AU2013277582B2 - Reversible covalent pyrrolo- or pyrazolopyrimidines useful for the treatment cancer and autoimmune diseases - Google Patents
Reversible covalent pyrrolo- or pyrazolopyrimidines useful for the treatment cancer and autoimmune diseases Download PDFInfo
- Publication number
- AU2013277582B2 AU2013277582B2 AU2013277582A AU2013277582A AU2013277582B2 AU 2013277582 B2 AU2013277582 B2 AU 2013277582B2 AU 2013277582 A AU2013277582 A AU 2013277582A AU 2013277582 A AU2013277582 A AU 2013277582A AU 2013277582 B2 AU2013277582 B2 AU 2013277582B2
- Authority
- AU
- Australia
- Prior art keywords
- amino
- carbonyl
- pyrazolo
- pyrimidin
- methyl
- 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
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 12
- 201000011510 cancer Diseases 0.000 title claims abstract description 12
- 208000023275 Autoimmune disease Diseases 0.000 title claims abstract description 10
- 230000002441 reversible effect Effects 0.000 title abstract description 13
- APXRHPDHORGIEB-UHFFFAOYSA-N 1H-pyrazolo[4,3-d]pyrimidine Chemical class N1=CN=C2C=NNC2=C1 APXRHPDHORGIEB-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 287
- 239000000203 mixture Substances 0.000 claims abstract description 219
- 238000009472 formulation Methods 0.000 claims abstract description 179
- 238000000034 method Methods 0.000 claims abstract description 48
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 34
- 201000010099 disease Diseases 0.000 claims abstract description 30
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 380
- 125000000217 alkyl group Chemical group 0.000 claims description 319
- 239000001257 hydrogen Substances 0.000 claims description 183
- 229910052739 hydrogen Inorganic materials 0.000 claims description 183
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 174
- -1 chloro, fluoro, cyclopropyl Chemical group 0.000 claims description 166
- 150000003839 salts Chemical class 0.000 claims description 140
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 112
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 claims description 99
- 238000009505 enteric coating Methods 0.000 claims description 96
- 239000002702 enteric coating Substances 0.000 claims description 96
- 125000001424 substituent group Chemical group 0.000 claims description 87
- 125000001153 fluoro group Chemical group F* 0.000 claims description 83
- 125000005843 halogen group Chemical group 0.000 claims description 78
- 238000000576 coating method Methods 0.000 claims description 74
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 72
- 239000011248 coating agent Substances 0.000 claims description 69
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 69
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 53
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 47
- 239000007787 solid Substances 0.000 claims description 46
- 125000004476 heterocycloamino group Chemical group 0.000 claims description 37
- 229910052760 oxygen Inorganic materials 0.000 claims description 37
- 239000003814 drug Substances 0.000 claims description 35
- 125000005842 heteroatom Chemical group 0.000 claims description 35
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 35
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 28
- 239000003795 chemical substances by application Substances 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- ISBHMJZRKAFTGE-ONEGZZNKSA-N (e)-pent-2-enenitrile Chemical compound CC\C=C\C#N ISBHMJZRKAFTGE-ONEGZZNKSA-N 0.000 claims description 14
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 14
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 14
- 201000004624 Dermatitis Diseases 0.000 claims description 10
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 9
- 229920006318 anionic polymer Polymers 0.000 claims description 9
- 230000005764 inhibitory process Effects 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 8
- 208000027866 inflammatory disease Diseases 0.000 claims description 8
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 8
- 229920002554 vinyl polymer Polymers 0.000 claims description 8
- MAUMSNABMVEOGP-UHFFFAOYSA-N (methyl-$l^{2}-azanyl)methane Chemical compound C[N]C MAUMSNABMVEOGP-UHFFFAOYSA-N 0.000 claims description 7
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 7
- 108091000080 Phosphotransferase Proteins 0.000 claims description 7
- 229920003174 cellulose-based polymer Polymers 0.000 claims description 7
- 206010025135 lupus erythematosus Diseases 0.000 claims description 7
- 102000020233 phosphotransferase Human genes 0.000 claims description 7
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 claims description 6
- 206010035664 Pneumonia Diseases 0.000 claims description 6
- 201000004681 Psoriasis Diseases 0.000 claims description 6
- 206010039710 Scleroderma Diseases 0.000 claims description 6
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 6
- 208000006673 asthma Diseases 0.000 claims description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 claims description 5
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 5
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 5
- 206010046851 Uveitis Diseases 0.000 claims description 5
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 5
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 5
- 206010003246 arthritis Diseases 0.000 claims description 5
- 229920000193 polymethacrylate Polymers 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- XHBRPKRNVSMGJI-FQEVSTJZSA-N 2-[(3S)-3-[4-amino-3-[4-(3,5-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enamide Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C=CC(OC=4C=C(F)C=C(F)C=4)=CC=3)=N2)N1C(=O)C(C(=O)N)=CC1CC1 XHBRPKRNVSMGJI-FQEVSTJZSA-N 0.000 claims description 4
- 230000001363 autoimmune Effects 0.000 claims description 4
- NKKBQDDLYMJHGR-GOSISDBHSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enamide Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C(=O)N)=CC1CC1 NKKBQDDLYMJHGR-GOSISDBHSA-N 0.000 claims description 3
- UCAYALHDCZYJHZ-LJQANCHMSA-N 2-[(3R)-3-[4-amino-3-[4-(2,5-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enamide Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C=CC(OC=4C(=CC=C(F)C=4)F)=CC=3)=N2)N1C(=O)C(C(=O)N)=CC1CC1 UCAYALHDCZYJHZ-LJQANCHMSA-N 0.000 claims description 3
- XQLJEEBGWWDTEO-GOSISDBHSA-N 2-[(3R)-3-[4-amino-3-[4-(2,6-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enamide Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C=CC(OC=4C(=CC=CC=4F)F)=CC=3)=N2)N1C(=O)C(C(=O)N)=CC1CC1 XQLJEEBGWWDTEO-GOSISDBHSA-N 0.000 claims description 3
- IKOLBTLCUOLRRS-LJQANCHMSA-N 2-[(3R)-3-[4-amino-3-[4-(2-fluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enamide Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C=CC(OC=4C(=CC=CC=4)F)=CC=3)=N2)N1C(=O)C(C(=O)N)=CC1CC1 IKOLBTLCUOLRRS-LJQANCHMSA-N 0.000 claims description 3
- XHBRPKRNVSMGJI-HXUWFJFHSA-N 2-[(3R)-3-[4-amino-3-[4-(3,5-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enamide Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C=CC(OC=4C=C(F)C=C(F)C=4)=CC=3)=N2)N1C(=O)C(C(=O)N)=CC1CC1 XHBRPKRNVSMGJI-HXUWFJFHSA-N 0.000 claims description 3
- NKKBQDDLYMJHGR-SFHVURJKSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enamide Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C(=O)N)=CC1CC1 NKKBQDDLYMJHGR-SFHVURJKSA-N 0.000 claims description 3
- DXDVDSICLCSCMN-SFHVURJKSA-N 2-[(3S)-3-[4-amino-3-[4-(2,3-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enamide Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)=N2)N1C(=O)C(C(=O)N)=CC1CC1 DXDVDSICLCSCMN-SFHVURJKSA-N 0.000 claims description 3
- IKOLBTLCUOLRRS-IBGZPJMESA-N 2-[(3S)-3-[4-amino-3-[4-(2-fluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enamide Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C=CC(OC=4C(=CC=CC=4)F)=CC=3)=N2)N1C(=O)C(C(=O)N)=CC1CC1 IKOLBTLCUOLRRS-IBGZPJMESA-N 0.000 claims description 3
- XSICWXCNWLHEJG-FQEVSTJZSA-N 2-[(3S)-3-[4-amino-3-[4-(3-fluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enamide Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C=CC(OC=4C=C(F)C=CC=4)=CC=3)=N2)N1C(=O)C(C(=O)N)=CC1CC1 XSICWXCNWLHEJG-FQEVSTJZSA-N 0.000 claims description 3
- 208000026872 Addison Disease Diseases 0.000 claims description 3
- 206010001767 Alopecia universalis Diseases 0.000 claims description 3
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 claims description 3
- 208000032467 Aplastic anaemia Diseases 0.000 claims description 3
- 206010003011 Appendicitis Diseases 0.000 claims description 3
- 206010003827 Autoimmune hepatitis Diseases 0.000 claims description 3
- 206010003840 Autonomic nervous system imbalance Diseases 0.000 claims description 3
- 208000023328 Basedow disease Diseases 0.000 claims description 3
- 208000009137 Behcet syndrome Diseases 0.000 claims description 3
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 3
- 208000033222 Biliary cirrhosis primary Diseases 0.000 claims description 3
- 206010006448 Bronchiolitis Diseases 0.000 claims description 3
- 206010006811 Bursitis Diseases 0.000 claims description 3
- 208000015943 Coeliac disease Diseases 0.000 claims description 3
- 206010010741 Conjunctivitis Diseases 0.000 claims description 3
- 206010011841 Dacryoadenitis acquired Diseases 0.000 claims description 3
- 206010012442 Dermatitis contact Diseases 0.000 claims description 3
- 201000009273 Endometriosis Diseases 0.000 claims description 3
- 208000004145 Endometritis Diseases 0.000 claims description 3
- 208000004232 Enteritis Diseases 0.000 claims description 3
- 201000011275 Epicondylitis Diseases 0.000 claims description 3
- 206010016228 Fasciitis Diseases 0.000 claims description 3
- 208000007882 Gastritis Diseases 0.000 claims description 3
- 208000005577 Gastroenteritis Diseases 0.000 claims description 3
- 208000007465 Giant cell arteritis Diseases 0.000 claims description 3
- 208000024869 Goodpasture syndrome Diseases 0.000 claims description 3
- 208000015023 Graves' disease Diseases 0.000 claims description 3
- 208000030836 Hashimoto thyroiditis Diseases 0.000 claims description 3
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 claims description 3
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 claims description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
- 208000005615 Interstitial Cystitis Diseases 0.000 claims description 3
- 208000000209 Isaacs syndrome Diseases 0.000 claims description 3
- 208000003456 Juvenile Arthritis Diseases 0.000 claims description 3
- 201000008197 Laryngitis Diseases 0.000 claims description 3
- 201000009906 Meningitis Diseases 0.000 claims description 3
- 208000003926 Myelitis Diseases 0.000 claims description 3
- 208000009525 Myocarditis Diseases 0.000 claims description 3
- 201000002481 Myositis Diseases 0.000 claims description 3
- HYMDWKLQUKDBKB-UHFFFAOYSA-N N-[2-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-1-cyano-2-cyclopropyl-N-methylethenesulfonamide Chemical compound C1CC1C=C(C#N)S(=O)(=O)N(C)CCN(C1=NC=NC(N)=C11)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 HYMDWKLQUKDBKB-UHFFFAOYSA-N 0.000 claims description 3
- BHDOETHUPUKOPG-UHFFFAOYSA-N N-[2-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-1-cyano-2-cyclopropylethenesulfonamide Chemical compound N1=C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)C=2C(N)=NC=NC=2N1CCNS(=O)(=O)C(C#N)=CC1CC1 BHDOETHUPUKOPG-UHFFFAOYSA-N 0.000 claims description 3
- 206010072359 Neuromyotonia Diseases 0.000 claims description 3
- 208000005225 Opsoclonus-Myoclonus Syndrome Diseases 0.000 claims description 3
- 208000003435 Optic Neuritis Diseases 0.000 claims description 3
- 206010031149 Osteitis Diseases 0.000 claims description 3
- 208000005141 Otitis Diseases 0.000 claims description 3
- 206010033645 Pancreatitis Diseases 0.000 claims description 3
- 206010034038 Parotitis Diseases 0.000 claims description 3
- 201000007100 Pharyngitis Diseases 0.000 claims description 3
- 206010035742 Pneumonitis Diseases 0.000 claims description 3
- 208000012654 Primary biliary cholangitis Diseases 0.000 claims description 3
- 206010036774 Proctitis Diseases 0.000 claims description 3
- 206010037596 Pyelonephritis Diseases 0.000 claims description 3
- 208000033464 Reiter syndrome Diseases 0.000 claims description 3
- 241001303601 Rosacea Species 0.000 claims description 3
- 208000007893 Salpingitis Diseases 0.000 claims description 3
- 208000001106 Takayasu Arteritis Diseases 0.000 claims description 3
- 208000000491 Tendinopathy Diseases 0.000 claims description 3
- 206010043255 Tendonitis Diseases 0.000 claims description 3
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 claims description 3
- 208000024780 Urticaria Diseases 0.000 claims description 3
- 208000006374 Uterine Cervicitis Diseases 0.000 claims description 3
- 206010046914 Vaginal infection Diseases 0.000 claims description 3
- 201000008100 Vaginitis Diseases 0.000 claims description 3
- 206010047115 Vasculitis Diseases 0.000 claims description 3
- 208000003728 Vulvodynia Diseases 0.000 claims description 3
- 206010069055 Vulvovaginal pain Diseases 0.000 claims description 3
- 208000002552 acute disseminated encephalomyelitis Diseases 0.000 claims description 3
- 208000032775 alopecia universalis congenita Diseases 0.000 claims description 3
- 208000010668 atopic eczema Diseases 0.000 claims description 3
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 claims description 3
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 claims description 3
- 208000010217 blepharitis Diseases 0.000 claims description 3
- 208000018339 bone inflammation disease Diseases 0.000 claims description 3
- 206010006451 bronchitis Diseases 0.000 claims description 3
- 206010008323 cervicitis Diseases 0.000 claims description 3
- 208000003167 cholangitis Diseases 0.000 claims description 3
- 201000001352 cholecystitis Diseases 0.000 claims description 3
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 claims description 3
- 206010009887 colitis Diseases 0.000 claims description 3
- 208000010247 contact dermatitis Diseases 0.000 claims description 3
- 201000003146 cystitis Diseases 0.000 claims description 3
- 201000004400 dacryoadenitis Diseases 0.000 claims description 3
- 201000001981 dermatomyositis Diseases 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 208000019479 dysautonomia Diseases 0.000 claims description 3
- 208000019258 ear infection Diseases 0.000 claims description 3
- 206010014599 encephalitis Diseases 0.000 claims description 3
- 206010014665 endocarditis Diseases 0.000 claims description 3
- 208000010227 enterocolitis Diseases 0.000 claims description 3
- 201000010063 epididymitis Diseases 0.000 claims description 3
- 206010016256 fatigue Diseases 0.000 claims description 3
- 208000006454 hepatitis Diseases 0.000 claims description 3
- 231100000283 hepatitis Toxicity 0.000 claims description 3
- 208000002557 hidradenitis Diseases 0.000 claims description 3
- 201000007162 hidradenitis suppurativa Diseases 0.000 claims description 3
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 claims description 3
- 230000003902 lesion Effects 0.000 claims description 3
- 208000004396 mastitis Diseases 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 206010028417 myasthenia gravis Diseases 0.000 claims description 3
- 201000008383 nephritis Diseases 0.000 claims description 3
- 208000005963 oophoritis Diseases 0.000 claims description 3
- 201000005737 orchitis Diseases 0.000 claims description 3
- 210000000056 organ Anatomy 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- 208000008494 pericarditis Diseases 0.000 claims description 3
- 206010034674 peritonitis Diseases 0.000 claims description 3
- 208000001297 phlebitis Diseases 0.000 claims description 3
- 208000008423 pleurisy Diseases 0.000 claims description 3
- 208000018290 primary dysautonomia Diseases 0.000 claims description 3
- 201000007094 prostatitis Diseases 0.000 claims description 3
- 230000001185 psoriatic effect Effects 0.000 claims description 3
- 208000002574 reactive arthritis Diseases 0.000 claims description 3
- 206010039083 rhinitis Diseases 0.000 claims description 3
- 201000004700 rosacea Diseases 0.000 claims description 3
- 230000037390 scarring Effects 0.000 claims description 3
- 201000009890 sinusitis Diseases 0.000 claims description 3
- 208000003265 stomatitis Diseases 0.000 claims description 3
- 201000004595 synovitis Diseases 0.000 claims description 3
- 206010043207 temporal arteritis Diseases 0.000 claims description 3
- 201000004415 tendinitis Diseases 0.000 claims description 3
- 206010043778 thyroiditis Diseases 0.000 claims description 3
- 206010044008 tonsillitis Diseases 0.000 claims description 3
- 208000002003 vulvitis Diseases 0.000 claims description 3
- OTEPSQCCLGCTHS-QFIPXVFZSA-N 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-(oxan-4-yl)prop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CCOCC1 OTEPSQCCLGCTHS-QFIPXVFZSA-N 0.000 claims description 2
- NZIQNLGMMJGSQU-HSZRJFAPSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-morpholin-4-ylpent-2-enenitrile Chemical compound C([C@H]1CCCN1C(=O)C(C#N)=CC(C)(C)N1CCOCC1)N(C1=NC=NC(N)=C11)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 NZIQNLGMMJGSQU-HSZRJFAPSA-N 0.000 claims description 2
- UCAYALHDCZYJHZ-IBGZPJMESA-N 2-[(3S)-3-[4-amino-3-[4-(2,5-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enamide Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C=CC(OC=4C(=CC=C(F)C=4)F)=CC=3)=N2)N1C(=O)C(C(=O)N)=CC1CC1 UCAYALHDCZYJHZ-IBGZPJMESA-N 0.000 claims description 2
- UKURDKADUIBPHB-QHCPKHFHSA-N 2-[(3S)-3-[4-amino-5-[4-(3,5-difluorophenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)C=C1C(C=C1)=CC=C1OC1=CC(F)=CC(F)=C1 UKURDKADUIBPHB-QHCPKHFHSA-N 0.000 claims description 2
- SOECMCJOWVYWNB-FQEVSTJZSA-N 2-[(3s)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(cyclopropylamino)-4-methylpent-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC(C)(C)NC1CC1 SOECMCJOWVYWNB-FQEVSTJZSA-N 0.000 claims description 2
- GHPBPQWNXYSLBJ-UHFFFAOYSA-N 2-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl 2-cyano-3-cyclopropylprop-2-enoate Chemical compound N1=C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)C=2C(N)=NC=NC=2N1CCOC(=O)C(C#N)=CC1CC1 GHPBPQWNXYSLBJ-UHFFFAOYSA-N 0.000 claims description 2
- NGQSBNHWNCYPJR-UHFFFAOYSA-N 2-[5-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-1,3-oxazol-2-yl]-3-cyclopropylprop-2-enenitrile Chemical compound N1=C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)C=2C(N)=NC=NC=2N1CC(O1)=CN=C1C(C#N)=CC1CC1 NGQSBNHWNCYPJR-UHFFFAOYSA-N 0.000 claims description 2
- GQUJDCOJPFVAOF-UHFFFAOYSA-N [1-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]-2-methylpropan-2-yl] 2-cyano-3-cyclopropylprop-2-enoate Chemical compound C1CC1C=C(C#N)C(=O)OC(C)(C)CN(C1=NC=NC(N)=C11)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 GQUJDCOJPFVAOF-UHFFFAOYSA-N 0.000 claims description 2
- RCZJEMPRLHUVEZ-UHFFFAOYSA-N n-[2-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-2-cyano-3-cyclopropylprop-2-enamide Chemical compound N1=C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)C=2C(N)=NC=NC=2N1CCNC(=O)C(C#N)=CC1CC1 RCZJEMPRLHUVEZ-UHFFFAOYSA-N 0.000 claims description 2
- HFGCWLQDFUJXGS-UHFFFAOYSA-N n-[3-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]-2,2-dimethylpropyl]-2-cyano-3-cyclopropylprop-2-enamide Chemical compound N1=C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)C2=C(N)N=CN=C2N1CC(C)(C)CNC(=O)C(C#N)=CC1CC1 HFGCWLQDFUJXGS-UHFFFAOYSA-N 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 5
- 230000003110 anti-inflammatory effect Effects 0.000 claims 3
- DXDVDSICLCSCMN-GOSISDBHSA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enamide Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)=N2)N1C(=O)C(C(=O)N)=CC1CC1 DXDVDSICLCSCMN-GOSISDBHSA-N 0.000 claims 2
- XSICWXCNWLHEJG-HXUWFJFHSA-N 2-[(3R)-3-[4-amino-3-[4-(3-fluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enamide Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C=CC(OC=4C=C(F)C=CC=4)=CC=3)=N2)N1C(=O)C(C(=O)N)=CC1CC1 XSICWXCNWLHEJG-HXUWFJFHSA-N 0.000 claims 2
- 208000001640 Fibromyalgia Diseases 0.000 claims 2
- 208000035895 Guillain-Barré syndrome Diseases 0.000 claims 2
- 206010049567 Miller Fisher syndrome Diseases 0.000 claims 2
- FRMUZCKAJXQYQC-KRWDZBQOSA-N N-[(2S)-1-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]propan-2-yl]-2-cyano-4,4-dimethylpent-2-enamide Chemical compound C12=C(N)N=CN=C2N(C[C@H](C)NC(=O)C(=CC(C)(C)C)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 FRMUZCKAJXQYQC-KRWDZBQOSA-N 0.000 claims 2
- HAUZZEVZYNEKHM-SFHVURJKSA-N N-[(2S)-1-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]propan-2-yl]-2-cyano-4-(dimethylamino)-4-methylpent-2-enamide Chemical compound C12=C(N)N=CN=C2N(C[C@H](C)NC(=O)C(=CC(C)(C)N(C)C)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 HAUZZEVZYNEKHM-SFHVURJKSA-N 0.000 claims 2
- PTHYZAKMYJLMJF-SFHVURJKSA-N N-[(2S)-1-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]propan-2-yl]-2-cyano-4-ethoxy-4-methylpent-2-enamide Chemical compound C12=C(N)N=CN=C2N(C[C@H](C)NC(=O)C(C#N)=CC(C)(C)OCC)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 PTHYZAKMYJLMJF-SFHVURJKSA-N 0.000 claims 2
- PWODFMKTYXDDTQ-KRWDZBQOSA-N n-[(2s)-1-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]propan-2-yl]-2-cyano-4-methylpent-2-enamide Chemical compound C12=C(N)N=CN=C2N(C[C@H](C)NC(=O)C(C#N)=CC(C)C)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 PWODFMKTYXDDTQ-KRWDZBQOSA-N 0.000 claims 2
- SLYGDRWTJRPLPE-HXUWFJFHSA-N 2-[(2R)-2-[[4-amino-3-(2-chloro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)Cl)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 SLYGDRWTJRPLPE-HXUWFJFHSA-N 0.000 claims 1
- QWENXYFISYOVAE-LJQANCHMSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-4,4-difluoropyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)C(F)(F)CN1C(=O)C(C#N)=CC1CC1 QWENXYFISYOVAE-LJQANCHMSA-N 0.000 claims 1
- YVFLIMWHLSVODD-HSZRJFAPSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-(1-methylpiperidin-4-yl)prop-2-enenitrile Chemical compound C1CN(C)CCC1C=C(C#N)C(=O)N1[C@@H](CN2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 YVFLIMWHLSVODD-HSZRJFAPSA-N 0.000 claims 1
- OTEPSQCCLGCTHS-JOCHJYFZSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-(oxan-4-yl)prop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CCOCC1 OTEPSQCCLGCTHS-JOCHJYFZSA-N 0.000 claims 1
- DJFYWYMNPNZOCD-NHCUHLMSSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[(2R)-pyrrolidin-2-yl]prop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=C[C@H]1CCCN1 DJFYWYMNPNZOCD-NHCUHLMSSA-N 0.000 claims 1
- VWKLJHJZMCQRTA-OAQYLSRUSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-(ethylamino)cyclopropyl]prop-2-enenitrile Chemical compound N1([C@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1)C(=O)C(C#N)=CC1(NCC)CC1 VWKLJHJZMCQRTA-OAQYLSRUSA-N 0.000 claims 1
- PRRNZFGBGPELQP-HXUWFJFHSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-(methylamino)cyclopropyl]prop-2-enenitrile Chemical compound N1([C@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1)C(=O)C(C#N)=CC1(NC)CC1 PRRNZFGBGPELQP-HXUWFJFHSA-N 0.000 claims 1
- HAPRCXSAULDFHG-JOCHJYFZSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-(propan-2-ylamino)cyclopropyl]prop-2-enenitrile Chemical compound N1([C@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1)C(=O)C(C#N)=CC1(NC(C)C)CC1 HAPRCXSAULDFHG-JOCHJYFZSA-N 0.000 claims 1
- DJFYWYMNPNZOCD-BPGUCPLFSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-pyrrolidin-2-ylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CCCN1 DJFYWYMNPNZOCD-BPGUCPLFSA-N 0.000 claims 1
- BESYWHDYQFWATR-HXUWFJFHSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 BESYWHDYQFWATR-HXUWFJFHSA-N 0.000 claims 1
- YQBZUMLDZJOWCG-OAQYLSRUSA-N 2-[(2R)-2-[[4-amino-3-(3-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C=C(F)C(OC=4C=CC=CC=4)=CC=3)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 YQBZUMLDZJOWCG-OAQYLSRUSA-N 0.000 claims 1
- ALWCTUAHGPPJIV-LJQANCHMSA-N 2-[(2R)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-(ethylamino)cyclopropyl]prop-2-enenitrile Chemical compound N1([C@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1)C(=O)C(C#N)=CC1(NCC)CC1 ALWCTUAHGPPJIV-LJQANCHMSA-N 0.000 claims 1
- KAAXGGACDPUIMN-HXUWFJFHSA-N 2-[(2R)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-(propan-2-ylamino)cyclopropyl]prop-2-enenitrile Chemical compound N1([C@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1)C(=O)C(C#N)=CC1(NC(C)C)CC1 KAAXGGACDPUIMN-HXUWFJFHSA-N 0.000 claims 1
- XWMMGGPZOBQKIG-JOCHJYFZSA-N 2-[(2R)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-[(dimethylamino)methyl]cyclopentyl]prop-2-enenitrile Chemical compound N1([C@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1)C(=O)C(C#N)=CC1(CN(C)C)CCCC1 XWMMGGPZOBQKIG-JOCHJYFZSA-N 0.000 claims 1
- ALECKWSRFHPUGK-MUMRKEEXSA-N 2-[(2R)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-pyrrolidin-2-ylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CCCN1 ALECKWSRFHPUGK-MUMRKEEXSA-N 0.000 claims 1
- JNAYDXFMMRTTAX-OAQYLSRUSA-N 2-[(2R)-2-[[4-amino-3-[4-(2,5-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C(=CC=C(F)C=4)F)=CC=3)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 JNAYDXFMMRTTAX-OAQYLSRUSA-N 0.000 claims 1
- WBPYSPBQYMHIEC-GOSISDBHSA-N 2-[(2R)-2-[[4-amino-3-[4-(2,6-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C(=CC=CC=4F)F)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 WBPYSPBQYMHIEC-GOSISDBHSA-N 0.000 claims 1
- CHUVQXPESSHLOM-JOCHJYFZSA-N 2-[(2R)-2-[[4-amino-5-(2-fluoro-4-phenoxyphenyl)-6-methylpyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C12=C(N)N=CN=C2N(C[C@@H]2N(CCC2)C(=O)C(=CC2CC2)C#N)C(C)=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 CHUVQXPESSHLOM-JOCHJYFZSA-N 0.000 claims 1
- SOHZZOWWQLHMBF-XMMPIXPASA-N 2-[(2R)-2-[[4-amino-5-[4-(3,5-difluorophenoxy)phenyl]-6-methylpyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C12=C(N)N=CN=C2N(C[C@@H]2N(CCC2)C(=O)C(=CC2CC2)C#N)C(C)=C1C(C=C1)=CC=C1OC1=CC(F)=CC(F)=C1 SOHZZOWWQLHMBF-XMMPIXPASA-N 0.000 claims 1
- SLYGDRWTJRPLPE-FQEVSTJZSA-N 2-[(2S)-2-[[4-amino-3-(2-chloro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)Cl)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 SLYGDRWTJRPLPE-FQEVSTJZSA-N 0.000 claims 1
- QWENXYFISYOVAE-IBGZPJMESA-N 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-4,4-difluoropyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)C(F)(F)CN1C(=O)C(C#N)=CC1CC1 QWENXYFISYOVAE-IBGZPJMESA-N 0.000 claims 1
- YVFLIMWHLSVODD-QHCPKHFHSA-N 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-(1-methylpiperidin-4-yl)prop-2-enenitrile Chemical compound C1CN(C)CCC1C=C(C#N)C(=O)N1[C@H](CN2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 YVFLIMWHLSVODD-QHCPKHFHSA-N 0.000 claims 1
- VWKLJHJZMCQRTA-NRFANRHFSA-N 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-(ethylamino)cyclopropyl]prop-2-enenitrile Chemical compound N1([C@@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1)C(=O)C(C#N)=CC1(NCC)CC1 VWKLJHJZMCQRTA-NRFANRHFSA-N 0.000 claims 1
- PRRNZFGBGPELQP-FQEVSTJZSA-N 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-(methylamino)cyclopropyl]prop-2-enenitrile Chemical compound N1([C@@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1)C(=O)C(C#N)=CC1(NC)CC1 PRRNZFGBGPELQP-FQEVSTJZSA-N 0.000 claims 1
- VILCMHIZGWATBW-DEOSSOPVSA-N 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-[(dimethylamino)methyl]cyclopentyl]prop-2-enenitrile Chemical compound N1([C@@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1)C(=O)C(C#N)=CC1(CN(C)C)CCCC1 VILCMHIZGWATBW-DEOSSOPVSA-N 0.000 claims 1
- QLFDACIJUUSZFJ-IAXKEJLGSA-N 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-piperidin-3-ylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CCCNC1 QLFDACIJUUSZFJ-IAXKEJLGSA-N 0.000 claims 1
- BESYWHDYQFWATR-FQEVSTJZSA-N 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 BESYWHDYQFWATR-FQEVSTJZSA-N 0.000 claims 1
- FFNPAVVGSXGKFD-QFIPXVFZSA-N 2-[(2S)-2-[[4-amino-3-(2-methyl-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C=1C=C(C=2C3=C(N)N=CN=C3N(C[C@H]3N(CCC3)C(=O)C(=CC3CC3)C#N)N=2)C(C)=CC=1OC1=CC=CC=C1 FFNPAVVGSXGKFD-QFIPXVFZSA-N 0.000 claims 1
- YQBZUMLDZJOWCG-NRFANRHFSA-N 2-[(2S)-2-[[4-amino-3-(3-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C=C(F)C(OC=4C=CC=CC=4)=CC=3)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 YQBZUMLDZJOWCG-NRFANRHFSA-N 0.000 claims 1
- HZSKWVTYHGCROU-DEOSSOPVSA-N 2-[(2S)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-(diethylaminomethyl)cyclopentyl]prop-2-enenitrile Chemical compound N1([C@@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1)C(=O)C(C#N)=CC1(CN(CC)CC)CCCC1 HZSKWVTYHGCROU-DEOSSOPVSA-N 0.000 claims 1
- ALWCTUAHGPPJIV-IBGZPJMESA-N 2-[(2S)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-(ethylamino)cyclopropyl]prop-2-enenitrile Chemical compound N1([C@@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1)C(=O)C(C#N)=CC1(NCC)CC1 ALWCTUAHGPPJIV-IBGZPJMESA-N 0.000 claims 1
- RYLUGFKKSWCGMS-SFHVURJKSA-N 2-[(2S)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-(methylamino)cyclopropyl]prop-2-enenitrile Chemical compound N1([C@@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1)C(=O)C(C#N)=CC1(NC)CC1 RYLUGFKKSWCGMS-SFHVURJKSA-N 0.000 claims 1
- XWMMGGPZOBQKIG-QFIPXVFZSA-N 2-[(2S)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-[(dimethylamino)methyl]cyclopentyl]prop-2-enenitrile Chemical compound N1([C@@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1)C(=O)C(C#N)=CC1(CN(C)C)CCCC1 XWMMGGPZOBQKIG-QFIPXVFZSA-N 0.000 claims 1
- ALECKWSRFHPUGK-GGYWPGCISA-N 2-[(2S)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-pyrrolidin-2-ylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CCCN1 ALECKWSRFHPUGK-GGYWPGCISA-N 0.000 claims 1
- ZYEDVNPMLFQSQS-FQEVSTJZSA-N 2-[(2S)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 ZYEDVNPMLFQSQS-FQEVSTJZSA-N 0.000 claims 1
- JNAYDXFMMRTTAX-NRFANRHFSA-N 2-[(2S)-2-[[4-amino-3-[4-(2,5-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C(=CC=C(F)C=4)F)=CC=3)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 JNAYDXFMMRTTAX-NRFANRHFSA-N 0.000 claims 1
- WBPYSPBQYMHIEC-SFHVURJKSA-N 2-[(2S)-2-[[4-amino-3-[4-(2,6-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C(=CC=CC=4F)F)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 WBPYSPBQYMHIEC-SFHVURJKSA-N 0.000 claims 1
- YLBOUHDKWPBHCU-FQEVSTJZSA-N 2-[(2S)-2-[[4-amino-3-[4-(2,6-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C(=CC=CC=4F)F)=CC=3)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 YLBOUHDKWPBHCU-FQEVSTJZSA-N 0.000 claims 1
- HWXKECVQNNJJPE-QFIPXVFZSA-N 2-[(2S)-2-[[4-amino-3-[4-(3,5-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C=C(F)C=C(F)C=4)=CC=3)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 HWXKECVQNNJJPE-QFIPXVFZSA-N 0.000 claims 1
- ODTVIGFDPJLHPJ-QFIPXVFZSA-N 2-[(2S)-2-[[4-amino-3-[4-(3-fluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C=C(F)C=CC=4)=CC=3)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 ODTVIGFDPJLHPJ-QFIPXVFZSA-N 0.000 claims 1
- CHUVQXPESSHLOM-QFIPXVFZSA-N 2-[(2S)-2-[[4-amino-5-(2-fluoro-4-phenoxyphenyl)-6-methylpyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C12=C(N)N=CN=C2N(C[C@H]2N(CCC2)C(=O)C(=CC2CC2)C#N)C(C)=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 CHUVQXPESSHLOM-QFIPXVFZSA-N 0.000 claims 1
- SOHZZOWWQLHMBF-DEOSSOPVSA-N 2-[(2S)-2-[[4-amino-5-[4-(3,5-difluorophenoxy)phenyl]-6-methylpyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C12=C(N)N=CN=C2N(C[C@H]2N(CCC2)C(=O)C(=CC2CC2)C#N)C(C)=C1C(C=C1)=CC=C1OC1=CC(F)=CC(F)=C1 SOHZZOWWQLHMBF-DEOSSOPVSA-N 0.000 claims 1
- CBXYWKLJGUCHPH-LJQANCHMSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-4,4-difluoropyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CC(F)(F)C[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 CBXYWKLJGUCHPH-LJQANCHMSA-N 0.000 claims 1
- DJFYWYMNPNZOCD-LEWJYISDSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[(2s)-pyrrolidin-2-yl]prop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=C[C@@H]1CCCN1 DJFYWYMNPNZOCD-LEWJYISDSA-N 0.000 claims 1
- JVLRCXYMHHEMSN-HXUWFJFHSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 JVLRCXYMHHEMSN-HXUWFJFHSA-N 0.000 claims 1
- NDLULCUHFGKSRR-HXUWFJFHSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile Chemical compound CC(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 NDLULCUHFGKSRR-HXUWFJFHSA-N 0.000 claims 1
- ZUCVBIOQSDKVLU-JOCHJYFZSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-(2-methoxyethylamino)-4-methylpent-2-enenitrile Chemical compound COCCNC(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 ZUCVBIOQSDKVLU-JOCHJYFZSA-N 0.000 claims 1
- UIAAIUOKBHHXCL-OAQYLSRUSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-(dimethylamino)-4-methylpent-2-enenitrile Chemical compound CN(C)C(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 UIAAIUOKBHHXCL-OAQYLSRUSA-N 0.000 claims 1
- VKBHKMKUFODMAW-OAQYLSRUSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-(ethylamino)-4-methylpent-2-enenitrile Chemical compound CCNC(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 VKBHKMKUFODMAW-OAQYLSRUSA-N 0.000 claims 1
- PVBDQCRWZPYKOP-OAQYLSRUSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-ethoxy-4-methylpent-2-enenitrile Chemical compound CCOC(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 PVBDQCRWZPYKOP-OAQYLSRUSA-N 0.000 claims 1
- PUFSHOBLKSMSCP-HXUWFJFHSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-(methylamino)pent-2-enenitrile Chemical compound CNC(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 PUFSHOBLKSMSCP-HXUWFJFHSA-N 0.000 claims 1
- DUOXDOVHDJDYMX-XMMPIXPASA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-piperidin-1-ylpent-2-enenitrile Chemical compound C([C@H]1CCCN1C(=O)C(C#N)=CC(C)(C)N1CCCCC1)N(C1=NC=NC(N)=C11)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 DUOXDOVHDJDYMX-XMMPIXPASA-N 0.000 claims 1
- DPEOIHCRFGFQBA-JOCHJYFZSA-N 2-[(2r)-2-[[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile Chemical compound CC(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=N1 DPEOIHCRFGFQBA-JOCHJYFZSA-N 0.000 claims 1
- ZSLSVCCZNWZIRV-GOSISDBHSA-N 2-[(2r)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 ZSLSVCCZNWZIRV-GOSISDBHSA-N 0.000 claims 1
- RZJWGRSPUSIWDU-HXUWFJFHSA-N 2-[(2r)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-(2-methoxyethylamino)-4-methylpent-2-enenitrile Chemical compound COCCNC(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 RZJWGRSPUSIWDU-HXUWFJFHSA-N 0.000 claims 1
- RFZCIQIWNBXPEH-LJQANCHMSA-N 2-[(2r)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-(ethylamino)-4-methylpent-2-enenitrile Chemical compound CCNC(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 RFZCIQIWNBXPEH-LJQANCHMSA-N 0.000 claims 1
- BKCICBNLQFMNEZ-LJQANCHMSA-N 2-[(2r)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-ethoxy-4-methylpent-2-enenitrile Chemical compound CCOC(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 BKCICBNLQFMNEZ-LJQANCHMSA-N 0.000 claims 1
- CJCOYQRLWHQOQL-GOSISDBHSA-N 2-[(2r)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-(methylamino)pent-2-enenitrile Chemical compound CNC(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 CJCOYQRLWHQOQL-GOSISDBHSA-N 0.000 claims 1
- BHHIRWVESSTTMY-HXUWFJFHSA-N 2-[(2r)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-(propan-2-ylamino)pent-2-enenitrile Chemical compound CC(C)NC(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 BHHIRWVESSTTMY-HXUWFJFHSA-N 0.000 claims 1
- XOPLJTJUGWMLNS-OAQYLSRUSA-N 2-[(2r)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-morpholin-4-ylpent-2-enenitrile Chemical compound C([C@H]1CCCN1C(=O)C(C#N)=CC(C)(C)N1CCOCC1)N(C1=NC=NC(N)=C11)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F XOPLJTJUGWMLNS-OAQYLSRUSA-N 0.000 claims 1
- ZYEDVNPMLFQSQS-HXUWFJFHSA-N 2-[(2r)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 ZYEDVNPMLFQSQS-HXUWFJFHSA-N 0.000 claims 1
- POGITRIJKUNOCX-HXUWFJFHSA-N 2-[(2r)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)=N1 POGITRIJKUNOCX-HXUWFJFHSA-N 0.000 claims 1
- GZOPCCOHXKUGIP-OAQYLSRUSA-N 2-[(2r)-2-[[4-amino-3-[4-(2,5-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C(=CC=C(F)C=3)F)=CC=2)=N1 GZOPCCOHXKUGIP-OAQYLSRUSA-N 0.000 claims 1
- YLBOUHDKWPBHCU-HXUWFJFHSA-N 2-[(2r)-2-[[4-amino-3-[4-(2,6-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C(=CC=CC=4F)F)=CC=3)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 YLBOUHDKWPBHCU-HXUWFJFHSA-N 0.000 claims 1
- CSUHSJHWBUGLCV-HXUWFJFHSA-N 2-[(2r)-2-[[4-amino-3-[4-(2,6-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C(=CC=CC=3F)F)=CC=2)=N1 CSUHSJHWBUGLCV-HXUWFJFHSA-N 0.000 claims 1
- ODTVIGFDPJLHPJ-JOCHJYFZSA-N 2-[(2r)-2-[[4-amino-3-[4-(3-fluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C=C(F)C=CC=4)=CC=3)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 ODTVIGFDPJLHPJ-JOCHJYFZSA-N 0.000 claims 1
- OGWLOAWKWZUJRA-JOCHJYFZSA-N 2-[(2r)-2-[[4-amino-5-(2-fluoro-4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-(dimethylamino)-4-methylpent-2-enenitrile Chemical compound CN(C)C(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=C1 OGWLOAWKWZUJRA-JOCHJYFZSA-N 0.000 claims 1
- KWBJZFXSWFLQKE-OAQYLSRUSA-N 2-[(2r)-2-[[4-amino-5-[4-(2,3-difluorophenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile Chemical compound CC(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)=C1 KWBJZFXSWFLQKE-OAQYLSRUSA-N 0.000 claims 1
- BEBHIEGBOKTQIO-JOCHJYFZSA-N 2-[(2r)-2-[[4-amino-5-[4-(2,3-difluorophenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-(dimethylamino)-4-methylpent-2-enenitrile Chemical compound CN(C)C(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)=C1 BEBHIEGBOKTQIO-JOCHJYFZSA-N 0.000 claims 1
- NEHLIDMTSGJVNM-OAQYLSRUSA-N 2-[(2r)-2-[[4-amino-5-[4-(2,3-difluorophenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)=C1 NEHLIDMTSGJVNM-OAQYLSRUSA-N 0.000 claims 1
- MGOWUKVRTVSTIO-RUZDIDTESA-N 2-[(2r)-2-[[4-amino-6-methyl-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-(dimethylamino)-4-methylpent-2-enenitrile Chemical compound CN(C)C(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=C1C MGOWUKVRTVSTIO-RUZDIDTESA-N 0.000 claims 1
- JVLRCXYMHHEMSN-FQEVSTJZSA-N 2-[(2s)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 JVLRCXYMHHEMSN-FQEVSTJZSA-N 0.000 claims 1
- ZUCVBIOQSDKVLU-QFIPXVFZSA-N 2-[(2s)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-(2-methoxyethylamino)-4-methylpent-2-enenitrile Chemical compound COCCNC(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 ZUCVBIOQSDKVLU-QFIPXVFZSA-N 0.000 claims 1
- VKBHKMKUFODMAW-NRFANRHFSA-N 2-[(2s)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-(ethylamino)-4-methylpent-2-enenitrile Chemical compound CCNC(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 VKBHKMKUFODMAW-NRFANRHFSA-N 0.000 claims 1
- PVBDQCRWZPYKOP-NRFANRHFSA-N 2-[(2s)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-ethoxy-4-methylpent-2-enenitrile Chemical compound CCOC(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 PVBDQCRWZPYKOP-NRFANRHFSA-N 0.000 claims 1
- PUFSHOBLKSMSCP-FQEVSTJZSA-N 2-[(2s)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-(methylamino)pent-2-enenitrile Chemical compound CNC(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 PUFSHOBLKSMSCP-FQEVSTJZSA-N 0.000 claims 1
- DUOXDOVHDJDYMX-DEOSSOPVSA-N 2-[(2s)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-piperidin-1-ylpent-2-enenitrile Chemical compound C([C@@H]1CCCN1C(=O)C(C#N)=CC(C)(C)N1CCCCC1)N(C1=NC=NC(N)=C11)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 DUOXDOVHDJDYMX-DEOSSOPVSA-N 0.000 claims 1
- DPEOIHCRFGFQBA-QFIPXVFZSA-N 2-[(2s)-2-[[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile Chemical compound CC(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=N1 DPEOIHCRFGFQBA-QFIPXVFZSA-N 0.000 claims 1
- KAAXGGACDPUIMN-FQEVSTJZSA-N 2-[(2s)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-(propan-2-ylamino)cyclopropyl]prop-2-enenitrile Chemical compound N1([C@@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1)C(=O)C(C#N)=CC1(NC(C)C)CC1 KAAXGGACDPUIMN-FQEVSTJZSA-N 0.000 claims 1
- ZSLSVCCZNWZIRV-SFHVURJKSA-N 2-[(2s)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 ZSLSVCCZNWZIRV-SFHVURJKSA-N 0.000 claims 1
- IMGDSBFPBQIDLG-SFHVURJKSA-N 2-[(2s)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile Chemical compound CC(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 IMGDSBFPBQIDLG-SFHVURJKSA-N 0.000 claims 1
- MZGCGLBHUPHJPP-FQEVSTJZSA-N 2-[(2s)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-(cyclopropylamino)-4-methylpent-2-enenitrile Chemical compound N1([C@@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1)C(=O)C(C#N)=CC(C)(C)NC1CC1 MZGCGLBHUPHJPP-FQEVSTJZSA-N 0.000 claims 1
- ANEDRESITAZMQR-IBGZPJMESA-N 2-[(2s)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-(dimethylamino)-4-methylpent-2-enenitrile Chemical compound CN(C)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 ANEDRESITAZMQR-IBGZPJMESA-N 0.000 claims 1
- RFZCIQIWNBXPEH-IBGZPJMESA-N 2-[(2s)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-(ethylamino)-4-methylpent-2-enenitrile Chemical compound CCNC(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 RFZCIQIWNBXPEH-IBGZPJMESA-N 0.000 claims 1
- CJCOYQRLWHQOQL-SFHVURJKSA-N 2-[(2s)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-(methylamino)pent-2-enenitrile Chemical compound CNC(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 CJCOYQRLWHQOQL-SFHVURJKSA-N 0.000 claims 1
- BHHIRWVESSTTMY-FQEVSTJZSA-N 2-[(2s)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-(propan-2-ylamino)pent-2-enenitrile Chemical compound CC(C)NC(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 BHHIRWVESSTTMY-FQEVSTJZSA-N 0.000 claims 1
- XOPLJTJUGWMLNS-NRFANRHFSA-N 2-[(2s)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-morpholin-4-ylpent-2-enenitrile Chemical compound C([C@@H]1CCCN1C(=O)C(C#N)=CC(C)(C)N1CCOCC1)N(C1=NC=NC(N)=C11)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F XOPLJTJUGWMLNS-NRFANRHFSA-N 0.000 claims 1
- GUAIRAQGQJAUSD-SFHVURJKSA-N 2-[(2s)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 GUAIRAQGQJAUSD-SFHVURJKSA-N 0.000 claims 1
- POGITRIJKUNOCX-FQEVSTJZSA-N 2-[(2s)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)=N1 POGITRIJKUNOCX-FQEVSTJZSA-N 0.000 claims 1
- GZOPCCOHXKUGIP-NRFANRHFSA-N 2-[(2s)-2-[[4-amino-3-[4-(2,5-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C(=CC=C(F)C=3)F)=CC=2)=N1 GZOPCCOHXKUGIP-NRFANRHFSA-N 0.000 claims 1
- CSUHSJHWBUGLCV-FQEVSTJZSA-N 2-[(2s)-2-[[4-amino-3-[4-(2,6-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C(=CC=CC=3F)F)=CC=2)=N1 CSUHSJHWBUGLCV-FQEVSTJZSA-N 0.000 claims 1
- OGWLOAWKWZUJRA-QFIPXVFZSA-N 2-[(2s)-2-[[4-amino-5-(2-fluoro-4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-(dimethylamino)-4-methylpent-2-enenitrile Chemical compound CN(C)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=C1 OGWLOAWKWZUJRA-QFIPXVFZSA-N 0.000 claims 1
- OEOUGSPJZLNTDO-DEOSSOPVSA-N 2-[(2s)-2-[[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-ethoxy-4-methylpent-2-enenitrile Chemical compound CCOC(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=C1 OEOUGSPJZLNTDO-DEOSSOPVSA-N 0.000 claims 1
- KWBJZFXSWFLQKE-NRFANRHFSA-N 2-[(2s)-2-[[4-amino-5-[4-(2,3-difluorophenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile Chemical compound CC(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)=C1 KWBJZFXSWFLQKE-NRFANRHFSA-N 0.000 claims 1
- NEHLIDMTSGJVNM-NRFANRHFSA-N 2-[(2s)-2-[[4-amino-5-[4-(2,3-difluorophenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)=C1 NEHLIDMTSGJVNM-NRFANRHFSA-N 0.000 claims 1
- MGOWUKVRTVSTIO-VWLOTQADSA-N 2-[(2s)-2-[[4-amino-6-methyl-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-(dimethylamino)-4-methylpent-2-enenitrile Chemical compound CN(C)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=C1C MGOWUKVRTVSTIO-VWLOTQADSA-N 0.000 claims 1
- JZJNGZMDAUNXTF-JOCHJYFZSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-(oxan-4-yl)prop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2CCOCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 JZJNGZMDAUNXTF-JOCHJYFZSA-N 0.000 claims 1
- BTWNIXPKIHIIBT-AREMUKBSSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(diethylaminomethyl)cyclopentyl]prop-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(CN(CC)CC)CCCC1 BTWNIXPKIHIIBT-AREMUKBSSA-N 0.000 claims 1
- SONFNRMAPPWUNU-OAQYLSRUSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(ethylamino)cyclopropyl]prop-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(NCC)CC1 SONFNRMAPPWUNU-OAQYLSRUSA-N 0.000 claims 1
- AFAVFCVQCOJERG-XMMPIXPASA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-[(dimethylamino)methyl]cyclopentyl]prop-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(CN(C)C)CCCC1 AFAVFCVQCOJERG-XMMPIXPASA-N 0.000 claims 1
- FXSMLAZXJKANGS-LWMIZPGFSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-piperidin-3-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2CNCCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 FXSMLAZXJKANGS-LWMIZPGFSA-N 0.000 claims 1
- KDXBHDLLRUHOBA-JOCHJYFZSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-piperidin-4-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2CCNCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 KDXBHDLLRUHOBA-JOCHJYFZSA-N 0.000 claims 1
- KIHVEXSGLLUDHS-BPGUCPLFSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-pyrrolidin-2-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2NCCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 KIHVEXSGLLUDHS-BPGUCPLFSA-N 0.000 claims 1
- KZMQPYCXSAGLTB-HXUWFJFHSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)C)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 KZMQPYCXSAGLTB-HXUWFJFHSA-N 0.000 claims 1
- FXEUQEMBQKIUER-HXUWFJFHSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)C)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 FXEUQEMBQKIUER-HXUWFJFHSA-N 0.000 claims 1
- JNSZJWMBASVFFG-OAQYLSRUSA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-(1-methylpiperidin-4-yl)prop-2-enenitrile Chemical compound C1CN(C)CCC1C=C(C#N)C(=O)N1C[C@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)CCC1 JNSZJWMBASVFFG-OAQYLSRUSA-N 0.000 claims 1
- XSXRHDHSVBTNAB-HXUWFJFHSA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-(oxan-4-yl)prop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2CCOCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F XSXRHDHSVBTNAB-HXUWFJFHSA-N 0.000 claims 1
- NNJAGWVFMOGWLK-XMMPIXPASA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(diethylaminomethyl)cyclopentyl]prop-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(CN(CC)CC)CCCC1 NNJAGWVFMOGWLK-XMMPIXPASA-N 0.000 claims 1
- GGMKESHSVKUWPX-LJQANCHMSA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(ethylamino)cyclopropyl]prop-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(NCC)CC1 GGMKESHSVKUWPX-LJQANCHMSA-N 0.000 claims 1
- OMCJCDOWQBLMQW-GOSISDBHSA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(methylamino)cyclopropyl]prop-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(NC)CC1 OMCJCDOWQBLMQW-GOSISDBHSA-N 0.000 claims 1
- PMNNGBDRAJTGMU-HXUWFJFHSA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(propan-2-ylamino)cyclopropyl]prop-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(NC(C)C)CC1 PMNNGBDRAJTGMU-HXUWFJFHSA-N 0.000 claims 1
- GWYIJCTYAAXOMT-JOCHJYFZSA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-[(dimethylamino)methyl]cyclopentyl]prop-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(CN(C)C)CCCC1 GWYIJCTYAAXOMT-JOCHJYFZSA-N 0.000 claims 1
- JSELVWXTZQCPKA-GOSISDBHSA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F JSELVWXTZQCPKA-GOSISDBHSA-N 0.000 claims 1
- JCDAJUALOINUEJ-ROPPNANJSA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-piperidin-3-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2CNCCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F JCDAJUALOINUEJ-ROPPNANJSA-N 0.000 claims 1
- GWSGAXGNGOQTFG-HXUWFJFHSA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-piperidin-4-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2CCNCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F GWSGAXGNGOQTFG-HXUWFJFHSA-N 0.000 claims 1
- YOEWVNKRGSFIBQ-MUMRKEEXSA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-pyrrolidin-2-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2NCCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F YOEWVNKRGSFIBQ-MUMRKEEXSA-N 0.000 claims 1
- UQLGRFKOEFQXTK-JOCHJYFZSA-N 2-[(3R)-3-[4-amino-5-(2-fluoro-4-phenoxyphenyl)-6-methylpyrrolo[2,3-d]pyrimidin-7-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)C(C)=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 UQLGRFKOEFQXTK-JOCHJYFZSA-N 0.000 claims 1
- SZZCEUUSTCQTDR-OAQYLSRUSA-N 2-[(3R)-3-[4-amino-5-(2-fluoro-4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)C=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 SZZCEUUSTCQTDR-OAQYLSRUSA-N 0.000 claims 1
- HRTOJHBVIFYGJC-XMMPIXPASA-N 2-[(3R)-3-[4-amino-5-[4-(3,5-difluorophenoxy)phenyl]-6-methylpyrrolo[2,3-d]pyrimidin-7-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)C(C)=C1C(C=C1)=CC=C1OC1=CC(F)=CC(F)=C1 HRTOJHBVIFYGJC-XMMPIXPASA-N 0.000 claims 1
- UKURDKADUIBPHB-HSZRJFAPSA-N 2-[(3R)-3-[4-amino-5-[4-(3,5-difluorophenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)C=C1C(C=C1)=CC=C1OC1=CC(F)=CC(F)=C1 UKURDKADUIBPHB-HSZRJFAPSA-N 0.000 claims 1
- YVXFHBBAHIDQJL-XMMPIXPASA-N 2-[(3R)-3-[4-amino-6-methyl-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)C(C)=C1C(C=C1)=CC=C1OC1=CC=CC=C1 YVXFHBBAHIDQJL-XMMPIXPASA-N 0.000 claims 1
- JZJNGZMDAUNXTF-QFIPXVFZSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-(oxan-4-yl)prop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CN(CCC2)C(=O)C(=CC2CCOCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 JZJNGZMDAUNXTF-QFIPXVFZSA-N 0.000 claims 1
- BTWNIXPKIHIIBT-SANMLTNESA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(diethylaminomethyl)cyclopentyl]prop-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(CN(CC)CC)CCCC1 BTWNIXPKIHIIBT-SANMLTNESA-N 0.000 claims 1
- SONFNRMAPPWUNU-NRFANRHFSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(ethylamino)cyclopropyl]prop-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(NCC)CC1 SONFNRMAPPWUNU-NRFANRHFSA-N 0.000 claims 1
- GCYHPPFYYPCIBY-FQEVSTJZSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(methylamino)cyclopropyl]prop-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(NC)CC1 GCYHPPFYYPCIBY-FQEVSTJZSA-N 0.000 claims 1
- FXSMLAZXJKANGS-IAXKEJLGSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-piperidin-3-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CN(CCC2)C(=O)C(=CC2CNCCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 FXSMLAZXJKANGS-IAXKEJLGSA-N 0.000 claims 1
- KDXBHDLLRUHOBA-QFIPXVFZSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-piperidin-4-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CN(CCC2)C(=O)C(=CC2CCNCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 KDXBHDLLRUHOBA-QFIPXVFZSA-N 0.000 claims 1
- KIHVEXSGLLUDHS-LBAQZLPGSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-pyrrolidin-2-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CN(CCC2)C(=O)C(=CC2NCCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 KIHVEXSGLLUDHS-LBAQZLPGSA-N 0.000 claims 1
- JNSZJWMBASVFFG-NRFANRHFSA-N 2-[(3S)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-(1-methylpiperidin-4-yl)prop-2-enenitrile Chemical compound C1CN(C)CCC1C=C(C#N)C(=O)N1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)CCC1 JNSZJWMBASVFFG-NRFANRHFSA-N 0.000 claims 1
- XSXRHDHSVBTNAB-FQEVSTJZSA-N 2-[(3S)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-(oxan-4-yl)prop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CN(CCC2)C(=O)C(=CC2CCOCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F XSXRHDHSVBTNAB-FQEVSTJZSA-N 0.000 claims 1
- NNJAGWVFMOGWLK-DEOSSOPVSA-N 2-[(3S)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(diethylaminomethyl)cyclopentyl]prop-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(CN(CC)CC)CCCC1 NNJAGWVFMOGWLK-DEOSSOPVSA-N 0.000 claims 1
- GGMKESHSVKUWPX-IBGZPJMESA-N 2-[(3S)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(ethylamino)cyclopropyl]prop-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(NCC)CC1 GGMKESHSVKUWPX-IBGZPJMESA-N 0.000 claims 1
- OMCJCDOWQBLMQW-SFHVURJKSA-N 2-[(3S)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(methylamino)cyclopropyl]prop-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(NC)CC1 OMCJCDOWQBLMQW-SFHVURJKSA-N 0.000 claims 1
- PMNNGBDRAJTGMU-FQEVSTJZSA-N 2-[(3S)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(propan-2-ylamino)cyclopropyl]prop-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(NC(C)C)CC1 PMNNGBDRAJTGMU-FQEVSTJZSA-N 0.000 claims 1
- GWYIJCTYAAXOMT-QFIPXVFZSA-N 2-[(3S)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-[(dimethylamino)methyl]cyclopentyl]prop-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(CN(C)C)CCCC1 GWYIJCTYAAXOMT-QFIPXVFZSA-N 0.000 claims 1
- JCDAJUALOINUEJ-IJHRGXPZSA-N 2-[(3S)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-piperidin-3-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CN(CCC2)C(=O)C(=CC2CNCCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F JCDAJUALOINUEJ-IJHRGXPZSA-N 0.000 claims 1
- UQLGRFKOEFQXTK-QFIPXVFZSA-N 2-[(3S)-3-[4-amino-5-(2-fluoro-4-phenoxyphenyl)-6-methylpyrrolo[2,3-d]pyrimidin-7-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)C(C)=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 UQLGRFKOEFQXTK-QFIPXVFZSA-N 0.000 claims 1
- SZZCEUUSTCQTDR-NRFANRHFSA-N 2-[(3S)-3-[4-amino-5-(2-fluoro-4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)C=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 SZZCEUUSTCQTDR-NRFANRHFSA-N 0.000 claims 1
- HRTOJHBVIFYGJC-DEOSSOPVSA-N 2-[(3S)-3-[4-amino-5-[4-(3,5-difluorophenoxy)phenyl]-6-methylpyrrolo[2,3-d]pyrimidin-7-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)C(C)=C1C(C=C1)=CC=C1OC1=CC(F)=CC(F)=C1 HRTOJHBVIFYGJC-DEOSSOPVSA-N 0.000 claims 1
- YVXFHBBAHIDQJL-DEOSSOPVSA-N 2-[(3S)-3-[4-amino-6-methyl-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)C(C)=C1C(C=C1)=CC=C1OC1=CC=CC=C1 YVXFHBBAHIDQJL-DEOSSOPVSA-N 0.000 claims 1
- HDRKIVDDSOTVRP-HSZRJFAPSA-N 2-[(3r)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-(1-methylpiperidin-4-yl)prop-2-enenitrile Chemical compound C1CN(C)CCC1C=C(C#N)C(=O)N1C[C@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 HDRKIVDDSOTVRP-HSZRJFAPSA-N 0.000 claims 1
- OQTDUHVOPVMWPL-JOCHJYFZSA-N 2-[(3r)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(2-methoxyethylamino)-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NCCOC)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 OQTDUHVOPVMWPL-JOCHJYFZSA-N 0.000 claims 1
- OYEWCPLOZQWRTA-JOCHJYFZSA-N 2-[(3r)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(cyclopropylamino)-4-methylpent-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC(C)(C)NC1CC1 OYEWCPLOZQWRTA-JOCHJYFZSA-N 0.000 claims 1
- MTMFUKIPDNCURW-OAQYLSRUSA-N 2-[(3r)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(ethylamino)-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NCC)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 MTMFUKIPDNCURW-OAQYLSRUSA-N 0.000 claims 1
- DKEBWKMVXXEPHV-OAQYLSRUSA-N 2-[(3r)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-ethoxy-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)OCC)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 DKEBWKMVXXEPHV-OAQYLSRUSA-N 0.000 claims 1
- STNWYIXKAQCFQK-HXUWFJFHSA-N 2-[(3r)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(methylamino)pent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NC)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 STNWYIXKAQCFQK-HXUWFJFHSA-N 0.000 claims 1
- IDUOQDBNMAPXQQ-JOCHJYFZSA-N 2-[(3r)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(propan-2-ylamino)pent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NC(C)C)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 IDUOQDBNMAPXQQ-JOCHJYFZSA-N 0.000 claims 1
- LTAXJGIDEGVGKY-GOSISDBHSA-N 2-[(3r)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)C)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 LTAXJGIDEGVGKY-GOSISDBHSA-N 0.000 claims 1
- BMHNUHSSZQGNFZ-HXUWFJFHSA-N 2-[(3r)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(2-methoxyethylamino)-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NCCOC)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 BMHNUHSSZQGNFZ-HXUWFJFHSA-N 0.000 claims 1
- SOECMCJOWVYWNB-HXUWFJFHSA-N 2-[(3r)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(cyclopropylamino)-4-methylpent-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC(C)(C)NC1CC1 SOECMCJOWVYWNB-HXUWFJFHSA-N 0.000 claims 1
- MPMKRFFUACUAAL-LJQANCHMSA-N 2-[(3r)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(dimethylamino)-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)N(C)C)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 MPMKRFFUACUAAL-LJQANCHMSA-N 0.000 claims 1
- ZGHDUMGETQJRHI-GOSISDBHSA-N 2-[(3r)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(methylamino)pent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NC)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 ZGHDUMGETQJRHI-GOSISDBHSA-N 0.000 claims 1
- GUWMWABHJKWLKX-HXUWFJFHSA-N 2-[(3r)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(propan-2-ylamino)pent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NC(C)C)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 GUWMWABHJKWLKX-HXUWFJFHSA-N 0.000 claims 1
- HDRKIVDDSOTVRP-QHCPKHFHSA-N 2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-(1-methylpiperidin-4-yl)prop-2-enenitrile Chemical compound C1CN(C)CCC1C=C(C#N)C(=O)N1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 HDRKIVDDSOTVRP-QHCPKHFHSA-N 0.000 claims 1
- KZMQPYCXSAGLTB-FQEVSTJZSA-N 2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)C)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 KZMQPYCXSAGLTB-FQEVSTJZSA-N 0.000 claims 1
- OQTDUHVOPVMWPL-QFIPXVFZSA-N 2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(2-methoxyethylamino)-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NCCOC)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 OQTDUHVOPVMWPL-QFIPXVFZSA-N 0.000 claims 1
- OYEWCPLOZQWRTA-QFIPXVFZSA-N 2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(cyclopropylamino)-4-methylpent-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC(C)(C)NC1CC1 OYEWCPLOZQWRTA-QFIPXVFZSA-N 0.000 claims 1
- MTMFUKIPDNCURW-NRFANRHFSA-N 2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(ethylamino)-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NCC)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 MTMFUKIPDNCURW-NRFANRHFSA-N 0.000 claims 1
- DKEBWKMVXXEPHV-NRFANRHFSA-N 2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-ethoxy-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)OCC)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 DKEBWKMVXXEPHV-NRFANRHFSA-N 0.000 claims 1
- STNWYIXKAQCFQK-FQEVSTJZSA-N 2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(methylamino)pent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NC)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 STNWYIXKAQCFQK-FQEVSTJZSA-N 0.000 claims 1
- IDUOQDBNMAPXQQ-QFIPXVFZSA-N 2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(propan-2-ylamino)pent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NC(C)C)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 IDUOQDBNMAPXQQ-QFIPXVFZSA-N 0.000 claims 1
- KYLMVBZZOSOHLD-QHCPKHFHSA-N 2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-morpholin-4-ylpent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@H]2CCCN(C2)C(=O)C(C#N)=CC(C)(C)N2CCOCC2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 KYLMVBZZOSOHLD-QHCPKHFHSA-N 0.000 claims 1
- FXEUQEMBQKIUER-FQEVSTJZSA-N 2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)C)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 FXEUQEMBQKIUER-FQEVSTJZSA-N 0.000 claims 1
- LTAXJGIDEGVGKY-SFHVURJKSA-N 2-[(3s)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)C)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 LTAXJGIDEGVGKY-SFHVURJKSA-N 0.000 claims 1
- BMHNUHSSZQGNFZ-FQEVSTJZSA-N 2-[(3s)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(2-methoxyethylamino)-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NCCOC)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 BMHNUHSSZQGNFZ-FQEVSTJZSA-N 0.000 claims 1
- MPMKRFFUACUAAL-IBGZPJMESA-N 2-[(3s)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(dimethylamino)-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)N(C)C)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 MPMKRFFUACUAAL-IBGZPJMESA-N 0.000 claims 1
- ZGHDUMGETQJRHI-SFHVURJKSA-N 2-[(3s)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(methylamino)pent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NC)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 ZGHDUMGETQJRHI-SFHVURJKSA-N 0.000 claims 1
- GUWMWABHJKWLKX-FQEVSTJZSA-N 2-[(3s)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(propan-2-ylamino)pent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NC(C)C)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 GUWMWABHJKWLKX-FQEVSTJZSA-N 0.000 claims 1
- NMPVOGJLOPRRNR-NRFANRHFSA-N 2-[(3s)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-morpholin-4-ylpent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@H]2CCCN(C2)C(=O)C(C#N)=CC(C)(C)N2CCOCC2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F NMPVOGJLOPRRNR-NRFANRHFSA-N 0.000 claims 1
- WNLTXZCOYCXQHU-UHFFFAOYSA-N 2-[2-[[4-amino-6-methyl-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C12=C(N)N=CN=C2N(CC2N(CCC2)C(=O)C(=CC2CC2)C#N)C(C)=C1C(C=C1)=CC=C1OC1=CC=CC=C1 WNLTXZCOYCXQHU-UHFFFAOYSA-N 0.000 claims 1
- KZMQPYCXSAGLTB-UHFFFAOYSA-N 2-[3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)C)CCCC1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 KZMQPYCXSAGLTB-UHFFFAOYSA-N 0.000 claims 1
- FWSRAJSFIOPBOE-IBGZPJMESA-N 3-(1-aminocyclopropyl)-2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]prop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1(N)CC1 FWSRAJSFIOPBOE-IBGZPJMESA-N 0.000 claims 1
- MJDAGXIQKUEWKR-KRWDZBQOSA-N 3-(1-aminocyclopropyl)-2-[(2S)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]prop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1(N)CC1 MJDAGXIQKUEWKR-KRWDZBQOSA-N 0.000 claims 1
- LPIVEEHDVHUKCB-LJQANCHMSA-N 3-(1-aminocyclopropyl)-2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]prop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2(N)CC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 LPIVEEHDVHUKCB-LJQANCHMSA-N 0.000 claims 1
- NDTWVIRMFIHLIV-QGZVFWFLSA-N 3-(1-aminocyclopropyl)-2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]prop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2(N)CC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F NDTWVIRMFIHLIV-QGZVFWFLSA-N 0.000 claims 1
- LPIVEEHDVHUKCB-IBGZPJMESA-N 3-(1-aminocyclopropyl)-2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]prop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CN(CCC2)C(=O)C(=CC2(N)CC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 LPIVEEHDVHUKCB-IBGZPJMESA-N 0.000 claims 1
- IDJHMBKQEPOZBR-LJQANCHMSA-N 4-amino-2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)(N)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 IDJHMBKQEPOZBR-LJQANCHMSA-N 0.000 claims 1
- GKPUEDXKXRHIKG-LJQANCHMSA-N 4-amino-2-[(2r)-2-[[4-amino-3-[2-fluoro-4-(3-fluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)(N)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=C(F)C=CC=3)=CC=2)F)=N1 GKPUEDXKXRHIKG-LJQANCHMSA-N 0.000 claims 1
- JMZCFVNQCJAXJS-QGZVFWFLSA-N 4-amino-2-[(2r)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)(N)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 JMZCFVNQCJAXJS-QGZVFWFLSA-N 0.000 claims 1
- ULPQBYOJXOUAAR-HXUWFJFHSA-N 4-amino-2-[(2r)-2-[[4-amino-5-(2-fluoro-4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)(N)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=C1 ULPQBYOJXOUAAR-HXUWFJFHSA-N 0.000 claims 1
- IDJHMBKQEPOZBR-IBGZPJMESA-N 4-amino-2-[(2s)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)(N)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 IDJHMBKQEPOZBR-IBGZPJMESA-N 0.000 claims 1
- GKPUEDXKXRHIKG-IBGZPJMESA-N 4-amino-2-[(2s)-2-[[4-amino-3-[2-fluoro-4-(3-fluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)(N)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=C(F)C=CC=3)=CC=2)F)=N1 GKPUEDXKXRHIKG-IBGZPJMESA-N 0.000 claims 1
- JMZCFVNQCJAXJS-KRWDZBQOSA-N 4-amino-2-[(2s)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)(N)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 JMZCFVNQCJAXJS-KRWDZBQOSA-N 0.000 claims 1
- ULPQBYOJXOUAAR-FQEVSTJZSA-N 4-amino-2-[(2s)-2-[[4-amino-5-(2-fluoro-4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)(N)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=C1 ULPQBYOJXOUAAR-FQEVSTJZSA-N 0.000 claims 1
- FGOLQFDTXCZDBI-LJQANCHMSA-N 4-amino-2-[(3r)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(N)C)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 FGOLQFDTXCZDBI-LJQANCHMSA-N 0.000 claims 1
- WZQVAMOQXUONAB-QGZVFWFLSA-N 4-amino-2-[(3r)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(N)C)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 WZQVAMOQXUONAB-QGZVFWFLSA-N 0.000 claims 1
- FGOLQFDTXCZDBI-IBGZPJMESA-N 4-amino-2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(N)C)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 FGOLQFDTXCZDBI-IBGZPJMESA-N 0.000 claims 1
- WZQVAMOQXUONAB-KRWDZBQOSA-N 4-amino-2-[(3s)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(N)C)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 WZQVAMOQXUONAB-KRWDZBQOSA-N 0.000 claims 1
- IZUCDIMZZBQYLR-MRXNPFEDSA-N 4-amino-n-[(2r)-1-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]propan-2-yl]-2-cyano-4-methylpent-2-enamide Chemical compound C12=C(N)N=CN=C2N(C[C@@H](C)NC(=O)C(=CC(C)(C)N)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 IZUCDIMZZBQYLR-MRXNPFEDSA-N 0.000 claims 1
- FRMUZCKAJXQYQC-QGZVFWFLSA-N N-[(2R)-1-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]propan-2-yl]-2-cyano-4,4-dimethylpent-2-enamide Chemical compound C12=C(N)N=CN=C2N(C[C@@H](C)NC(=O)C(=CC(C)(C)C)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 FRMUZCKAJXQYQC-QGZVFWFLSA-N 0.000 claims 1
- HAUZZEVZYNEKHM-GOSISDBHSA-N N-[(2R)-1-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]propan-2-yl]-2-cyano-4-(dimethylamino)-4-methylpent-2-enamide Chemical compound C12=C(N)N=CN=C2N(C[C@@H](C)NC(=O)C(=CC(C)(C)N(C)C)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 HAUZZEVZYNEKHM-GOSISDBHSA-N 0.000 claims 1
- PWODFMKTYXDDTQ-QGZVFWFLSA-N N-[(2R)-1-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]propan-2-yl]-2-cyano-4-methylpent-2-enamide Chemical compound C12=C(N)N=CN=C2N(C[C@@H](C)NC(=O)C(C#N)=CC(C)C)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 PWODFMKTYXDDTQ-QGZVFWFLSA-N 0.000 claims 1
- PTHYZAKMYJLMJF-GOSISDBHSA-N n-[(2r)-1-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]propan-2-yl]-2-cyano-4-ethoxy-4-methylpent-2-enamide Chemical compound C12=C(N)N=CN=C2N(C[C@@H](C)NC(=O)C(C#N)=CC(C)(C)OCC)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 PTHYZAKMYJLMJF-GOSISDBHSA-N 0.000 claims 1
- RYFMFRFVFBNQJL-INIZCTEOSA-N n-[(2s)-1-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]propan-2-yl]-2-cyano-3-cyclopropylprop-2-enamide Chemical compound C([C@H](C)NC(=O)C(=CC1CC1)C#N)N(C1=NC=NC(N)=C11)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 RYFMFRFVFBNQJL-INIZCTEOSA-N 0.000 claims 1
- BTNDELYZHVXSMM-UHFFFAOYSA-N n-[1-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]-2-methylpropan-2-yl]-2-cyano-3-cyclopropylprop-2-enamide Chemical compound C1CC1C=C(C#N)C(=O)NC(C)(C)CN(C1=NC=NC(N)=C11)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 BTNDELYZHVXSMM-UHFFFAOYSA-N 0.000 claims 1
- KRSHNHGJOPQJFM-UHFFFAOYSA-N n-[2-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]-2-methylpropyl]-2-cyano-3-cyclopropylprop-2-enamide Chemical compound N1=C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)C2=C(N)N=CN=C2N1C(C)(C)CNC(=O)C(C#N)=CC1CC1 KRSHNHGJOPQJFM-UHFFFAOYSA-N 0.000 claims 1
- ZCEIOGLJLHVJDY-UHFFFAOYSA-N n-[2-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-2-cyano-3-cyclopropylprop-2-enamide Chemical compound N1=C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)C=2C(N)=NC=NC=2N1CCNC(=O)C(C#N)=CC1CC1 ZCEIOGLJLHVJDY-UHFFFAOYSA-N 0.000 claims 1
- NMDUHIKHSSEMNE-UHFFFAOYSA-N n-[2-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-2-cyano-3-cyclopropyl-n-methylprop-2-enamide Chemical compound C1CC1C=C(C#N)C(=O)N(C)CCN(C1=NC=NC(N)=C11)N=C1C(C=C1)=CC=C1OC1=CC=CC=C1 NMDUHIKHSSEMNE-UHFFFAOYSA-N 0.000 claims 1
- 230000008569 process Effects 0.000 abstract description 6
- 239000008203 oral pharmaceutical composition Substances 0.000 abstract description 3
- 235000002639 sodium chloride Nutrition 0.000 description 139
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 115
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 76
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 62
- 125000001188 haloalkyl group Chemical group 0.000 description 61
- 125000001072 heteroaryl group Chemical group 0.000 description 59
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 57
- 125000003118 aryl group Chemical group 0.000 description 51
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 46
- 125000003545 alkoxy group Chemical group 0.000 description 46
- 125000002947 alkylene group Chemical group 0.000 description 45
- 239000010410 layer Substances 0.000 description 37
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 34
- 239000002552 dosage form Substances 0.000 description 33
- 229940079593 drug Drugs 0.000 description 33
- 125000004414 alkyl thio group Chemical group 0.000 description 29
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 28
- 125000000623 heterocyclic group Chemical group 0.000 description 27
- 239000002253 acid Substances 0.000 description 26
- 229920000642 polymer Polymers 0.000 description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 26
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 24
- 239000002775 capsule Substances 0.000 description 24
- 239000004094 surface-active agent Substances 0.000 description 24
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 23
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 22
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 22
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 22
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 22
- 239000011162 core material Substances 0.000 description 21
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 21
- 239000004014 plasticizer Substances 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 210000000936 intestine Anatomy 0.000 description 20
- 229920001223 polyethylene glycol Polymers 0.000 description 20
- 229910001868 water Inorganic materials 0.000 description 20
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 19
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 19
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 18
- 239000013543 active substance Substances 0.000 description 18
- 229910052757 nitrogen Inorganic materials 0.000 description 18
- 239000003826 tablet Substances 0.000 description 18
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 17
- 229920002301 cellulose acetate Polymers 0.000 description 16
- 150000003254 radicals Chemical class 0.000 description 16
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 15
- 239000000370 acceptor Substances 0.000 description 15
- 125000003710 aryl alkyl group Chemical group 0.000 description 15
- 239000011230 binding agent Substances 0.000 description 15
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 15
- 239000000463 material Substances 0.000 description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 description 15
- 235000015424 sodium Nutrition 0.000 description 15
- 239000011734 sodium Substances 0.000 description 15
- 229940083542 sodium Drugs 0.000 description 15
- 229910052708 sodium Inorganic materials 0.000 description 15
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 14
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 14
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 14
- 125000002950 monocyclic group Chemical group 0.000 description 14
- 239000004215 Carbon black (E152) Substances 0.000 description 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 13
- 239000001913 cellulose Substances 0.000 description 13
- 235000010980 cellulose Nutrition 0.000 description 13
- 229920002678 cellulose Polymers 0.000 description 13
- 229930195733 hydrocarbon Natural products 0.000 description 13
- 229940100467 polyvinyl acetate phthalate Drugs 0.000 description 13
- 229920006395 saturated elastomer Polymers 0.000 description 13
- 125000003107 substituted aryl group Chemical group 0.000 description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- 239000002202 Polyethylene glycol Substances 0.000 description 12
- 229910052799 carbon Inorganic materials 0.000 description 12
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 12
- 239000008188 pellet Substances 0.000 description 12
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 12
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 11
- 229920002472 Starch Polymers 0.000 description 11
- IYKJEILNJZQJPU-UHFFFAOYSA-N acetic acid;butanedioic acid Chemical compound CC(O)=O.OC(=O)CCC(O)=O IYKJEILNJZQJPU-UHFFFAOYSA-N 0.000 description 11
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 11
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 11
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 11
- 229910052703 rhodium Inorganic materials 0.000 description 11
- 125000006413 ring segment Chemical group 0.000 description 11
- 235000019698 starch Nutrition 0.000 description 11
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 10
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 10
- 239000000839 emulsion Substances 0.000 description 10
- 239000000945 filler Substances 0.000 description 10
- 125000004475 heteroaralkyl group Chemical group 0.000 description 10
- 229920000053 polysorbate 80 Polymers 0.000 description 10
- 238000012545 processing Methods 0.000 description 10
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 9
- 239000000654 additive Substances 0.000 description 9
- 229920001577 copolymer Polymers 0.000 description 9
- 239000006071 cream Substances 0.000 description 9
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 9
- 230000003111 delayed effect Effects 0.000 description 9
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 description 9
- 239000003085 diluting agent Substances 0.000 description 9
- 239000002270 dispersing agent Substances 0.000 description 9
- 125000001207 fluorophenyl group Chemical group 0.000 description 9
- 125000004415 heterocyclylalkyl group Chemical group 0.000 description 9
- 239000000314 lubricant Substances 0.000 description 9
- 229920000609 methyl cellulose Polymers 0.000 description 9
- 235000010981 methylcellulose Nutrition 0.000 description 9
- 239000001923 methylcellulose Substances 0.000 description 9
- 229960002900 methylcellulose Drugs 0.000 description 9
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 9
- 239000003381 stabilizer Substances 0.000 description 9
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 8
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 8
- 239000002518 antifoaming agent Substances 0.000 description 8
- 150000001735 carboxylic acids Chemical class 0.000 description 8
- 239000011247 coating layer Substances 0.000 description 8
- 239000006185 dispersion Substances 0.000 description 8
- 125000005610 enamide group Chemical group 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 239000012530 fluid Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 125000003373 pyrazinyl group Chemical group 0.000 description 8
- 125000000714 pyrimidinyl group Chemical group 0.000 description 8
- 210000000813 small intestine Anatomy 0.000 description 8
- 239000008107 starch Substances 0.000 description 8
- 229940032147 starch Drugs 0.000 description 8
- 210000002784 stomach Anatomy 0.000 description 8
- 235000000346 sugar Nutrition 0.000 description 8
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 7
- 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 7
- 239000004372 Polyvinyl alcohol Substances 0.000 description 7
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 7
- 239000003963 antioxidant agent Substances 0.000 description 7
- 235000006708 antioxidants Nutrition 0.000 description 7
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 7
- 239000003086 colorant Substances 0.000 description 7
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 7
- 229920001983 poloxamer Polymers 0.000 description 7
- 229920002744 polyvinyl acetate phthalate Polymers 0.000 description 7
- 229920002451 polyvinyl alcohol Polymers 0.000 description 7
- 229940068984 polyvinyl alcohol Drugs 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 239000000454 talc Substances 0.000 description 7
- 229910052623 talc Inorganic materials 0.000 description 7
- 235000012222 talc Nutrition 0.000 description 7
- 125000005591 trimellitate group Chemical group 0.000 description 7
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 6
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 6
- 101100063435 Caenorhabditis elegans din-1 gene Proteins 0.000 description 6
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 6
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 6
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 6
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 229930195725 Mannitol Natural products 0.000 description 6
- 235000021355 Stearic acid Nutrition 0.000 description 6
- 229930006000 Sucrose Natural products 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- 235000010443 alginic acid Nutrition 0.000 description 6
- 229920000615 alginic acid Polymers 0.000 description 6
- 150000001733 carboxylic acid esters Chemical class 0.000 description 6
- 239000008121 dextrose Substances 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 6
- 230000003628 erosive effect Effects 0.000 description 6
- 210000001035 gastrointestinal tract Anatomy 0.000 description 6
- 239000007903 gelatin capsule Substances 0.000 description 6
- 239000001087 glyceryl triacetate Substances 0.000 description 6
- 235000013773 glyceryl triacetate Nutrition 0.000 description 6
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 235000010355 mannitol Nutrition 0.000 description 6
- 239000000594 mannitol Substances 0.000 description 6
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 6
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 6
- 239000003755 preservative agent Substances 0.000 description 6
- 235000013772 propylene glycol Nutrition 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 229940005550 sodium alginate Drugs 0.000 description 6
- 235000010413 sodium alginate Nutrition 0.000 description 6
- 239000000661 sodium alginate Substances 0.000 description 6
- 239000000600 sorbitol Substances 0.000 description 6
- 235000010356 sorbitol Nutrition 0.000 description 6
- 239000008117 stearic acid Substances 0.000 description 6
- 239000005720 sucrose Substances 0.000 description 6
- 229960004793 sucrose Drugs 0.000 description 6
- 150000003573 thiols Chemical class 0.000 description 6
- 229960002622 triacetin Drugs 0.000 description 6
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 5
- WROUWQQRXUBECT-UHFFFAOYSA-N 2-ethylacrylic acid Chemical compound CCC(=C)C(O)=O WROUWQQRXUBECT-UHFFFAOYSA-N 0.000 description 5
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Polymers CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 5
- 241000416162 Astragalus gummifer Species 0.000 description 5
- 241000207199 Citrus Species 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 239000001856 Ethyl cellulose Substances 0.000 description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 5
- 229920001800 Shellac Polymers 0.000 description 5
- 229920001615 Tragacanth Polymers 0.000 description 5
- 125000002252 acyl group Chemical group 0.000 description 5
- 125000003282 alkyl amino group Chemical group 0.000 description 5
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 239000002246 antineoplastic agent Substances 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 235000020971 citrus fruits Nutrition 0.000 description 5
- 239000007884 disintegrant Substances 0.000 description 5
- 210000001198 duodenum Anatomy 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 235000019441 ethanol Nutrition 0.000 description 5
- 235000019325 ethyl cellulose Nutrition 0.000 description 5
- 229920001249 ethyl cellulose Polymers 0.000 description 5
- 235000003599 food sweetener Nutrition 0.000 description 5
- 125000000524 functional group Chemical group 0.000 description 5
- 229940075507 glyceryl monostearate Drugs 0.000 description 5
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 5
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 5
- 229920000639 hydroxypropylmethylcellulose acetate succinate Polymers 0.000 description 5
- 125000001041 indolyl group Chemical group 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 229960001375 lactose Drugs 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 239000006186 oral dosage form Substances 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 229920000136 polysorbate Polymers 0.000 description 5
- 229920002689 polyvinyl acetate Polymers 0.000 description 5
- 229940075065 polyvinyl acetate Drugs 0.000 description 5
- 239000011118 polyvinyl acetate Substances 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- 125000004076 pyridyl group Chemical group 0.000 description 5
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 5
- 229940113147 shellac Drugs 0.000 description 5
- 239000004208 shellac Substances 0.000 description 5
- 235000013874 shellac Nutrition 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000003765 sweetening agent Substances 0.000 description 5
- 229920001285 xanthan gum Polymers 0.000 description 5
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 4
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 4
- 125000004487 4-tetrahydropyranyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- KEQCALBHWWLEGG-UHFFFAOYSA-N 5-ethyl-1-[3-(5-ethyl-6-methylsulfanyl-4-oxopyrazolo[3,4-d]pyrimidin-1-yl)propyl]-6-methylsulfanylpyrazolo[3,4-d]pyrimidin-4-one Chemical compound N1=CC(C(N(CC)C(SC)=N2)=O)=C2N1CCCN1C(N=C(SC)N(C2=O)CC)=C2C=N1 KEQCALBHWWLEGG-UHFFFAOYSA-N 0.000 description 4
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical group NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- 229920000881 Modified starch Polymers 0.000 description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 4
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 4
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 4
- AOBORMOPSGHCAX-UHFFFAOYSA-N Tocophersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-UHFFFAOYSA-N 0.000 description 4
- 102100029823 Tyrosine-protein kinase BTK Human genes 0.000 description 4
- SPTSIOTYTJZTOG-UHFFFAOYSA-N acetic acid;octadecanoic acid Chemical compound CC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O SPTSIOTYTJZTOG-UHFFFAOYSA-N 0.000 description 4
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 description 4
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 4
- 239000006172 buffering agent Substances 0.000 description 4
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 235000015165 citric acid Nutrition 0.000 description 4
- 235000018417 cysteine Nutrition 0.000 description 4
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 4
- 238000009792 diffusion process Methods 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 238000005469 granulation Methods 0.000 description 4
- 230000003179 granulation Effects 0.000 description 4
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 4
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 4
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 4
- 229920001477 hydrophilic polymer Polymers 0.000 description 4
- 210000003405 ileum Anatomy 0.000 description 4
- 210000001630 jejunum Anatomy 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 210000004379 membrane Anatomy 0.000 description 4
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 4
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 4
- 229920000058 polyacrylate Polymers 0.000 description 4
- 229940068968 polysorbate 80 Drugs 0.000 description 4
- 230000002035 prolonged effect Effects 0.000 description 4
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 4
- 239000007909 solid dosage form Substances 0.000 description 4
- 229940035049 sorbitan monooleate Drugs 0.000 description 4
- 235000011069 sorbitan monooleate Nutrition 0.000 description 4
- 239000001593 sorbitan monooleate Substances 0.000 description 4
- 238000005507 spraying Methods 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 150000008163 sugars Chemical class 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- 125000000335 thiazolyl group Chemical group 0.000 description 4
- 239000001069 triethyl citrate Substances 0.000 description 4
- 235000013769 triethyl citrate Nutrition 0.000 description 4
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 4
- 239000001993 wax Substances 0.000 description 4
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 3
- QHZLMUACJMDIAE-SFHVURJKSA-N 1-hexadecanoyl-sn-glycerol Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)CO QHZLMUACJMDIAE-SFHVURJKSA-N 0.000 description 3
- WECGLUPZRHILCT-GSNKCQISSA-N 1-linoleoyl-sn-glycerol Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OC[C@@H](O)CO WECGLUPZRHILCT-GSNKCQISSA-N 0.000 description 3
- 239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 description 3
- ZJXIRDNUWLAVEN-UHFFFAOYSA-N 2-cyclopropylprop-2-enenitrile Chemical compound N#CC(=C)C1CC1 ZJXIRDNUWLAVEN-UHFFFAOYSA-N 0.000 description 3
- RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 description 3
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 3
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 3
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 3
- 240000007472 Leucaena leucocephala Species 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 239000005642 Oleic acid Substances 0.000 description 3
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 3
- QHZLMUACJMDIAE-UHFFFAOYSA-N Palmitic acid monoglyceride Natural products CCCCCCCCCCCCCCCC(=O)OCC(O)CO QHZLMUACJMDIAE-UHFFFAOYSA-N 0.000 description 3
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 3
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 3
- 241001290151 Prunus avium subsp. avium Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 239000000783 alginic acid Substances 0.000 description 3
- 229960001126 alginic acid Drugs 0.000 description 3
- 150000004781 alginic acids Chemical class 0.000 description 3
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 235000012216 bentonite Nutrition 0.000 description 3
- 229920001400 block copolymer Polymers 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 3
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 3
- 235000019693 cherries Nutrition 0.000 description 3
- 229920001688 coating polymer Polymers 0.000 description 3
- 238000007906 compression Methods 0.000 description 3
- 230000006835 compression Effects 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 229940099371 diacetylated monoglycerides Drugs 0.000 description 3
- 125000004663 dialkyl amino group Chemical group 0.000 description 3
- 125000004472 dialkylaminosulfonyl group Chemical group 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 3
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 3
- 125000006575 electron-withdrawing group Chemical group 0.000 description 3
- GDCRSXZBSIRSFR-UHFFFAOYSA-N ethyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.CCOC(=O)C=C GDCRSXZBSIRSFR-UHFFFAOYSA-N 0.000 description 3
- 238000001125 extrusion Methods 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 230000030136 gastric emptying Effects 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 3
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 3
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000002427 irreversible effect Effects 0.000 description 3
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 3
- 229960001855 mannitol Drugs 0.000 description 3
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 3
- 239000004530 micro-emulsion Substances 0.000 description 3
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 description 3
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 125000004043 oxo group Chemical group O=* 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000000049 pigment Substances 0.000 description 3
- 229940068917 polyethylene glycols Drugs 0.000 description 3
- 229940069328 povidone Drugs 0.000 description 3
- 230000002335 preservative effect Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000002062 proliferating effect Effects 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 3
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 3
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical class [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 3
- 229940080313 sodium starch Drugs 0.000 description 3
- 239000002594 sorbent Substances 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 238000001694 spray drying Methods 0.000 description 3
- 238000002626 targeted therapy Methods 0.000 description 3
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 3
- 235000010487 tragacanth Nutrition 0.000 description 3
- 239000000196 tragacanth Substances 0.000 description 3
- 229940116362 tragacanth Drugs 0.000 description 3
- 125000004306 triazinyl group Chemical group 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- 239000000811 xylitol Substances 0.000 description 3
- 235000010447 xylitol Nutrition 0.000 description 3
- 229960002675 xylitol Drugs 0.000 description 3
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- AHJKTMQDOYBLSR-UHFFFAOYSA-N 3-cyclopropylprop-2-enenitrile Chemical compound N#CC=CC1CC1 AHJKTMQDOYBLSR-UHFFFAOYSA-N 0.000 description 2
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
- YZRARHFKUZRMCC-UHFFFAOYSA-N 4-methylpent-2-enenitrile Chemical compound CC(C)C=CC#N YZRARHFKUZRMCC-UHFFFAOYSA-N 0.000 description 2
- 235000006491 Acacia senegal Nutrition 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 229920000856 Amylose Polymers 0.000 description 2
- 108010011485 Aspartame Proteins 0.000 description 2
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- 208000011691 Burkitt lymphomas Diseases 0.000 description 2
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- PBYKCYPLADSNDM-QXMHVHEDSA-N CCCCCCCCCC\C=C/CCCCCCCC(=O)OCC(O)CO Chemical compound CCCCCCCCCC\C=C/CCCCCCCC(=O)OCC(O)CO PBYKCYPLADSNDM-QXMHVHEDSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 229920001661 Chitosan Polymers 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 235000005979 Citrus limon Nutrition 0.000 description 2
- 244000131522 Citrus pyriformis Species 0.000 description 2
- 102000005927 Cysteine Proteases Human genes 0.000 description 2
- 108010005843 Cysteine Proteases Proteins 0.000 description 2
- 102100027907 Cytoplasmic tyrosine-protein kinase BMX Human genes 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 229920003138 Eudragit® L 30 D-55 Polymers 0.000 description 2
- 235000016623 Fragaria vesca Nutrition 0.000 description 2
- 240000009088 Fragaria x ananassa Species 0.000 description 2
- 235000011363 Fragaria x ananassa Nutrition 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 229920002907 Guar gum Polymers 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- 239000002146 L01XE16 - Crizotinib Substances 0.000 description 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 235000014749 Mentha crispa Nutrition 0.000 description 2
- 244000246386 Mentha pulegium Species 0.000 description 2
- 235000016257 Mentha pulegium Nutrition 0.000 description 2
- 244000078639 Mentha spicata Species 0.000 description 2
- 235000004357 Mentha x piperita Nutrition 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 2
- 229920003091 Methocel™ Polymers 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 2
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 2
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 2
- 206010038563 Reocclusion Diseases 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 239000004376 Sucralose Substances 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 2
- ZFOZVQLOBQUTQQ-UHFFFAOYSA-N Tributyl citrate Chemical compound CCCCOC(=O)CC(O)(C(=O)OCCCC)CC(=O)OCCCC ZFOZVQLOBQUTQQ-UHFFFAOYSA-N 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- 102100027053 Tyrosine-protein kinase Blk Human genes 0.000 description 2
- 102100039079 Tyrosine-protein kinase TXK Human genes 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000619 acesulfame-K Substances 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000002399 angioplasty Methods 0.000 description 2
- 125000000129 anionic group Chemical group 0.000 description 2
- 230000000181 anti-adherent effect Effects 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 239000003911 antiadherent Substances 0.000 description 2
- 239000002216 antistatic agent Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 239000000605 aspartame Substances 0.000 description 2
- 235000010357 aspartame Nutrition 0.000 description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 2
- 229960003438 aspartame Drugs 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 235000013871 bee wax Nutrition 0.000 description 2
- 239000012166 beeswax Substances 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 235000021028 berry Nutrition 0.000 description 2
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 2
- 229960004853 betadex Drugs 0.000 description 2
- 210000000941 bile Anatomy 0.000 description 2
- 239000003833 bile salt Substances 0.000 description 2
- 229940093761 bile salts Drugs 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 2
- 235000010338 boric acid Nutrition 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 235000010216 calcium carbonate Nutrition 0.000 description 2
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- OEUVSBXAMBLPES-UHFFFAOYSA-L calcium stearoyl-2-lactylate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC(=O)OC(C)C(=O)OC(C)C([O-])=O.CCCCCCCCCCCCCCCCCC(=O)OC(C)C(=O)OC(C)C([O-])=O OEUVSBXAMBLPES-UHFFFAOYSA-L 0.000 description 2
- 235000011132 calcium sulphate Nutrition 0.000 description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 229940105329 carboxymethylcellulose Drugs 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 229960000541 cetyl alcohol Drugs 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 238000005336 cracking Methods 0.000 description 2
- KTEIFNKAUNYNJU-GFCCVEGCSA-N crizotinib Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C(=C1)C=NN1C1CCNCC1 KTEIFNKAUNYNJU-GFCCVEGCSA-N 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 150000001945 cysteines Chemical class 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 229940096516 dextrates Drugs 0.000 description 2
- 235000019700 dicalcium phosphate Nutrition 0.000 description 2
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 2
- RBLGLDWTCZMLRW-UHFFFAOYSA-K dicalcium;phosphate;dihydrate Chemical compound O.O.[Ca+2].[Ca+2].[O-]P([O-])([O-])=O RBLGLDWTCZMLRW-UHFFFAOYSA-K 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- OSVXSBDYLRYLIG-UHFFFAOYSA-N dioxidochlorine(.) Chemical compound O=Cl=O OSVXSBDYLRYLIG-UHFFFAOYSA-N 0.000 description 2
- 238000007907 direct compression Methods 0.000 description 2
- UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 235000013601 eggs Nutrition 0.000 description 2
- 239000003792 electrolyte Substances 0.000 description 2
- 239000002662 enteric coated tablet Substances 0.000 description 2
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 2
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 2
- RRAFCDWBNXTKKO-UHFFFAOYSA-N eugenol Chemical compound COC1=CC(CC=C)=CC=C1O RRAFCDWBNXTKKO-UHFFFAOYSA-N 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 229960003180 glutathione Drugs 0.000 description 2
- 125000005456 glyceride group Chemical group 0.000 description 2
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 2
- GGJRAQULURVTAJ-UHFFFAOYSA-N glyceryl monolinolenate Natural products CCC=CCC=CCC=CCCCCCCCC(=O)OCC(O)CO GGJRAQULURVTAJ-UHFFFAOYSA-N 0.000 description 2
- 235000010417 guar gum Nutrition 0.000 description 2
- 239000000665 guar gum Substances 0.000 description 2
- 229960002154 guar gum Drugs 0.000 description 2
- 235000001050 hortel pimenta Nutrition 0.000 description 2
- 235000011167 hydrochloric acid Nutrition 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 229960003943 hypromellose Drugs 0.000 description 2
- VKOBVWXKNCXXDE-UHFFFAOYSA-N icosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 229940043355 kinase inhibitor Drugs 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 239000004973 liquid crystal related substance Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 229940041616 menthol Drugs 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- IWVKTOUOPHGZRX-UHFFFAOYSA-N methyl 2-methylprop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.COC(=O)C(C)=C IWVKTOUOPHGZRX-UHFFFAOYSA-N 0.000 description 2
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- TXXHDPDFNKHHGW-UHFFFAOYSA-N muconic acid Chemical group OC(=O)C=CC=CC(O)=O TXXHDPDFNKHHGW-UHFFFAOYSA-N 0.000 description 2
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- UTOPWMOLSKOLTQ-UHFFFAOYSA-N octacosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCC(O)=O UTOPWMOLSKOLTQ-UHFFFAOYSA-N 0.000 description 2
- 238000005192 partition Methods 0.000 description 2
- 239000003961 penetration enhancing agent Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 235000011007 phosphoric acid Nutrition 0.000 description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920001987 poloxamine Polymers 0.000 description 2
- 239000002861 polymer material Substances 0.000 description 2
- 229940068965 polysorbates Drugs 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical group [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- GGJRAQULURVTAJ-PDBXOOCHSA-N rac-1-alpha-linolenoylglycerol Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(=O)OCC(O)CO GGJRAQULURVTAJ-PDBXOOCHSA-N 0.000 description 2
- 208000037803 restenosis Diseases 0.000 description 2
- 235000019204 saccharin Nutrition 0.000 description 2
- 229940081974 saccharin Drugs 0.000 description 2
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 2
- ZMQAAUBTXCXRIC-UHFFFAOYSA-N safrole Chemical compound C=CCC1=CC=C2OCOC2=C1 ZMQAAUBTXCXRIC-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical group OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 2
- 229960002920 sorbitol Drugs 0.000 description 2
- 238000005563 spheronization Methods 0.000 description 2
- 229960004274 stearic acid Drugs 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 235000019408 sucralose Nutrition 0.000 description 2
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000007916 tablet composition Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 239000004408 titanium dioxide Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- VHOCUJPBKOZGJD-UHFFFAOYSA-N triacontanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC(O)=O VHOCUJPBKOZGJD-UHFFFAOYSA-N 0.000 description 2
- 150000003626 triacylglycerols Chemical class 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
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 229960004418 trolamine Drugs 0.000 description 2
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 2
- 238000005550 wet granulation Methods 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- DNISEZBAYYIQFB-PHDIDXHHSA-N (2r,3r)-2,3-diacetyloxybutanedioic acid Chemical compound CC(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(C)=O DNISEZBAYYIQFB-PHDIDXHHSA-N 0.000 description 1
- WJTCHBVEUFDSIK-NWDGAFQWSA-N (2r,5s)-1-benzyl-2,5-dimethylpiperazine Chemical compound C[C@@H]1CN[C@@H](C)CN1CC1=CC=CC=C1 WJTCHBVEUFDSIK-NWDGAFQWSA-N 0.000 description 1
- FELGMEQIXOGIFQ-CYBMUJFWSA-N (3r)-9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1h-carbazol-4-one Chemical compound CC1=NC=CN1C[C@@H]1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 FELGMEQIXOGIFQ-CYBMUJFWSA-N 0.000 description 1
- MEJYDZQQVZJMPP-ULAWRXDQSA-N (3s,3ar,6r,6ar)-3,6-dimethoxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan Chemical compound CO[C@H]1CO[C@@H]2[C@H](OC)CO[C@@H]21 MEJYDZQQVZJMPP-ULAWRXDQSA-N 0.000 description 1
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 1
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- ICLYJLBTOGPLMC-KVVVOXFISA-N (z)-octadec-9-enoate;tris(2-hydroxyethyl)azanium Chemical compound OCCN(CCO)CCO.CCCCCCCC\C=C/CCCCCCCC(O)=O ICLYJLBTOGPLMC-KVVVOXFISA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- HJTAZXHBEBIQQX-UHFFFAOYSA-N 1,5-bis(chloromethyl)naphthalene Chemical compound C1=CC=C2C(CCl)=CC=CC2=C1CCl HJTAZXHBEBIQQX-UHFFFAOYSA-N 0.000 description 1
- WDQFELCEOPFLCZ-UHFFFAOYSA-N 1-(2-hydroxyethyl)pyrrolidin-2-one Chemical compound OCCN1CCCC1=O WDQFELCEOPFLCZ-UHFFFAOYSA-N 0.000 description 1
- SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 description 1
- 102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 description 1
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 1
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 1
- MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 description 1
- GFMMXOIFOQCCGU-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide Chemical compound C=1C=C(I)C=C(Cl)C=1NC1=C(F)C(F)=CC=C1C(=O)NOCC1CC1 GFMMXOIFOQCCGU-UHFFFAOYSA-N 0.000 description 1
- CTPDSKVQLSDPLC-UHFFFAOYSA-N 2-(oxolan-2-ylmethoxy)ethanol Chemical compound OCCOCC1CCCO1 CTPDSKVQLSDPLC-UHFFFAOYSA-N 0.000 description 1
- XQLJEEBGWWDTEO-SFHVURJKSA-N 2-[(3S)-3-[4-amino-3-[4-(2,6-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enamide Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C=CC(OC=4C(=CC=CC=4F)F)=CC=3)=N2)N1C(=O)C(C(=O)N)=CC1CC1 XQLJEEBGWWDTEO-SFHVURJKSA-N 0.000 description 1
- OIQOAYVCKAHSEJ-UHFFFAOYSA-N 2-[2,3-bis(2-hydroxyethoxy)propoxy]ethanol;hexadecanoic acid;octadecanoic acid Chemical compound OCCOCC(OCCO)COCCO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O OIQOAYVCKAHSEJ-UHFFFAOYSA-N 0.000 description 1
- QQWUXSRRYFNTTC-UHFFFAOYSA-N 2-[2-(2,3-dihydroxypropoxy)-2-oxoethyl]-2-hydroxy-4-octadecoxy-4-oxobutanoic acid Chemical compound CCCCCCCCCCCCCCCCCCOC(=O)CC(O)(C(O)=O)CC(=O)OCC(O)CO QQWUXSRRYFNTTC-UHFFFAOYSA-N 0.000 description 1
- HNLXNOZHXNSSPN-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CC(C)(C)CC(C)(C)C1=CC=C(OCCOCCOCCOCCOCCOCCOCCO)C=C1 HNLXNOZHXNSSPN-UHFFFAOYSA-N 0.000 description 1
- CITHEXJVPOWHKC-UUWRZZSWSA-O 2-[[(2r)-2,3-di(tetradecanoyloxy)propoxy]-hydroxyphosphoryl]oxyethyl-trimethylazanium Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCC CITHEXJVPOWHKC-UUWRZZSWSA-O 0.000 description 1
- GGCILSXUAHLDMF-CQSZACIVSA-N 2-[[2-[(3r)-3-aminopiperidin-1-yl]-5-bromo-6-oxopyrimidin-1-yl]methyl]benzonitrile Chemical compound C1[C@H](N)CCCN1C1=NC=C(Br)C(=O)N1CC1=CC=CC=C1C#N GGCILSXUAHLDMF-CQSZACIVSA-N 0.000 description 1
- FICQFRCPSFCFBY-UHFFFAOYSA-N 2-[bis(methylsulfanyl)methylidene]propanedinitrile Chemical compound CSC(SC)=C(C#N)C#N FICQFRCPSFCFBY-UHFFFAOYSA-N 0.000 description 1
- SSRYCUAIDZWRAT-UHFFFAOYSA-N 2-cyano-3-cyclopropylprop-2-enamide Chemical compound NC(=O)C(C#N)=CC1CC1 SSRYCUAIDZWRAT-UHFFFAOYSA-N 0.000 description 1
- FZERGXZRBYBPDM-UHFFFAOYSA-N 2-cyano-3-cyclopropylprop-2-enoic acid Chemical compound OC(=O)C(C#N)=CC1CC1 FZERGXZRBYBPDM-UHFFFAOYSA-N 0.000 description 1
- HGBFVOSZYVRIHY-UHFFFAOYSA-N 2-cyanoprop-2-enamide Chemical compound NC(=O)C(=C)C#N HGBFVOSZYVRIHY-UHFFFAOYSA-N 0.000 description 1
- AVNRGMVELRMJLJ-UHFFFAOYSA-N 2-cyclopropylprop-2-enamide Chemical compound NC(=O)C(=C)C1CC1 AVNRGMVELRMJLJ-UHFFFAOYSA-N 0.000 description 1
- UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical group C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 1
- MLPZAALXVQOBFB-UHFFFAOYSA-N 2-methylpent-2-enenitrile Chemical compound CCC=C(C)C#N MLPZAALXVQOBFB-UHFFFAOYSA-N 0.000 description 1
- 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- MIDXCONKKJTLDX-UHFFFAOYSA-N 3,5-dimethylcyclopentane-1,2-dione Chemical compound CC1CC(C)C(=O)C1=O MIDXCONKKJTLDX-UHFFFAOYSA-N 0.000 description 1
- AFLPARVXOVRZRT-UHFFFAOYSA-N 3-[4-(2,5-difluorophenoxy)phenyl]-2H-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound NC1=C2C(=NC=N1)NN=C2C1=CC=C(C=C1)OC1=C(C=CC(=C1)F)F AFLPARVXOVRZRT-UHFFFAOYSA-N 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
- ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- JLAKCHGEEBPDQI-UHFFFAOYSA-N 4-(4-fluorobenzyl)piperidine Chemical compound C1=CC(F)=CC=C1CC1CCNCC1 JLAKCHGEEBPDQI-UHFFFAOYSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- WPZUTPREYAMLOQ-UHFFFAOYSA-N 5-[4-(2,3-difluorophenoxy)-2-fluorophenyl]-1H-pyrazol-4-amine Chemical compound NC1=CNN=C1C1=C(F)C=C(OC2=C(F)C(F)=CC=C2)C=C1 WPZUTPREYAMLOQ-UHFFFAOYSA-N 0.000 description 1
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
- 241000208140 Acer Species 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 102220487426 Actin-related protein 2/3 complex subunit 3_K15M_mutation Human genes 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 244000208874 Althaea officinalis Species 0.000 description 1
- 235000006576 Althaea officinalis Nutrition 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 244000144730 Amygdalus persica Species 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010002412 Angiocentric lymphomas Diseases 0.000 description 1
- 108010024976 Asparaginase Proteins 0.000 description 1
- 229920003084 Avicel® PH-102 Polymers 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000028564 B-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 208000032568 B-cell prolymphocytic leukaemia Diseases 0.000 description 1
- 235000021357 Behenic acid Nutrition 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- DPUOLQHDNGRHBS-UHFFFAOYSA-N Brassidinsaeure Natural products CCCCCCCCC=CCCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-UHFFFAOYSA-N 0.000 description 1
- 208000023611 Burkitt leukaemia Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 1
- 235000013912 Ceratonia siliqua Nutrition 0.000 description 1
- 240000008886 Ceratonia siliqua Species 0.000 description 1
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
- NPBVQXIMTZKSBA-UHFFFAOYSA-N Chavibetol Natural products COC1=CC=C(CC=C)C=C1O NPBVQXIMTZKSBA-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 239000004155 Chlorine dioxide Substances 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
- 244000241235 Citrullus lanatus Species 0.000 description 1
- 235000012828 Citrullus lanatus var citroides Nutrition 0.000 description 1
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
- 241000675108 Citrus tangerina Species 0.000 description 1
- 240000000560 Citrus x paradisi Species 0.000 description 1
- 235000016795 Cola Nutrition 0.000 description 1
- 235000011824 Cola pachycarpa Nutrition 0.000 description 1
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 244000007835 Cyamopsis tetragonoloba Species 0.000 description 1
- 229920001651 Cyanoacrylate Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Chemical group OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 1
- 206010051055 Deep vein thrombosis Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 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
- PYGXAGIECVVIOZ-UHFFFAOYSA-N Dibutyl decanedioate Chemical compound CCCCOC(=O)CCCCCCCCC(=O)OCCCC PYGXAGIECVVIOZ-UHFFFAOYSA-N 0.000 description 1
- CYQFCXCEBYINGO-DLBZAZTESA-N Dronabinol Natural products C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@H]21 CYQFCXCEBYINGO-DLBZAZTESA-N 0.000 description 1
- 229920005682 EO-PO block copolymer Polymers 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- URXZXNYJPAJJOQ-UHFFFAOYSA-N Erucic acid Natural products CCCCCCC=CCCCCCCCCCCCC(O)=O URXZXNYJPAJJOQ-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000004144 Ethoxylated Mono- and Di-Glyceride Substances 0.000 description 1
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 244000004281 Eucalyptus maculata Species 0.000 description 1
- 229920003137 Eudragit® S polymer Polymers 0.000 description 1
- 229920003134 Eudragit® polymer Polymers 0.000 description 1
- 239000005770 Eugenol Substances 0.000 description 1
- 108010029961 Filgrastim Proteins 0.000 description 1
- 229920006358 Fluon Polymers 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 240000001238 Gaultheria procumbens Species 0.000 description 1
- 235000007297 Gaultheria procumbens Nutrition 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Chemical group OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 240000004670 Glycyrrhiza echinata Species 0.000 description 1
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 description 1
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 1
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 1
- 229920003114 HPC-L Polymers 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000935548 Homo sapiens Cytoplasmic tyrosine-protein kinase BMX Proteins 0.000 description 1
- 101000801619 Homo sapiens Long-chain-fatty-acid-CoA ligase ACSBG1 Proteins 0.000 description 1
- 101000984551 Homo sapiens Tyrosine-protein kinase Blk Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
- 208000001718 Immediate Hypersensitivity Diseases 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 240000007049 Juglans regia Species 0.000 description 1
- 235000009496 Juglans regia Nutrition 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 229920003085 Kollidon® CL Polymers 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical group OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-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
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 1
- 239000005511 L01XE05 - Sorafenib Substances 0.000 description 1
- 239000002136 L01XE07 - Lapatinib Substances 0.000 description 1
- 229920006063 Lamide® Polymers 0.000 description 1
- XNRVGTHNYCNCFF-UHFFFAOYSA-N Lapatinib ditosylate monohydrate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1.O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 XNRVGTHNYCNCFF-UHFFFAOYSA-N 0.000 description 1
- 241000218652 Larix Species 0.000 description 1
- 235000005590 Larix decidua Nutrition 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102100033564 Long-chain-fatty-acid-CoA ligase ACSBG1 Human genes 0.000 description 1
- 206010052178 Lymphocytic lymphoma Diseases 0.000 description 1
- 241001082241 Lythrum hyssopifolia Species 0.000 description 1
- 201000003791 MALT lymphoma Diseases 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 235000011430 Malus pumila Nutrition 0.000 description 1
- 235000015103 Malus silvestris Nutrition 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 1
- 235000014766 Mentha X piperi var citrata Nutrition 0.000 description 1
- 235000006679 Mentha X verticillata Nutrition 0.000 description 1
- 235000007421 Mentha citrata Nutrition 0.000 description 1
- 235000002899 Mentha suaveolens Nutrition 0.000 description 1
- 235000008660 Mentha x piperita subsp citrata Nutrition 0.000 description 1
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 1
- MWCLLHOVUTZFKS-UHFFFAOYSA-N Methyl cyanoacrylate Chemical compound COC(=O)C(=C)C#N MWCLLHOVUTZFKS-UHFFFAOYSA-N 0.000 description 1
- 238000006957 Michael reaction Methods 0.000 description 1
- 240000003637 Monarda citriodora Species 0.000 description 1
- 235000002431 Monarda citriodora Nutrition 0.000 description 1
- 229920000715 Mucilage Polymers 0.000 description 1
- 102000015728 Mucins Human genes 0.000 description 1
- 108010063954 Mucins Proteins 0.000 description 1
- TXXHDPDFNKHHGW-CCAGOZQPSA-N Muconic acid Chemical group OC(=O)\C=C/C=C\C(O)=O TXXHDPDFNKHHGW-CCAGOZQPSA-N 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 240000005561 Musa balbisiana Species 0.000 description 1
- 235000018290 Musa x paradisiaca Nutrition 0.000 description 1
- 240000009023 Myrrhis odorata Species 0.000 description 1
- 235000007265 Myrrhis odorata Nutrition 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010029461 Nodal marginal zone B-cell lymphomas Diseases 0.000 description 1
- 102100022673 Nuclear receptor subfamily 4 group A member 3 Human genes 0.000 description 1
- 235000010676 Ocimum basilicum Nutrition 0.000 description 1
- 240000007926 Ocimum gratissimum Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 1
- 235000012550 Pimpinella anisum Nutrition 0.000 description 1
- 229920003072 Plasdone™ povidone Polymers 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 208000007452 Plasmacytoma Diseases 0.000 description 1
- 229920002534 Polyethylene Glycol 1450 Polymers 0.000 description 1
- 229920002556 Polyethylene Glycol 300 Polymers 0.000 description 1
- 229920002562 Polyethylene Glycol 3350 Polymers 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
- 229920002582 Polyethylene Glycol 600 Polymers 0.000 description 1
- 229920002593 Polyethylene Glycol 800 Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 241000206607 Porphyra umbilicalis Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010065857 Primary Effusion Lymphoma Diseases 0.000 description 1
- 206010036711 Primary mediastinal large B-cell lymphomas Diseases 0.000 description 1
- 208000035416 Prolymphocytic B-Cell Leukemia Diseases 0.000 description 1
- 235000010401 Prunus avium Nutrition 0.000 description 1
- 235000006040 Prunus persica var persica Nutrition 0.000 description 1
- 240000008296 Prunus serotina Species 0.000 description 1
- 235000014441 Prunus serotina Nutrition 0.000 description 1
- UVMRYBDEERADNV-UHFFFAOYSA-N Pseudoeugenol Natural products COC1=CC(C(C)=C)=CC=C1O UVMRYBDEERADNV-UHFFFAOYSA-N 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- 235000014443 Pyrus communis Nutrition 0.000 description 1
- 240000001987 Pyrus communis Species 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 240000001890 Ribes hudsonianum Species 0.000 description 1
- 235000016954 Ribes hudsonianum Nutrition 0.000 description 1
- 235000001466 Ribes nigrum Nutrition 0.000 description 1
- 240000007651 Rubus glaucus Species 0.000 description 1
- 235000011034 Rubus glaucus Nutrition 0.000 description 1
- 235000009122 Rubus idaeus Nutrition 0.000 description 1
- ZQUSFAUAYSEREK-WKILWMFISA-N SB-239063 Chemical compound COC1=NC=CC(C=2N(C=NC=2C=2C=CC(F)=CC=2)[C@@H]2CC[C@@H](O)CC2)=N1 ZQUSFAUAYSEREK-WKILWMFISA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 235000019887 Solka-Floc® Nutrition 0.000 description 1
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
- 235000015125 Sterculia urens Nutrition 0.000 description 1
- 240000001058 Sterculia urens Species 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 239000001833 Succinylated monoglyceride Substances 0.000 description 1
- CYQFCXCEBYINGO-UHFFFAOYSA-N THC Natural products C1=C(C)CCC2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3C21 CYQFCXCEBYINGO-UHFFFAOYSA-N 0.000 description 1
- 102000006463 Talin Human genes 0.000 description 1
- 108010083809 Talin Proteins 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229920002359 Tetronic® Polymers 0.000 description 1
- 235000009470 Theobroma cacao Nutrition 0.000 description 1
- 235000011941 Tilia x europaea Nutrition 0.000 description 1
- 240000006909 Tilia x europaea Species 0.000 description 1
- 206010045240 Type I hypersensitivity Diseases 0.000 description 1
- 102100023345 Tyrosine-protein kinase ITK/TSK Human genes 0.000 description 1
- 235000009499 Vanilla fragrans Nutrition 0.000 description 1
- 244000263375 Vanilla tahitensis Species 0.000 description 1
- 235000012036 Vanilla tahitensis Nutrition 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 208000016025 Waldenstroem macroglobulinemia Diseases 0.000 description 1
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
- 235000006886 Zingiber officinale Nutrition 0.000 description 1
- 244000273928 Zingiber officinale Species 0.000 description 1
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 description 1
- WRWYGOVGIGCDLE-UHFFFAOYSA-N [O]c1ccccc1F Chemical group [O]c1ccccc1F WRWYGOVGIGCDLE-UHFFFAOYSA-N 0.000 description 1
- 235000010358 acesulfame potassium Nutrition 0.000 description 1
- 229960004998 acesulfame potassium Drugs 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 229960000548 alemtuzumab Drugs 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 229920013820 alkyl cellulose Polymers 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 208000002205 allergic conjunctivitis Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229960003459 allopurinol Drugs 0.000 description 1
- OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 229960004977 anhydrous lactose Drugs 0.000 description 1
- 239000000420 anogeissus latifolia wall. gum Substances 0.000 description 1
- ACPOUJIDANTYHO-UHFFFAOYSA-N anthra[1,9-cd]pyrazol-6(2H)-one Chemical compound C1=CC(C(=O)C=2C3=CC=CC=2)=C2C3=NNC2=C1 ACPOUJIDANTYHO-UHFFFAOYSA-N 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 229940027983 antiseptic and disinfectant quaternary ammonium compound Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- GOLCXWYRSKYTSP-UHFFFAOYSA-N arsenic trioxide Inorganic materials O1[As]2O[As]1O2 GOLCXWYRSKYTSP-UHFFFAOYSA-N 0.000 description 1
- 229960002594 arsenic trioxide Drugs 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 229960003272 asparaginase Drugs 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 208000010216 atopic IgE responsiveness Diseases 0.000 description 1
- 208000024998 atopic conjunctivitis Diseases 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 1
- 235000011956 bavarian cream Nutrition 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 229940116226 behenic acid Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 235000010634 bubble gum Nutrition 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229960005069 calcium Drugs 0.000 description 1
- 229960003563 calcium carbonate Drugs 0.000 description 1
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 1
- 239000001354 calcium citrate Substances 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 235000011116 calcium hydroxide Nutrition 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 235000010957 calcium stearoyl-2-lactylate Nutrition 0.000 description 1
- UBWYRXFZPXBISJ-UHFFFAOYSA-L calcium;2-hydroxypropanoate;trihydrate Chemical compound O.O.O.[Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O UBWYRXFZPXBISJ-UHFFFAOYSA-L 0.000 description 1
- ZHZFKLKREFECML-UHFFFAOYSA-L calcium;sulfate;hydrate Chemical compound O.[Ca+2].[O-]S([O-])(=O)=O ZHZFKLKREFECML-UHFFFAOYSA-L 0.000 description 1
- 229960000846 camphor Drugs 0.000 description 1
- 229930008380 camphor Natural products 0.000 description 1
- 235000013736 caramel Nutrition 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- 229960001927 cetylpyridinium chloride Drugs 0.000 description 1
- NFCRBQADEGXVDL-UHFFFAOYSA-M cetylpyridinium chloride monohydrate Chemical compound O.[Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 NFCRBQADEGXVDL-UHFFFAOYSA-M 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 235000019398 chlorine dioxide Nutrition 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000017803 cinnamon Nutrition 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000005056 compaction Methods 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229960005061 crizotinib Drugs 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229940109275 cyclamate Drugs 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004976 cyclobutylene group Chemical group 0.000 description 1
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
- 229940097362 cyclodextrins Drugs 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
- 125000004956 cyclohexylene group Chemical group 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 125000004980 cyclopropylene group Chemical group 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 229940031954 dibutyl sebacate Drugs 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 229960003724 dimyristoylphosphatidylcholine Drugs 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- VUXNZDYAHSFXBM-UHFFFAOYSA-N docos-13-ynoic acid Chemical compound CCCCCCCCC#CCCCCCCCCCCCC(O)=O VUXNZDYAHSFXBM-UHFFFAOYSA-N 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical group CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229960004242 dronabinol Drugs 0.000 description 1
- 238000009506 drug dissolution testing Methods 0.000 description 1
- 238000007580 dry-mixing Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 229940046085 endocrine therapy drug gonadotropin releasing hormone analogues Drugs 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 1
- DPUOLQHDNGRHBS-KTKRTIGZSA-N erucic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-KTKRTIGZSA-N 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 229940031098 ethanolamine Drugs 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 235000019334 ethoxylated mono- and di- glycerides Nutrition 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 229960002217 eugenol Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 229960004177 filgrastim Drugs 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000004428 fluoroalkoxy group Chemical group 0.000 description 1
- 125000003709 fluoroalkyl group Chemical group 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 201000003444 follicular lymphoma Diseases 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- LQJBNNIYVWPHFW-QXMHVHEDSA-N gadoleic acid Chemical compound CCCCCCCCCC\C=C/CCCCCCCC(O)=O LQJBNNIYVWPHFW-QXMHVHEDSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 235000008397 ginger Nutrition 0.000 description 1
- 239000000174 gluconic acid Chemical group 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 239000004220 glutamic acid Chemical group 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 229940049654 glyceryl behenate Drugs 0.000 description 1
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical class C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- MFWNKCLOYSRHCJ-BTTYYORXSA-N granisetron Chemical compound C1=CC=C2C(C(=O)N[C@H]3C[C@H]4CCC[C@@H](C3)N4C)=NN(C)C2=C1 MFWNKCLOYSRHCJ-BTTYYORXSA-N 0.000 description 1
- 229960003727 granisetron Drugs 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 235000019314 gum ghatti Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000004474 heteroalkylene group Chemical group 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 239000010903 husk Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000008173 hydrogenated soybean oil Substances 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 1
- 229960002411 imatinib Drugs 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 208000026876 intravascular large B-cell lymphoma Diseases 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 239000002563 ionic surfactant Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- GURKHSYORGJETM-WAQYZQTGSA-N irinotecan hydrochloride (anhydrous) Chemical compound Cl.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 GURKHSYORGJETM-WAQYZQTGSA-N 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 239000000905 isomalt Substances 0.000 description 1
- 235000010439 isomalt Nutrition 0.000 description 1
- HPIGCVXMBGOWTF-UHFFFAOYSA-N isomaltol Natural products CC(=O)C=1OC=CC=1O HPIGCVXMBGOWTF-UHFFFAOYSA-N 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- BJHIKXHVCXFQLS-PQLUHFTBSA-N keto-D-tagatose Chemical compound OC[C@@H](O)[C@H](O)[C@H](O)C(=O)CO BJHIKXHVCXFQLS-PQLUHFTBSA-N 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 239000000832 lactitol Substances 0.000 description 1
- 235000010448 lactitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 description 1
- 229960003451 lactitol Drugs 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 235000019223 lemon-lime Nutrition 0.000 description 1
- 235000005772 leucine Nutrition 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 229940010454 licorice Drugs 0.000 description 1
- 239000004571 lime Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 208000006116 lymphomatoid granulomatosis Diseases 0.000 description 1
- 229940091250 magnesium supplement Drugs 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 235000001035 marshmallow Nutrition 0.000 description 1
- 239000013521 mastic Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 238000007909 melt granulation Methods 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000006261 methyl amino sulfonyl group Chemical group [H]N(C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- CPRRHERYRRXBRZ-SRVKXCTJSA-N methyl n-[(2s)-1-[[(2s)-1-hydroxy-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CO)C[C@@H]1CCNC1=O CPRRHERYRRXBRZ-SRVKXCTJSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 229940051875 mucins Drugs 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 1
- RDWBWBOPAWKJAZ-UHFFFAOYSA-N n-(ethylamino)-n-(methylamino)propan-1-amine Chemical compound CCCN(NC)NCC RDWBWBOPAWKJAZ-UHFFFAOYSA-N 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- LBWFXVZLPYTWQI-IPOVEDGCSA-N n-[2-(diethylamino)ethyl]-5-[(z)-(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-2,4-dimethyl-1h-pyrrole-3-carboxamide;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C LBWFXVZLPYTWQI-IPOVEDGCSA-N 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- ITVGXXMINPYUHD-CUVHLRMHSA-N neohesperidin dihydrochalcone Chemical compound C1=C(O)C(OC)=CC=C1CCC(=O)C(C(=C1)O)=C(O)C=C1O[C@H]1[C@H](O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 ITVGXXMINPYUHD-CUVHLRMHSA-N 0.000 description 1
- 239000000879 neohesperidine DC Substances 0.000 description 1
- 235000010434 neohesperidine DC Nutrition 0.000 description 1
- 229940080607 nexavar Drugs 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- ZVEZMVFBMOOHAT-UHFFFAOYSA-N nonane-1-thiol Chemical compound CCCCCCCCCS ZVEZMVFBMOOHAT-UHFFFAOYSA-N 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- VNLRTFSQCPNNIM-UHFFFAOYSA-N octadecyl octanoate Chemical compound CCCCCCCCCCCCCCCCCCOC(=O)CCCCCCC VNLRTFSQCPNNIM-UHFFFAOYSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical class CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 229960002446 octanoic acid Drugs 0.000 description 1
- YYZUSRORWSJGET-UHFFFAOYSA-N octanoic acid ethyl ester Natural products CCCCCCCC(=O)OCC YYZUSRORWSJGET-UHFFFAOYSA-N 0.000 description 1
- 229920004905 octoxynol-10 Polymers 0.000 description 1
- 229920004914 octoxynol-40 Polymers 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 229960002969 oleic acid Drugs 0.000 description 1
- 235000021313 oleic acid Nutrition 0.000 description 1
- 229960005343 ondansetron Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 239000002357 osmotic agent Substances 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960002131 palonosetron Drugs 0.000 description 1
- CPZBLNMUGSZIPR-NVXWUHKLSA-N palonosetron Chemical compound C1N(CC2)CCC2[C@@H]1N1C(=O)C(C=CC=C2CCC3)=C2[C@H]3C1 CPZBLNMUGSZIPR-NVXWUHKLSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Chemical group OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 229960000292 pectin Drugs 0.000 description 1
- VXVHHXPTNQANQX-UHFFFAOYSA-N pent-2-enamide Chemical compound [CH2]CC=CC(N)=O VXVHHXPTNQANQX-UHFFFAOYSA-N 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000003021 phthalic acid derivatives Chemical class 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229940113116 polyethylene glycol 1000 Drugs 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 229920000223 polyglycerol Chemical class 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
- 235000019814 powdered cellulose Nutrition 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 229910052705 radium Inorganic materials 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000009490 roller compaction Methods 0.000 description 1
- 235000021572 root beer Nutrition 0.000 description 1
- 235000013533 rum Nutrition 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- CYOHGALHFOKKQC-UHFFFAOYSA-N selumetinib Chemical compound OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1Cl CYOHGALHFOKKQC-UHFFFAOYSA-N 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 235000010378 sodium ascorbate Nutrition 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229960002668 sodium chloride Drugs 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 229940080352 sodium stearoyl lactylate Drugs 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 229960003787 sorafenib Drugs 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 206010062113 splenic marginal zone lymphoma Diseases 0.000 description 1
- 238000010922 spray-dried dispersion Methods 0.000 description 1
- 229940114926 stearate Drugs 0.000 description 1
- ABTZKZVAJTXGNN-UHFFFAOYSA-N stearyl heptanoate Chemical compound CCCCCCCCCCCCCCCCCCOC(=O)CCCCCC ABTZKZVAJTXGNN-UHFFFAOYSA-N 0.000 description 1
- 229940098758 stearyl heptanoate Drugs 0.000 description 1
- 235000019327 succinylated monoglyceride Nutrition 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229940034785 sutent Drugs 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 229940120982 tarceva Drugs 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 239000000892 thaumatin Substances 0.000 description 1
- 235000010436 thaumatin Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229960004906 thiomersal Drugs 0.000 description 1
- 125000005505 thiomorpholino group Chemical group 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 229960003087 tioguanine Drugs 0.000 description 1
- MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 229960001295 tocopherol Drugs 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
- 230000000699 topical effect Effects 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 229940055764 triaz Drugs 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- LADGBHLMCUINGV-UHFFFAOYSA-N tricaprin Chemical compound CCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCC)COC(=O)CCCCCCCCC LADGBHLMCUINGV-UHFFFAOYSA-N 0.000 description 1
- 229940117013 triethanolamine oleate Drugs 0.000 description 1
- WEAPVABOECTMGR-UHFFFAOYSA-N triethyl 2-acetyloxypropane-1,2,3-tricarboxylate Chemical compound CCOC(=O)CC(C(=O)OCC)(OC(C)=O)CC(=O)OCC WEAPVABOECTMGR-UHFFFAOYSA-N 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 229940094060 tykerb Drugs 0.000 description 1
- 229920001664 tyloxapol Polymers 0.000 description 1
- MDYZKJNTKZIUSK-UHFFFAOYSA-N tyloxapol Chemical compound O=C.C1CO1.CC(C)(C)CC(C)(C)C1=CC=C(O)C=C1 MDYZKJNTKZIUSK-UHFFFAOYSA-N 0.000 description 1
- 229960004224 tyloxapol Drugs 0.000 description 1
- 230000009959 type I hypersensitivity Effects 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 235000020234 walnut Nutrition 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- QDLHCMPXEPAAMD-QAIWCSMKSA-N wortmannin Chemical compound C1([C@]2(C)C3=C(C4=O)OC=C3C(=O)O[C@@H]2COC)=C4[C@@H]2CCC(=O)[C@@]2(C)C[C@H]1OC(C)=O QDLHCMPXEPAAMD-QAIWCSMKSA-N 0.000 description 1
- QDLHCMPXEPAAMD-UHFFFAOYSA-N wortmannin Natural products COCC1OC(=O)C2=COC(C3=O)=C2C1(C)C1=C3C2CCC(=O)C2(C)CC1OC(C)=O QDLHCMPXEPAAMD-UHFFFAOYSA-N 0.000 description 1
- 229940049068 xalkori Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
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
- A61K31/519—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
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- 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
- A61K9/4891—Coated capsules; Multilayered drug free capsule shells
-
- 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
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- 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
- A61P17/04—Antipruritics
-
- 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- 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
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- 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
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Endocrinology (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Physical Education & Sports Medicine (AREA)
- Neurosurgery (AREA)
- Urology & Nephrology (AREA)
- Gastroenterology & Hepatology (AREA)
- Transplantation (AREA)
- Reproductive Health (AREA)
- Obesity (AREA)
- Otolaryngology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Oncology (AREA)
- Emergency Medicine (AREA)
- Cardiology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261661203P | 2012-06-18 | 2012-06-18 | |
| US61/661,203 | 2012-06-18 | ||
| PCT/US2013/045266 WO2013191965A1 (en) | 2012-06-18 | 2013-06-11 | Reversible covalent pyrrolo- or pyrazolopyrimidines useful for the treatment cancer and autoimmune diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2013277582A1 AU2013277582A1 (en) | 2015-01-22 |
| AU2013277582B2 true AU2013277582B2 (en) | 2017-11-30 |
Family
ID=48692669
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2013277582A Active AU2013277582B2 (en) | 2012-06-18 | 2013-06-11 | Reversible covalent pyrrolo- or pyrazolopyrimidines useful for the treatment cancer and autoimmune diseases |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20160045503A1 (enExample) |
| EP (1) | EP2861599B1 (enExample) |
| JP (1) | JP6189945B2 (enExample) |
| KR (1) | KR102150432B1 (enExample) |
| CN (1) | CN104487441B (enExample) |
| AU (1) | AU2013277582B2 (enExample) |
| CA (1) | CA2874461C (enExample) |
| DK (1) | DK2861599T3 (enExample) |
| ES (1) | ES2776175T3 (enExample) |
| MX (1) | MX368112B (enExample) |
| WO (1) | WO2013191965A1 (enExample) |
Families Citing this family (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| PH12014500122A1 (en) | 2011-07-13 | 2014-03-24 | Pharmacyclics Inc | Inhibitors of bruton's tyrosine kinase |
| 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 |
| EA201492082A1 (ru) | 2012-06-04 | 2015-03-31 | Фармасайкликс, Инк. | Кристаллические формы ингибитора тирозинкиназы брутона |
| EP2890691B1 (en) | 2012-08-31 | 2018-04-25 | Principia Biopharma Inc. | Benzimidazole derivatives as itk inhibitors |
| PL2892900T3 (pl) | 2012-09-10 | 2018-02-28 | Principia Biopharma Inc. | Związki pyrazolopirymidonowe jako inhibitory kinazy |
| MA38183A1 (fr) | 2012-11-15 | 2017-03-31 | Pharmacyclics Inc | Composés pyrrolopyrimidines en tant qu'inhibiteurs de kinase |
| US8957080B2 (en) | 2013-04-09 | 2015-02-17 | Principia Biopharma Inc. | Tyrosine kinase inhibitors |
| 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 |
| CA2939186C (en) | 2014-02-21 | 2023-03-07 | Principia Biopharma Inc. | Salts and solid form of a btk inhibitor |
| CN106456642A (zh) | 2014-03-12 | 2017-02-22 | 诺华股份有限公司 | 含btk抑制剂与akt抑制剂的组合 |
| 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 |
| GB201410430D0 (en) | 2014-06-11 | 2014-07-23 | Redx Pharma Ltd | Compounds |
| CA2959602A1 (en) | 2014-08-01 | 2016-02-04 | Pharmacyclics Llc | Inhibitors of bruton's tyrosine kinase |
| EP3193877A4 (en) | 2014-08-07 | 2018-04-04 | Pharmacyclics LLC | Novel formulations of a bruton's tyrosine kinase inhibitor |
| US10196397B2 (en) | 2014-11-19 | 2019-02-05 | Sun Pharmaceutical Industries Limited | Process for the preparation of ibrutinib |
| US10485797B2 (en) * | 2014-12-18 | 2019-11-26 | Principia Biopharma Inc. | Treatment of pemphigus |
| WO2016105582A1 (en) * | 2014-12-24 | 2016-06-30 | Nunn Philip A | Compositions for ileo-jejunal drug delivery |
| IL252913B (en) * | 2014-12-24 | 2022-06-01 | Principia Biopharma Inc | Dose of site-specific btk inhibitor |
| IL315294A (en) | 2015-03-03 | 2024-10-01 | Pharmacyclics Llc | Pharmaceutical formulations of bruton's tyrosine kinase inhibitor |
| 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 |
| WO2016154998A1 (zh) * | 2015-04-03 | 2016-10-06 | 安润医药科技（苏州）有限公司 | 吡唑并嘧啶衍生物、制备方法、药物组合物及用途 |
| CN106146511A (zh) * | 2015-04-03 | 2016-11-23 | 安润医药科技（苏州）有限公司 | 吡唑并嘧啶衍生物、制备方法、药物组合物及用途 |
| SI3303334T1 (sl) * | 2015-06-03 | 2021-09-30 | Principia Biopharma Inc. | Zaviralci tirozin kinaz |
| MA42242A (fr) | 2015-06-24 | 2018-05-02 | Principia Biopharma Inc | Inhibiteurs de la tyrosine kinase |
| WO2017027883A1 (en) | 2015-08-13 | 2017-02-16 | San Diego State University Research Foundation | Atropisomerism for increased kinase inhibitor selectivity |
| EP4116303A1 (en) | 2015-09-16 | 2023-01-11 | Loxo Oncology, Inc. | Pyrazolopyrimidine derivatives as btk inhibitors for the treatment of cancer |
| EP3782994B1 (en) | 2015-12-16 | 2025-07-16 | Loxo Oncology, Inc. | Compounds useful as kinase inhibitors |
| WO2017172596A1 (en) | 2016-03-28 | 2017-10-05 | Incyte Corporation | Pyrrolotriazine compounds as tam inhibitors |
| 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 |
| MX390619B (es) | 2016-06-29 | 2025-03-21 | Principia Biopharma Inc | Formulaciones de liberacion modificada de 2-[3-[4-amino-3-(2-fluoro-4-fenoxi-fenil)pirazolo[3,4-d]pirimidin-1-il]piperidina-1-carbonil]-4-metil-4-[4-(oxetan-3-il)piperazin-1-il]pent-2-enenitrilo |
| 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 |
| CN110483521B (zh) * | 2018-05-14 | 2022-06-07 | 杭州和正医药有限公司 | 一种可逆共价布鲁顿酪氨酸激酶抑制剂、药物组合物及其应用 |
| KR102300092B1 (ko) * | 2018-11-05 | 2021-09-09 | 가톨릭대학교 산학협력단 | pH 민감성 탄소 나노입자, 이의 제조방법 및 이를 이용한 약물전달 |
| 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 |
| WO2020263822A1 (en) | 2019-06-25 | 2020-12-30 | San Diego State University Foundation | Selective btk irreversible inhibitors |
| WO2021029467A1 (en) * | 2019-08-14 | 2021-02-18 | Sam Chun Dang Pharm. Co., Ltd. | A solid dosage form for orally administration |
| CN110448557A (zh) * | 2019-09-05 | 2019-11-15 | 黄筱茜 | 抗凝血药达比加群酯的新药用途 |
| MX2022004427A (es) | 2019-10-14 | 2022-07-12 | Principia Biopharma Inc | Metodos para el tratamiento de la trombocitopenia inmunitaria mediante la administracion de (r)-2-[3-[4-amino-3-(2-fluoro-4-feno xi-fenil)pirazolo[3,4-d]pirimidin-1-il]piperidino-1-carbonil]-4-m etil-4-[4-(oxetan-3-il)piperazin-1-il]pent-2-enonitrilo. |
| US11583533B2 (en) | 2020-01-08 | 2023-02-21 | Principia Biopharma Inc. | Topical pharmaceutical compositions comprising 2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile |
| MX2022008875A (es) | 2020-01-20 | 2022-08-11 | Genzyme Corp | Inhibidores terapeuticos de tirosina quinasa para esclerosis multiple recidivante (emr). |
| KR20220130184A (ko) | 2020-01-22 | 2022-09-26 | 프린시피아 바이오파마, 인코퍼레이티드 | 2-[3-[4-아미노-3-(2-플루오로-4-페녹시-페닐)-1H-피라졸로[3,4-d]피리미딘-1-일]피페리딘-1-카르보닐]-4-메틸-4-[4-(옥세탄-3-일)피페라진-1-일]펜트-2-엔니트릴의 결정질 형태 |
| JP2023545414A (ja) * | 2020-10-05 | 2023-10-30 | デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド | Ｈｅｒ２の強力かつ選択的な阻害剤 |
| IL302807A (en) | 2020-11-18 | 2023-07-01 | Deciphera Pharmaceuticals Llc | Gcn2 and perk kinase inhibitors and methods of use thereof |
| CA3201936A1 (en) | 2020-12-10 | 2022-06-16 | Minhua Chen | Crystal form of tolebrutinib and preparation method thereof |
| CN116669770A (zh) * | 2020-12-23 | 2023-08-29 | 耶达研究与发展有限公司 | 甲基丙烯酰胺蛋白质结合剂及其用途 |
| KR102806844B1 (ko) * | 2022-06-03 | 2025-05-16 | 주식회사 서흥 | 장용성 경질캡슐의 제조를 위한 밴딩 용액과 이를 이용하여 제조한 장용성 경질캡슐 |
| EP4540226A1 (en) * | 2022-06-16 | 2025-04-23 | Amphista Therapeutics Ltd | Bifunctional molecules for targeted protein degradation |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012158843A2 (en) * | 2011-05-17 | 2012-11-22 | The Regents Of The University Of California | Kinase inhibitors |
| WO2012158764A1 (en) * | 2011-05-17 | 2012-11-22 | Principia Biopharma Inc. | Tyrosine kinase inhibitors |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2809918A (en) | 1955-10-17 | 1957-10-15 | Victor M Hermelin | Sustained release pharmaceutical preparations |
| DE2010416B2 (de) | 1970-03-05 | 1979-03-29 | Hoechst Ag, 6000 Frankfurt | Oral anwendbare Arzneiform mit Retardwirkung |
| US4728512A (en) | 1985-05-06 | 1988-03-01 | American Home Products Corporation | Formulations providing three distinct releases |
| US4794001A (en) | 1986-03-04 | 1988-12-27 | American Home Products Corporation | Formulations providing three distinct releases |
| US20060045822A1 (en) | 2004-09-01 | 2006-03-02 | Board Of Regents, The University Of Texas System | Plasma polymerization for encapsulating particles |
| EP2526934B1 (en) * | 2006-09-22 | 2015-12-09 | Pharmacyclics LLC | Inhibitors of bruton's tyrosine kinase |
| MX2012005678A (es) | 2009-11-16 | 2012-09-07 | Univ California | Enhibidores de cinasas. |
-
2013
- 2013-06-11 US US14/403,744 patent/US20160045503A1/en not_active Abandoned
- 2013-06-11 CN CN201380031739.2A patent/CN104487441B/zh active Active
- 2013-06-11 EP EP13731218.7A patent/EP2861599B1/en active Active
- 2013-06-11 ES ES13731218T patent/ES2776175T3/es active Active
- 2013-06-11 WO PCT/US2013/045266 patent/WO2013191965A1/en not_active Ceased
- 2013-06-11 KR KR1020157000923A patent/KR102150432B1/ko active Active
- 2013-06-11 AU AU2013277582A patent/AU2013277582B2/en active Active
- 2013-06-11 DK DK13731218.7T patent/DK2861599T3/da active
- 2013-06-11 JP JP2015517370A patent/JP6189945B2/ja active Active
- 2013-06-11 CA CA2874461A patent/CA2874461C/en active Active
- 2013-06-11 MX MX2014015346A patent/MX368112B/es active IP Right Grant
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012158843A2 (en) * | 2011-05-17 | 2012-11-22 | The Regents Of The University Of California | Kinase inhibitors |
| WO2012158764A1 (en) * | 2011-05-17 | 2012-11-22 | Principia Biopharma Inc. | Tyrosine kinase inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| US20160045503A1 (en) | 2016-02-18 |
| EP2861599A1 (en) | 2015-04-22 |
| JP6189945B2 (ja) | 2017-08-30 |
| ES2776175T3 (es) | 2020-08-14 |
| JP2015519401A (ja) | 2015-07-09 |
| AU2013277582A1 (en) | 2015-01-22 |
| CA2874461A1 (en) | 2013-12-27 |
| MX368112B (es) | 2019-09-18 |
| WO2013191965A1 (en) | 2013-12-27 |
| CN104487441A (zh) | 2015-04-01 |
| MX2014015346A (es) | 2015-03-05 |
| HK1209103A1 (en) | 2016-03-24 |
| CA2874461C (en) | 2021-10-12 |
| KR102150432B1 (ko) | 2020-09-01 |
| CN104487441B (zh) | 2018-06-01 |
| EP2861599B1 (en) | 2019-12-18 |
| DK2861599T3 (da) | 2020-03-02 |
| KR20150023752A (ko) | 2015-03-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2013277582B2 (en) | Reversible covalent pyrrolo- or pyrazolopyrimidines useful for the treatment cancer and autoimmune diseases | |
| US11155544B2 (en) | Heterocycle comprising tyrosine kinase inhibitors | |
| JP6985433B2 (ja) | チロシンキナーゼ阻害剤 | |
| US9090621B2 (en) | Tyrosine kinase inhibitors | |
| HK40086068A (en) | Tyrosine kinase inhibitors | |
| BR122021003286B1 (pt) | Compostos inibidores de tirosina quinase, seus usos e composição farmacêutica | |
| BR112017025850B1 (pt) | Compostos inibidores de tirosina quinase, seus usos e composição farmacêutica | |
| HK1209103B (en) | Reversible covalent pyrrolo- or pyrazolopyrimidines useful for the treatment cancer and autoimmune diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) |