BRPI0708619A2 - uso de um composto, e, métodos para previnir e/ou tratar distúrbios ou condições relacionados com o osso, para previnir e/ou tratar osteoporose, para aumentar a formação óssea, para aumentar a densidade mineral óssea, para reduzir a incidência de fratura, e para realçar a cicatrização da fratura - Google Patents
uso de um composto, e, métodos para previnir e/ou tratar distúrbios ou condições relacionados com o osso, para previnir e/ou tratar osteoporose, para aumentar a formação óssea, para aumentar a densidade mineral óssea, para reduzir a incidência de fratura, e para realçar a cicatrização da fratura Download PDFInfo
- Publication number
- BRPI0708619A2 BRPI0708619A2 BRPI0708619-9A BRPI0708619A BRPI0708619A2 BR PI0708619 A2 BRPI0708619 A2 BR PI0708619A2 BR PI0708619 A BRPI0708619 A BR PI0708619A BR PI0708619 A2 BRPI0708619 A2 BR PI0708619A2
- Authority
- BR
- Brazil
- Prior art keywords
- pyridin
- carboxamide
- amino
- methylpiperazin
- phenyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 60
- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 54
- 230000011164 ossification Effects 0.000 title claims abstract description 32
- 238000000034 method Methods 0.000 title claims abstract description 31
- 208000001132 Osteoporosis Diseases 0.000 title claims abstract description 20
- 229910052500 inorganic mineral Inorganic materials 0.000 title claims abstract description 17
- 239000011707 mineral Substances 0.000 title claims abstract description 17
- 230000035876 healing Effects 0.000 title claims abstract description 9
- 230000001965 increasing effect Effects 0.000 title claims description 21
- 206010017076 Fracture Diseases 0.000 title claims description 17
- 208000010392 Bone Fractures Diseases 0.000 title claims description 16
- 208000020084 Bone disease Diseases 0.000 title claims description 11
- 230000002708 enhancing effect Effects 0.000 title claims description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 33
- 239000012458 free base Substances 0.000 claims abstract description 29
- 238000011282 treatment Methods 0.000 claims abstract description 22
- -1 4-methyl-1,4 -diazepan-1-yl Chemical group 0.000 claims abstract description 17
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 17
- 239000003814 drug Substances 0.000 claims abstract description 17
- 239000001257 hydrogen Substances 0.000 claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 238000004519 manufacturing process Methods 0.000 claims abstract description 11
- 230000002265 prevention Effects 0.000 claims abstract description 11
- 208000035475 disorder Diseases 0.000 claims abstract description 10
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000011737 fluorine Substances 0.000 claims abstract description 8
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 8
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract 4
- 241000124008 Mammalia Species 0.000 claims description 35
- 150000002431 hydrogen Chemical group 0.000 claims description 6
- SSXRGZQGLUZVSY-UHFFFAOYSA-N 3-amino-n-pyridin-3-yl-6-(4-sulfamoylphenyl)pyrazine-2-carboxamide Chemical group NC1=NC=C(C=2C=CC(=CC=2)S(N)(=O)=O)N=C1C(=O)NC1=CC=CN=C1 SSXRGZQGLUZVSY-UHFFFAOYSA-N 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- SIHCAYJFXRKGEG-UHFFFAOYSA-N 3-amino-6-(4-piperazin-1-ylsulfonylphenyl)-n-pyridin-3-ylpyrazine-2-carboxamide Chemical group NC1=NC=C(C=2C=CC(=CC=2)S(=O)(=O)N2CCNCC2)N=C1C(=O)NC1=CC=CN=C1 SIHCAYJFXRKGEG-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 241000251539 Vertebrata <Metazoa> Species 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- YBHIUCZMSLXCCR-UHFFFAOYSA-N 3-amino-6-[2,5-difluoro-4-(4-methylpiperazin-1-yl)sulfonylphenyl]-n-pyridin-3-ylpyrazine-2-carboxamide Chemical compound C1CN(C)CCN1S(=O)(=O)C1=CC(F)=C(C=2N=C(C(N)=NC=2)C(=O)NC=2C=NC=CC=2)C=C1F YBHIUCZMSLXCCR-UHFFFAOYSA-N 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 239000007943 implant Substances 0.000 description 56
- 241000700159 Rattus Species 0.000 description 15
- 102000002254 Glycogen Synthase Kinase 3 Human genes 0.000 description 9
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 9
- FHCSBLWRGCOVPT-UHFFFAOYSA-N AZD2858 Chemical compound C1CN(C)CCN1S(=O)(=O)C1=CC=C(C=2N=C(C(N)=NC=2)C(=O)NC=2C=NC=CC=2)C=C1 FHCSBLWRGCOVPT-UHFFFAOYSA-N 0.000 description 8
- 102000003982 Parathyroid hormone Human genes 0.000 description 8
- 108090000445 Parathyroid hormone Proteins 0.000 description 8
- 238000002513 implantation Methods 0.000 description 8
- 239000000199 parathyroid hormone Substances 0.000 description 8
- 229960001319 parathyroid hormone Drugs 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- 210000000689 upper leg Anatomy 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- PPCLIZMPLOGMKQ-UHFFFAOYSA-N 3-pyridin-3-ylpyrazine-2-carboxamide Chemical compound NC(=O)C1=NC=CN=C1C1=CC=CN=C1 PPCLIZMPLOGMKQ-UHFFFAOYSA-N 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 229910052751 metal Inorganic materials 0.000 description 5
- 239000002184 metal Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 102000004067 Osteocalcin Human genes 0.000 description 4
- 108090000573 Osteocalcin Proteins 0.000 description 4
- 239000004053 dental implant Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000000399 orthopedic effect Effects 0.000 description 4
- 210000000963 osteoblast Anatomy 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 208000006386 Bone Resorption Diseases 0.000 description 3
- 102000055006 Calcitonin Human genes 0.000 description 3
- 108060001064 Calcitonin Proteins 0.000 description 3
- 238000008157 ELISA kit Methods 0.000 description 3
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000024279 bone resorption Effects 0.000 description 3
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 3
- 229960004015 calcitonin Drugs 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 239000010936 titanium Substances 0.000 description 3
- 229910052719 titanium Inorganic materials 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QIQMSOAIXLCDMT-UHFFFAOYSA-N 3-amino-6-[2,5-dimethyl-4-(4-methylpiperazin-1-yl)sulfonylphenyl]-n-pyridin-3-ylpyrazine-2-carboxamide Chemical compound C1CN(C)CCN1S(=O)(=O)C1=CC(C)=C(C=2N=C(C(N)=NC=2)C(=O)NC=2C=NC=CC=2)C=C1C QIQMSOAIXLCDMT-UHFFFAOYSA-N 0.000 description 2
- AFLCJXMOBVSHJB-UHFFFAOYSA-N 3-amino-6-[3-fluoro-4-(4-methylpiperazin-1-yl)sulfonylphenyl]-n-pyridin-3-ylpyrazine-2-carboxamide Chemical compound C1CN(C)CCN1S(=O)(=O)C1=CC=C(C=2N=C(C(N)=NC=2)C(=O)NC=2C=NC=CC=2)C=C1F AFLCJXMOBVSHJB-UHFFFAOYSA-N 0.000 description 2
- YCEFMZAYKBJXMZ-UHFFFAOYSA-N 3-amino-6-[3-methyl-4-(4-methylpiperazin-1-yl)sulfonylphenyl]-n-pyridin-3-ylpyrazine-2-carboxamide Chemical compound C1CN(C)CCN1S(=O)(=O)C1=CC=C(C=2N=C(C(N)=NC=2)C(=O)NC=2C=NC=CC=2)C=C1C YCEFMZAYKBJXMZ-UHFFFAOYSA-N 0.000 description 2
- BAFHCYGGRZCGPE-UHFFFAOYSA-N 3-amino-6-[4-(4-ethylpiperazin-1-yl)sulfonylphenyl]-n-pyridin-3-ylpyrazine-2-carboxamide Chemical compound C1CN(CC)CCN1S(=O)(=O)C1=CC=C(C=2N=C(C(N)=NC=2)C(=O)NC=2C=NC=CC=2)C=C1 BAFHCYGGRZCGPE-UHFFFAOYSA-N 0.000 description 2
- LTOTZKJOKALPBS-UHFFFAOYSA-N 3-amino-6-[4-(4-methylpiperazin-1-yl)sulfonyl-3-(trifluoromethoxy)phenyl]-n-pyridin-3-ylpyrazine-2-carboxamide Chemical compound C1CN(C)CCN1S(=O)(=O)C1=CC=C(C=2N=C(C(N)=NC=2)C(=O)NC=2C=NC=CC=2)C=C1OC(F)(F)F LTOTZKJOKALPBS-UHFFFAOYSA-N 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102000015735 Beta-catenin Human genes 0.000 description 2
- 108060000903 Beta-catenin Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229910045601 alloy Inorganic materials 0.000 description 2
- 239000000956 alloy Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 150000003857 carboxamides Chemical class 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 238000003305 oral gavage Methods 0.000 description 2
- 230000004072 osteoblast differentiation Effects 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 238000013222 sprague-dawley male rat Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 1
- YBRZBLHVSSPQEW-UHFFFAOYSA-N 3-amino-6-[3-ethyl-4-(4-methylpiperazin-1-yl)sulfonylphenyl]-n-pyridin-3-ylpyrazine-2-carboxamide Chemical compound CCC1=CC(C=2N=C(C(N)=NC=2)C(=O)NC=2C=NC=CC=2)=CC=C1S(=O)(=O)N1CCN(C)CC1 YBRZBLHVSSPQEW-UHFFFAOYSA-N 0.000 description 1
- OBMADRXYXXTZEF-UHFFFAOYSA-N 3-amino-6-[4-(4-methylpiperazin-1-yl)sulfonyl-2-(trifluoromethyl)phenyl]-n-pyridin-3-ylpyrazine-2-carboxamide Chemical compound C1CN(C)CCN1S(=O)(=O)C(C=C1C(F)(F)F)=CC=C1C1=CN=C(N)C(C(=O)NC=2C=NC=CC=2)=N1 OBMADRXYXXTZEF-UHFFFAOYSA-N 0.000 description 1
- LABUFJUSVZZTTN-UHFFFAOYSA-N 3-amino-6-[4-[(4-methyl-1,4-diazepan-1-yl)sulfonyl]phenyl]-n-pyridin-3-ylpyrazine-2-carboxamide Chemical compound C1CN(C)CCCN1S(=O)(=O)C1=CC=C(C=2N=C(C(N)=NC=2)C(=O)NC=2C=NC=CC=2)C=C1 LABUFJUSVZZTTN-UHFFFAOYSA-N 0.000 description 1
- YBVANFPAAINPHY-UHFFFAOYSA-N 3-amino-6-[5-fluoro-2-methyl-4-(4-methylpiperazin-1-yl)sulfonylphenyl]-n-pyridin-3-ylpyrazine-2-carboxamide Chemical compound C1CN(C)CCN1S(=O)(=O)C1=CC(C)=C(C=2N=C(C(N)=NC=2)C(=O)NC=2C=NC=CC=2)C=C1F YBVANFPAAINPHY-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282832 Camelidae Species 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 108010001483 Glycogen Synthase Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108010042653 IgA receptor Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 238000011887 Necropsy Methods 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000002565 Open Fractures Diseases 0.000 description 1
- 241000906034 Orthops Species 0.000 description 1
- 102000008108 Osteoprotegerin Human genes 0.000 description 1
- 108010035042 Osteoprotegerin Proteins 0.000 description 1
- 102000005877 Peptide Initiation Factors Human genes 0.000 description 1
- 108010044843 Peptide Initiation Factors Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 102100034014 Prolyl 3-hydroxylase 3 Human genes 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010039984 Senile osteoporosis Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
- 229910001069 Ti alloy Inorganic materials 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 210000003423 ankle Anatomy 0.000 description 1
- 238000007743 anodising Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000033558 biomineral tissue development Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037182 bone density Effects 0.000 description 1
- 230000008468 bone growth Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 230000004097 bone metabolism Effects 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000006369 cell cycle progression Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 210000003275 diaphysis Anatomy 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
- 229960002986 dinoprostone Drugs 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 210000000959 ear middle Anatomy 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 201000010934 exostosis Diseases 0.000 description 1
- 210000000521 femorotibial joint Anatomy 0.000 description 1
- 210000002436 femur neck Anatomy 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 210000001624 hip Anatomy 0.000 description 1
- 210000004394 hip joint Anatomy 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 201000010930 hyperostosis Diseases 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 210000003127 knee Anatomy 0.000 description 1
- 210000002414 leg Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- KPSDPFLPBDTMPM-UHFFFAOYSA-N n-pyridin-3-ylpyrazine-2-carboxamide Chemical compound C=1N=CC=NC=1C(=O)NC1=CC=CN=C1 KPSDPFLPBDTMPM-UHFFFAOYSA-N 0.000 description 1
- 229910052758 niobium Inorganic materials 0.000 description 1
- 239000010955 niobium Substances 0.000 description 1
- GUCVJGMIXFAOAE-UHFFFAOYSA-N niobium atom Chemical compound [Nb] GUCVJGMIXFAOAE-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- XXUPLYBCNPLTIW-UHFFFAOYSA-N octadec-7-ynoic acid Chemical compound CCCCCCCCCCC#CCCCCCC(O)=O XXUPLYBCNPLTIW-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 238000010883 osseointegration Methods 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 230000001599 osteoclastic effect Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- 208000001685 postmenopausal osteoporosis Diseases 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 210000001562 sternum Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229910052715 tantalum Inorganic materials 0.000 description 1
- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 description 1
- 108010026424 tau Proteins Proteins 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000005495 thyroid hormone Substances 0.000 description 1
- 229940036555 thyroid hormone Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 229910052726 zirconium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- 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
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic 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
- A61K31/55—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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/08—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing alicyclic rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US78025206P | 2006-03-08 | 2006-03-08 | |
| US60/780252 | 2006-03-08 | ||
| PCT/SE2007/000216 WO2007102770A1 (en) | 2006-03-08 | 2007-03-06 | Gsk-3 inhibitors for the treatment of osteoporosis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BRPI0708619A2 true BRPI0708619A2 (pt) | 2011-06-07 |
Family
ID=38475142
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0708619-9A BRPI0708619A2 (pt) | 2006-03-08 | 2007-03-06 | uso de um composto, e, métodos para previnir e/ou tratar distúrbios ou condições relacionados com o osso, para previnir e/ou tratar osteoporose, para aumentar a formação óssea, para aumentar a densidade mineral óssea, para reduzir a incidência de fratura, e para realçar a cicatrização da fratura |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US7576093B2 (https=) |
| EP (1) | EP1993550A4 (https=) |
| JP (1) | JP2009529041A (https=) |
| KR (1) | KR20080114717A (https=) |
| CN (1) | CN101394851A (https=) |
| AR (1) | AR059754A1 (https=) |
| AU (1) | AU2007222199A1 (https=) |
| BR (1) | BRPI0708619A2 (https=) |
| CA (1) | CA2644751A1 (https=) |
| IL (1) | IL193484A0 (https=) |
| MX (1) | MX2008011417A (https=) |
| NO (1) | NO20084182L (https=) |
| TW (1) | TW200800203A (https=) |
| UY (1) | UY30192A1 (https=) |
| WO (1) | WO2007102770A1 (https=) |
| ZA (1) | ZA200807234B (https=) |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100137330A1 (en) * | 2007-03-08 | 2010-06-03 | Ratan Bhat | Use |
| KR20170015566A (ko) | 2008-11-10 | 2017-02-08 | 버텍스 파마슈티칼스 인코포레이티드 | Ａｔｒ 키나제의 억제제로서 유용한 화합물 |
| ES2663222T3 (es) | 2008-12-19 | 2018-04-11 | Vertex Pharmaceuticals Incorporated | Derivados de pirazina útiles como inhibidores de la quinasa ATR |
| WO2011089416A1 (en) * | 2010-01-19 | 2011-07-28 | Astrazeneca Ab | Pyrazine derivatives |
| US9630956B2 (en) | 2010-05-12 | 2017-04-25 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| US8969356B2 (en) | 2010-05-12 | 2015-03-03 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| JP5856151B2 (ja) | 2010-05-12 | 2016-02-09 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | Ａｔｒキナーゼ阻害剤として有用な２−アミノピリジン誘導体 |
| JP2013526540A (ja) | 2010-05-12 | 2013-06-24 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ａｔｒキナーゼ阻害剤として有用な化合物 |
| JP2013529200A (ja) | 2010-05-12 | 2013-07-18 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ａｔｒキナーゼ阻害剤として有用な化合物 |
| JP2013526539A (ja) | 2010-05-12 | 2013-06-24 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ａｔｒキナーゼ阻害剤として有用なピラジン |
| CA2803802A1 (en) | 2010-06-23 | 2011-12-29 | Vertex Pharmaceuticals Incorporated | Pyrrolo- pyrazine derivatives useful as inhibitors of atr kinase |
| JP2014510151A (ja) | 2011-04-05 | 2014-04-24 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ａｔｒキナーゼ（ｔｒａｋｉｎａｓｅ）阻害剤として有用なアミノピラジン化合物 |
| WO2012161877A1 (en) | 2011-05-23 | 2012-11-29 | Merck Patent Gmbh | Pyridine-and pyrazine derivatives |
| WO2012178124A1 (en) | 2011-06-22 | 2012-12-27 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| WO2012178125A1 (en) | 2011-06-22 | 2012-12-27 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| EP2723745A1 (en) | 2011-06-22 | 2014-04-30 | Vertex Pharmaceuticals Inc. | Compounds useful as inhibitors of atr kinase |
| KR20140084112A (ko) | 2011-09-30 | 2014-07-04 | 버텍스 파마슈티칼스 인코포레이티드 | Ａｔｒ 키나제의 억제제로서 유용한 화합물 |
| US8853217B2 (en) | 2011-09-30 | 2014-10-07 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| WO2013049859A1 (en) | 2011-09-30 | 2013-04-04 | Vertex Pharmaceuticals Incorporated | Treating pancreatic cancer and non-small cell lung cancer with atr inhibitors |
| SG10201606774UA (en) | 2011-09-30 | 2016-10-28 | Vertex Pharma | Processes for making compounds useful as inhibitors of atr kinase |
| WO2013049719A1 (en) | 2011-09-30 | 2013-04-04 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| WO2013071088A1 (en) | 2011-11-09 | 2013-05-16 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| WO2013071085A1 (en) | 2011-11-09 | 2013-05-16 | Vertex Pharmaceuticals Incorporated | Pyrazine compounds useful as inhibitors of atr kinase |
| US8841337B2 (en) | 2011-11-09 | 2014-09-23 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| WO2013071094A1 (en) | 2011-11-09 | 2013-05-16 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| US8841450B2 (en) | 2011-11-09 | 2014-09-23 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| CA2869309C (en) | 2012-04-05 | 2021-02-09 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase and combination therapies thereof |
| US8999632B2 (en) | 2012-10-04 | 2015-04-07 | Vertex Pharmaceuticals Incorporated | Method for measuring ATR inhibition mediated increases in DNA damage |
| US8912198B2 (en) | 2012-10-16 | 2014-12-16 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| SI2941432T1 (en) | 2012-12-07 | 2018-07-31 | Vertex Pharmaceuticals Incorporated | 2-AMINO-6-FLUORO-N- (5-FLUORO-4- (4- (4- (OXETHAN-3-YL) PIPERAZIN-1-CARBONYL) PIPERIDIN-1-YLIPRIDIN-3-YL) 1,5 ALFA) PYRIMIDINE-3-CARBOXAMIDE AS ATR KINAZE INHIBITOR |
| LT2970890T (lt) | 2013-03-14 | 2020-07-10 | The Brigham And Women`S Hospital, Inc. | Kompozicijos ir būdai, skirti epitelinių kamieninių ląstelių padauginimui ir kultivavimui |
| JP2016512815A (ja) | 2013-03-15 | 2016-05-09 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | Ａｔｒキナーゼの阻害剤として有用な縮合ピラゾロピリミジン誘導体 |
| DK3077397T3 (da) | 2013-12-06 | 2019-12-16 | Vertex Pharma | 2-amino-6-fluor-n-[5-fluor-pyridin-3-yl]pyrazolo[1,5-a]pyrimidin-3-carboxamidforbindelse anvendelig som atr-kinase-inhibitor, dens fremstilling, forskellige faste former og radiomarkerede derivater deraf |
| CN103804312B (zh) * | 2014-02-17 | 2016-04-20 | 四川百利药业有限责任公司 | 一类氮杂环化合物及其制备方法和用途 |
| PL3152212T3 (pl) | 2014-06-05 | 2020-06-15 | Vertex Pharmaceuticals Inc. | Radioznakowane pochodne związku 2-amino-6-fluoro-n-[5-fluoro-piridyn-3-ylo]-pirazolo[1,5-a]pirymidino-3-karboksamidu przydatne jako inhibitor kinazy atr, wytwarzanie tego związku i jego różnych postaci stałych |
| LT3157566T (lt) | 2014-06-17 | 2019-08-12 | Vertex Pharmaceuticals Incorporated | Vėžio gydymo būdas, panaudojant chk1 ir atr inhibitorių derinį |
| WO2016037016A1 (en) | 2014-09-03 | 2016-03-10 | The Brigham And Women's Hospital, Inc. | Compositions, systems, and methods for generating inner ear hair cells for treatment of hearing loss |
| HK1258570A1 (zh) | 2015-09-30 | 2019-11-15 | Vertex Pharmaceuticals Inc. | 使用dna损伤剂及atr抑制剂的组合治疗癌症的方法 |
| CN108779437A (zh) | 2016-01-08 | 2018-11-09 | 麻省理工学院 | 分化的肠内分泌细胞和胰岛素产生细胞的制备 |
| US10201540B2 (en) | 2016-03-02 | 2019-02-12 | Frequency Therapeutics, Inc. | Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using GSK3 inhibitors: I |
| US11260130B2 (en) | 2016-03-02 | 2022-03-01 | Frequency Therapeutics, Inc. | Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using a GSK3 inhibitor: IV |
| US10213511B2 (en) | 2016-03-02 | 2019-02-26 | Frequency Therapeutics, Inc. | Thermoreversible compositions for administration of therapeutic agents |
| US11066419B2 (en) | 2016-12-30 | 2021-07-20 | Frequency Therapeutics, Inc. | 1H-pyrrole-2,5-dione compounds and methods of using same |
| CN113195707A (zh) | 2018-08-17 | 2021-07-30 | 频率治疗公司 | 用于通过上调jag-1来生成毛细胞的组合物和方法 |
| US11617745B2 (en) | 2018-08-17 | 2023-04-04 | Frequency Therapeutics, Inc. | Compositions and methods for generating hair cells by downregulating FOXO |
| EP3920885A1 (en) | 2019-02-08 | 2021-12-15 | Frequency Therapeutics, Inc. | Valproic acid compounds and wnt agonists for treating ear disorders |
| TW202517268A (zh) * | 2023-07-14 | 2025-05-01 | 美商塞萊托藥品股份有限公司 | 包含ａｔｒ抑制劑之脂質體組合物之使用方法 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HUP0202332A2 (en) | 2000-02-05 | 2002-10-28 | Vertex Pharma | Pyrazole compositions useful as inhibitors of erk |
| SE0102438D0 (sv) * | 2001-07-05 | 2001-07-05 | Astrazeneca Ab | New compounds |
| SE0102439D0 (sv) * | 2001-07-05 | 2001-07-05 | Astrazeneca Ab | New compounds |
| AU2003235798A1 (en) * | 2002-01-10 | 2003-07-24 | F. Hoffmann-La Roche Ag | Use of a gsk-3beta inhibitor in the manufacture of a medicament for increasing bone formation |
| DK1483265T3 (da) | 2002-03-05 | 2007-03-19 | Lilly Co Eli | Purinderivater som kinaseinhibitorer |
| SE0203752D0 (sv) * | 2002-12-17 | 2002-12-17 | Astrazeneca Ab | New compounds |
| EP1636388A2 (en) * | 2003-06-06 | 2006-03-22 | Wyeth | Methods and materials for identifying agents which modulate bone remodeling and agents identified thereby |
| JP2007502300A (ja) * | 2003-08-13 | 2007-02-08 | カイロン コーポレイション | Ｇｓｋ−３インヒビターおよびその使用 |
| US20050064044A1 (en) * | 2003-09-19 | 2005-03-24 | Georges Rawadi | GSK-3beta inhibitors in the treatment of bone-related diseases |
-
2007
- 2007-03-02 TW TW096107083A patent/TW200800203A/zh unknown
- 2007-03-06 WO PCT/SE2007/000216 patent/WO2007102770A1/en not_active Ceased
- 2007-03-06 AU AU2007222199A patent/AU2007222199A1/en not_active Abandoned
- 2007-03-06 AR ARP070100917A patent/AR059754A1/es not_active Application Discontinuation
- 2007-03-06 MX MX2008011417A patent/MX2008011417A/es not_active Application Discontinuation
- 2007-03-06 JP JP2008558230A patent/JP2009529041A/ja active Pending
- 2007-03-06 KR KR1020087021787A patent/KR20080114717A/ko not_active Withdrawn
- 2007-03-06 CA CA002644751A patent/CA2644751A1/en not_active Abandoned
- 2007-03-06 EP EP07716035A patent/EP1993550A4/en not_active Withdrawn
- 2007-03-06 BR BRPI0708619-9A patent/BRPI0708619A2/pt not_active IP Right Cessation
- 2007-03-06 CN CNA2007800079632A patent/CN101394851A/zh active Pending
- 2007-03-07 UY UY30192A patent/UY30192A1/es not_active Application Discontinuation
- 2007-03-08 US US11/683,458 patent/US7576093B2/en not_active Expired - Fee Related
-
2008
- 2008-08-14 IL IL193484A patent/IL193484A0/en unknown
- 2008-08-21 ZA ZA200807234A patent/ZA200807234B/xx unknown
- 2008-10-06 NO NO20084182A patent/NO20084182L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| US7576093B2 (en) | 2009-08-18 |
| MX2008011417A (es) | 2008-09-22 |
| WO2007102770A1 (en) | 2007-09-13 |
| IL193484A0 (en) | 2009-08-03 |
| ZA200807234B (en) | 2009-09-30 |
| AU2007222199A1 (en) | 2007-09-13 |
| UY30192A1 (es) | 2007-10-31 |
| EP1993550A1 (en) | 2008-11-26 |
| US20070213322A1 (en) | 2007-09-13 |
| WO2007102770A8 (en) | 2008-01-31 |
| TW200800203A (en) | 2008-01-01 |
| AR059754A1 (es) | 2008-04-30 |
| EP1993550A4 (en) | 2010-04-21 |
| JP2009529041A (ja) | 2009-08-13 |
| KR20080114717A (ko) | 2008-12-31 |
| CN101394851A (zh) | 2009-03-25 |
| CA2644751A1 (en) | 2007-09-13 |
| NO20084182L (no) | 2008-12-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| BRPI0708619A2 (pt) | uso de um composto, e, métodos para previnir e/ou tratar distúrbios ou condições relacionados com o osso, para previnir e/ou tratar osteoporose, para aumentar a formação óssea, para aumentar a densidade mineral óssea, para reduzir a incidência de fratura, e para realçar a cicatrização da fratura | |
| De Angelis et al. | Implant survival and success rates in patients with risk factors: results from a long-term retrospective study with a 10 to 18 years follow-up | |
| RU2166940C2 (ru) | Способ уменьшения потерь костной ткани, способ лечения остеопороза и применение соединения | |
| Eder et al. | Treatment of a patient with severe osteoporosis and chronic polyarthritis with fixed implant-supported prosthesis: a case report. | |
| Yang et al. | Bone responses to simvastatin-loaded porous implant surfaces in an ovariectomized model. | |
| Balatsouka et al. | The impact of nicotine on bone healing and osseointegration: An experimental study in rabbits | |
| Yıldırım et al. | The effects of metformin on the bone filling ration around of TiAl6Va4 implants in non diabetic rats | |
| JP2008127369A (ja) | 外分泌障害を処置するための医薬 | |
| Goodman et al. | COX-2 selective inhibitors and bone | |
| Kim et al. | Benign paroxysmal positional vertigo as a complication of sinus floor elevation | |
| US9056105B2 (en) | Method for treatment of bone diseases and fractures | |
| WO2004019873A9 (en) | Methods of promoting osteogenesis | |
| Dalkiz et al. | Treatment of a microvascular reconstructed mandible using an implant-supported fixed partial denture: case report | |
| RU2176519C1 (ru) | Способ профилактики потери костной ткани вокруг имплантантов при эндопротезировании | |
| UA76254C2 (en) | Use of desoxypeganine for treating clinical depression | |
| US20100137330A1 (en) | Use | |
| Vuletić et al. | Implant prosthodontic rehabilitation after surgical treatment for an oropharyngeal malignant tumour using tantalum dental implants | |
| Georgiev | Method of treatment of periimplantitis | |
| Adachi et al. | Inhibition of osteoclast recruitment at a local site by 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) | |
| KR20220108543A (ko) | 페노피브레이트를 유효성분으로 포함하는 체내 콜레스테롤 배출 조절에 의한골관절염 예방 또는 치료용 약제학적 조성물 | |
| Wang et al. | Expression of XBP1s in fibroblasts is critical for TiAl6V4 particle‐induced RANKL expression and osteolysis | |
| JP2008505068A (ja) | 骨折治療用薬学的組成物 | |
| Verma et al. | Assessment of role of selective serotonin reuptake inhibitors in prognosis of dental implant treatment | |
| RU2383348C1 (ru) | Способ лечения хронического генерализованного пародонтита с агрессивным течением | |
| Golden | Bisphosphonates in improving the osseointegration of dental implants |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B08F | Application dismissed because of non-payment of annual fees [chapter 8.6 patent gazette] |
Free format text: REFERENTE A 5A ANUIDADE. |
|
| B08K | Patent lapsed as no evidence of payment of the annual fee has been furnished to inpi [chapter 8.11 patent gazette] |
Free format text: REFERENTE AO DESPACHO 8.6 PUBLICADO NA RPI 2161 DE 05/06/2012. |