RU2643326C2 - Ингибитор рецептора фрф для применения в лечении гипофосфатемических заболеваний - Google Patents
Ингибитор рецептора фрф для применения в лечении гипофосфатемических заболеваний Download PDFInfo
- Publication number
- RU2643326C2 RU2643326C2 RU2014143517A RU2014143517A RU2643326C2 RU 2643326 C2 RU2643326 C2 RU 2643326C2 RU 2014143517 A RU2014143517 A RU 2014143517A RU 2014143517 A RU2014143517 A RU 2014143517A RU 2643326 C2 RU2643326 C2 RU 2643326C2
- Authority
- RU
- Russia
- Prior art keywords
- treatment
- vitamin
- ethylpiperazin
- dimethoxyphenyl
- phenylamino
- Prior art date
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 45
- 108091006082 receptor inhibitors Proteins 0.000 title claims description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 26
- 201000010099 disease Diseases 0.000 title abstract description 21
- 230000003553 hypophosphatemic effect Effects 0.000 title abstract description 12
- QADPYRIHXKWUSV-UHFFFAOYSA-N BGJ-398 Chemical compound C1CN(CC)CCN1C(C=C1)=CC=C1NC1=CC(N(C)C(=O)NC=2C(=C(OC)C=C(OC)C=2Cl)Cl)=NC=N1 QADPYRIHXKWUSV-UHFFFAOYSA-N 0.000 claims abstract description 70
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 34
- 239000011575 calcium Substances 0.000 claims abstract description 34
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 34
- 239000000126 substance Substances 0.000 claims abstract description 25
- 230000000694 effects Effects 0.000 claims abstract description 20
- 102100024802 Fibroblast growth factor 23 Human genes 0.000 claims abstract description 4
- 101001051973 Homo sapiens Fibroblast growth factor 23 Proteins 0.000 claims abstract 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 39
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 39
- 239000010452 phosphate Substances 0.000 claims description 39
- 210000000988 bone and bone Anatomy 0.000 claims description 34
- 229930003316 Vitamin D Natural products 0.000 claims description 32
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims description 32
- 235000019166 vitamin D Nutrition 0.000 claims description 32
- 239000011710 vitamin D Substances 0.000 claims description 32
- 150000003710 vitamin D derivatives Chemical class 0.000 claims description 32
- 229940046008 vitamin d Drugs 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 30
- 230000014509 gene expression Effects 0.000 claims description 29
- 108090000445 Parathyroid hormone Proteins 0.000 claims description 25
- 150000001875 compounds Chemical class 0.000 claims description 24
- 239000000199 parathyroid hormone Substances 0.000 claims description 23
- 229960001319 parathyroid hormone Drugs 0.000 claims description 23
- 208000029663 Hypophosphatemia Diseases 0.000 claims description 13
- 201000003674 autosomal dominant hypophosphatemic rickets Diseases 0.000 claims description 8
- 201000003672 autosomal recessive hypophosphatemic rickets Diseases 0.000 claims description 8
- 208000005050 Familial Hypophosphatemic Rickets Diseases 0.000 claims description 7
- 102000004264 Osteopontin Human genes 0.000 claims description 7
- 108010081689 Osteopontin Proteins 0.000 claims description 7
- 208000031878 X-linked hypophosphatemia Diseases 0.000 claims description 7
- 208000035724 X-linked hypophosphatemic rickets Diseases 0.000 claims description 7
- 238000002054 transplantation Methods 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 208000005072 Oncogenic osteomalacia Diseases 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 239000012458 free base Substances 0.000 claims description 3
- 208000011580 syndromic disease Diseases 0.000 claims description 3
- 102100036893 Parathyroid hormone Human genes 0.000 claims 2
- 230000000926 neurological effect Effects 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 abstract description 20
- 108091008794 FGF receptors Proteins 0.000 abstract description 14
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 abstract description 14
- 239000003112 inhibitor Substances 0.000 abstract description 12
- 239000003814 drug Substances 0.000 abstract description 6
- 238000010606 normalization Methods 0.000 abstract description 5
- 230000004060 metabolic process Effects 0.000 abstract description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 abstract description 2
- 239000011574 phosphorus Substances 0.000 abstract description 2
- 229910052698 phosphorus Inorganic materials 0.000 abstract description 2
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 100
- 102000004042 Fibroblast Growth Factor-23 Human genes 0.000 description 42
- 108090000569 Fibroblast Growth Factor-23 Proteins 0.000 description 42
- 210000002966 serum Anatomy 0.000 description 35
- 102000005962 receptors Human genes 0.000 description 34
- 108020003175 receptors Proteins 0.000 description 34
- 102000003982 Parathyroid hormone Human genes 0.000 description 23
- 210000003734 kidney Anatomy 0.000 description 22
- -1 2,6-dichloro-3,5-dimethoxyphenyl Chemical group 0.000 description 20
- 239000012453 solvate Substances 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 108090000623 proteins and genes Proteins 0.000 description 14
- 210000002303 tibia Anatomy 0.000 description 14
- 150000001204 N-oxides Chemical class 0.000 description 13
- 210000000689 upper leg Anatomy 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 11
- 230000012010 growth Effects 0.000 description 11
- 230000037396 body weight Effects 0.000 description 10
- 239000008194 pharmaceutical composition Substances 0.000 description 10
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 9
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 9
- 230000033228 biological regulation Effects 0.000 description 9
- 230000002035 prolonged effect Effects 0.000 description 9
- 101150099181 Cyp27b1 gene Proteins 0.000 description 8
- 230000001771 impaired effect Effects 0.000 description 8
- 108020004999 messenger RNA Proteins 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 239000000546 pharmaceutical excipient Substances 0.000 description 8
- 230000009038 pharmacological inhibition Effects 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 208000013038 Hypocalcemia Diseases 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 230000000705 hypocalcaemia Effects 0.000 description 6
- 208000007442 rickets Diseases 0.000 description 6
- 230000011664 signaling Effects 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 5
- 210000004349 growth plate Anatomy 0.000 description 5
- 210000004560 pineal gland Anatomy 0.000 description 5
- 101100447432 Danio rerio gapdh-2 gene Proteins 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 4
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 4
- 101150112014 Gapdh gene Proteins 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 239000000945 filler Substances 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000011866 long-term treatment Methods 0.000 description 4
- 238000003753 real-time PCR Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- GMRQFYUYWCNGIN-ZVUFCXRFSA-N 1,25-dihydroxy vitamin D3 Chemical compound C1([C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=CC=C1C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-ZVUFCXRFSA-N 0.000 description 3
- 208000028060 Albright disease Diseases 0.000 description 3
- 208000031213 Epidermal nevus syndrome Diseases 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 201000001853 McCune-Albright syndrome Diseases 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000033558 biomineral tissue development Effects 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 208000011111 hypophosphatemic rickets Diseases 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 238000010603 microCT Methods 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 230000008520 organization Effects 0.000 description 3
- 208000020037 osteoglophonic dysplasia Diseases 0.000 description 3
- 208000001061 polyostotic fibrous dysplasia Diseases 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 230000002335 preservative effect Effects 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 102100027518 1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial Human genes 0.000 description 2
- 108010073030 25-Hydroxyvitamin D3 1-alpha-Hydroxylase Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 238000011530 RNeasy Mini Kit Methods 0.000 description 2
- 238000011529 RT qPCR Methods 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 108010026102 Vitamin D3 24-Hydroxylase Proteins 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 230000008468 bone growth Effects 0.000 description 2
- 230000004094 calcium homeostasis Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 210000001612 chondrocyte Anatomy 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 210000002745 epiphysis Anatomy 0.000 description 2
- 230000013632 homeostatic process Effects 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 230000011164 ossification Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000008092 positive effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 230000008521 reorganization Effects 0.000 description 2
- 230000008054 signal transmission Effects 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 230000004584 weight gain Effects 0.000 description 2
- 235000019786 weight gain Nutrition 0.000 description 2
- LFGDCUQVRIGRAI-TYYBGVCCSA-N (e)-but-2-enedioic acid;ethane-1,2-disulfonic acid Chemical compound OC(=O)\C=C\C(O)=O.OS(=O)(=O)CCS(O)(=O)=O LFGDCUQVRIGRAI-TYYBGVCCSA-N 0.000 description 1
- GMRQFYUYWCNGIN-UHFFFAOYSA-N 1,25-Dihydroxy-vitamin D3' Natural products C1CCC2(C)C(C(CCCC(C)(C)O)C)CCC2C1=CC=C1CC(O)CC(O)C1=C GMRQFYUYWCNGIN-UHFFFAOYSA-N 0.000 description 1
- 101150090724 3 gene Proteins 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 239000004135 Bone phosphate Substances 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 208000004434 Calcinosis Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- 101100433782 Drosophila melanogaster Hydr2 gene Proteins 0.000 description 1
- 101150021185 FGF gene Proteins 0.000 description 1
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 101001136717 Homo sapiens 26S proteasome non-ATPase regulatory subunit 8 Proteins 0.000 description 1
- 101000613820 Homo sapiens Osteopontin Proteins 0.000 description 1
- 101000703512 Homo sapiens Sphingosine-1-phosphate phosphatase 1 Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 101100061197 Mus musculus Cyp27b1 gene Proteins 0.000 description 1
- 101100281002 Mus musculus Fgf23 gene Proteins 0.000 description 1
- 101000617395 Mus musculus Probable peptidyl-tRNA hydrolase Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102100037571 Neurosecretory protein VGF Human genes 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 102100022927 Nuclear receptor coactivator 4 Human genes 0.000 description 1
- 102100040557 Osteopontin Human genes 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 229920002556 Polyethylene Glycol 300 Polymers 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 208000005770 Secondary Hyperparathyroidism Diseases 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 208000020221 Short stature Diseases 0.000 description 1
- 101150012700 Slc34a3 gene Proteins 0.000 description 1
- 102000046202 Sodium-Phosphate Cotransporter Proteins Human genes 0.000 description 1
- 102100038440 Sodium-dependent phosphate transport protein 2C Human genes 0.000 description 1
- 101710168942 Sphingosine-1-phosphate phosphatase 1 Proteins 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 101800003344 Vaccinia growth factor Proteins 0.000 description 1
- 101800001863 Variola growth factor Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 230000018678 bone mineralization Effects 0.000 description 1
- 235000019347 bone phosphate Nutrition 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 230000002308 calcification Effects 0.000 description 1
- 229960002882 calcipotriol Drugs 0.000 description 1
- LWQQLNNNIPYSNX-UROSTWAQSA-N calcipotriol Chemical group C1([C@H](O)/C=C/[C@@H](C)[C@@H]2[C@]3(CCCC(/[C@@H]3CC2)=C\C=C\2C([C@@H](O)C[C@H](O)C/2)=C)C)CC1 LWQQLNNNIPYSNX-UROSTWAQSA-N 0.000 description 1
- 229960005084 calcitriol Drugs 0.000 description 1
- GMRQFYUYWCNGIN-NKMMMXOESA-N calcitriol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-NKMMMXOESA-N 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000005056 compaction Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229960001731 gluceptate Drugs 0.000 description 1
- KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940097042 glucuronate Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 102000051312 human SPP1 Human genes 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- TVZISJTYELEYPI-UHFFFAOYSA-N hypodiphosphoric acid Chemical compound OP(O)(=O)P(O)(O)=O TVZISJTYELEYPI-UHFFFAOYSA-N 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000019948 ion homeostasis Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 210000002414 leg Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 210000000110 microvilli Anatomy 0.000 description 1
- 230000037230 mobility Effects 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 208000008798 osteoma Diseases 0.000 description 1
- 208000005368 osteomalacia Diseases 0.000 description 1
- 229940039748 oxalate Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 210000000512 proximal kidney tubule Anatomy 0.000 description 1
- 210000005234 proximal tubule cell Anatomy 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000002601 radiography Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000003340 retarding agent Substances 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 102000035025 signaling receptors Human genes 0.000 description 1
- 108091005475 signaling receptors Proteins 0.000 description 1
- 231100001055 skeletal defect Toxicity 0.000 description 1
- 108091006284 sodium-phosphate co-transporters Proteins 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229940114926 stearate Drugs 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229940071103 sulfosalicylate Drugs 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- ABZLKHKQJHEPAX-UHFFFAOYSA-N tetramethylrhodamine Chemical compound C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=CC=C1C([O-])=O ABZLKHKQJHEPAX-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000037426 transcriptional repression Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229930003231 vitamin Chemical class 0.000 description 1
- 239000011782 vitamin Chemical class 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
Classifications
-
- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and 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
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/42—Phosphorus; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/29—Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Endocrinology (AREA)
- Physical Education & Sports Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Hematology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Obesity (AREA)
- Marine Sciences & Fisheries (AREA)
- Nutrition Science (AREA)
- Toxicology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261617889P | 2012-03-30 | 2012-03-30 | |
| US61/617,889 | 2012-03-30 | ||
| PCT/EP2013/056811 WO2013144339A1 (en) | 2012-03-30 | 2013-03-29 | Fgfr inhibitor for use in the treatment of hypophosphatemic disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2014143517A RU2014143517A (ru) | 2016-05-27 |
| RU2643326C2 true RU2643326C2 (ru) | 2018-01-31 |
Family
ID=47998482
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2014143517A RU2643326C2 (ru) | 2012-03-30 | 2013-03-29 | Ингибитор рецептора фрф для применения в лечении гипофосфатемических заболеваний |
Country Status (11)
| Country | Link |
|---|---|
| US (4) | US20150072019A1 (https=) |
| EP (1) | EP2830626B1 (https=) |
| JP (1) | JP6190871B2 (https=) |
| KR (1) | KR102126092B1 (https=) |
| CN (2) | CN109718239B (https=) |
| AU (1) | AU2013241664B2 (https=) |
| CA (1) | CA2866229C (https=) |
| IN (1) | IN2014DN08969A (https=) |
| MX (1) | MX354783B (https=) |
| RU (1) | RU2643326C2 (https=) |
| WO (1) | WO2013144339A1 (https=) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8754114B2 (en) | 2010-12-22 | 2014-06-17 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of FGFR3 |
| ES2704744T3 (es) | 2012-06-13 | 2019-03-19 | Incyte Holdings Corp | Compuestos tricíclicos sustituidos como inhibidores de FGFR |
| US9388185B2 (en) | 2012-08-10 | 2016-07-12 | Incyte Holdings Corporation | Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors |
| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| EA035095B1 (ru) | 2013-04-19 | 2020-04-27 | Инсайт Холдингс Корпорейшн | Бициклические гетероциклы в качестве ингибиторов fgfr |
| EA028614B1 (ru) * | 2014-05-22 | 2017-12-29 | Общество С Ограниченной Ответственностью "Русские Фармацевтические Технологии" | Селективные ингибиторы, нарушающие взаимодействие рецептора фактора роста фибробластов и frs2, для профилактики и лечения рака |
| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| MX373169B (es) | 2015-02-20 | 2020-04-24 | Incyte Holdings Corp | Heterociclos bicíclicos como inhibidores de receptores del factor de crecimiento fibroblástico (fgfr). |
| WO2016134294A1 (en) | 2015-02-20 | 2016-08-25 | Incyte Corporation | Bicyclic heterocycles as fgfr4 inhibitors |
| WO2016189472A1 (en) * | 2015-05-28 | 2016-12-01 | Novartis Ag | Fgfr inhibitor for use in the treatment of the phosphaturic mesenchymal tumor |
| BR112018001053A2 (pt) | 2015-07-20 | 2018-09-11 | Univ Taipei Medical | compostos, composição farmacêutica e método para inibir, prevenir ou tratar um câncer em um indivíduo |
| BR112018001438A2 (en) * | 2015-07-24 | 2018-12-04 | Debiopharm International S.A. | gffr expression and susceptibility to a gffr inhibitor |
| EP3566705B1 (en) | 2017-01-06 | 2022-11-23 | Lemonex Inc. | Composition for preventing or treating metastatic ovarian cancer, endometrial cancer or breast cancer |
| WO2018128510A1 (ko) * | 2017-01-06 | 2018-07-12 | 주식회사 레모넥스 | 전이성 난소암, 자궁내막암 또는 유방암의 예방 또는 치료용 조성물 |
| US10886468B2 (en) | 2017-04-14 | 2021-01-05 | Sakai Display Products Corporation | Manufacturing method and manufacturing apparatus for organic EL display device |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| CR20200590A (es) | 2018-05-04 | 2021-04-26 | Incyte Corp | Formas sólidas de un inhibidor de fgfr y procesos para prepararlas |
| MA52493A (fr) | 2018-05-04 | 2021-03-10 | Incyte Corp | Sels d'un inhibiteur de fgfr |
| WO2020185532A1 (en) | 2019-03-08 | 2020-09-17 | Incyte Corporation | Methods of treating cancer with an fgfr inhibitor |
| US20220143049A1 (en) | 2019-03-21 | 2022-05-12 | Onxeo | A dbait molecule in combination with kinase inhibitor for the treatment of cancer |
| WO2021007269A1 (en) | 2019-07-09 | 2021-01-14 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| WO2021067374A1 (en) | 2019-10-01 | 2021-04-08 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| TWI891666B (zh) | 2019-10-14 | 2025-08-01 | 美商英塞特公司 | 作為ｆｇｆｒ抑制劑之雙環雜環 |
| WO2021076728A1 (en) | 2019-10-16 | 2021-04-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| EP4054579A1 (en) | 2019-11-08 | 2022-09-14 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Methods for the treatment of cancers that have acquired resistance to kinase inhibitors |
| EP4069696A1 (en) | 2019-12-04 | 2022-10-12 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| BR112022010664A2 (pt) | 2019-12-04 | 2022-08-16 | Incyte Corp | Derivados de um inibidor de fgfr |
| WO2021119108A1 (en) * | 2019-12-09 | 2021-06-17 | Cedars-Sinai Medical Center | Use of fgfr inhibitors for treatment of idiopathic short stature |
| WO2021146424A1 (en) | 2020-01-15 | 2021-07-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| TW202304459A (zh) | 2021-04-12 | 2023-02-01 | 美商英塞特公司 | 包含ｆｇｆｒ抑制劑及ｎｅｃｔｉｎ－４靶向劑之組合療法 |
| EP4352059A1 (en) | 2021-06-09 | 2024-04-17 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| WO2022261159A1 (en) | 2021-06-09 | 2022-12-15 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2003123108A (ru) * | 2000-12-26 | 2005-02-27 | Чугаи Сейяку Кабусики Кайся (Jp) | Мутантные формы человеческого белка fgf23, снижающие содержание фосфора в крови |
| WO2009133101A1 (en) * | 2008-04-29 | 2009-11-05 | Novartis Ag | Methods of monitoring the modulation of the kinase activity of fibroblast growth factor receptor and uses of said methods |
| WO2011051425A1 (en) * | 2009-10-30 | 2011-05-05 | Novartis Ag | N-oxide of 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0512324D0 (en) * | 2005-06-16 | 2005-07-27 | Novartis Ag | Organic compounds |
| EP1882475A1 (en) * | 2006-07-26 | 2008-01-30 | Novartis AG | Method of treating disorders mediated by the fibroblast growth factor receptor |
| AR079257A1 (es) * | 2009-12-07 | 2012-01-04 | Novartis Ag | Formas cristalinas de 3-(2,6-dicloro-3-5-dimetoxi-fenil)-1-{6-[4-(4-etil-piperazin-1-il)-fenil-amino]-pirimidin-4-il}-1-metil-urea y sales de las mismas |
| US20120258940A1 (en) * | 2009-12-18 | 2012-10-11 | Giordano Caponigro | Method for treating haematological cancers |
| WO2013088191A1 (en) | 2011-12-12 | 2013-06-20 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Antagonist of the fibroblast growth factor receptor 3 (fgfr3) for use in the treatment or the prevention of skeletal disorders linked with abnormal activation of fgfr3 |
-
2013
- 2013-03-29 US US14/388,978 patent/US20150072019A1/en not_active Abandoned
- 2013-03-29 MX MX2014011841A patent/MX354783B/es active IP Right Grant
- 2013-03-29 RU RU2014143517A patent/RU2643326C2/ru active
- 2013-03-29 IN IN8969DEN2014 patent/IN2014DN08969A/en unknown
- 2013-03-29 KR KR1020147026889A patent/KR102126092B1/ko active Active
- 2013-03-29 CN CN201811194059.3A patent/CN109718239B/zh active Active
- 2013-03-29 EP EP13712589.4A patent/EP2830626B1/en active Active
- 2013-03-29 CN CN201380015597.0A patent/CN104321058A/zh active Pending
- 2013-03-29 CA CA2866229A patent/CA2866229C/en active Active
- 2013-03-29 WO PCT/EP2013/056811 patent/WO2013144339A1/en not_active Ceased
- 2013-03-29 JP JP2015502373A patent/JP6190871B2/ja active Active
- 2013-03-29 AU AU2013241664A patent/AU2013241664B2/en active Active
-
2016
- 2016-09-22 US US15/272,633 patent/US10028955B2/en active Active
-
2018
- 2018-06-12 US US16/005,966 patent/US20210308132A1/en not_active Abandoned
-
2024
- 2024-01-09 US US18/407,729 patent/US20240398798A1/en not_active Abandoned
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2003123108A (ru) * | 2000-12-26 | 2005-02-27 | Чугаи Сейяку Кабусики Кайся (Jp) | Мутантные формы человеческого белка fgf23, снижающие содержание фосфора в крови |
| WO2009133101A1 (en) * | 2008-04-29 | 2009-11-05 | Novartis Ag | Methods of monitoring the modulation of the kinase activity of fibroblast growth factor receptor and uses of said methods |
| WO2011051425A1 (en) * | 2009-10-30 | 2011-05-05 | Novartis Ag | N-oxide of 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea |
Non-Patent Citations (3)
| Title |
|---|
| MARSELL R. et al. "Relation between fibroblast growth factor-23, body weight and bone mineral density in elderly men". Osteoporos.Int. 2009 Jul;20(7):1167-73, , найдено 05.07.2017 из PubMed PMID:18974917. * |
| MOSEKILDE L. "Primery hyperparathyroidism and the skeleton". Clin Endocrinol(Oxf) 2008 Jul;69(1):1-19, , найдено 05.07.2017 из PubMed PMID:18167138. * |
| MOSEKILDE L. "Primery hyperparathyroidism and the skeleton". Clin Endocrinol(Oxf) 2008 Jul;69(1):1-19, реферат, найдено 05.07.2017 из PubMed PMID:18167138. MARSELL R. et al. "Relation between fibroblast growth factor-23, body weight and bone mineral density in elderly men". Osteoporos.Int. 2009 Jul;20(7):1167-73, реферат, найдено 05.07.2017 из PubMed PMID:18974917. * |
Also Published As
| Publication number | Publication date |
|---|---|
| US20240398798A1 (en) | 2024-12-05 |
| US20170007606A1 (en) | 2017-01-12 |
| RU2014143517A (ru) | 2016-05-27 |
| US10028955B2 (en) | 2018-07-24 |
| EP2830626B1 (en) | 2019-01-02 |
| EP2830626A1 (en) | 2015-02-04 |
| CA2866229C (en) | 2020-09-15 |
| JP6190871B2 (ja) | 2017-08-30 |
| KR20140145133A (ko) | 2014-12-22 |
| MX354783B (es) | 2018-03-21 |
| IN2014DN08969A (https=) | 2015-05-22 |
| CN104321058A (zh) | 2015-01-28 |
| KR102126092B1 (ko) | 2020-06-24 |
| CN109718239B (zh) | 2024-09-10 |
| US20210308132A1 (en) | 2021-10-07 |
| CN109718239A (zh) | 2019-05-07 |
| MX2014011841A (es) | 2015-02-10 |
| US20150072019A1 (en) | 2015-03-12 |
| JP2015511621A (ja) | 2015-04-20 |
| CA2866229A1 (en) | 2013-10-03 |
| WO2013144339A1 (en) | 2013-10-03 |
| AU2013241664B2 (en) | 2016-05-19 |
| AU2013241664A1 (en) | 2014-10-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2643326C2 (ru) | Ингибитор рецептора фрф для применения в лечении гипофосфатемических заболеваний | |
| Yanagita et al. | Gas6 regulates mesangial cell proliferation through Axl in experimental glomerulonephritis | |
| Zhou et al. | Histamine-4 receptor antagonist JNJ7777120 inhibits pro-inflammatory microglia and prevents the progression of Parkinson-like pathology and behaviour in a rat model | |
| JP2012509859A (ja) | 中皮腫の治療のためのｃｄｋ阻害物質 | |
| Lim et al. | Co-deletion of Lrp5 and Lrp6 in the skeleton severely diminishes bone gain from sclerostin antibody administration | |
| Myśliwiec et al. | Dithranol treatment of plaque-type psoriasis increases serum TNF-like weak inducer of apoptosis (TWEAK) | |
| Katerelos et al. | The AMPK activator ATX-304 alters cellular metabolism to protect against cisplatin-induced acute kidney injury | |
| Mehta et al. | Antipyrine kinetics in liver disease and liver transplantation | |
| Nie et al. | 1, 25-Dihydroxyvitamin D enhances alveolar fluid clearance by upregulating the expression of epithelial sodium channels | |
| Rabb et al. | Possible molecular basis for changes in potassium handling in acute renal failure | |
| Traxl et al. | Hepatocyte-specific deletion of EGFR in mice reduces hepatic Abcg2 transport activity measured by [11C] erlotinib and positron emission tomography | |
| EP3403652A1 (en) | Prevention and treatment of fibroblast growth factor 23 (fgf23)-associated disorders including chronic kidney disease (ckd) | |
| KR100977625B1 (ko) | 그렐린을 함유하는 척수 손상 치료용 약학적 조성물 | |
| HK40008771A (en) | Fgfr inhibitor for use in the treatment of hypophosphatemic disorders | |
| Yoshii et al. | Mechanism for distribution of acotiamide, a novel gastroprokinetic agent for the treatment of functional dyspepsia, in rat stomach | |
| HK40008771B (zh) | 用於治疗低磷血性疾病的fgfr抑制剂 | |
| Behm et al. | Kidney-specific claudin-2 deficiency leads to medullary nephrocalcinosis in mice | |
| EP1720552A2 (en) | Methods for treating inflammatory and autoimmune diseases | |
| US20130196980A1 (en) | Diagnostic agent, diagnostic method and therapeutic agent for fibromyalgia | |
| Fricke et al. | Developmental fluoxetine exposure affects adolescent and adult bone depending on the dose and period of exposure | |
| EP1109579A1 (en) | Use of tgf-beta inhibitors for treating cerebral disorders | |
| Cai et al. | SUN-133 G-protein Pathway Suppressor 2 (GPS2) Enhanced the Large Conductance Ca2+ Activated Potassium (BK) Channels Activity through modulating WNK4 Ubiquitination | |
| WO2022019235A1 (ja) | 腎障害の抑制におけるビタミンｂ１２の利用 | |
| Tiosano et al. | Bone and Mineral Metabolism | |
| Andrukhova et al. | Fgf-23 stimulates renal tubular calcium reabsorption by regulating membrane trafficking of glycosylated TRPV5 through SGK1 and WNK4 |