-Ci_ 8 alkyl) 2 -amino-Ci_ 8 alkyl,
  • heterocyclyl-Ci_ 8 alkyl (Ci_ 8 alkyl)amino-Ci_ 8 alkyl, heterocyclyl-oxy, heterocyclyl-carbonyl, heterocyclyl-carbonyl-oxy, aryl-Ci_8alkyl-amino, (aryl-Ci_8alkyl) 2 -amino,
  • aryl-Ci_ 8 alkyl 2 -amino-Ci_ 8 alkyl, (aryl-Ci_ 8 alkyl)(Ci_ 8 alkyl)amino-Ci_ 8 alkyl, heteroaryl, heteroaryl-Ci_8alkyl, heteroaryl-Ci_8alkoxy, heteroaryl-amino, heteroaryl-Ci_8alkyl-amino, (heteroaryl-Ci_8alkyl) 2 -amino, (heteroaryl-Ci_8alkyl)(Ci_8alkyl)amino,
  • heteroaryl-Ci_ 8 alkyl-amino-Ci_ 8 alkyl (heteroaryl-Ci_ 8 alkyl) 2 -amino-Ci_ 8 alkyl or
  • each instance of heterocyclyl and heteroaryl is optionally substituted with one, two or three R 3 substituents and one additional, optional R 4 substituent;
  • each instance of heterocyclyl and heteroaryl is optionally substituted with one, two, three or four R 3 substituents;
  • R 2 is aryl, aryl-amino, aryl-amino-carbonyl, heterocyclyl, heteroaryl or
  • each instance of aryl, heterocyclyl and heteroaryl is optionally substituted with one, two or three 3 ⁇ 4 substituents and one additional, optional R 7 substituent;
  • R a is, in each instance, independently selected from hydrogen, halogen, Ci_ 8 alkyl or deuterium;
  • R b is hydrogen, halogen, Ci_salkyl, Ci_ 8 alkoxy or deuterium;
  • R 3 is, in each instance, independently selected from cyano, halogen, hydroxy, oxo,
  • Ci_ 8 alkoxy-Ci_ 8 alkyl-amino Ci_ 8 alkyl-carbonyl-amino, Ci_ 8 alkoxy-carbonyl-amino,
  • R4 is C 3 _i 4 cycloalkyl, C 3 -i 4 cycloalkyl-Ci_galkyl, C 3 _i 4 cycloalkyl-amino, aryl-Ci_salkyl, aryl-Ci.galkoxy-carbonyl, aryl-sulfonyloxy-Ci_galkyl, heterocyclyl or heterocyclyl-Ci_galkyl; wherein, each instance of C 3 _i 4 cycloalkyl, aryl and heterocyclyl is optionally substituted with one, two or three R 5 substituents;
  • R 5 is, in each instance, independently selected from halogen, hydroxy, cyano, nitro, Ci_ 8 alkyl, halo-Ci_ 8 alkyl, Ci_ 8 alkoxy, halo-Ci_ 8 alkoxy, amino, Ci_ 8 alkyl-amino,
  • Ci_ 8 alkyl 2 -amino or Ci_ 8 alkyl-thio
  • Re is, in each instance, independently selected from halogen, hydroxy, cyano, nitro, Ci_salkyl, C 2 -galkenyl, halo-Ci_salkyl, hydroxy-Ci_galkyl, Ci_galkoxy, halo-Ci_galkoxy, amino, Ci_galkyl-amino, (Ci_galkyl) 2 -amino or Ci_galkyl-thio; and,
  • R 7 is C 3 _i 4 cycloalkyl, C 3 _i 4 cycloalkyl-oxy, aryl, heterocyclyl or heteroaryl.
  • Ri is Ci_ 8 alkyl, amino, Ci.galkyl-amino, (Ci_galkyl) 2 -amino, Ci_galkoxy-Ci_galkyl-amino, (Ci_galkoxy-Ci_galkyl) 2 -amino, (Ci_galkoxy-Ci_galkyl)(Ci_galkyl)amino, amino-Ci_galkyl, Ci_galkyl-amino-Ci_galkyl,
  • Ci_galkyl 2 -amino-Ci_galkyl
  • Ci_galkyl-amino-C 2 -galkynyl Ci_galkyl-amino-C 2 -galkynyl, (Ci_galkyl) 2 -amino-C 2 -galkynyl,
  • halo-Ci_galkyl-amino (halo-Ci_galkyl) 2 -amino, (halo-Ci_galkyl)(Ci_galkyl)amino, hydroxy-Ci-galkyl, hydroxy-Ci-galkoxy-Ci.galkyl, hydroxy-Ci.galkyl-amino,
  • heterocyclyl-Ci.galkyl heterocyclyl-Ci_galkoxy, heterocyclyl-amino
  • heterocyclyl (Ci_galkyl)amino
  • heterocyclyl-amino-Ci_galkyl heterocyclyl-Ci_galkyl-amino
  • heterocyclyl-Ci_ 8 alkyl 2 -amino
  • heterocyclyl-Ci_ 8 alkyl (heterocyclyl-Ci_ 8 alkyl)(Ci_galkyl)amino,
  • heterocyclyl-Ci_ 8 alkyl-amino-Ci_ 8 alkyl (heterocyclyl-Ci_ 8 alkyl) 2 -amino-Ci_ 8 alkyl,
  • heterocyclyl-Ci_ 8 alkyl (Ci_ 8 alkyl)amino-Ci_ 8 alkyl, heterocyclyl-oxy, heterocyclyl-carbonyl, heterocyclyl-carbonyl-oxy, aryl-Ci_8alkyl-amino, (aryl-Ci_8alkyl) 2 -amino,
  • aryl-Ci_ 8 alkyl 2 -amino-Ci_ 8 alkyl, (aryl-Ci_ 8 alkyl)(Ci_ 8 alkyl)amino-Ci_ 8 alkyl, heteroaryl, heteroaryl-Ci_8alkyl, heteroaryl-Ci_8alkoxy, heteroaryl-amino, heteroaryl-Ci_8alkyl-amino, (heteroaryl-Ci_8alkyl) 2 -amino, (heteroaryl-Ci_8alkyl)(Ci_8alkyl)amino,
  • heteroaryl-Ci_ 8 alkyl-amino-Ci_ 8 alkyl (heteroaryl-Ci_ 8 alkyl) 2 -amino-Ci_ 8 alkyl or
  • heteroaryl-Ci_ 8 alkyl (Ci_ 8 alkyl)amino-Ci_ 8 alkyl; wherein, each instance of heterocyclyl and heteroaryl is optionally substituted.
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • Ci_8alkoxy-Ci_8alkyl-amino Ci_8alkoxy-Ci_8alkyl-amino, (Ci_8alkoxy-Ci_8alkyl) 2 -amino,
  • Ci_ 8 alkyl-amino-C 2 - 8 alkynyl Ci_ 8 alkyl-amino-C 2 - 8 alkynyl, (Ci_ 8 alkyl) 2 -amino-C 2 - 8 alkynyl,
  • halo-Ci_ 8 alkyl-amino (halo-Ci_ 8 alkyl) 2 -amino, hydroxy-Ci_ 8 alkyl, hydroxy-Ci_ 8 alkoxy-Ci_ 8 alkyl, hydroxy-C i_ 8 alkyl-amino, (hydroxy-Ci_ 8 alkyl) 2 -amino, (hydroxy-Ci_ 8 alkyl)(Ci_ 8 alkyl)amino, hydroxy-Ci_ 8 alkyl-amino-Ci_ 8 alkyl, (hydroxy-Ci_ 8 alkyl) 2 -amino-Ci_ 8 alkyl,
  • heterocyclyl (Ci_ 8 alkyl)amino
  • heterocyclyl-amino-Ci.salkyl heterocyclyl-Ci_ 8 alkyl-amino
  • heterocyclyl-Ci_ 8 alkyl-amino heterocyclyl-Ci_ 8 alkyl 2 -amino
  • heterocyclyl-Ci_ 8 alkyl (Ci_ 8 alkyl)amino
  • heterocyclyl-Ci_ 8 alkyl-amino-Ci_ 8 alkyl (heterocyclyl-Ci_ 8 alkyl) 2 -amino-Ci_ 8 alkyl,
  • heterocyclyl-Ci_ 8 alkyl (Ci_ 8 alkyl)amino-Ci_ 8 alkyl, heterocyclyl-oxy, heterocyclyl-carbonyl, heterocyclyl-carbonyl-oxy, aryl-Ci_ 8 alkyl-amino, (aryl-Ci_ 8 alkyl) 2 -amino,
  • aryl-Ci_ 8 alkyl 2 -amino-Ci_ 8 alkyl, (aryl-Ci_ 8 alkyl)(Ci_ 8 alkyl)amino-Ci_ 8 alkyl, heteroaryl, heteroaryl-Ci_ 8 alkyl, heteroaryl-Ci_ 8 alkoxy, heteroaryl-amino, heteroaryl-Ci_ 8 alkyl-amino, (heteroaryl-Ci_ 8 alkyl) 2 -amino, (heteroaryl-Ci_ 8 alkyl)(Ci_ 8 alkyl)amino,
  • heteroaryl-Ci_ 8 alkyl-amino-Ci_ 8 alkyl (heteroaryl-Ci_ 8 alkyl) 2 -amino-Ci_ 8 alkyl or
  • Ri is heterocyclyl selected from azetidinyl, tetrahydrofuranyl, pyrrolidinyl, piperidinyl, piperazinyl, 1 ,4-diazepanyl, 1 ,2,5,6-tetrahydropyridinyl, 1 ,2,3,6-tetrahydropyridinyl, hexahydropyrrolo[3,4-3 ⁇ 4]pyrrol-(lH)-yl, (3a5',6a5)-hexahydropyrrolo[3,4-3 ⁇ 4]pyrrol-(lH)-yl,
  • Ri is heterocyclyl selected from azetidin-l-yl, tetrahydrofuran-3-yl, pyrrolidin-l-yl, piperidin-l-yl, piperidin-4-yl, piperazin- 1 -yl, 1 ,4-diazepan- 1 -yl, 1 ,2,5 ,6-tetrahydropyridin-3-yl, 1 ,2,3 ,6-tetrahydropyridin-4-yl, hexahydropyrrolo[3,4-£]pyrrol-l(2H)-yl, (3a5',6a5)-hexahydropyrrolo[3,4-3 ⁇ 4]pyrrol-l(2H)-yl, (3 aS ⁇ a ⁇ -hexahydropyrrolo [3 ,4-3 ⁇ 4]pyrrol-5 ( lH)-yl,
  • Ri is substituted heterocyclyl selected from (3a5',6a5)-l-methylhexahydropyrrolo[3,4-3 ⁇ 4]pyrrol-5(lH)-yl,
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • heterocyclyl-Ci_ 8 alkyl wherein heterocyclyl is selected from morpholinyl, piperidinyl, piperazinyl, imidazolyl or pyrrolidinyl; and, wherein, each instance of heterocyclyl is optionally substituted.
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • heterocyclyl-Ci_galkyl selected from morpholin-4-yl-methyl, morpholin-4-yl-ethyl,
  • morpholin-4-yl-propyl piperidin-l-yl-methyl, piperazin-l-yl-methyl, piperazin-l-yl-ethyl, piperazin-l-yl-propyl, piperazin-l-yl-butyl, imidazol-l-yl-methyl, imidazol-l-yl-ethyl, imidazol-l-yl-propyl, imidazol-l-yl-butyl, pyrrolidin-l-yl-methyl, pyrrolidin-l-yl-ethyl, pyrrolidin-l-yl-propyl or pyrrolidin-l-yl-butyl; wherein, each instance of heterocyclyl is optionally substituted.
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • heterocyclyl-Ci.galkoxy wherein heterocyclyl is selected from pyrrolidinyl, piperidinyl or morpholinyl; and, wherein, each instance of heterocyclyl is optionally substituted.
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • heterocyclyl-Ci_8alkoxy selected from pyrrolidin-2-yl-methoxy, pyrrolidin-2-yl-ethoxy, pyrrolidin-l-yl-methoxy, pyrrolidin-l-yl-ethoxy, piperidin-l-yl-methoxy, piperidin-l-yl-ethoxy, morpholin-4-yl-methoxy or morpholin-4-yl-ethoxy; wherein, each instance of heterocyclyl is optionally substituted.
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • heterocyclyl-amino wherein heterocyclyl is selected from azetidinyl, pyrrolidinyl, piperidinyl, 9-azabicyclo[3.3.1]nonyl or (li?,55)-9-azabicyclo[3.3.1]nonyl; and, wherein, each instance of heterocyclyl is optionally substituted.
  • Ri is heterocyclyl-amino selected from azetidin-3-yl-amino, pyrrolidin-3-yl-amino, piperidin-4-yl-amino,
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • heterocyclyl (Ci_8alkyl)amino, wherein heterocyclyl is selected from pyrrolidinyl or piperidinyl; and, wherein, each instance of heterocyclyl is optionally substituted.
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • heterocyclyl-amino-Ci_ 8 alkyl wherein heterocyclyl is selected from tetrahydrofuranyl; and, wherein, each instance of heterocyclyl is optionally substituted.
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • heterocyclyl-amino-Ci.galkyl selected from 3-(tetrahydrofuran-3-yl-amino)propyl; wherein, each instance of heterocyclyl is optionally substituted.
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • heterocyclyl-Ci_ 8 alkyl-amino-Ci_ 8 alkyl wherein heterocyclyl is selected from tetrahydrofuranyl, thienyl or pyridinyl; and, wherein, each instance of heterocyclyl is optionally substituted.
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • heterocyclyl-Ci_ 8 alkyl-amino-Ci_ 8 alkyl selected from 3-[(tetrahydrofuran-2- ylmethyl)amino]propyl, 3 - [(thiophenyl-3 -ylmethyl)amino]propyl, 3 - [(pyridin-2- ylmethyl)amino]propyl or 3-[(pyridin-4-ylmethyl)amino]propyl; wherein, each instance of heterocyclyl is optionally substituted.
  • Ri is heterocyclyl-oxy, wherein heterocyclyl is selected from pyrrolidinyl or piperidinyl; and, wherein, each instance of heterocyclyl is optionally substituted.
  • Ri is heterocyclyl-oxy selected from pyrrolidin-3-yl-oxy or piperidin-4-yl-oxy; wherein, each instance of heterocyclyl is optionally substituted. [0052] In one embodiment of the use of a compound of Formula (I), Ri is
  • heterocyclyl-carbonyl wherein heterocyclyl is selected from piperazinyl; and, wherein, each instance of heterocyclyl is optionally substituted.
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • heterocyclyl-carbonyl selected from piperazin-l-yl-carbonyl; wherein, each instance of heterocyclyl is optionally substituted.
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • heterocyclyl-carbonyl-oxy wherein heterocyclyl is selected from piperazinyl; and, wherein, each instance of heterocyclyl is optionally substituted.
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • heterocyclyl-carbonyl-oxy selected from piperazin-l-yl-carbonyl-oxy; wherein, each instance of heterocyclyl is optionally substituted.
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • aryl-Ci_ 8 alkyl-amino-Ci_ 8 alkyl wherein aryl is selected from phenyl; wherein, each instance of aryl is optionally substituted.
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • aryl-Ci_ 8 alkyl-amino-Ci_ 8 alkyl selected from 3-(benzylamino)propyl; wherein, each instance of aryl is optionally substituted.
  • Ri is heteroaryl, wherein heteroaryl is selected from pyridinyl; and, wherein, each instance of heteroaryl is optionally substituted.
  • Ri is heteroaryl selected from pyridin-4-yl; wherein, each instance of heteroaryl is optionally substituted.
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • heteroaryl-Ci_ 8 alkyl wherein heteroaryl is selected from lH-imidazolyl; and, wherein, each instance of heteroaryl is optionally substituted.
  • Ri is heteroaryl-Ci_salkyl selected from lH-imidazol-l-yl-methyl; wherein, each instance of heteroaryl is optionally substituted.
  • Ri is
  • heteroaryl-Ci_ 8 alkyl (Ci_ 8 alkyl)amino, wherein heteroaryl is selected from pyridinyl; and, wherein, each instance of heteroaryl is optionally substituted.
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • heteroaryl-Ci_8alkyl (Ci_8alkyl)amino selected from (pyridin-3-yl-methyl)(methyl)amino; wherein, each instance of heteroaryl is optionally substituted.
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • heteroaryl-Ci_ 8 alkyl-amino-Ci_ 8 alkyl wherein heteroaryl is selected from thienyl or pyridinyl; and, wherein, each instance of heteroaryl is optionally substituted.
  • Ri is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • R 3 is selected from cyano, halogen, hydroxy, oxo, Ci_salkyl, halo-Ci_salkyl, Ci_galkyl-carbonyl, Ci_galkoxy, halo-Ci_ 8 alkoxy, Ci_ 8 alkoxy-Ci_ 8 alkyl, Ci_ 8 alkoxy-carbonyl, amino, Ci_ 8 alkyl-amino,
  • Ci_ 8 alkoxy-Ci_ 8 alkyl-amino Ci_galkyl-carbonyl-amino, Ci_galkoxy-carbonyl-amino,
  • R 3 is selected from cyano, halogen, hydroxy, oxo, Ci_ 8 alkyl, halo-Ci_ 8 alkyl, Ci_ 8 alkoxy, Ci_ 8 alkoxy-Ci_galkyl,
  • Ci_galkoxy-carbonyl amino, Ci_galkyl-amino, (Ci_galkyl) 2 -amino, amino-Ci_galkyl,
  • Ci_galkoxy-Ci_galkyl-amino Ci_galkoxy-carbonyl-amino, hydroxy-C i_galkyl,
  • R 3 is Ci_galkyl selected from methyl, ethyl, propyl, isopropyl or tert-butyl. [0069] In one embodiment of the use of a compound of Formula (I), R 3 is Ci.galkyl selected from ethyl, propyl, isopropyl or tert-butyl.
  • R 3 is halo-Ci_galkyl selected from trihalo-methyl, dihalo-methyl, halo-methyl, trihalo-ethyl, dihalo-ethyl, halo-ethyl, trihalo-propyl, dihalo-propyl or halo-propyl; wherein, halo is selected from fluoro, chloro, bromo or iodo.
  • R 3 is halo-Ci_ 8 alkyl selected from trihalo-methyl, dihalo-methyl, halo-methyl, trihalo-ethyl, dihalo-ethyl,
  • halo is selected from fluoro, chloro, bromo or iodo.
  • R 3 is hydroxy-Ci_ 8 alkyl selected from hydroxy-methyl, hydroxy-ethyl, hydroxy-propyl, dihydroxy-propyl, hydroxy-butyl or dihydroxy-butyl.
  • R 3 is hydroxy-Ci_galkyl selected from hydroxy-methyl, dihydroxy-propyl, hydroxy-butyl or dihydroxy-butyl.
  • R 3 is Ci_ 8 alkoxy selected from methoxy, ethoxy, propoxy or isopropoxy.
  • R 3 is halo-Ci_8alkoxy selected from trihalo-methoxy, dihalo-methoxy, halo-methoxy, trihalo-ethoxy, dihalo-ethoxy, halo-ethoxy, trihalo-propoxy, dihalo-propoxy or halo-propoxy; wherein, halo is selected from fluoro, chloro, bromo or iodo.
  • R 3 is
  • Ci_8alkoxy-carbonyl-amino selected from methoxy-carbonyl-amino, ethoxy-carbonyl-amino, propoxy-carbonyl-amino, isopropoxy-carbonyl-amino, tert-butoxy-carbonyl-amino.
  • R a is, in each instance, independently selected from hydrogen, halogen, Ci.galkyl.
  • R a is, in each instance, optionally and independently deuterium.
  • R b is hydrogen, halogen, Ci_8alkyl, Ci_8alkoxy.
  • R b is deuterium.
  • R4 is C 3 _i 4 cycloalkyl selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; wherein, each instance of C3-i 4 cycloalkyl is optionally substituted.
  • R4 is C3- 8 cycloalkyl selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; wherein, each instance of C 3 _ 8 cycloalkyl is optionally substituted.
  • R4 is
  • C 3 -i 4 cycloalkyl-Ci_ 8 alkyl wherein C 3 _i 4 cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; and, wherein, each instance of C 3 _i 4 cycloalkyl is optionally substituted.
  • R4 is
  • C 3 _ 8 Cycloalkyl-Ci_ 8 alkyl, wherein C 3 _gcycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; and, wherein, each instance of C 3 _gcycloalkyl is optionally substituted.
  • R4 is
  • C 3 _i 4 cycloalkyl-amino wherein C 3 _i 4 cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; and, wherein, each instance of C 3 _i 4 cycloalkyl is optionally substituted.
  • R4 is
  • C 3 _8Cycloalkyl-amino wherein C 3 _gcycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; and, wherein, each instance of C 3 _gcycloalkyl is optionally substituted.
  • R4 is aryl-Ci_ 8 alkyl, aryl-Ci_ 8 alkoxy-carbonyl or aryl-sulfonyloxy-Ci_ 8 alkyl, wherein each instance of aryl is selected from phenyl; and, wherein, each instance of aryl is optionally substituted.
  • R4 is aryl-Ci_ 8 alkyl or aryl-Ci_ 8 alkoxy-carbonyl, wherein each instance of aryl is selected from phenyl; and, wherein, each instance of aryl is optionally substituted.
  • R4 is heterocyclyl selected from oxetanyl, pyrrolidinyl, piperidinyl, piperazinyl, 1,3-dioxanyl or morpholinyl; wherein, each instance of heterocyclyl is optionally substituted.
  • R 4 is heterocyclyl selected from oxetan-3-yl, pyrrolidin-l-yl, piperidin-l-yl, piperazin-l-yl, l,3-dioxan-5-yl or morpholin-4-yl; wherein, each instance of heterocyclyl is optionally substituted.
  • R 4 is
  • heterocyclyl-Ci_ 8 alkyl wherein each instance of heterocyclyl is selected from pyrrolidinyl or piperidinyl; and, wherein, each instance of heterocyclyl is optionally substituted.
  • R 4 is
  • heterocyclyl-Ci.galkyl selected from pyrrolidin-l-yl-Ci_galkyl or piperidin-l-yl-Ci_galkyl;
  • each instance of heterocyclyl is optionally substituted.
  • R 5 is selected from halogen, hydroxy, cyano, nitro, halo-Ci_galkyl, Ci_galkoxy, halo-Ci_galkoxy, amino,
  • Ci_galkyl-amino (Ci_galkyl)2-amino or Ci_galkyl-thio.
  • R5 is hydroxy
  • R 5 is Ci_ 8 alkyl selected from methyl, ethyl, propyl, isopropyl, n-butyl or tert-butyl.
  • R 5 is Ci_galkyl selected from ethyl, propyl, isopropyl or tert-butyl.
  • R 5 is halo-Ci_ 8 alkyl selected from trihalo-methyl, dihalo-methyl, halo-methyl, trihalo-ethyl, dihalo-ethyl, halo-ethyl, trihalo-propyl, dihalo-propyl or halo-propyl; wherein, halo is selected from fluoro, chloro, bromo or iodo.
  • R 5 is Ci_galkoxy selected from methoxy, ethoxy, propoxy or isopropoxy.
  • R 5 is halo-Ci_galkoxy selected from trihalo-methoxy, dihalo-methoxy, halo-methoxy, trihalo-ethoxy, dihalo-ethoxy, halo-ethoxy, trihalo-propoxy, dihalo-propoxy or halo-propoxy; wherein, halo is selected from fluoro, chloro, bromo or iodo.
  • R 2 is aryl selected from phenyl; wherein, each instance of aryl is optionally substituted.
  • R 2 is aryl-amino, wherein aryl is selected from phenyl; and, wherein, each instance of aryl is optionally substituted.
  • R 2 is aryl-amino selected from phenyl-amino; wherein, each instance of aryl is optionally substituted.
  • R 2 is
  • aryl-amino-carbonyl wherein aryl is selected from phenyl; wherein, each instance of aryl is optionally substituted.
  • R 2 is
  • aryl-amino-carbonyl selected from phenyl-amino-carbonyl; wherein, each instance of aryl is optionally substituted.
  • R 2 is heterocyclyl selected from 1,2,3,6-tetrahydropyridinyl, 1,3-benzodioxolyl,
  • R 2 is heterocyclyl selected from l,2,3,6-tetrahydropyridin-4-yl, l,3-benzodioxol-5-yl or
  • R 2 is heteroaryl selected from thienyl, IH-pyrazolyl, IH-imidazolyl, 1,3-thiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, pyridinyl, pyrimidinyl, indolyl, lH-indazolyl, 2H-indazolyl, indolizinyl, benzofuranyl, benzothienyl, lH-benzimidazolyl, 1,3-benzothiazolyl, 1,3-benzooxazolyl, 9H-purinyl, furo[3,2-3 ⁇ 4]pyridinyl, furo[3,2-c]pyridinyl, furo[2,3-c]pyridinyl, thieno[3,2-c]pyridinyl, thieno[2,3-d]pyrimidinyl, lH
  • R 2 is heteroaryl selected from thien-2-yl, thien-3-yl, lH-pyrazol-3-yl, lH-pyrazol-4-yl, lH-pyrazol-5-yl,
  • R 2 is substituted heteroaryl selected from 4-methylthiophen-2-yl, l-methyl-lH-pyrazol-3-yl, 4-methyl-lH- pyrazol-3-yl, 1 -phenyl- lH-pyrazol-3-yl, 1 -phenyl- lH-imidazol-4-yl, 2-methyl-l-(pyridin-2-yl)- lH-imidazol-4-yl, 4-methyl-l,3-thiazol-2-yl, 4-(trifluoromethyl)-l,3-thiazol-2-yl, 4-phenyl-l,3- thiazol-2-yl, 5-phenyl-l,2,4-oxadiazol-3-yl, 3-fluoropyridin-4-yl, 6-fluoropyridin-2-yl, 2- chloropyridin-4-yl, 4-chloropyridin-3-yl
  • 6-cyanoimidazo[l,2-a]pyridin-2-yl also referred to as 2-imidazo[l,2-a]pyridine-6-carbonitrile
  • R 2 is heteroaryl-amino, wherein heteroaryl is selected from pyridinyl or pyrimidinyl; and, wherein, each instance of heteroaryl is optionally substituted.
  • R 2 is
  • heteroaryl-amino selected from pyridin-2-yl-amino, pyridin-3-yl-amino or pyrimidin-2-yl-amino; wherein, each instance of heteroaryl is optionally substituted.
  • a compound of Formula (I) is selected from halogen, hydroxy, cyano, nitro, Ci_galkyl, halo-Ci_galkyl, hydroxy-Ci_galkyl, Ci_galkoxy, halo-Ci_galkoxy, (Ci_galkyl) 2 -amino or Ci_galkyl-thio
  • 3 ⁇ 4 is Ci_ 8 alkyl selected from methyl, ethyl, propyl, isopropyl or tert-butyl.
  • Ci_galkyl selected from ethyl, propyl, isopropyl or tert-butyl.
  • 3 ⁇ 4 is C 2 _ 8 alkenyl selected from ethenyl, allyl or buta-l,3-dienyl.
  • a compound of Formula (I) is C 2 _galkenyl selected from ethenyl or allyl.
  • halo-Ci_galkyl selected from trihalo-methyl, dihalo-methyl, halo-methyl, trihalo-ethyl, dihalo-ethyl, halo-ethyl, trihalo-propyl, dihalo-propyl or halo-propyl; wherein, halo is selected from fluoro, chloro, bromo or iodo.
  • a compound of Formula (I) is hydroxy-Ci_galkyl selected from hydroxy-methyl, hydroxy-ethyl, hydroxy-propyl, dihydroxy-propyl, hydroxy-butyl or dihydroxy-butyl.
  • a compound of Formula (I) is hydroxy-Ci_galkyl selected from hydroxy-methyl, dihydroxy-propyl, hydroxy-butyl or dihydroxy-butyl.
  • Ci_galkoxy selected from methoxy, ethoxy, propoxy or isopropoxy.
  • R ⁇ is halo-Ci_ 8 alkoxy selected from trihalo-methoxy, dihalo-methoxy, halo-methoxy, trihalo-ethoxy, dihalo-ethoxy, halo-ethoxy, trihalo-propoxy, dihalo-propoxy or halo-propoxy; wherein, halo is selected from fluoro, chloro, bromo or iodo.
  • R 7 is C 3 _i 4 cycloalkyl, C 3 _i 4 cycloalkyl-oxy, aryl, heterocyclyl or heteroaryl; wherein C 3 -i 4 cycloalkyl is selected from cyclopropyl or cyclobutoxy; wherein aryl is selected from phenyl; wherein heterocyclyl is selected from pyrrolidinyl or 1,2,3,6-tetrahydropyridinyl; and, wherein heteroaryl is selected from thienyl or pyridinyl.
  • R 7 is C 3 _i 4 cycloalkyl or C 3 _i 4 cycloalkyl-oxy, wherein each instance of C 3 _i 4 cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.
  • R 7 is C 3 _ 8 cycloalkyl or C 3 _ 8 cycloalkyl-oxy, wherein each instance of C 3 -scycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.
  • R 7 is aryl selected from phenyl.
  • R 7 is heterocyclyl selected from pyrrolidinyl or 1,2,3,6-tetrahydropyridinyl.
  • R 7 is heterocyclyl selected from pyrrolidin-l-yl or l,2,3,6-tetrahydropyridin-4-yl.
  • R 7 is heteroaryl selected from thienyl or pyridinyl.
  • R 7 is heteroaryl selected from pyridinyl.
  • R 7 is heteroaryl selected from thien-2-yl or pyridin-2-yl.
  • R 7 is heteroaryl selected from pyridin-2-yl.
  • the compound is selected from Formula (la) or Formula (lb):
  • w 2 is C-R 2 and Ri is selected from (methyl) 2 -amino and R 2 is benzothiazol-2-yl optionally substituted with one R 6 substituent, then R ⁇ is other than chloro.
  • R 2 is benzothiazol-2-yl substituted with one, two or three R 6 substituents and one additional, optional R 7 substituent.
  • w 2 is C-R 2 and Ri is piperazin-l-yl substituted with one R 3 substituent selected from methyl, 2-fluoro- ethyl, 2-hydroxy-ethyl or 3 -hydroxy-propyl; or, one R4 substituent selected from
  • R 2 is benzothiazol-2-yl substituted with one, two or three R6 substituents and one additional, optional R 7 substituent.
  • w 2 is C-R 2 and Ri is piperazin-l-yl substituted with one R 3 substituent selected from 2-fluoro-ethyl and R 2 is imidazo[l ,2-a]pyridin-2-yl optionally substituted with one R 6 substituent, then 5 is other than chloro.
  • R 2 is benzooxazol-2-yl substituted with one, two or three 3 ⁇ 4 substituents and one additional, optional R 7 substituent.
  • w 2 is C-R 2 and Ri is selected from (methyl) 2 -amino and R 2 is benzooxazol-2-yl optionally substituted with one R 6 substituent, then R ⁇ is other than chloro.
  • R 2 is lH-benzoimidazol-2-yl substituted with one, two or three 3 ⁇ 4 substituents and one additional, optional R 7 substituent.
  • w 2 is C-R 2 and Ri is selected from (methyl) 2 -amino and R 2 is lH-benzoimidazol-2-yl substituted with one substituent, then R 6 is other than methyl.
  • the compound of Formula (I) is other than:
  • wi and w 2 are C-Ri or C-R 2 ; wherein, one of wi and w 2 is C-Ri and the other is C-R 2 , provided that, when wi is C-Ri, then w 2 is C-R 2 ; or, when wi is C-R 2 , then w 2 is C-Ri;
  • Ri is amino, Ci.galkoxy-Ci.galkyl-amino, (Ci_ 8 alkoxy-Ci_ 8 alkyl) 2 -amino,
  • Ci_8alkyl-amino-C i.salkyl-amino (C i_8alkyl-amino-C i_8alkyl) 2 -amino,
  • Ci_ 8 alkyl-amino-C 2 - 8 alkynyl Ci_ 8 alkyl-amino-C 2 - 8 alkynyl, (Ci_ 8 alkyl) 2 -amino-C 2 - 8 alkynyl,
  • halo-Ci_ 8 alkyl-amino (halo-Ci_ 8 alkyl) 2 -amino, hydroxy-Ci_salkyl, hydroxy-Ci.galkoxy-Ci.galkyl, hydroxy-Ci-galkyl-amino, (hydroxy-Ci_8alkyl) 2 -amino, (hydroxy-Ci_8alkyl)(Ci_8alkyl)amino, hydroxy-Ci-galkyl-amino-Ci-galkyl, (hydroxy-Ci_ 8 alkyl) 2 -amino-Ci_ 8 alkyl,
  • heterocyclyl-Ci_salkyl heterocyclyl-Ci_salkoxy, heterocyclyl-amino
  • heterocyclyl (Ci_8alkyl)amino
  • heterocyclyl-amino-Ci_8alkyl heterocyclyl-Ci_8alkyl-amino
  • heterocyclyl-Ci_8alkyl 2 -amino
  • heterocyclyl-Ci_8alkyl (heterocyclyl-Ci_8alkyl)(Ci_8alkyl)amino
  • heterocyclyl-Ci_ 8 alkyl-amino-Ci_ 8 alkyl (heterocyclyl-Ci_ 8 alkyl) 2 -amino-Ci_ 8 alkyl,
  • heterocyclyl-Ci_ 8 alkyl (Ci_ 8 alkyl)amino-Ci_ 8 alkyl, heterocyclyl-oxy, heterocyclyl-carbonyl, heterocyclyl-carbonyl-oxy, aryl-Ci_8alkyl-amino, (aryl-Ci_8alkyl) 2 -amino,
  • aryl-Ci_ 8 alkyl 2 -amino-Ci_ 8 alkyl, (aryl-Ci_ 8 alkyl)(Ci_ 8 alkyl)amino-Ci_ 8 alkyl, heteroaryl, heteroaryl-Ci_salkyl, heteroaryl-Ci_galkoxy, heteroaryl-amino, heteroaryl-Ci.galkyl-amino, (heteroaryl-Ci_8alkyl) 2 -amino, (heteroaryl-Ci_8alkyl)(Ci_8alkyl)amino,
  • heteroaryl-Ci_ 8 alkyl-amino-Ci_ 8 alkyl (heteroaryl-Ci_ 8 alkyl) 2 -amino-Ci_ 8 alkyl or
  • each instance of heterocyclyl and heteroaryl is optionally substituted with one, two or three R 3 substituents and one additional, optional R 4 substituent;
  • each instance of heterocyclyl and heteroaryl is optionally substituted with one, two, three or four R 3 substituents;
  • R 2 is aryl, aryl-amino, aryl-amino-carbonyl, heterocyclyl, heteroaryl or heteroaryl-amino;
  • each instance of aryl, heterocyclyl and heteroaryl is optionally substituted with one, two or three 3 ⁇ 4 substituents and one additional, optional R 7 substituent;
  • Ra is, in each instance, independently selected from hydrogen, halogen, Ci_ 8 alkyl or deuterium;
  • R b is hydrogen, halogen, Ci_ 8 alkyl, Ci_ 8 alkoxy or deuterium;
  • R 3 is, in each instance, independently selected from cyano, halogen, hydroxy, oxo, Ci.galkyl, halo-Ci_galkyl, Ci_galkyl-carbonyl, Ci_galkoxy, halo-Ci_galkoxy, Ci_galkoxy-Ci_galkyl, Ci_galkoxy-carbonyl, amino, Ci_galkyl-amino, (Ci_galkyl) 2 -amino, amino-Ci_galkyl,
  • Ci_galkoxy-Ci_galkyl-amino Ci_galkyl-carbonyl-amino, Ci_galkoxy-carbonyl-amino,
  • R4 is C 3 -i 4 cycloalkyl, C 3 _i 4 cycloalkyl-Ci_ 8 alkyl, C 3 _i 4 cycloalkyl-amino, aryl-Ci_ 8 alkyl, aryl-Ci_ 8 alkoxy-carbonyl, heterocyclyl or heterocyclyl-Ci_ 8 alkyl; wherein, each instance of C 3 _i 4 cycloalkyl, aryl and heterocyclyl is optionally substituted with one, two or three R 5 substituents;
  • R 5 is, in each instance, independently selected from halogen, hydroxy, cyano, nitro, Ci_ 8 alkyl, halo-Ci_ 8 alkyl, Ci_ 8 alkoxy, halo-Ci_ 8 alkoxy, amino, Ci_ 8 alkyl-amino,
  • Ci_ 8 alkyl 2 -amino or Ci_ 8 alkyl-thio
  • Re is, in each instance, independently selected from halogen, hydroxy, cyano, nitro, Ci_ 8 alkyl, halo-Ci_ 8 alkyl, hydroxy-Ci_ 8 alkyl, Ci_ 8 alkoxy, halo-Ci_ 8 alkoxy, amino,
  • Ci_ 8 alkyl-amino (Ci_ 8 alkyl) 2 -amino or Ci_ 8 alkyl-thio;
  • R 7 is C 3 _i 4 cycloalkyl, C 3 _i 4 cycloalkyl-oxy, aryl, heterocyclyl or heteroaryl.
  • R 3 is, in each instance, independently selected from cyano, halogen, hydroxy, oxo, Ci_ 8 alkyl-carbonyl, Ci_ 8 alkoxy, halo-Ci_ 8 alkoxy, Ci_ 8 alkoxy-Ci_ 8 alkyl, Ci_ 8 alkoxy-carbonyl, amino, Ci_ 8 alkyl-amino,
  • a compound of Formula (I) is, in each instance, independently selected from hydroxy, cyano, nitro, halo-Ci_ 8 alkyl, hydroxy-Ci_ 8 alkyl,
  • R 7 is C 3 _i 4 cycloalkyl, C 3 _i 4 Cycloalkyl-oxy, aryl or heterocyclyl.
  • the compound of Formula (I) used in a method disclosed herein is a com ound from the group consisting of:
  • the compound of Formula (I) used in a method disclosed herein is a compound selected from the group consisting of:

Abstract

La présente invention concerne des procédés permettant de moduler la quantité d'un produit génétique et des composés destinés à être utilisés dans de tels procédés. Plus particulièrement, l'invention concerne des procédés permettant de moduler la quantité d'un produit de la transcription d'ARN ou d'un produit protéinique résultats de l'expression génétique et des composés destinés à être utilisés dans de tels procédés.
PCT/US2014/071032 2013-12-19 2014-12-18 Procédés pour la modulation de la quantité de produits de la transcription d'arn WO2015095449A1 (fr)

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US10195202B2 (en) 2013-12-19 2019-02-05 Ptc Therapeutics, Inc. Methods for modulating the amount of RNA transcripts
US10688099B2 (en) 2013-12-19 2020-06-23 Ptc Therapeutics, Inc. Methods for modulating the amount of RNA transcripts
US9944628B2 (en) 2014-12-11 2018-04-17 President And Fellows Of Harvard College Inhibitors of cellular necrosis and related methods
US10508102B2 (en) 2014-12-11 2019-12-17 President And Fellows Of Harvard College Inhibitors of cellular necrosis and related methods
US9499521B2 (en) 2014-12-11 2016-11-22 President And Fellows Of Harvard College Inhibitors of cellular necrosis and related methods
US11602567B2 (en) 2015-05-30 2023-03-14 Ptc Therapeutics, Inc. Methods for modulating RNA splicing
US10668171B2 (en) 2015-05-30 2020-06-02 Ptc Therapeutics, Inc. Methods for modulating RNA splicing
US11638706B2 (en) 2015-12-10 2023-05-02 Ptc Therapeutics, Inc. Methods for treating Huntington's disease
US10881658B2 (en) 2015-12-10 2021-01-05 Ptc Therapeutics, Inc. Methods for treating Huntington's disease
US10874672B2 (en) 2015-12-10 2020-12-29 Ptc Therapeutics, Inc. Methods for treating Huntington's disease
US11702646B2 (en) 2016-11-28 2023-07-18 Ptc Therapeutics, Inc. Methods for modulating RNA splicing
US11407753B2 (en) 2017-06-05 2022-08-09 Ptc Therapeutics, Inc. Compounds for treating Huntington's disease
US11608501B2 (en) 2017-06-14 2023-03-21 Ptc Therapeutics, Inc. Methods for modifying RNA splicing
US11382918B2 (en) 2017-06-28 2022-07-12 Ptc Therapeutics, Inc. Methods for treating Huntington's Disease
US11395822B2 (en) 2017-06-28 2022-07-26 Ptc Therapeutics, Inc. Methods for treating Huntington's disease
US10730874B2 (en) 2018-03-13 2020-08-04 Shire Human Genetic Therapies, Inc. Inhibitors of plasma kallikrein and uses thereof
US11352356B2 (en) 2018-03-13 2022-06-07 Takeda Pharmaceutical Company Limited Inhibitors of plasma kallikrein and uses thereof
US11780839B2 (en) 2018-03-27 2023-10-10 Ptc Therapeutics, Inc. Compounds for treating Huntington's disease
US11685746B2 (en) 2018-06-27 2023-06-27 Ptc Therapeutics, Inc. Heteroaryl compounds for treating Huntington's disease
US11858941B2 (en) 2018-06-27 2024-01-02 Ptc Therapeutics, Inc. Heterocyclic and heteroaryl compounds for treating Huntington's disease
US11370803B2 (en) 2019-09-18 2022-06-28 Takeda Pharmaceutical Company Limited Heteroaryl plasma kallikrein inhibitors
US11787796B2 (en) 2019-09-18 2023-10-17 Takeda Pharmaceutical Company Limited Plasma Kallikrein inhibitors and uses thereof
WO2021169762A1 (fr) * 2020-02-25 2021-09-02 苏州大学 Marqueur de fluorescence mitochondrial neutre basé sur un hétérocycle contenant de l'azote, procédé de préparation correspondant et utilisation associée
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