ES2590905T3 - Inhibidores de la tirosina quinasa de Bruton - Google Patents
Inhibidores de la tirosina quinasa de Bruton Download PDFInfo
- Publication number
- ES2590905T3 ES2590905T3 ES13166272.8T ES13166272T ES2590905T3 ES 2590905 T3 ES2590905 T3 ES 2590905T3 ES 13166272 T ES13166272 T ES 13166272T ES 2590905 T3 ES2590905 T3 ES 2590905T3
- Authority
- ES
- Spain
- Prior art keywords
- approximately
- groups
- refers
- tyrosine kinase
- less
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 108010029445 Agammaglobulinaemia Tyrosine Kinase Proteins 0.000 title description 7
- 102000001714 Agammaglobulinaemia Tyrosine Kinase Human genes 0.000 title description 7
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 title description 2
- 239000005483 tyrosine kinase inhibitor Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 abstract description 41
- 150000003839 salts Chemical class 0.000 abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 20
- 150000001412 amines Chemical group 0.000 description 19
- 125000003118 aryl group Chemical group 0.000 description 17
- 238000000034 method Methods 0.000 description 17
- 230000002427 irreversible effect Effects 0.000 description 16
- 239000003112 inhibitor Substances 0.000 description 15
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 14
- 108091000080 Phosphotransferase Proteins 0.000 description 14
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 14
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 14
- 150000001298 alcohols Chemical class 0.000 description 14
- 150000001448 anilines Chemical class 0.000 description 14
- 102000020233 phosphotransferase Human genes 0.000 description 14
- 201000010099 disease Diseases 0.000 description 13
- 150000002148 esters Chemical class 0.000 description 13
- 125000006239 protecting group Chemical group 0.000 description 13
- -1 -Ohaloalkyl C1– C6 Chemical group 0.000 description 12
- 229960002433 cysteine Drugs 0.000 description 12
- 235000018417 cysteine Nutrition 0.000 description 12
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- 150000003573 thiols Chemical class 0.000 description 11
- OGEBRHQLRGFBNV-RZDIXWSQSA-N chembl2036808 Chemical class C12=NC(NCCCC)=NC=C2C(C=2C=CC(F)=CC=2)=NN1C[C@H]1CC[C@H](N)CC1 OGEBRHQLRGFBNV-RZDIXWSQSA-N 0.000 description 10
- 125000003275 alpha amino acid group Chemical group 0.000 description 9
- 229940024606 amino acid Drugs 0.000 description 9
- 235000001014 amino acid Nutrition 0.000 description 9
- 150000001413 amino acids Chemical class 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 150000001735 carboxylic acids Chemical class 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 125000001072 heteroaryl group Chemical group 0.000 description 8
- 150000002989 phenols Chemical class 0.000 description 8
- 229940124291 BTK inhibitor Drugs 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 125000000623 heterocyclic group Chemical group 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 150000003568 thioethers Chemical class 0.000 description 7
- 230000004071 biological effect Effects 0.000 description 6
- 150000003857 carboxamides Chemical class 0.000 description 6
- 125000000524 functional group Chemical group 0.000 description 6
- 230000036470 plasma concentration Effects 0.000 description 6
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 229920001184 polypeptide Polymers 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 4
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 150000003973 alkyl amines Chemical class 0.000 description 4
- 150000001350 alkyl halides Chemical class 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 4
- 239000013038 irreversible inhibitor Substances 0.000 description 4
- 150000007523 nucleic acids Chemical group 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 229960004441 tyrosine Drugs 0.000 description 4
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 4
- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 description 3
- 241000282414 Homo sapiens Species 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 3
- 150000008052 alkyl sulfonates Chemical class 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 3
- 239000012039 electrophile Substances 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 239000012038 nucleophile Substances 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- 108091033319 polynucleotide Proteins 0.000 description 3
- 102000040430 polynucleotide Human genes 0.000 description 3
- 239000002157 polynucleotide Substances 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
- 241000252212 Danio rerio Species 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 108020002076 NR2 subfamily Proteins 0.000 description 2
- 229910004727 OSO3H Inorganic materials 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001266 acyl halides Chemical class 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 150000005215 alkyl ethers Chemical class 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 150000001356 alkyl thiols Chemical class 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 150000001502 aryl halides Chemical class 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000010256 biochemical assay Methods 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 150000002118 epoxides Chemical class 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 238000002825 functional assay Methods 0.000 description 2
- 150000002429 hydrazines Chemical class 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000012948 isocyanate Substances 0.000 description 2
- 150000002513 isocyanates Chemical class 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 238000000021 kinase assay Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000007781 signaling event Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 150000003461 sulfonyl halides Chemical class 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- UIYCHXAGWOYNNA-UHFFFAOYSA-N vinyl sulfide Chemical compound C=CSC=C UIYCHXAGWOYNNA-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- 150000003923 2,5-pyrrolediones Chemical class 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- 102100036409 Activated CDC42 kinase 1 Human genes 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 102100022631 Glutamate receptor ionotropic, NMDA 2C Human genes 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 101000928956 Homo sapiens Activated CDC42 kinase 1 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-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
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 238000006957 Michael reaction Methods 0.000 description 1
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 229910006069 SO3H Inorganic materials 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108010009978 Tec protein-tyrosine kinase Proteins 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Chemical group CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229960003767 alanine Drugs 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 125000000732 arylene group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 150000001576 beta-amino acids Chemical class 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 125000005621 boronate group Chemical group 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical class OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 125000004990 dihydroxyalkyl group Chemical group 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 235000004554 glutamine Nutrition 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical group OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 125000004404 heteroalkyl group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 150000002443 hydroxylamines Chemical class 0.000 description 1
- 150000002463 imidates Chemical class 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 229960003136 leucine Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 150000008301 phosphite esters Chemical class 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000001012 protector Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229960001153 serine Drugs 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- DRNXZGJGRSUXHW-UHFFFAOYSA-N silyl carbamate Chemical class NC(=O)O[SiH3] DRNXZGJGRSUXHW-UHFFFAOYSA-N 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical group CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 1
- 108091008646 testicular receptors Proteins 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- 229960002898 threonine Drugs 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- QQOWHRYOXYEMTL-UHFFFAOYSA-N triazin-4-amine Chemical class N=C1C=CN=NN1 QQOWHRYOXYEMTL-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 150000003673 urethanes Chemical class 0.000 description 1
- 229960004295 valine Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
- A61P17/06—Antipsoriatics
-
- 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
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25078709P | 2009-10-12 | 2009-10-12 | |
| US250787P | 2009-10-12 | ||
| US12/581,044 US7718662B1 (en) | 2009-10-12 | 2009-10-16 | Pyrazolo-pyrimidine inhibitors of bruton's tyrosine kinase |
| US581062 | 2009-10-16 | ||
| US581044 | 2009-10-16 | ||
| US12/581,062 US7741330B1 (en) | 2009-10-12 | 2009-10-16 | Pyrazolo-pyrimidine inhibitors of Bruton's tyrosine kinase |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| ES2590905T3 true ES2590905T3 (es) | 2016-11-24 |
| ES2590905T8 ES2590905T8 (es) | 2020-12-09 |
Family
ID=42166572
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES13166272.8T Active ES2590905T3 (es) | 2009-10-12 | 2010-10-12 | Inhibidores de la tirosina quinasa de Bruton |
Country Status (21)
| Country | Link |
|---|---|
| US (4) | US7718662B1 (OSRAM) |
| EP (2) | EP2393816A4 (OSRAM) |
| JP (2) | JP5717109B2 (OSRAM) |
| KR (1) | KR20120097376A (OSRAM) |
| CN (1) | CN102656173B (OSRAM) |
| AU (1) | AU2010306921C1 (OSRAM) |
| BR (1) | BR112012008624A2 (OSRAM) |
| CA (1) | CA2776543A1 (OSRAM) |
| CL (1) | CL2012000917A1 (OSRAM) |
| CO (1) | CO6531429A2 (OSRAM) |
| CR (1) | CR20120244A (OSRAM) |
| EA (1) | EA021715B1 (OSRAM) |
| ES (1) | ES2590905T3 (OSRAM) |
| IL (1) | IL219076A (OSRAM) |
| IN (1) | IN2012DN03012A (OSRAM) |
| MX (1) | MX2012004258A (OSRAM) |
| NZ (1) | NZ599396A (OSRAM) |
| PH (1) | PH12012500712A1 (OSRAM) |
| SG (1) | SG10201506776RA (OSRAM) |
| WO (1) | WO2011046964A2 (OSRAM) |
| ZA (1) | ZA201202552B (OSRAM) |
Families Citing this family (142)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK2529622T3 (en) | 2006-09-22 | 2018-05-07 | Pharmacyclics Llc | INHIBITORS OF BRUTON-TYROSINKINASE |
| US20120101114A1 (en) | 2007-03-28 | 2012-04-26 | Pharmacyclics, Inc. | Inhibitors of bruton's tyrosine kinase |
| US20090301928A1 (en) * | 2008-06-05 | 2009-12-10 | United Comb & Novelty Corporation | Packaging For Lipped Containers |
| US8338439B2 (en) | 2008-06-27 | 2012-12-25 | Celgene Avilomics Research, Inc. | 2,4-disubstituted pyrimidines useful as kinase inhibitors |
| US11351168B1 (en) | 2008-06-27 | 2022-06-07 | Celgene Car Llc | 2,4-disubstituted pyrimidines useful as kinase inhibitors |
| NZ589843A (en) | 2008-06-27 | 2012-12-21 | Avila Therapeutics Inc | Pyrimidine heteroaryl compounds and uses thereof as protein kinase inhibitors |
| US20110224235A1 (en) | 2008-07-16 | 2011-09-15 | Pharmacyclics, Inc. | Inhibitors of bruton's tyrosine kinase for the treatment of solid tumors |
| JP5918693B2 (ja) | 2009-05-05 | 2016-05-18 | ダナ ファーバー キャンサー インスティテュート インコーポレイテッド | Ｅｇｆｒ阻害剤及び疾患の治療方法 |
| US7718662B1 (en) * | 2009-10-12 | 2010-05-18 | Pharmacyclics, Inc. | Pyrazolo-pyrimidine inhibitors of bruton's tyrosine kinase |
| KR101580714B1 (ko) | 2010-06-03 | 2016-01-04 | 파마싸이클릭스 엘엘씨 | 브루톤 티로신 인산화효소(ｂｔｋ)의 억제제의 용도 |
| CA2804648C (en) * | 2010-07-09 | 2019-01-22 | The Walter And Eliza Hall Institute Of Medical Research | Protein kinase inhibitors and methods of treatment |
| ES2617763T3 (es) | 2010-08-10 | 2017-06-19 | Celgene Avilomics Research, Inc. | Sal de besilato de un inhibidor de BTK |
| WO2012061299A1 (en) | 2010-11-01 | 2012-05-10 | Avila Therapeutics, Inc. | Heterocyclic compounds and uses thereof |
| US9238629B2 (en) | 2010-11-01 | 2016-01-19 | Celgene Avilomics Research, Inc. | Heteroaryl compounds and uses thereof |
| EP2637502B1 (en) | 2010-11-10 | 2018-01-10 | Celgene CAR LLC | Mutant-selective egfr inhibitors and uses thereof |
| JP6147727B2 (ja) * | 2011-04-01 | 2017-06-14 | ユニヴァーシティー オブ ユタ リサーチ ファウンデーション | チロシン受容体キナーゼｂｔｋ阻害剤としての置換ｎ−（３−（ピリミジン−４−イル）フェニル）アクリルアミド類似体 |
| JP6118794B2 (ja) | 2011-04-01 | 2017-04-19 | ザ ユニバーシティ オブ ユタ リサーチ ファウンデイション | Ａｘｌキナーゼの阻害剤としての置換ｎ−フェニルピリミジン−２−アミン類似体 |
| SI2710005T1 (sl) | 2011-05-17 | 2017-03-31 | Principia Biopharma Inc. | Zaviralci tirozinske kinaze |
| US9376438B2 (en) | 2011-05-17 | 2016-06-28 | Principia Biopharma, Inc. | Pyrazolopyrimidine derivatives as tyrosine kinase inhibitors |
| BR112013029508B1 (pt) | 2011-05-17 | 2022-05-03 | Principia Biopharma, Inc. | Composto, composição farmacêutica, e, uso do referido composto |
| AU2012275275A1 (en) * | 2011-06-28 | 2014-01-23 | Pharmacyclics Llc | Methods and compositions for inhibition of bone resorption |
| EA201490265A1 (ru) * | 2011-07-13 | 2014-12-30 | Фармасайкликс, Инк. | Ингибиторы тирозинкиназы брутона |
| JP6105578B2 (ja) | 2011-07-21 | 2017-03-29 | トレロ ファーマシューティカルズ， インコーポレイテッド | 複素環式プロテインキナーゼ阻害剤 |
| JP2014532658A (ja) | 2011-10-28 | 2014-12-08 | セルジーン アヴィロミクス リサーチ， インコーポレイテッド | ブルトン型チロシンキナーゼ疾患または障害を治療する方法 |
| US8377946B1 (en) | 2011-12-30 | 2013-02-19 | Pharmacyclics, Inc. | Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors |
| TW201336847A (zh) * | 2012-02-07 | 2013-09-16 | Taiho Pharmaceutical Co Ltd | 喹啉基吡咯并嘧啶化合物或其鹽 |
| SG11201402876UA (en) * | 2012-02-23 | 2014-12-30 | Taiho Pharmaceutical Co Ltd | Quinolylpyrrolopyrimidyl fused-ring compound or salt thereof |
| JP6317320B2 (ja) | 2012-03-15 | 2018-04-25 | セルジーン シーエーアール エルエルシー | 上皮成長因子受容体キナーゼ阻害剤の塩 |
| WO2013138495A1 (en) | 2012-03-15 | 2013-09-19 | Celgene Avilomics Research, Inc. | Solid forms of an epidermal growth factor receptor kinase inhibitor |
| US9522917B2 (en) | 2012-04-11 | 2016-12-20 | Acerta Pharma B.V. | Bruton's tyrosine kinase inhibitors for hematopoietic mobilization |
| CA2869954C (en) | 2012-04-20 | 2023-01-03 | Advinus Therapeutics Limited | Substituted hetero-bicyclic compounds, compositions and medicinal applications thereof in medical conditions related to modulation of bruton's tyrosine kinase activity |
| WO2013157021A1 (en) | 2012-04-20 | 2013-10-24 | Advinus Therapeutics Limited | Bicyclic compounds, compositions and medicinal applications thereof |
| US9796716B2 (en) * | 2012-05-31 | 2017-10-24 | Pharmascience, Inc. | Selective inhibitors of Tec and Src protein kinase families |
| KR20250151610A (ko) | 2012-06-04 | 2025-10-21 | 파마싸이클릭스 엘엘씨 | 브루톤 타이로신 키나아제 저해제의 결정 형태 |
| BR112015001690A2 (pt) | 2012-07-24 | 2017-11-07 | Pharmacyclics Inc | mutações associadas com a resistência a inibidores da tirosina quinase de bruton (btk) |
| RS58956B1 (sr) | 2012-09-10 | 2019-08-30 | Principia Biopharma Inc | Jedinjenja pirazolopirimidina kao inhibitori kinaze |
| US9296703B2 (en) | 2012-10-04 | 2016-03-29 | University Of Utah Research Foundation | Substituted N-(3-(pyrimidin-4-yl)phenyl)acrylamide analogs as tyrosine receptor kinase BTK inhibitors |
| EP3680238A1 (en) | 2012-10-04 | 2020-07-15 | University of Utah Research Foundation | Substituted n-(3-(pyrimidin-4-yl)phenyl)acrylamide analogs as tyrosine receptor kinase btk inhibitors |
| WO2014078578A1 (en) | 2012-11-15 | 2014-05-22 | Pharmacyclics, Inc. | Pyrrolopyrimidine compounds as kinase inhibitors |
| CN103848810A (zh) | 2012-11-30 | 2014-06-11 | 北京赛林泰医药技术有限公司 | 鲁顿酪氨酸激酶抑制剂 |
| US9126950B2 (en) | 2012-12-21 | 2015-09-08 | Celgene Avilomics Research, Inc. | Heteroaryl compounds and uses thereof |
| AU2014214846A1 (en) | 2013-02-08 | 2015-07-23 | Celgene Avilomics Research, Inc. | ERK inhibitors and uses thereof |
| MX2015010934A (es) * | 2013-02-22 | 2015-10-29 | Taiho Pharmaceutical Co Ltd | Metodo para producir un compuesto triciclico, y un compuesto triciclico capaz de producirse por dicho metodo de produccion. |
| US10202356B2 (en) | 2013-03-14 | 2019-02-12 | Tolero Pharmaceuticals, Inc. | JAK2 and ALK2 inhibitors and methods for their use |
| EP2970300B1 (en) * | 2013-03-15 | 2018-05-16 | Boehringer Ingelheim International GmbH | Heteroaromatic compounds as btk inhibitors |
| AU2014230935A1 (en) * | 2013-03-15 | 2015-09-03 | Janssen Pharmaceutica Nv | Processes and intermediates for preparing a medicament |
| AU2014251038A1 (en) | 2013-04-08 | 2015-11-26 | Dennis M. Brown | Therapeutic benefit of suboptimally administered chemical compounds |
| US8957080B2 (en) | 2013-04-09 | 2015-02-17 | Principia Biopharma Inc. | Tyrosine kinase inhibitors |
| CN104884458B (zh) | 2013-04-25 | 2017-04-12 | 百济神州有限公司 | 作为蛋白质激酶抑制剂的稠合杂环化合物 |
| GB201309085D0 (en) | 2013-05-20 | 2013-07-03 | Redx Pharma Ltd | Compounds |
| AU2014293013A1 (en) | 2013-07-26 | 2016-03-17 | Race Oncology Ltd. | Combinatorial methods to improve the therapeutic benefit of bisantrene |
| JP6800750B2 (ja) | 2013-08-02 | 2020-12-16 | ファーマサイクリックス エルエルシー | 固形腫瘍の処置方法 |
| WO2015023703A1 (en) | 2013-08-12 | 2015-02-19 | Pharmacyclics, Inc. | Methods for the treatment of her2 amplified cancer |
| WO2015025936A1 (ja) | 2013-08-22 | 2015-02-26 | 大鵬薬品工業株式会社 | 新規キノリン置換化合物 |
| US9550770B2 (en) | 2013-08-23 | 2017-01-24 | Neupharma, Inc. | Substituted quinazolines for inhibiting kinase activity |
| US9492471B2 (en) | 2013-08-27 | 2016-11-15 | Celgene Avilomics Research, Inc. | Methods of treating a disease or disorder associated with Bruton'S Tyrosine Kinase |
| SG11201601844TA (en) | 2013-09-13 | 2016-04-28 | Beigene Ltd | Anti-pd1 antibodies and their use as therapeutics and diagnostics |
| JP2016531941A (ja) | 2013-09-30 | 2016-10-13 | ファーマサイクリックス エルエルシー | ブルトン型チロシンキナーゼの阻害剤 |
| WO2015057992A1 (en) | 2013-10-16 | 2015-04-23 | Izumi Raquel | Btk inhibitors for hematopoietic mobilization |
| RU2653504C2 (ru) * | 2013-12-13 | 2018-05-10 | Ф. Хоффманн-Ля Рош Аг | Ингибиторы тирозинкиназы брутона |
| US9415049B2 (en) | 2013-12-20 | 2016-08-16 | Celgene Avilomics Research, Inc. | Heteroaryl compounds and uses thereof |
| EP3102579B1 (en) * | 2014-02-03 | 2019-04-10 | Cadila Healthcare Limited | Heterocyclic compounds |
| EA033900B1 (ru) | 2014-02-21 | 2019-12-06 | Принсипиа Биофарма Инк. | СОЛЕВЫЕ И АМОРФНЫЕ ФОРМЫ 2-[(3R)-3-[4-АМИНО-3-(2-ФТОР-4-ФЕНОКСИФЕНИЛ)ПИРАЗОЛО[3,4-d]ПИРИМИДИН-1-ИЛ]ПИПЕРИДИН-1-КАРБОНИЛ]-4-МЕТИЛ-4-[4-(ОКСЕТАН-3-ИЛ)ПИПЕРАЗИН-1-ИЛ]ПЕНТ-2-ЕННИТРИЛА, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ И СПОСОБ ЛЕЧЕНИЯ ПУЗЫРЧАТКИ ОБЫКНОВЕННОЙ И ПУЗЫРЧАТКИ ЛИСТОВИДНОЙ С ИХ ПРИМЕНЕНИЕМ |
| JP2017509336A (ja) | 2014-03-20 | 2017-04-06 | ファーマサイクリックス エルエルシー | ホスホリパーゼｃガンマ２及び耐性に関連した変異 |
| WO2015181633A2 (en) | 2014-04-11 | 2015-12-03 | Acerta Pharma B.V. | Methods of blocking the cxcr-4/sdf-1 signaling pathway with inhibitors of bruton's tyrosine kinase |
| EP3134418A4 (en) | 2014-04-23 | 2018-01-03 | The Research Foundation for The State University of New York | A rapid and efficient bioorthogonal ligation reaction and boron-containing heterocycles useful in conjuction therewith |
| CN105017256A (zh) * | 2014-04-29 | 2015-11-04 | 浙江导明医药科技有限公司 | 多氟化合物作为布鲁顿酪氨酸激酶抑制剂 |
| WO2015172713A1 (zh) * | 2014-05-13 | 2015-11-19 | 广东东阳光药业有限公司 | 一种中间体的制备方法 |
| CN104086551B (zh) * | 2014-06-06 | 2016-09-21 | 人福医药集团股份公司 | 化合物及其制备方法和用途 |
| GB201410430D0 (en) | 2014-06-11 | 2014-07-23 | Redx Pharma Ltd | Compounds |
| CN110156892B (zh) | 2014-07-03 | 2023-05-16 | 百济神州有限公司 | 抗pd-l1抗体及其作为治疗剂及诊断剂的用途 |
| US9533991B2 (en) | 2014-08-01 | 2017-01-03 | Pharmacyclics Llc | Inhibitors of Bruton's tyrosine kinase |
| CA2955747A1 (en) | 2014-08-07 | 2016-02-11 | Pharmacyclics Llc | Novel formulations of a bruton's tyrosine kinase inhibitor |
| WO2016025561A1 (en) | 2014-08-13 | 2016-02-18 | Celgene Avilomics Research, Inc. | Forms and compositions of an erk inhibitor |
| WO2016050422A1 (en) * | 2014-10-01 | 2016-04-07 | Ratiopharm Gmbh | Acid addition salt of ibrutinib |
| TW201702218A (zh) | 2014-12-12 | 2017-01-16 | 美國杰克森實驗室 | 關於治療癌症、自體免疫疾病及神經退化性疾病之組合物及方法 |
| CA2970723C (en) | 2014-12-18 | 2023-09-05 | Principia Biopharma Inc. | Treatment of pemphigus |
| EP3042903B1 (en) | 2015-01-06 | 2019-08-14 | Impetis Biosciences Ltd. | Substituted hetero-bicyclic compounds, compositions and medicinal applications thereof |
| MA41350A (fr) * | 2015-01-14 | 2017-11-21 | Janssen Pharmaceutica Nv | Synthèse d'un inhibiteur de la tyrosine kinase de bruton |
| EP3248979B1 (en) * | 2015-01-21 | 2021-04-14 | Hefei Institutes of Physical Science, Chinese Academy of Sciences | Novel inhibitor of flt3 kinase and use thereof |
| CN105481862B (zh) * | 2015-01-21 | 2018-08-21 | 中国科学院合肥物质科学研究院 | Flt3激酶的新型抑制剂及其用途 |
| CN105859721B (zh) * | 2015-01-22 | 2018-04-17 | 浙江京新药业股份有限公司 | 一种伊布鲁替尼的制备方法 |
| WO2016127915A1 (zh) | 2015-02-12 | 2016-08-18 | 上海度德医药科技有限公司 | 伊布替尼的制备方法 |
| CA2976227C (en) | 2015-02-17 | 2023-10-24 | Neupharma, Inc. | Quinazoline derivatives and their use in treatment of cancer |
| IL315294A (en) | 2015-03-03 | 2024-10-01 | Pharmacyclics Llc | Pharmaceutical formulations of bruton's tyrosine kinase inhibitor |
| WO2016141044A1 (en) | 2015-03-04 | 2016-09-09 | Arizona Board Of Regents On Behalf Of Arizona State University | Erbb4 inhibitors and methods of use thereof |
| US9717745B2 (en) | 2015-03-19 | 2017-08-01 | Zhejiang DTRM Biopharma Co. Ltd. | Pharmaceutical compositions and their use for treatment of cancer and autoimmune diseases |
| CN106146508A (zh) * | 2015-03-19 | 2016-11-23 | 浙江导明医药科技有限公司 | 优化的联合用药及其治疗癌症和自身免疫疾病的用途 |
| CN106146516B (zh) * | 2015-04-20 | 2019-02-15 | 北京睿创康泰医药研究院有限公司 | 依鲁替尼药物杂质的制备方法 |
| KR102666352B1 (ko) * | 2015-06-03 | 2024-05-17 | 프린시피아 바이오파마, 인코퍼레이티드 | 티로신 키나제 억제제 |
| US9394312B1 (en) * | 2015-06-14 | 2016-07-19 | Mark Quang Nguyen | Ibrutinib prodrugs, pharmaceutical compositions thereof, and methods of use |
| EP3313839A1 (en) | 2015-06-24 | 2018-05-02 | Principia Biopharma Inc. | Tyrosine kinase inhibitors |
| KR20180109842A (ko) | 2015-09-16 | 2018-10-08 | 록쏘 온콜로지, 인코포레이티드 | 화합물 |
| MX380907B (es) * | 2015-12-16 | 2025-03-12 | Loxo Oncology Inc | Compuestos útiles como inhibidores de cinasa. |
| PL3394045T3 (pl) | 2015-12-24 | 2021-09-27 | Takeda Pharmaceutical Company Limited | Kokryształ, sposób jego wytwarzania i lek zawierający kokryształ |
| WO2017118277A1 (zh) * | 2016-01-05 | 2017-07-13 | 江苏恒瑞医药股份有限公司 | 一种btk激酶抑制剂的结晶形式及其制备方法 |
| MX2018008771A (es) * | 2016-01-19 | 2018-11-09 | Janssen Pharmaceutica Nv | Formulaciones/composiciones que comprenden un inhibidor de btk. |
| US10793566B2 (en) | 2016-01-21 | 2020-10-06 | Zibo Biopolar Changsheng Pharmaceutical Co. Ltd. | Bruton's tyrosine kinase inhibitors |
| AU2017208998B2 (en) | 2016-01-21 | 2021-07-15 | Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences | Bruton's tyrosine kinase inhibitors |
| CN106995446B (zh) * | 2016-01-22 | 2021-07-02 | 山东新时代药业有限公司 | 布鲁顿酪氨酸激酶抑制剂制备方法 |
| MX388026B (es) | 2016-03-11 | 2025-03-19 | Angel Pharmaceutical Co Ltd | Compuestos y métodos para modular la tirosina cinasa de bruton. |
| CN111153906B (zh) * | 2016-05-16 | 2020-09-11 | 苏州信诺维医药科技有限公司 | 作为btk抑制剂的吡唑并嘧啶衍生物及其制备方法和药物组合物 |
| SG11201811255WA (en) | 2016-06-29 | 2019-01-30 | Principia Biopharma Inc | Modified release formulations of 2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile |
| WO2018007885A1 (en) | 2016-07-05 | 2018-01-11 | Beigene, Ltd. | COMBINATION OF A PD-l ANTAGONIST AND A RAF INHIBITOR FOR TREATING CANCER |
| EP3497087B1 (en) * | 2016-08-15 | 2021-11-10 | Neupharma, Inc. | Pyrrolo[1,2-c]pyrimidine, imidazo[1,5-c]pyrimidine, quinazoline, purine and imidazo[1,5-a][1,3,5]triazine derivatives as tyrosine kinase inhibitors for the treatment of cancer |
| EA201990519A1 (ru) | 2016-08-16 | 2019-08-30 | Бейджин, Лтд. | КРИСТАЛЛИЧЕСКАЯ ФОРМА (S)-7-(1-АКРИЛОИЛПИПЕРИДИН-4-ИЛ)-2-(4-ФЕНОКСИФЕНИЛ)-4,5,6,7-ТЕТРАГИДРОПИРАЗОЛО[1,5-a]ПИРИМИДИН-3-КАРБОКСАМИДА, ЕЕ ПОЛУЧЕНИЕ И ПРИМЕНЕНИЯ |
| AU2017313085B2 (en) | 2016-08-19 | 2024-06-20 | Beone Medicines I Gmbh | Use of a combination comprising a Btk inhibitor for treating cancers |
| MA46285A (fr) | 2016-09-19 | 2019-07-31 | Mei Pharma Inc | Polythérapie |
| JOP20190073A1 (ar) | 2016-10-31 | 2019-04-07 | Taiho Pharmaceutical Co Ltd | مثبط انتقائي لمستقبل عامل نمو بشروي (egfr) لطافر إدخال exon 20 |
| JOP20190113A1 (ar) * | 2016-11-18 | 2019-05-15 | Biocad Joint Stock Co | مثبطات بروتون تيروزين كيناز |
| JP2020511462A (ja) | 2016-12-03 | 2020-04-16 | ジュノー セラピューティクス インコーポレイテッド | キナーゼ阻害剤との組み合わせで治療用ｔ細胞を使用するための方法および組成物 |
| TWI774726B (zh) | 2017-01-25 | 2022-08-21 | 英屬開曼群島商百濟神州有限公司 | (S)-7-(1-(丁-2-炔醯基)哌啶-4-基)-2-(4-苯氧基苯基)-4,5,6,7-四氫吡唑并[1,5-a]嘧啶-3-甲醯胺的晶型、及其製備和用途 |
| WO2018145280A1 (zh) * | 2017-02-09 | 2018-08-16 | 合肥合源药业有限公司 | Flt3激酶抑制剂或其盐的晶型及其制备方法 |
| TWI877099B (zh) | 2017-06-26 | 2025-03-21 | 英屬開曼群島商百濟神州有限公司 | 抗ｐｄ－１抗體或其抗原結合片段在製備治療用於患有肝細胞癌（ｈｃｃ）之藥物的用途 |
| US11377449B2 (en) | 2017-08-12 | 2022-07-05 | Beigene, Ltd. | BTK inhibitors with improved dual selectivity |
| KR102676530B1 (ko) | 2017-09-01 | 2024-06-20 | 다이호야쿠힌고교 가부시키가이샤 | 엑손18 및/또는 엑손21 변이형 egfr 선택적 저해제 |
| TW201922256A (zh) | 2017-10-27 | 2019-06-16 | 中國大陸商浙江導明醫藥科技有限公司 | 治療淋巴樣惡性疾病之方法 |
| US11786529B2 (en) | 2017-11-29 | 2023-10-17 | Beigene Switzerland Gmbh | Treatment of indolent or aggressive B-cell lymphomas using a combination comprising BTK inhibitors |
| CN108191871B (zh) * | 2018-01-02 | 2020-02-18 | 成都倍特药业有限公司 | 新型布鲁顿酪氨酸激酶抑制剂及其制备方法和应用 |
| BR112020020246A8 (pt) | 2018-04-05 | 2022-10-18 | Sumitomo Dainippon Pharma Oncology Inc | Inibidores de cinase axl e uso dos mesmos |
| CN112236139A (zh) | 2018-04-13 | 2021-01-15 | 大日本住友制药肿瘤公司 | 用于治疗骨髓增殖性肿瘤和与癌症相关的纤维化的pim激酶抑制剂 |
| EP3826684A4 (en) | 2018-07-26 | 2022-04-06 | Sumitomo Dainippon Pharma Oncology, Inc. | METHODS OF TREATMENT OF DISEASES ASSOCIATED WITH ABNORMAL ACVR1 EXPRESSION AND ACVR1 INHIBITORS FOR USE IN THE SAME |
| CN109134472B (zh) * | 2018-09-20 | 2020-02-11 | 浙江理工大学 | 一种3-(4-苯氧基苯基)-1H-吡唑并[3,4-d]嘧啶-4-胺的合成工艺 |
| CN110964016B (zh) * | 2018-09-29 | 2021-05-28 | 南京药捷安康生物科技有限公司 | 氨基降茨烷衍生物及其制备方法与应用 |
| CN109369654A (zh) * | 2018-11-20 | 2019-02-22 | 山东大学 | 1，3-二取代-4-氨基吡唑并嘧啶类化合物及其制备方法和应用 |
| US12180207B2 (en) | 2018-12-19 | 2024-12-31 | Array Biopharma Inc. | Substituted pyrazolo[1,5-a]pyridine compounds as inhibitors of FGFR tyrosine kinases |
| CN113474337A (zh) | 2018-12-19 | 2021-10-01 | 奥瑞生物药品公司 | 作为fgfr抑制剂用于治疗癌症的7-((3，5-二甲氧基苯基)氨基)喹喔啉衍生物 |
| CN111454268B (zh) * | 2019-01-18 | 2023-09-08 | 明慧医药（上海）有限公司 | 作为布鲁顿酪氨酸激酶抑制剂的环状分子 |
| JP7662528B2 (ja) | 2019-02-12 | 2025-04-15 | スミトモ ファーマ アメリカ， インコーポレイテッド | 複素環式タンパク質キナーゼ阻害剤を含む製剤 |
| CN113544130B (zh) | 2019-05-31 | 2024-01-09 | 西藏海思科制药有限公司 | 一种btk抑制剂环衍生物及其制备方法和药学上的应用 |
| EP3981399A4 (en) | 2019-06-10 | 2023-05-31 | BeiGene Switzerland GmbH | ORAL SOLID TABLET WITH A TYROSINE KINAS INHIBITOR AND METHOD OF MANUFACTURE THEREOF |
| CN110606848A (zh) * | 2019-08-27 | 2019-12-24 | 药雅科技(上海)有限公司 | 一种5-氮杂吲哚衍生物Bruton′s酪氨酸激酶抑制剂及其制备方法与用途 |
| CN115209899A (zh) | 2019-10-14 | 2022-10-18 | 普林斯匹亚生物制药公司 | 通过施用(R)-2-[3-[4-氨基-3-(2-氟-4-苯氧基-苯基)吡唑并[3,4-d]嘧啶-1-基]哌啶-1-羰基]-4-甲基-4-[4-(氧杂环丁-3-基)哌嗪-1-基]戊-2-烯腈治疗免疫性血小板减少症的方法 |
| CN115038700B (zh) | 2019-11-08 | 2025-07-25 | 内尔维亚诺医疗科学公司 | 偕二取代的杂环化合物及其作为idh抑制剂的用途 |
| TWI883107B (zh) | 2020-01-20 | 2025-05-11 | 美商普林斯匹亞生物製藥公司 | 用於復發型多發性硬化症的治療性酪胺酸激酶抑制劑 |
| MX2022009009A (es) | 2020-01-22 | 2022-08-15 | Principia Biopharma Inc | Formas cristalinas de 2-[3-[4-amino-3-(2-fluoro-4-fenoxi-fenil)-1h -pirazolo[3,4-d]pirimidin-1-il]piperidin-1-carbonil]-4-metil-4-[4 -(oxetan-3-il)piperazin-1-il]pent-2-enonitrilo. |
| CN113943294A (zh) * | 2020-07-15 | 2022-01-18 | 成都海博为药业有限公司 | 一种作为btk抑制剂的化合物及其制备方法与用途 |
| WO2022111447A1 (zh) * | 2020-11-25 | 2022-06-02 | 四川海思科制药有限公司 | 一种btk降解剂的制备方法 |
| WO2022121670A1 (zh) | 2020-12-10 | 2022-06-16 | 苏州科睿思制药有限公司 | Tolebrutinib的晶型及其制备方法和用途 |
| CN113004246B (zh) * | 2021-02-22 | 2022-02-01 | 广西医科大学 | 1，3，5-三嗪-2-胺-4，6取代衍生物或其药学上可接受的盐和用途 |
| US11786531B1 (en) | 2022-06-08 | 2023-10-17 | Beigene Switzerland Gmbh | Methods of treating B-cell proliferative disorder |
| EP4611753A1 (en) | 2022-10-31 | 2025-09-10 | Sumitomo Pharma America, Inc. | Pim1 inhibitor for treating myeloproliferative neoplasms |
Family Cites Families (85)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2008A (en) * | 1841-03-18 | Gas-lamp eok conducting gas pkom ah elevated buhner to one below it | ||
| US3598123A (en) | 1969-04-01 | 1971-08-10 | Alza Corp | Bandage for administering drugs |
| US3598122A (en) | 1969-04-01 | 1971-08-10 | Alza Corp | Bandage for administering drugs |
| US3993073A (en) | 1969-04-01 | 1976-11-23 | Alza Corporation | Novel drug delivery device |
| US3710795A (en) | 1970-09-29 | 1973-01-16 | Alza Corp | Drug-delivery device with stretched, rate-controlling membrane |
| US4069307A (en) | 1970-10-01 | 1978-01-17 | Alza Corporation | Drug-delivery device comprising certain polymeric materials for controlled release of drug |
| US3731683A (en) | 1971-06-04 | 1973-05-08 | Alza Corp | Bandage for the controlled metering of topical drugs to the skin |
| US3742951A (en) | 1971-08-09 | 1973-07-03 | Alza Corp | Bandage for controlled release of vasodilators |
| US3996934A (en) | 1971-08-09 | 1976-12-14 | Alza Corporation | Medical bandage |
| BE795384A (fr) | 1972-02-14 | 1973-08-13 | Ici Ltd | Pansements |
| US3921636A (en) | 1973-01-15 | 1975-11-25 | Alza Corp | Novel drug delivery device |
| US3993072A (en) | 1974-08-28 | 1976-11-23 | Alza Corporation | Microporous drug delivery device |
| US4151273A (en) | 1974-10-31 | 1979-04-24 | The Regents Of The University Of California | Increasing the absorption rate of insoluble drugs |
| US3972995A (en) | 1975-04-14 | 1976-08-03 | American Home Products Corporation | Dosage form |
| US4077407A (en) | 1975-11-24 | 1978-03-07 | Alza Corporation | Osmotic devices having composite walls |
| US4031894A (en) | 1975-12-08 | 1977-06-28 | Alza Corporation | Bandage for transdermally administering scopolamine to prevent nausea |
| US4060084A (en) | 1976-09-07 | 1977-11-29 | Alza Corporation | Method and therapeutic system for providing chemotherapy transdermally |
| US4201211A (en) | 1977-07-12 | 1980-05-06 | Alza Corporation | Therapeutic system for administering clonidine transdermally |
| JPS5562012A (en) | 1978-11-06 | 1980-05-10 | Teijin Ltd | Slow-releasing preparation |
| US4230105A (en) | 1978-11-13 | 1980-10-28 | Merck & Co., Inc. | Transdermal delivery of drugs |
| US4229447A (en) | 1979-06-04 | 1980-10-21 | American Home Products Corporation | Intraoral methods of using benzodiazepines |
| CA1146866A (en) | 1979-07-05 | 1983-05-24 | Yamanouchi Pharmaceutical Co. Ltd. | Process for the production of sustained release pharmaceutical composition of solid medical material |
| US4291015A (en) | 1979-08-14 | 1981-09-22 | Key Pharmaceuticals, Inc. | Polymeric diffusion matrix containing a vasodilator |
| US4327725A (en) | 1980-11-25 | 1982-05-04 | Alza Corporation | Osmotic device with hydrogel driving member |
| US5116817A (en) | 1982-12-10 | 1992-05-26 | Syntex (U.S.A.) Inc. | LHRH preparations for intranasal administration |
| US4476116A (en) | 1982-12-10 | 1984-10-09 | Syntex (U.S.A.) Inc. | Polypeptides/chelating agent nasal compositions having enhanced peptide absorption |
| US4596795A (en) | 1984-04-25 | 1986-06-24 | The United States Of America As Represented By The Secretary, Dept. Of Health & Human Services | Administration of sex hormones in the form of hydrophilic cyclodextrin derivatives |
| US4624848A (en) | 1984-05-10 | 1986-11-25 | Ciba-Geigy Corporation | Active agent containing hydrogel devices wherein the active agent concentration profile contains a sigmoidal concentration gradient for improved constant release, their manufacture and use |
| GB8518301D0 (en) | 1985-07-19 | 1985-08-29 | Fujisawa Pharmaceutical Co | Hydrodynamically explosive systems |
| DE3684446D1 (de) | 1985-12-28 | 1992-04-23 | Sumitomo Pharma | Arzneimittel mit verzoegerter stossweiser freisetzung. |
| US4755386A (en) | 1986-01-22 | 1988-07-05 | Schering Corporation | Buccal formulation |
| US5312325A (en) | 1987-05-28 | 1994-05-17 | Drug Delivery Systems Inc | Pulsating transdermal drug delivery system |
| US4968509A (en) | 1987-07-27 | 1990-11-06 | Mcneilab, Inc. | Oral sustained release acetaminophen formulation and process |
| US5033252A (en) | 1987-12-23 | 1991-07-23 | Entravision, Inc. | Method of packaging and sterilizing a pharmaceutical product |
| US5052558A (en) | 1987-12-23 | 1991-10-01 | Entravision, Inc. | Packaged pharmaceutical product |
| IL92966A (en) | 1989-01-12 | 1995-07-31 | Pfizer | Dispensing devices powered by hydrogel |
| US5739136A (en) | 1989-10-17 | 1998-04-14 | Ellinwood, Jr.; Everett H. | Intraoral dosing method of administering medicaments |
| US5017381A (en) | 1990-05-02 | 1991-05-21 | Alza Corporation | Multi-unit pulsatile delivery system |
| US5633009A (en) | 1990-11-28 | 1997-05-27 | Sano Corporation | Transdermal administration of azapirones |
| DE69222847T3 (de) | 1991-04-16 | 2005-09-15 | Nippon Shinyaku Co., Ltd. | Verfahren zur herstellung einer festen dispersion |
| US5229135A (en) | 1991-11-22 | 1993-07-20 | Prographarm Laboratories | Sustained release diltiazem formulation |
| CA2122479C (en) | 1991-11-22 | 1998-08-25 | Richard John Dansereau | Risedronate delayed-release compositions |
| US5340591A (en) | 1992-01-24 | 1994-08-23 | Fujisawa Pharmaceutical Co., Ltd. | Method of producing a solid dispersion of the sparingly water-soluble drug, nilvadipine |
| US5461140A (en) | 1992-04-30 | 1995-10-24 | Pharmaceutical Delivery Systems | Bioerodible polymers for solid controlled release pharmaceutical compositions |
| US5260068A (en) | 1992-05-04 | 1993-11-09 | Anda Sr Pharmaceuticals Inc. | Multiparticulate pulsatile drug delivery system |
| US5281420A (en) | 1992-05-19 | 1994-01-25 | The Procter & Gamble Company | Solid dispersion compositions of tebufelone |
| US5323907A (en) | 1992-06-23 | 1994-06-28 | Multi-Comp, Inc. | Child resistant package assembly for dispensing pharmaceutical medications |
| AU4198793A (en) | 1992-07-24 | 1994-01-27 | Takeda Chemical Industries Ltd. | Microparticle preparation and production thereof |
| US5700485A (en) | 1992-09-10 | 1997-12-23 | Children's Medical Center Corporation | Prolonged nerve blockade by the combination of local anesthetic and glucocorticoid |
| EP0665010B1 (en) | 1992-10-16 | 2002-09-11 | Nippon Shinyaku Company, Limited | Method of manufacturing wax matrices |
| US5260069A (en) | 1992-11-27 | 1993-11-09 | Anda Sr Pharmaceuticals Inc. | Pulsatile particles drug delivery system |
| US5686105A (en) | 1993-10-19 | 1997-11-11 | The Procter & Gamble Company | Pharmaceutical dosage form with multiple enteric polymer coatings for colonic delivery |
| US6326469B1 (en) | 1994-04-22 | 2001-12-04 | Sugen, Inc. | Megakaryocytic protein tyrosine kinases |
| US5665378A (en) | 1994-09-30 | 1997-09-09 | Davis; Roosevelt | Transdermal therapeutic formulation |
| US5567441A (en) | 1995-03-24 | 1996-10-22 | Andrx Pharmaceuticals Inc. | Diltiazem controlled release formulation |
| CA2220451A1 (en) | 1995-05-17 | 1996-11-21 | Cedars-Sinai Medical Center | Methods and compositions for improving digestion and absorption in the small intestine |
| SE9502244D0 (sv) | 1995-06-20 | 1995-06-20 | Bioglan Ab | A composition and a process for the preparation thereof |
| US5837284A (en) | 1995-12-04 | 1998-11-17 | Mehta; Atul M. | Delivery of multiple doses of medications |
| US5858401A (en) | 1996-01-22 | 1999-01-12 | Sidmak Laboratories, Inc. | Pharmaceutical composition for cyclosporines |
| US6923983B2 (en) | 1996-02-19 | 2005-08-02 | Acrux Dds Pty Ltd | Transdermal delivery of hormones |
| US6929801B2 (en) | 1996-02-19 | 2005-08-16 | Acrux Dds Pty Ltd | Transdermal delivery of antiparkinson agents |
| US6458373B1 (en) | 1997-01-07 | 2002-10-01 | Sonus Pharmaceuticals, Inc. | Emulsion vehicle for poorly soluble drugs |
| EP0970084B1 (en) * | 1997-03-19 | 2003-06-04 | Basf Aktiengesellschaft | Pyrrolo 2,3d]pyrimidines and their use as tyrosine kinase inhibitors |
| US5840329A (en) | 1997-05-15 | 1998-11-24 | Bioadvances Llc | Pulsatile drug delivery system |
| US6391452B1 (en) | 1997-07-18 | 2002-05-21 | Bayer Corporation | Compositions for nasal drug delivery, methods of making same, and methods of removing residual solvent from pharmaceutical preparations |
| US5869090A (en) | 1998-01-20 | 1999-02-09 | Rosenbaum; Jerry | Transdermal delivery of dehydroepiandrosterone |
| US6946144B1 (en) | 1998-07-08 | 2005-09-20 | Oryxe | Transdermal delivery system |
| TR200101186T2 (tr) * | 1998-09-18 | 2001-10-22 | Basf Aktiengesellschaft | Protein kinaz engelleyiciler olarak pyrrolopyrimidin'ler |
| DE60039379D1 (de) | 1999-02-10 | 2008-08-21 | Pfizer Prod Inc | Pharmazeutische feste Dispersionen |
| US6395300B1 (en) | 1999-05-27 | 2002-05-28 | Acusphere, Inc. | Porous drug matrices and methods of manufacture thereof |
| US6921763B2 (en) * | 1999-09-17 | 2005-07-26 | Abbott Laboratories | Pyrazolopyrimidines as therapeutic agents |
| NZ517758A (en) | 1999-09-17 | 2004-06-25 | Abbott Gmbh & Co | Pyrazolopyrimidines useful as therapeutic agents |
| AU2001262960A1 (en) | 2000-04-28 | 2001-11-12 | Zengen, Inc. | New antibodies to biological membranes |
| US6465014B1 (en) | 2001-03-21 | 2002-10-15 | Isp Investments Inc. | pH-dependent sustained release, drug-delivery composition |
| MXPA03008560A (es) | 2001-03-22 | 2004-06-30 | Abbot Gmbh & Co Kg | Pirazolopirimidinas como agentes terapeuticos. |
| US6960563B2 (en) | 2001-08-31 | 2005-11-01 | Morton Grove Pharmaceuticals, Inc. | Spontaneous emulsions containing cyclosporine |
| BRPI0418031A (pt) * | 2003-12-22 | 2007-04-17 | Gilead Sciences Inc | inibidores de quinase fosfonato-substituìdos |
| CA2548951A1 (en) * | 2003-12-22 | 2005-07-14 | Gilead Sciences, Inc. | Kinase inhibitor phosphonate conjugates |
| CA2553724A1 (en) * | 2004-02-03 | 2005-08-18 | Abbott Laboratories | Aminobenzoxazoles as therapeutic agents |
| EP1831225A2 (en) * | 2004-11-19 | 2007-09-12 | The Regents of the University of California | Anti-inflammatory pyrazolopyrimidines |
| KR20090017498A (ko) * | 2006-04-04 | 2009-02-18 | 더 리젠트스 오브 더 유니이버시티 오브 캘리포니아 | Ｐｉ３ 키나제 길항물질 |
| DK2529622T3 (en) | 2006-09-22 | 2018-05-07 | Pharmacyclics Llc | INHIBITORS OF BRUTON-TYROSINKINASE |
| NZ579911A (en) * | 2007-03-28 | 2012-05-25 | Pharmacyclics Inc | Inhibitors of bruton's tyrosine kinase |
| US7718662B1 (en) * | 2009-10-12 | 2010-05-18 | Pharmacyclics, Inc. | Pyrazolo-pyrimidine inhibitors of bruton's tyrosine kinase |
| PH12012500713A1 (en) | 2009-10-14 | 2012-11-26 | Merck Sharp & Dohme | Substituted piperidines that increase p53 activity and the uses thereof |
-
2009
- 2009-10-16 US US12/581,044 patent/US7718662B1/en active Active
- 2009-10-16 US US12/581,062 patent/US7741330B1/en active Active
-
2010
- 2010-10-12 JP JP2012534294A patent/JP5717109B2/ja not_active Expired - Fee Related
- 2010-10-12 PH PH1/2012/500712A patent/PH12012500712A1/en unknown
- 2010-10-12 US US12/903,101 patent/US9012463B2/en active Active
- 2010-10-12 CA CA2776543A patent/CA2776543A1/en not_active Abandoned
- 2010-10-12 MX MX2012004258A patent/MX2012004258A/es active IP Right Grant
- 2010-10-12 EA EA201270553A patent/EA021715B1/ru unknown
- 2010-10-12 CN CN201080056387.2A patent/CN102656173B/zh not_active Expired - Fee Related
- 2010-10-12 BR BR112012008624A patent/BR112012008624A2/pt not_active IP Right Cessation
- 2010-10-12 KR KR20127011767A patent/KR20120097376A/ko not_active Ceased
- 2010-10-12 ES ES13166272.8T patent/ES2590905T3/es active Active
- 2010-10-12 IN IN3012DEN2012 patent/IN2012DN03012A/en unknown
- 2010-10-12 AU AU2010306921A patent/AU2010306921C1/en not_active Ceased
- 2010-10-12 WO PCT/US2010/052377 patent/WO2011046964A2/en not_active Ceased
- 2010-10-12 NZ NZ59939610A patent/NZ599396A/en not_active IP Right Cessation
- 2010-10-12 EP EP10823966A patent/EP2393816A4/en not_active Withdrawn
- 2010-10-12 EP EP13166272.8A patent/EP2650294B1/en not_active Not-in-force
- 2010-10-12 SG SG10201506776RA patent/SG10201506776RA/en unknown
-
2012
- 2012-04-05 IL IL219076A patent/IL219076A/en active IP Right Grant
- 2012-04-09 CO CO12057551A patent/CO6531429A2/es active IP Right Grant
- 2012-04-10 ZA ZA2012/02552A patent/ZA201202552B/en unknown
- 2012-04-11 CL CL2012000917A patent/CL2012000917A1/es unknown
- 2012-05-11 CR CR20120244A patent/CR20120244A/es unknown
-
2013
- 2013-11-20 US US14/085,722 patent/US20140080844A1/en not_active Abandoned
-
2015
- 2015-03-10 JP JP2015047643A patent/JP2015134802A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2590905T3 (es) | Inhibidores de la tirosina quinasa de Bruton | |
| EP3328827B1 (en) | Prodrugs of glutamine analogs | |
| ES2375843T3 (es) | Procedimientos y compuestos para la preparación de an�?logos de cc-1065. | |
| ES2584331T3 (es) | Inhibidores de tirosina cinasa de Bruton | |
| JP6227707B2 (ja) | Ｍｃｌ‐１を調節する小分子、並びに細胞死、細胞分裂、細胞分化を調節する方法、及び疾患を治療する方法。 | |
| JP7358342B2 (ja) | 新規なグルタミンアンタゴニストおよびそれらの使用 | |
| ES2826443T3 (es) | Inhibidores de proteínas mutantes KRAS G12C | |
| ES2930050T3 (es) | Inhibidores heterocíclicos de ERK1 y ERK2 y su uso en el tratamiento de cáncer | |
| ES2912035T3 (es) | Compuestos | |
| BRPI0712882A2 (pt) | pirrolopirimidinas para composições farmacêuticas | |
| KR20180035894A (ko) | 화학치료제로서의 베타-치환된 베타-아미노산 및 유사체 및 이들의 용도 | |
| ES2773266T3 (es) | Métodos de tratamiento utilizando moduladores de SIRT2 | |
| ES2764279T3 (es) | Compuestos de sulfonamida y su uso como inhibidores de stat5 | |
| CN107531759A (zh) | 非膜破坏性p53活化装订肽 | |
| KR20180117636A (ko) | 소마토스타틴 수용체 길항제 화합물 및 이의 이용 방법 | |
| AU2019216757B2 (en) | Mebendazole prodrugs with enhanced solubility and oral bioavailability | |
| ES2731525T3 (es) | Aminas terciarias para su uso en el tratamiento de trastornos cardíacos | |
| CA3164153A1 (en) | Modulators of cullin 3 adaptor kbtbd4 as anti-cancer compounds | |
| Nandi et al. | Signal transduction through JAK-STAT and NF-κB regulated pim-1 kinase: novel target for anticancer leads | |
| ES3038030T3 (en) | Estrogen receptor-modulating compounds | |
| ES2749512T3 (es) | Derivados de tetrahidroquinolina y su uso como inhibidores de Epac | |
| ES2881960T3 (es) | Inhibidores de proteina quinasa | |
| US20250304585A1 (en) | Sulfamate based covalent ligand-directed release (coldr) compounds | |
| WO2020127958A1 (en) | Covalent inhibitors of enzyme targets with specific tyrosine-containing motifs | |
| RU2570576C2 (ru) | Новые сложные эфиры (ацилоксиметил)акриламида, фармацевтическая композиция, содержащая их, и их применение в качестве ингибиторов системы тиоредоксин - тиоредоксин-редуктаза |