US2017204073A1PendingUtilityA1
Compounds for nonsense suppression, and methods for their use
Est. expiryOct 13, 2024(expired)· nominal 20-yr term from priority
Inventors:Neil Gregory AlmsteadGuangming ChenGary Mitchell KarpEllen WelchRichard WildeJeffrey Allen Campbell
A61P 37/06A61P 9/10A61P 43/00A61P 9/00A61P 3/06A61P 7/00A61P 3/10A61P 7/04A61P 35/02A61P 37/02A61P 5/14A61P 37/00A61P 25/00A61P 3/04A61P 27/02A61P 25/28A61P 35/00A61P 25/16A61P 29/00C07D 249/08C07D 417/04C07D 333/24C07D 263/32C07D 403/04C07D 231/12A61P 19/02C07D 413/12C07D 285/12C07D 271/10C07D 271/06A61P 1/16C07D 271/107A61P 13/12A61P 11/00C07D 307/68A61P 19/08C07D 413/04C07F 9/65306C07D 233/64C07D 405/04A61P 21/00C07D 401/04C07D 413/06A61P 19/00C07D 261/08C07D 251/24C07D 277/30C07D 409/04A61K 31/53A61K 31/4155
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Claims
Abstract
The present invention relates to methods, compounds, and compositions for treating or preventing diseases associated with nonsense mutations in an mRNA by administering the compounds or compositions of the present invention. More particularly, the present invention relates to methods, compounds, and compositions for suppressing premature translation termination associated with a nonsense mutation in an mRNA.
Claims
exact text as granted — not AI-modified1 .- 31 . (canceled)
32 . A compound of Formula (1-C) or Formula (1-D):
wherein:
R 1 is hydrogen, C 1 -C 6 alkyl, or Na + , or Mg 2+ ;
R 3 is absent or independently selected from halogen, hydroxy, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, or nitro;
W is selected from:
(a) a C 2 -C 6 alkynyl, optionally substituted with a phenyl;
(b) a C 1 -C 8 straight chain or branched chain alkyl which is optionally substituted with one or more of the following independently selected groups: a C 1 -C 6 alkyl; a halogen; a —C(═O)—NH-phenyl which phenyl is optionally substituted with one or more independently selected halogens or C 1 -C 4 alkyl groups; a five to six-membered heterocycle; a C 6 -C 8 aryl which is optionally substituted with one or more groups independently selected from a hydroxy, a halogen, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group or an amino group which is optionally substituted with one or more C 1 -C 4 alkyl groups; an aryloxy which is optionally substituted with one or more of the following independently selected groups: a hydroxy, a halogen, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group or an amino group which is optionally substituted with one or more C 1 -C 4 alkyl groups;
(c) a C 2 to C 8 alkenyl;
(d) a C 3 -C 8 cycloalkyl optionally substituted with a C 1 -C 6 alkyl;
(e) a C 6 -C 8 aryl which is optionally substituted with one or more of the following independently selected groups: a hydroxy; a halogen; a C 1 -C 4 straight chain or branched chain alkyl which is optionally substituted with one or more independently selected halogen or hydroxy groups; a C 1 -C 4 alkoxy which is optionally substituted with one or more independently selected halogen or phenyl groups; a C 3 -C 8 cycloalkyl which is optionally substituted with one or more independently selected C 1 -C 4 alkyl groups; a C 6 -C 8 aryl which is optionally substituted with one or more independently selected C 1 -C 4 alkyl groups; an aryloxy which is optionally substituted with one or more of the following independently selected groups: a hydroxy, a halogen, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, or an amino group which is optionally substituted with one or more independently selected C 1 -C 4 alkyl groups; a five to six-membered heterocycle which is optionally substituted with one or more independently selected C 1 -C 4 alkyl, oxo, or C 6 -C 8 aryl which is optionally substituted with one or more of the following independently selected groups: a hydroxy, a halogen, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, or an amino group which is optionally substituted with one or more independently selected C 1 -C 4 alkyl groups; a naphthyl group which is optionally substituted with an amino or aminoalkyl or alkoxy group; a —C(O)—NR x R y group; a —C(O)—R x group; a isoindole-1,3-dione group; a nitro group; a cyano group; a —SO 3 H group; alkylthio group; alkyl sulfonyl group; a —NR x —C(O)—R z group; a —NR x R y group; a —NR x —SO 2 —R z group; a —NR x —C(O)—NR x R y group; a —NR x —C(O)O—R z group;
(f) a C 10 -C 14 aryl group optionally substituted with one or more independently selected halogens, amino groups or aminoalkyl groups, or alkoxy groups;
(g) a —C(O)—NR x R y group;
(h) a five or six membered heterocycle which is optionally substituted with one or more independently selected oxo groups; halogens; C 1 -C 4 alkyl groups; C 1 -C 4 alkoxy groups; C 1 -C 4 haloalkyl groups; C 1 -C 4 haloalkoxy groups; aryloxy groups; —NR x R y groups; alkylthio groups; —C(O)—R x groups; or C 6 to C 8 aryl groups which are optionally substituted with one or more independently selected halogens, C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups;
(i) a heterocycle group having two to three ring structures that is optionally substituted with one or more independently selected halogens, oxo groups, C 1 -C 4 alkyl groups, C 1 -C 4 haloalkyl groups, or C 1 -C 4 alkoxy groups;
wherein R x is hydrogen, a C 1 -C 6 alkyl group, or R x and R y together with the atoms to which they are attached form a four to seven membered carbocycle or heterocycle;
R y is hydrogen, a C 1 -C 6 alkyl group; an aryl group optionally substituted with one or more independently selected C 1 -C 4 alkyl groups, or R x and R y together with the atoms to which they are attached form a four to seven membered carbocycle or heterocycle; and
R z is an C 1 -C 6 alkyl optionally substituted with an aryl or a halogen; or an aryl optionally substituted with a halogen, a C 1 -C 6 alkyl, or a C 1 -C 6 alkoxy;
or a pharmaceutically acceptable salt, hydrate, solvate, clathrate, racemate, stereoisomer, or polymorph thereof.
33 . The compound of claim 32 , wherein:
R 1 is hydrogen, C 1 -C 6 alkyl, or Na + , or Mg 2+ ; R 3 is absent or independently selected from halogen, hydroxy, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, or nitro; W is selected from:
(a) a C 1 -C 8 straight chain or branched chain alkyl which is optionally substituted with one or more of the following: a C 1 -C 6 alkyl, a halogen, a five to six-membered heterocycle, a C 6 -C 8 aryl which is optionally substituted with one or more of the following: a hydroxy, a halogen, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group or an amino group which is optionally substituted with one or more C 1 -C 4 alkyl groups; an aryloxy which is optionally substituted with one or more of the following: a hydroxy, a halogen, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group or an amino group which is optionally substituted with one or more C 1 -C 4 alkyl groups;
(b) a C 2 to C 8 alkenyl;
(c) a C 3 -C 8 cycloalkyl optionally substituted with a C 1 to C 6 alkyl;
(d) a C 6 -C 8 aryl which is optionally substituted with one or more of the following: a hydroxy, a halogen; a C 1 -C 4 straight chain or branched chain alkyl which is optionally substituted with one or more independently selected halogen or hydroxy groups; a C 1 -C 4 alkoxy which is optionally substituted with one or more independently selected halogen or phenyl groups; a C 3 -C 8 cycloalkyl which is optionally substituted with one or more independently selected C 1 -C 4 alkyl groups; a C 6 -C 8 aryl which is optionally substituted with one or more independently selected C 1 -C 4 alkyl groups; an aryloxy which is optionally substituted with one or more of the following: a hydroxy, a halogen, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, or an amino group which is optionally substituted with one or more C 1 -C 4 alkyl groups; a five to six-membered heterocycle which is optionally substituted with one or more independently selected C 1 -C 4 alkyl, oxo, or C 6 -C 8 aryl which is optionally substituted with one or more of the following: a hydroxy, a halogen, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, or an amino group which is optionally substituted with one or more C 1 -C 4 alkyl groups; a naphthyl group which is optionally substituted with an amino or aminoalkyl group; a —C(O)—NR x R y group; a —C(O)—R x group; a isoindole-1,3-dione group; a nitro group; a cyano group; a —SO 3 H group; alkylthio group; alkyl sulfonyl group; a —NR x —C(O)—R z group; a —NR x R y group; a —NR x —SO 2 —R z group; a —NR x —C(O)—NR x R y group; a —NR x —C(O)O—R z group;
(e) a —C(O)—NR x R y group;
(f) a five or six membered heterocycle which is optionally substituted with one or more oxo groups, halogens, C 1 to C 4 alkyl groups, C 1 to C 4 haloalkyl groups, —C(O)—R x groups, and/or C 6 to C 8 aryl groups which are optionally substituted with one or more independently selected halogens, C 1 to C 4 alkyl groups, C 1 to C 4 alkoxy groups, aryloxy groups, —NR x R y groups, and/or alkylthio groups;
(g) a heterocycle group having two to three ring structures that is optionally substituted with one or more halogens, C 1 to C 4 alkyl groups, C 1 to C 4 haloalkyl groups, and/or C 1 to C 4 alkoxy groups;
wherein R x is hydrogen, a C 1 to C 6 alkyl group, or R x and R y together with the atoms to which they are attached form a four to seven membered carbocycle or heterocycle;
R y is hydrogen, a C 1 to C 6 alkyl group; an optionally substituted aryl, or R x and R y together with the atoms to which they are attached form a four to seven membered carbocycle or heterocycle; and
R z is an C 1 to C 6 alkyl optionally substituted with an aryl or a halogen; or an aryl optionally substituted with a halogen, a C 1 to C 6 alkyl, or a C 1 to C 6 alkoxy;
or a pharmaceutically acceptable salt, hydrate, solvate, clathrate, racemate, stereoisomer, or polymorph thereof.
34 . The compound of claim 32 , wherein the compound of Formula (1-D) is selected from a compound of Formula (1-D1):
wherein all other variables are as previously defined.
35 . The compound of claim 32 , wherein W is selected from the group consisting of:
36 . The compound of claim 32 , wherein the compound of Formula (1-C) is selected from the group consisting of:
and a pharmaceutically acceptable salt, hydrate, solvate, clathrate, racemate, stereoisomer or polymorph thereof.
37 . The compound of claim 32 , wherein the compound of Formula (1-D) is selected from the group consisting of:
and a pharmaceutically acceptable salt, hydrate, solvate, clathrate, racemate, stereoisomer or polymorph thereof.
38 . A method for preventing or treating a disease associated with a gene having a nonsense mutation encoding a premature stop codon in mRNA in a patient in need thereof, comprising administering to said patient a compound of Formula (1-C) or Formula (1-D)
wherein:
R 1 is hydrogen, C 1 -C 6 alkyl, or Na + , or Mg 2+ ;
R 3 is absent or independently selected from halogen, hydroxy, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, or nitro;
W is selected from:
(a) a C 2 -C 6 alkynyl, optionally substituted with a phenyl;
(b) a C 1 -C 8 straight chain or branched chain alkyl which is optionally substituted with one or more of the following independently selected groups: a C 1 -C 6 alkyl; a halogen; a —C(═O)—NH-phenyl which phenyl is optionally substituted with one or more independently selected halogens or C 1 -C 4 alkyl groups; a five to six-membered heterocycle; a C 6 -C 8 aryl which is optionally substituted with one or more groups independently selected from a hydroxy, a halogen, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group or an amino group which is optionally substituted with one or more C 1 -C 4 alkyl groups; an aryloxy which is optionally substituted with one or more of the following independently selected groups: a hydroxy, a halogen, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group or an amino group which is optionally substituted with one or more C 1 -C 4 alkyl groups;
(c) a C 2 to C 8 alkenyl;
(d) a C 3 -C 8 cycloalkyl optionally substituted with a C 1 -C 6 alkyl;
(e) a C 6 -C 8 aryl which is optionally substituted with one or more of the following independently selected groups: a hydroxy; a halogen; a C 1 -C 4 straight chain or branched chain alkyl which is optionally substituted with one or more independently selected halogen or hydroxy groups; a C 1 -C 4 alkoxy which is optionally substituted with one or more independently selected halogen or phenyl groups; a C 3 -C 8 cycloalkyl which is optionally substituted with one or more independently selected C 1 -C 4 alkyl groups; a C 6 -C 8 aryl which is optionally substituted with one or more independently selected C 1 -C 4 alkyl groups; an aryloxy which is optionally substituted with one or more of the following independently selected groups: a hydroxy, a halogen, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, or an amino group which is optionally substituted with one or more independently selected C 1 -C 4 alkyl groups; a five to six-membered heterocycle which is optionally substituted with one or more independently selected C 1 -C 4 alkyl, oxo, or C 6 -C 8 aryl which is optionally substituted with one or more of the following independently selected groups: a hydroxy, a halogen, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, or an amino group which is optionally substituted with one or more independently selected C 1 -C 4 alkyl groups; a naphthyl group which is optionally substituted with an amino or aminoalkyl or alkoxy group; a —C(O)—NR x R y group; a —C(O)—R x group; a isoindole-1,3-dione group; a nitro group; a cyano group; a —SO 3 H group; alkylthio group; alkyl sulfonyl group; a —NR x —C(O)—R z group; a —NR x R y group; a —NR x —SO 2 —R z group; a —NR x —C(O)—NR x R y group; a —NR x —C(O)O—R z group;
(f) a C 10 -C 14 aryl group optionally substituted with one or more independently selected halogens, amino groups or aminoalkyl groups, or alkoxy groups;
(g) a —C(O)—NR x R y group;
(h) a five or six membered heterocycle which is optionally substituted with one or more independently selected oxo groups; halogens; C 1 -C 4 alkyl groups; C 1 -C 4 alkoxy groups; C 1 -C 4 haloalkyl groups; C 1 -C 4 haloalkoxy groups; aryloxy groups; —NR x R y groups; alkylthio groups; —C(O)—R x groups; or C 6 to C 8 aryl groups which are optionally substituted with one or more independently selected halogens, C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups;
(i) a heterocycle group having two to three ring structures that is optionally substituted with one or more independently selected halogens, oxo groups, C 1 -C 4 alkyl groups, C 1 -C 4 haloalkyl groups, or C 1 -C 4 alkoxy groups;
wherein R x is hydrogen, a C 1 -C 6 alkyl group, or R x and R y together with the atoms to which they are attached form a four to seven membered carbocycle or heterocycle;
R y is hydrogen, a C 1 -C 6 alkyl group; an aryl group optionally substituted with one or more independently selected C 1 -C 4 alkyl groups, or R x and R y together with the atoms to which they are attached form a four to seven membered carbocycle or heterocycle; and
R z is an C 1 -C 6 alkyl optionally substituted with an aryl or a halogen; or an aryl optionally substituted with a halogen, a C 1 -C 6 alkyl, or a C 1 -C 6 alkoxy;
or a pharmaceutically acceptable salt, hydrate, solvate, clathrate, racemate, stereoisomer, or polymorph thereof,
wherein the premature stop codon results in either or both premature mRNA translation termination or nonsense-mediated mRNA decay, and wherein the disease is selected from cancer, a lysosomal storage disorder, an autoimmune disease, a blood disease, a collagen disease, diabetes, a cardiovascular disease, a pulmonary disease, an inflammatory disease, a central nervous system disease, heart disease, kidney disease, a muscular dystrophy, macular degeneration, retinitis pigmentosa, amyloidosis, giantism, dwarfism, hypothyroidism, hyperthyroidism, aging or obesity.
39 . The method of claim 38 , wherein:
R 1 is hydrogen, C 1 -C 6 alkyl, or Na + , or Mg 2+ ; R 3 is absent or independently selected from halogen, hydroxy, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, or nitro; W is selected from:
(a) a C 1 -C 8 straight chain or branched chain alkyl which is optionally substituted with one or more of the following: a C 1 -C 6 alkyl, a halogen, a five to six-membered heterocycle, a C 6 -C 8 aryl which is optionally substituted with one or more of the following: a hydroxy, a halogen, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group or an amino group which is optionally substituted with one or more C 1 -C 4 alkyl groups; an aryloxy which is optionally substituted with one or more of the following: a hydroxy, a halogen, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group or an amino group which is optionally substituted with one or more C 1 -C 4 alkyl groups;
(b) a C 2 to C 8 alkenyl;
(c) a C 3 -C 8 cycloalkyl optionally substituted with a C 1 to C 6 alkyl;
(d) a C 6 -C 8 aryl which is optionally substituted with one or more of the following: a hydroxy, a halogen; a C 1 -C 4 straight chain or branched chain alkyl which is optionally substituted with one or more independently selected halogen or hydroxy groups; a C 1 -C 4 alkoxy which is optionally substituted with one or more independently selected halogen or phenyl groups; a C 3 -C 8 cycloalkyl which is optionally substituted with one or more independently selected C 1 -C 4 alkyl groups; a C 6 -C 8 aryl which is optionally substituted with one or more independently selected C 1 -C 4 alkyl groups; an aryloxy which is optionally substituted with one or more of the following: a hydroxy, a halogen, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, or an amino group which is optionally substituted with one or more C 1 -C 4 alkyl groups; a five to six-membered heterocycle which is optionally substituted with one or more independently selected C 1 -C 4 alkyl, oxo, or C 6 -C 8 aryl which is optionally substituted with one or more of the following: a hydroxy, a halogen, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, or an amino group which is optionally substituted with one or more C 1 -C 4 alkyl groups; a naphthyl group which is optionally substituted with an amino or aminoalkyl group; a —C(O)—NR x R y group; a —C(O)—R x group; a isoindole-1,3-dione group; a nitro group; a cyano group; a —SO 3 H group; alkylthio group; alkyl sulfonyl group; a —NR x —C(O)—R z group; a —NR x R y group; a —NR x —SO 2 —R z group; a —NR x —C(O)—NR x R y group; a —NR x —C(O)O—R z group;
(e) a —C(O)—NR x R y group;
(f) a five or six membered heterocycle which is optionally substituted with one or more oxo groups, halogens, C 1 to C 4 alkyl groups, C 1 to C 4 haloalkyl groups, —C(O)—R x groups, and/or C 6 to C 8 aryl groups which are optionally substituted with one or more independently selected halogens, C 1 to C 4 alkyl groups, C 1 to C 4 alkoxy groups, aryloxy groups, —NR x R y groups, and/or alkylthio groups;
(g) a heterocycle group having two to three ring structures that is optionally substituted with one or more halogens, C 1 to C 4 alkyl groups, C 1 to C 4 haloalkyl groups, and/or C 1 to C 4 alkoxy groups;
wherein R x is hydrogen, a C 1 to C 6 alkyl group, or R x and R y together with the atoms to which they are attached form a four to seven membered carbocycle or heterocycle;
R y is hydrogen, a C 1 to C 6 alkyl group; an optionally substituted aryl, or R x and R y together with the atoms to which they are attached form a four to seven membered carbocycle or heterocycle; and
R z is an C 1 to C 6 alkyl optionally substituted with an aryl or a halogen; or an aryl optionally substituted with a halogen, a C 1 to C 6 alkyl, or a C 1 to C 6 alkoxy;
or a pharmaceutically acceptable salt, hydrate, solvate, clathrate, racemate, stereoisomer, or polymorph thereof.
40 . The method of claim 38 , wherein the compound of Formula (1-D) is selected from a compound of Formula (1-D1):
wherein all other variables are as previously defined.
41 . The method of claim 38 , wherein W for the compound of Formula (1-C) or (1-D) is selected from the group consisting of:
42 . The method of claim 38 , wherein the autoimmune disease is immunodeficiency, severe combined immunodeficiency, rheumatoid arthritis or graft versus host disease; wherein the blood disease is familial polycythemia, hemophilia, Von Willebrand disease, ataxia-telangiectasia or β-thalassemia; wherein the collagen disease is epidermolysis bullosa, Marfan syndrome, osteogenesis imperfecta or cirrhosis; wherein the inflammatory disease is arthritis, rheumatoid arthritis or osteoarthritis; wherein the central nervous system disease is multiple sclerosis, classical late infantile neuronal ceroid lipofuscinosis, Alzheimer's disease or Tay Sachs disease; wherein the lysosomal storage disorder is tuberous sclerosis, Niemann Pick disease, mucopolysaccharidosis type VII, metachromatic leukodystrophy, Sandhoff disease, mucopolysaccharidosis type IIIA or mucopolysaccharidosis type VI; wherein the kidney disease is kidney stones; wherein the cardiovascular disease is familial hypercholesterolemia or atherosclerosis; wherein the pulmonary disease is cystic fibrosis; and, wherein the muscular dystrophy is Duchenne muscular dystrophy.
43 . The method of claim 38 , wherein the disease is cancer associated with a genetic or a somatic nonsense mutation in a tumor suppressor gene in a human subject in need thereof.
44 . The method of claim 43 , wherein the tumor suppressor gene is selected from the group consisting of PTEN, BRCA1, BRCA2, Rb, and p53.
45 . The method of claim 43 , wherein the cancer is of the head and neck, eye, skin, mouth, throat, esophagus, chest, bone, blood, lung, colon, sigmoid, rectum, stomach, prostate, breast, ovaries, kidney, liver, pancreas, brain, intestine, heart or adrenals.
46 . The method of claim 43 , wherein the cancer is a solid tumor cancer selected from sarcoma, carcinoma, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms' tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, Kaposi's sarcoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, menangioma, melanoma, neuroblastoma or retinoblastoma.
47 . The method of claim 43 , wherein the cancer is a blood-born tumor selected from acute lymphoblastic leukemia, acute lymphoblastic B-cell leukemia, acute lymphoblastic T-cell leukemia, acute myeloblastic leukemia, acute promyelocytic leukemia, acute monoblastic leukemia, acute erythroleukemic leukemia, acute megakaryoblastic leukemia, acute myelomonocytic leukemia, acute nonlymphocytic leukemia, acute undifferentiated leukemia, chronic myelocytic leukemia, chronic lymphocytic leukemia, hairy cell leukemia, or multiple myeloma.
48 . The method of claim 38 , for inhibiting the growth of a cancer cell or for selectively producing a protein in a mammal by the suppression of a genetic or somatic nonsense mutation.
49 . The method of claim 38 , wherein the compound of Formula 1-C is selected from the group consisting of:
and a pharmaceutically acceptable salt, hydrate, solvate, clathrate, racemate, stereoisomer or polymorph thereof.
50 . The method of claim 38 , wherein the compound of Formula 1-D is selected from the group consisting of:
and a pharmaceutically acceptable salt, hydrate, solvate, clathrate, racemate, stereoisomer or polymorph thereof.Cited by (0)
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