JP2014520793A5 - - Google Patents
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- JP2014520793A5 JP2014520793A5 JP2014517980A JP2014517980A JP2014520793A5 JP 2014520793 A5 JP2014520793 A5 JP 2014520793A5 JP 2014517980 A JP2014517980 A JP 2014517980A JP 2014517980 A JP2014517980 A JP 2014517980A JP 2014520793 A5 JP2014520793 A5 JP 2014520793A5
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- JP
- Japan
- Prior art keywords
- phenyl
- methyl
- pyrrolo
- fluoro
- dihydro
- 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.)
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 19
- 201000010099 disease Diseases 0.000 claims description 17
- 150000001875 compounds Chemical class 0.000 claims description 16
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 claims description 13
- 206010052779 Transplant rejections Diseases 0.000 claims description 13
- 230000001404 mediated effect Effects 0.000 claims description 12
- 208000035475 disorder Diseases 0.000 claims description 8
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 7
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 7
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 7
- 208000024376 chronic urticaria Diseases 0.000 claims description 7
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 7
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 7
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 6
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 6
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 6
- 208000026935 allergic disease Diseases 0.000 claims description 6
- 201000010105 allergic rhinitis Diseases 0.000 claims description 6
- 201000008937 atopic dermatitis Diseases 0.000 claims description 6
- 201000006417 multiple sclerosis Diseases 0.000 claims description 6
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 5
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 5
- 208000023328 Basedow disease Diseases 0.000 claims description 5
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 5
- 208000015023 Graves' disease Diseases 0.000 claims description 5
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 claims description 5
- 208000003456 Juvenile Arthritis Diseases 0.000 claims description 5
- 208000028018 Lymphocytic leukaemia Diseases 0.000 claims description 5
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 5
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 5
- 201000011152 Pemphigus Diseases 0.000 claims description 5
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 claims description 5
- 206010047115 Vasculitis Diseases 0.000 claims description 5
- 230000001154 acute effect Effects 0.000 claims description 5
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 claims description 5
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 5
- 201000003278 cryoglobulinemia Diseases 0.000 claims description 5
- 230000001086 cytosolic effect Effects 0.000 claims description 5
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 claims description 5
- 208000003747 lymphoid leukemia Diseases 0.000 claims description 5
- 206010028417 myasthenia gravis Diseases 0.000 claims description 5
- 208000025113 myeloid leukemia Diseases 0.000 claims description 5
- 201000001976 pemphigus vulgaris Diseases 0.000 claims description 5
- 230000009885 systemic effect Effects 0.000 claims description 5
- 208000011231 Crohn disease Diseases 0.000 claims description 4
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 claims description 4
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 claims description 4
- 206010002383 Angina Pectoris Diseases 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 3
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
- 206010012442 Dermatitis contact Diseases 0.000 claims description 3
- 208000024869 Goodpasture syndrome Diseases 0.000 claims description 3
- 201000005569 Gout Diseases 0.000 claims description 3
- 208000030836 Hashimoto thyroiditis Diseases 0.000 claims description 3
- 206010025323 Lymphomas Diseases 0.000 claims description 3
- 206010033645 Pancreatitis Diseases 0.000 claims description 3
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- 206010043561 Thrombocytopenic purpura Diseases 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 208000010247 contact dermatitis Diseases 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 230000000302 ischemic effect Effects 0.000 claims description 3
- 208000032839 leukemia Diseases 0.000 claims description 3
- 208000010125 myocardial infarction Diseases 0.000 claims description 3
- 206010043554 thrombocytopenia Diseases 0.000 claims description 3
- 208000007536 Thrombosis Diseases 0.000 claims description 2
- 201000005787 hematologic cancer Diseases 0.000 claims description 2
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims description 2
- 230000009424 thromboembolic effect Effects 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 35
- 239000001257 hydrogen Substances 0.000 claims 35
- 229910052736 halogen Chemical group 0.000 claims 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 21
- -1 C 1 -C 6 alkoxy Chemical group 0.000 claims 15
- 150000002367 halogens Chemical group 0.000 claims 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 13
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 11
- 150000002431 hydrogen Chemical group 0.000 claims 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 10
- 125000001153 fluoro group Chemical group F* 0.000 claims 9
- 125000005843 halogen group Chemical group 0.000 claims 9
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 9
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims 9
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 8
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 6
- YWPMKTWUFVOFPL-UHFFFAOYSA-N 3,4-dihydro-2h-isoquinolin-1-one Chemical group C1=CC=C2C(=O)NCCC2=C1 YWPMKTWUFVOFPL-UHFFFAOYSA-N 0.000 claims 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 4
- 229910052760 oxygen Inorganic materials 0.000 claims 4
- 229910052717 sulfur Inorganic materials 0.000 claims 4
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical group O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims 3
- ZAUVEVHTVQJRTN-UHFFFAOYSA-N 4-[4-[3-[(4-acetylbenzoyl)amino]-5-fluoro-2-methylphenyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-dimethyl-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C1N(C(=O)N(C)C)CCC(C=2NC3=NC=NC(=C3C=2)C=2C(=C(NC(=O)C=3C=CC(=CC=3)C(C)=O)C=C(F)C=2)C)=C1 ZAUVEVHTVQJRTN-UHFFFAOYSA-N 0.000 claims 2
- UZQDYTBAPMZXKM-UHFFFAOYSA-N 4-cyclopropyl-n-[5-fluoro-2-methyl-3-[6-[1-(pyrrolidine-1-carbonyl)-3,6-dihydro-2h-pyridin-4-yl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]phenyl]benzamide Chemical compound C1=C(F)C=C(C=2C=3C=C(NC=3N=CN=2)C=2CCN(CC=2)C(=O)N2CCCC2)C(C)=C1NC(=O)C(C=C1)=CC=C1C1CC1 UZQDYTBAPMZXKM-UHFFFAOYSA-N 0.000 claims 2
- CKEMXFLXVHEYLO-UHFFFAOYSA-N 4-tert-butyl-n-[3-[6-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]-5-fluoro-2-methylphenyl]benzamide Chemical compound C1=C(F)C=C(C=2C=3C=C(NC=3N=CN=2)C=2CCC3(CC=2)OCCO3)C(C)=C1NC(=O)C1=CC=C(C(C)(C)C)C=C1 CKEMXFLXVHEYLO-UHFFFAOYSA-N 0.000 claims 2
- ZWWQAKIQAPSJRV-UHFFFAOYSA-N 4-tert-butyl-n-[3-[6-(3,6-dihydro-2h-thiopyran-4-yl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]-5-fluoro-2-methylphenyl]benzamide Chemical compound C1=C(F)C=C(C=2C=3C=C(NC=3N=CN=2)C=2CCSCC=2)C(C)=C1NC(=O)C1=CC=C(C(C)(C)C)C=C1 ZWWQAKIQAPSJRV-UHFFFAOYSA-N 0.000 claims 2
- DEDSPQBYYGKANF-UHFFFAOYSA-N 4-tert-butyl-n-[5-fluoro-3-[6-(4-hydroxycyclohexen-1-yl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]-2-methylphenyl]benzamide Chemical compound C1=C(F)C=C(C=2C=3C=C(NC=3N=CN=2)C=2CCC(O)CC=2)C(C)=C1NC(=O)C1=CC=C(C(C)(C)C)C=C1 DEDSPQBYYGKANF-UHFFFAOYSA-N 0.000 claims 2
- RJHGOPBGEROWRB-UHFFFAOYSA-N [2-[4-[4-[3-[(4-cyclopropylbenzoyl)amino]-5-fluoro-2-methylphenyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2h-pyridin-1-yl]-2-oxoethyl] acetate Chemical compound C1N(C(=O)COC(=O)C)CCC(C=2NC3=NC=NC(=C3C=2)C=2C(=C(NC(=O)C=3C=CC(=CC=3)C3CC3)C=C(F)C=2)C)=C1 RJHGOPBGEROWRB-UHFFFAOYSA-N 0.000 claims 2
- 125000002393 azetidinyl group Chemical group 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- BXZGCFXOZWMQQC-UHFFFAOYSA-N n-[3-[6-(3,6-dihydro-2h-pyran-4-yl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]-2-(hydroxymethyl)phenyl]-2-fluoro-4-(2-hydroxypropan-2-yl)benzamide Chemical compound FC1=CC(C(C)(O)C)=CC=C1C(=O)NC1=CC=CC(C=2C=3C=C(NC=3N=CN=2)C=2CCOCC=2)=C1CO BXZGCFXOZWMQQC-UHFFFAOYSA-N 0.000 claims 2
- PSLXNEVDCJSLEL-UHFFFAOYSA-N n-[3-[6-(3,6-dihydro-2h-pyran-4-yl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]-5-fluoro-2-methylphenyl]-2-fluoro-4-(2-hydroxypropan-2-yl)benzamide Chemical compound C1=C(F)C=C(C=2C=3C=C(NC=3N=CN=2)C=2CCOCC=2)C(C)=C1NC(=O)C1=CC=C(C(C)(C)O)C=C1F PSLXNEVDCJSLEL-UHFFFAOYSA-N 0.000 claims 2
- 229910052757 nitrogen Inorganic materials 0.000 claims 2
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims 1
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 1
- 125000006420 1-fluorocyclopropyl group Chemical group [H]C1([H])C([H])([H])C1(F)* 0.000 claims 1
- SQWBWWKSKVGXAC-UHFFFAOYSA-N 1-methylpyrrolo[2,3-b]pyridine-6-carboxylic acid Chemical compound C1=C(C(O)=O)N=C2N(C)C=CC2=C1 SQWBWWKSKVGXAC-UHFFFAOYSA-N 0.000 claims 1
- SZMBVFYZJRXDCM-UHFFFAOYSA-N 4-[4-[2-(hydroxymethyl)-3-[6-(2-hydroxypropan-2-yl)-1-oxo-3,4-dihydroisoquinolin-2-yl]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-dimethyl-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C1N(C(=O)N(C)C)CCC(C=2NC3=NC=NC(=C3C=2)C=2C(=C(N3C(C4=CC=C(C=C4CC3)C(C)(C)O)=O)C=CC=2)CO)=C1 SZMBVFYZJRXDCM-UHFFFAOYSA-N 0.000 claims 1
- VDPHWIWWROGXAO-UHFFFAOYSA-N 4-[4-[3-(6-tert-butyl-1-oxo-3,4-dihydroisoquinolin-2-yl)-2-(hydroxymethyl)phenyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-dimethyl-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C1N(C(=O)N(C)C)CCC(C=2NC3=NC=NC(=C3C=2)C=2C(=C(N3C(C4=CC=C(C=C4CC3)C(C)(C)C)=O)C=CC=2)CO)=C1 VDPHWIWWROGXAO-UHFFFAOYSA-N 0.000 claims 1
- JSHGXUDFCKQNOV-UHFFFAOYSA-N 4-[4-[3-[(4-cyclopropylbenzoyl)amino]-2-(hydroxymethyl)phenyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-dimethyl-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C1N(C(=O)N(C)C)CCC(C=2NC3=NC=NC(=C3C=2)C=2C(=C(NC(=O)C=3C=CC(=CC=3)C3CC3)C=CC=2)CO)=C1 JSHGXUDFCKQNOV-UHFFFAOYSA-N 0.000 claims 1
- GZABPYMEPKWSAR-UHFFFAOYSA-N 4-[4-[3-[(4-cyclopropylbenzoyl)amino]-4-fluorophenyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-dimethyl-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C1N(C(=O)N(C)C)CCC(C=2NC3=NC=NC(=C3C=2)C=2C=C(NC(=O)C=3C=CC(=CC=3)C3CC3)C(F)=CC=2)=C1 GZABPYMEPKWSAR-UHFFFAOYSA-N 0.000 claims 1
- IIYOOOONDUTPRD-UHFFFAOYSA-N 4-[4-[3-[(4-tert-butylbenzoyl)amino]-5-fluoro-2-methylphenyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-dimethyl-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C1N(C(=O)N(C)C)CCC(C=2NC3=NC=NC(=C3C=2)C=2C(=C(NC(=O)C=3C=CC(=CC=3)C(C)(C)C)C=C(F)C=2)C)=C1 IIYOOOONDUTPRD-UHFFFAOYSA-N 0.000 claims 1
- YEUUOSNTDSZKQF-UHFFFAOYSA-N 4-[4-[3-[[2-fluoro-4-(2-hydroxypropan-2-yl)benzoyl]amino]-2-(hydroxymethyl)phenyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-dimethyl-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C1N(C(=O)N(C)C)CCC(C=2NC3=NC=NC(=C3C=2)C=2C(=C(NC(=O)C=3C(=CC(=CC=3)C(C)(C)O)F)C=CC=2)CO)=C1 YEUUOSNTDSZKQF-UHFFFAOYSA-N 0.000 claims 1
- JWXICKMBHDHSJV-UHFFFAOYSA-N 4-[4-[3-[[4-(dimethylamino)benzoyl]amino]-5-fluoro-2-methylphenyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-dimethyl-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C1N(C(=O)N(C)C)CCC(C=2NC3=NC=NC(=C3C=2)C=2C(=C(NC(=O)C=3C=CC(=CC=3)N(C)C)C=C(F)C=2)C)=C1 JWXICKMBHDHSJV-UHFFFAOYSA-N 0.000 claims 1
- LJCBNGBBWDIUJW-UHFFFAOYSA-N 4-[4-[3-[benzoyl(prop-1-en-2-yl)amino]-5-fluoro-2-methylphenyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-dimethyl-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C1N(C(=O)N(C)C)CCC(C=2NC3=NC=NC(=C3C=2)C=2C(=C(N(C(C)=C)C(=O)C=3C=CC=CC=3)C=C(F)C=2)C)=C1 LJCBNGBBWDIUJW-UHFFFAOYSA-N 0.000 claims 1
- WMTYXEKVXXLDOO-UHFFFAOYSA-N 4-[4-[4-fluoro-2-methyl-3-[[3-[(2-methylpropan-2-yl)oxy]azetidine-1-carbonyl]amino]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-dimethyl-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C1N(C(=O)N(C)C)CCC(C=2NC3=NC=NC(=C3C=2)C=2C(=C(NC(=O)N3CC(C3)OC(C)(C)C)C(F)=CC=2)C)=C1 WMTYXEKVXXLDOO-UHFFFAOYSA-N 0.000 claims 1
- IJUNVOJIYZFJBT-UHFFFAOYSA-N 4-[4-[4-fluoro-3-[[3-[(2-methylpropan-2-yl)oxy]azetidine-1-carbonyl]amino]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-dimethyl-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C1N(C(=O)N(C)C)CCC(C=2NC3=NC=NC(=C3C=2)C=2C=C(NC(=O)N3CC(C3)OC(C)(C)C)C(F)=CC=2)=C1 IJUNVOJIYZFJBT-UHFFFAOYSA-N 0.000 claims 1
- ZMZQAZFJKRCEGJ-UHFFFAOYSA-N 4-[4-[5-fluoro-2-methyl-3-[(4-piperidin-1-ylbenzoyl)amino]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-dimethyl-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C1N(C(=O)N(C)C)CCC(C=2NC3=NC=NC(=C3C=2)C=2C(=C(NC(=O)C=3C=CC(=CC=3)N3CCCCC3)C=C(F)C=2)C)=C1 ZMZQAZFJKRCEGJ-UHFFFAOYSA-N 0.000 claims 1
- AWMQABFYTUZIJL-UHFFFAOYSA-N 4-[4-[5-fluoro-2-methyl-3-[(4-propan-2-yloxybenzoyl)amino]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-dimethyl-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C1=CC(OC(C)C)=CC=C1C(=O)NC1=CC(F)=CC(C=2C=3C=C(NC=3N=CN=2)C=2CCN(CC=2)C(=O)N(C)C)=C1C AWMQABFYTUZIJL-UHFFFAOYSA-N 0.000 claims 1
- WLNMTYVVPHKNPT-UHFFFAOYSA-N 4-[4-[5-fluoro-2-methyl-3-[[3-[(2-methylpropan-2-yl)oxy]azetidine-1-carbonyl]amino]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-dimethyl-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C1N(C(=O)N(C)C)CCC(C=2NC3=NC=NC(=C3C=2)C=2C(=C(NC(=O)N3CC(C3)OC(C)(C)C)C=C(F)C=2)C)=C1 WLNMTYVVPHKNPT-UHFFFAOYSA-N 0.000 claims 1
- YAOURPFQCBCOGE-UHFFFAOYSA-N 4-[4-[5-fluoro-2-methyl-3-[[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)benzoyl]amino]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-dimethyl-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C1N(C(=O)N(C)C)CCC(C=2NC3=NC=NC(=C3C=2)C=2C(=C(NC(=O)C=3C=CC(=CC=3)C(C)(O)C(F)(F)F)C=C(F)C=2)C)=C1 YAOURPFQCBCOGE-UHFFFAOYSA-N 0.000 claims 1
- IEGRMNYULFKAKP-UHFFFAOYSA-N 4-[4-[5-fluoro-2-methyl-3-[[4-[1-(trifluoromethyl)cyclopropyl]benzoyl]amino]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-dimethyl-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C1N(C(=O)N(C)C)CCC(C=2NC3=NC=NC(=C3C=2)C=2C(=C(NC(=O)C=3C=CC(=CC=3)C3(CC3)C(F)(F)F)C=C(F)C=2)C)=C1 IEGRMNYULFKAKP-UHFFFAOYSA-N 0.000 claims 1
- MLKDBPSLDGNZKN-UHFFFAOYSA-N 4-[4-[5-fluoro-3-[[2-fluoro-4-(2-hydroxypropan-2-yl)benzoyl]amino]-2-methylphenyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-dimethyl-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C1N(C(=O)N(C)C)CCC(C=2NC3=NC=NC(=C3C=2)C=2C(=C(NC(=O)C=3C(=CC(=CC=3)C(C)(C)O)F)C=C(F)C=2)C)=C1 MLKDBPSLDGNZKN-UHFFFAOYSA-N 0.000 claims 1
- YYDRDORQKKYAEN-UHFFFAOYSA-N 4-[4-[5-fluoro-3-[[3-(1,1,1,3,3,3-hexafluoropropan-2-yloxy)azetidine-1-carbonyl]amino]-2-methylphenyl]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid Chemical compound FC=1C=C(C(=C(C=1)C=1C2=C(N=CN=1)NC(=C2)C=1CCN(CC=1)C(=O)O)C)NC(=O)N1CC(C1)OC(C(F)(F)F)C(F)(F)F YYDRDORQKKYAEN-UHFFFAOYSA-N 0.000 claims 1
- ZMMYFCIEQJSJGU-UHFFFAOYSA-N 4-[4-[5-fluoro-3-[[4-(1-hydroxy-2-methylpropan-2-yl)benzoyl]amino]-2-methylphenyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-dimethyl-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C1N(C(=O)N(C)C)CCC(C=2NC3=NC=NC(=C3C=2)C=2C(=C(NC(=O)C=3C=CC(=CC=3)C(C)(C)CO)C=C(F)C=2)C)=C1 ZMMYFCIEQJSJGU-UHFFFAOYSA-N 0.000 claims 1
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- RXTLGQQWYGOUNM-UHFFFAOYSA-N 4-[4-[5-fluoro-3-[[4-(2-methoxypropan-2-yl)benzoyl]amino]-2-methylphenyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-dimethyl-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C1=CC(C(C)(C)OC)=CC=C1C(=O)NC1=CC(F)=CC(C=2C=3C=C(NC=3N=CN=2)C=2CCN(CC=2)C(=O)N(C)C)=C1C RXTLGQQWYGOUNM-UHFFFAOYSA-N 0.000 claims 1
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| EA034666B1 (ru) | 2013-09-13 | 2020-03-04 | Бейджин Свитзерланд Гмбх | Антитело против pd-1 и его применение для лечения рака или вирусной инфекции и фрагмент антитела |
| US9512084B2 (en) | 2013-11-29 | 2016-12-06 | Novartis Ag | Amino pyrimidine derivatives |
| TW202402295A (zh) * | 2013-12-02 | 2024-01-16 | 美商製藥公司 | 治療及預防異體抗體所驅動之慢性移植體對抗宿主疾病之方法 |
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| ES2905980T3 (es) | 2016-05-26 | 2022-04-12 | Incyte Corp | Compuestos heterocíclicos como inmunomoduladores |
| BR112018076534A2 (pt) | 2016-06-20 | 2019-04-02 | Incyte Corporation | compostos heterocíclicos como imunomoduladores |
| US10864203B2 (en) | 2016-07-05 | 2020-12-15 | Beigene, Ltd. | Combination of a PD-1 antagonist and a RAF inhibitor for treating cancer |
| MA45669A (fr) | 2016-07-14 | 2019-05-22 | Incyte Corp | Composés hétérocycliques utilisés comme immunomodulateurs |
| CA3033827A1 (en) | 2016-08-16 | 2018-02-22 | Beigene, Ltd. | Crystalline form of (s)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl )-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide,preparation, and uses thereof |
| PT3500299T (pt) | 2016-08-19 | 2024-02-21 | Beigene Switzerland Gmbh | Combinação de zanubrutinib com um anticorpo anti-cd20 ou anti-pd-1 para utilização no tratamento do cancro |
| ES2941716T3 (es) | 2016-08-29 | 2023-05-25 | Incyte Corp | Compuestos heterocíclicos como inmunomoduladores |
| CN109982687A (zh) | 2016-09-19 | 2019-07-05 | 梅制药公司 | 联合疗法 |
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- 2012-07-07 WO PCT/IB2012/001699 patent/WO2013008095A1/en not_active Ceased
- 2012-07-07 ES ES12761655.5T patent/ES2548414T3/es active Active
- 2012-07-07 JP JP2014517980A patent/JP6145451B2/ja not_active Expired - Fee Related
- 2012-07-07 CA CA2841111A patent/CA2841111A1/en not_active Abandoned
- 2012-07-07 CN CN201280033935.9A patent/CN103732596B/zh not_active Expired - Fee Related
- 2012-07-07 MX MX2014000338A patent/MX2014000338A/es unknown
- 2012-07-07 AU AU2012282229A patent/AU2012282229B2/en not_active Expired - Fee Related
- 2012-07-07 EA EA201490229A patent/EA201490229A1/ru unknown
- 2012-07-07 US US14/130,536 patent/US9233111B2/en not_active Expired - Fee Related
- 2012-07-07 BR BR112014000314A patent/BR112014000314A2/pt not_active IP Right Cessation
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