DK2536730T3 - Pyrrolopyrimidinforbindelser as CDK4 / 6 inhibitors - Google Patents

Info

Publication number

DK2536730T3

DK2536730T3 DK11707115.9T DK11707115T DK2536730T3 DK 2536730 T3 DK2536730 T3 DK 2536730T3 DK 11707115 T DK11707115 T DK 11707115T DK 2536730 T3 DK2536730 T3 DK 2536730T3

Authority

DK

Denmark

Prior art keywords

pyrrolo

ylamino

pyrimidine

pyridin

cyclopentyl

Prior art date

2010-02-19

Links

• Espacenet
• Global Dossier
• Discuss

• 229940124297 CDK 4/6 inhibitor Drugs 0.000 title description 3
• 150000001875 compounds Chemical class 0.000 claims description 180
• 229910052739 hydrogen Inorganic materials 0.000 claims description 119
• 150000003839 salts Chemical class 0.000 claims description 80
• -1 5- (2,6-diazaspiro [3.3] heptane-2-carbonyl) pyridin-2-ylamino Chemical group 0.000 claims description 73
• 206010028980 Neoplasm Diseases 0.000 claims description 46
• 210000004027 cell Anatomy 0.000 claims description 40
• 229910052805 deuterium Inorganic materials 0.000 claims description 32
• 239000003814 drug Substances 0.000 claims description 32
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 30
• 125000001424 substituent group Chemical group 0.000 claims description 30
• 125000000217 alkyl group Chemical group 0.000 claims description 23
• 239000008194 pharmaceutical composition Substances 0.000 claims description 23
• 201000011510 cancer Diseases 0.000 claims description 22
• 239000001257 hydrogen Substances 0.000 claims description 20
• 229940124597 therapeutic agent Drugs 0.000 claims description 17
• 229910052757 nitrogen Inorganic materials 0.000 claims description 16
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
• FJWYXWJQDPCIEZ-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4)C3)N=C2N1C1CCCC1 FJWYXWJQDPCIEZ-UHFFFAOYSA-N 0.000 claims description 14
• 201000001441 melanoma Diseases 0.000 claims description 12
• 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 11
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 10
• 206010006187 Breast cancer Diseases 0.000 claims description 9
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 9
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
• PXFIUPLVBBAUKD-WMZOPIPTSA-N 2-[[5-[(3as,7ar)-6-oxo-2,3,3a,4,7,7a-hexahydro-1h-pyrrolo[3,4-c]pyridin-5-yl]pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(C[C@H]4CNC[C@H]4C3)=O)N=C2N1C1CCCC1 PXFIUPLVBBAUKD-WMZOPIPTSA-N 0.000 claims description 8
• PBGMYLLXSOFMTR-MSOLQXFVSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-[(1r,6s)-3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@]1(CC[C@@](C2)(N1)[H])[H])C(=O)N2C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 PBGMYLLXSOFMTR-MSOLQXFVSA-N 0.000 claims description 8
• 208000026310 Breast neoplasm Diseases 0.000 claims description 8
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 8
• 201000002528 pancreatic cancer Diseases 0.000 claims description 8
• 208000008443 pancreatic carcinoma Diseases 0.000 claims description 8
• WBCAOAIDJLJRCZ-UHFFFAOYSA-N 7-(3-tert-butylphenyl)-2-[[5-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4)C3)N=C2N1C1=CC=CC(C(C)(C)C)=C1 WBCAOAIDJLJRCZ-UHFFFAOYSA-N 0.000 claims description 7
• GAAOQIXOPLWYKD-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(2-oxo-1-oxa-3,9-diazaspiro[4.5]decan-3-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C(O1)=O)CC21CCCNC2 GAAOQIXOPLWYKD-UHFFFAOYSA-N 0.000 claims description 7
• PBGMYLLXSOFMTR-ZWKOTPCHSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-[(1s,6r)-3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@@]1(CC[C@](C2)(N1)[H])[H])C(=O)N2C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 PBGMYLLXSOFMTR-ZWKOTPCHSA-N 0.000 claims description 7
• 208000034578 Multiple myelomas Diseases 0.000 claims description 7
• 206010042971 T-cell lymphoma Diseases 0.000 claims description 7
• 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 claims description 7
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
• 206010024627 liposarcoma Diseases 0.000 claims description 7
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
• BXALLQBVYDONPU-ICSRJNTNSA-N 2-[[5-[(3as,7ar)-6-oxo-2,3,3a,4,7,7a-hexahydro-1h-pyrrolo[3,4-c]pyridin-5-yl]pyridin-2-yl]amino]-7-cycloheptyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(C[C@H]4CNC[C@H]4C3)=O)N=C2N1C1CCCCCC1 BXALLQBVYDONPU-ICSRJNTNSA-N 0.000 claims description 6
• SBXGKKOSDIUNGQ-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(2-oxo-1-oxa-3,9-diazaspiro[4.6]undecan-3-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C(O1)=O)CC21CCCNCC2 SBXGKKOSDIUNGQ-UHFFFAOYSA-N 0.000 claims description 6
• GAAOQIXOPLWYKD-SANMLTNESA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-[(5s)-2-oxo-1-oxa-3,9-diazaspiro[4.5]decan-3-yl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C(O1)=O)C[C@]21CCCNC2 GAAOQIXOPLWYKD-SANMLTNESA-N 0.000 claims description 6
• 206010035226 Plasma cell myeloma Diseases 0.000 claims description 6
• 210000000481 breast Anatomy 0.000 claims description 6
• WXCGPYFNDWQWHG-UHFFFAOYSA-N n,n-dimethyl-2-[[5-(3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl)pyridin-2-yl]amino]-7-phenylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(CC4CCC(N4)C3)=O)N=C2N1C1=CC=CC=C1 WXCGPYFNDWQWHG-UHFFFAOYSA-N 0.000 claims description 6
• 210000003491 skin Anatomy 0.000 claims description 6
• HBBBOMMFSYNTJJ-SJORKVTESA-N 7-cyclobutyl-n,n-dimethyl-2-[[5-[(1r,6s)-3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@]1(CC[C@@](C2)(N1)[H])[H])C(=O)N2C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCC1 HBBBOMMFSYNTJJ-SJORKVTESA-N 0.000 claims description 5
• JFBMZUGLNFOQBA-UHFFFAOYSA-N 7-cycloheptyl-2-[[5-(2,7-diazaspiro[3.5]nonane-7-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1C(=O)N(CC1)CCC21CNC2 JFBMZUGLNFOQBA-UHFFFAOYSA-N 0.000 claims description 5
• VMHOCSPSLUBLHE-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-(3,6-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4NCC(C4)C3)N=C2N1C1CCCC1 VMHOCSPSLUBLHE-UHFFFAOYSA-N 0.000 claims description 5
• FIMQVRFSGKERNW-PZJWPPBQSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-[(1s,6r)-9-methyl-3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@@]1(CC[C@](C2)(N1C)[H])[H])C(=O)N2C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 FIMQVRFSGKERNW-PZJWPPBQSA-N 0.000 claims description 5
• GAAOQIXOPLWYKD-AREMUKBSSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-[(5r)-2-oxo-1-oxa-3,9-diazaspiro[4.5]decan-3-yl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C(O1)=O)C[C@@]21CCCNC2 GAAOQIXOPLWYKD-AREMUKBSSA-N 0.000 claims description 5
• 201000009030 Carcinoma Diseases 0.000 claims description 5
• 206010025323 Lymphomas Diseases 0.000 claims description 5
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
• 150000002431 hydrogen Chemical group 0.000 claims description 5
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
• NGJPQECPPQEKSH-YLJYHZDGSA-N 2-[[5-[(3as,6ar)-2-methyl-4-oxo-3,3a,6,6a-tetrahydro-1h-pyrrolo[3,4-c]pyrrol-5-yl]pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C([C@@H]4CN(C)C[C@@H]4C3)=O)N=C2N1C1CCCC1 NGJPQECPPQEKSH-YLJYHZDGSA-N 0.000 claims description 4
• VTSDFHMWTKRCAL-UHFFFAOYSA-N 7-(4-tert-butylphenyl)-2-[[5-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4)C3)N=C2N1C1=CC=C(C(C)(C)C)C=C1 VTSDFHMWTKRCAL-UHFFFAOYSA-N 0.000 claims description 4
• SOBQJDMKGXGEQA-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)-6-methylpyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=C(C)C(C(=O)N4CC5CCC(N5)C4)=CC=3)N=C2N1C1CCCC1 SOBQJDMKGXGEQA-UHFFFAOYSA-N 0.000 claims description 4
• QUGUCRTXIGFAAB-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-(3,8-diazabicyclo[3.2.1]octane-8-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3C4CCC3CNC4)N=C2N1C1CCCC1 QUGUCRTXIGFAAB-UHFFFAOYSA-N 0.000 claims description 4
• LCQFIXPBRDGHGG-HKUYNNGSSA-N 7-cyclopentyl-2-[[5-[(1s,4s)-2,5-diazabicyclo[2.2.1]heptane-2-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@]1(NC[C@]2([H])C1)[H])N2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 LCQFIXPBRDGHGG-HKUYNNGSSA-N 0.000 claims description 4
• JMYHPWJJCGPKPL-VQTJNVASSA-N 7-cyclopentyl-2-[[5-[(1s,6r)-4,9-diazabicyclo[4.2.1]nonane-4-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@]1(CC[C@@](CC2)(N1)[H])[H])N2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 JMYHPWJJCGPKPL-VQTJNVASSA-N 0.000 claims description 4
• UHLMUTYUXRIVIZ-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(1-oxo-3,4,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-2-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(C4CCCN4CC3)=O)N=C2N1C1CCCC1 UHLMUTYUXRIVIZ-UHFFFAOYSA-N 0.000 claims description 4
• YCUZSIPULIEBBG-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(3-oxo-1,4-diazabicyclo[3.2.2]nonan-4-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(CN4CCC3CC4)=O)N=C2N1C1CCCC1 YCUZSIPULIEBBG-UHFFFAOYSA-N 0.000 claims description 4
• RGGRAERHROXLKH-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(8-methyl-3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4C)C3)N=C2N1C1CCCC1 RGGRAERHROXLKH-UHFFFAOYSA-N 0.000 claims description 4
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
• 229910052760 oxygen Inorganic materials 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• 210000001685 thyroid gland Anatomy 0.000 claims description 4
• YYUJVQQJCJMRSG-UHFFFAOYSA-N 7-[4-(2-cyanopropan-2-yl)phenyl]-2-[[5-(3,8-diazabicyclo[3.2.1]octane-8-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3C4CCC3CNC4)N=C2N1C1=CC=C(C(C)(C)C#N)C=C1 YYUJVQQJCJMRSG-UHFFFAOYSA-N 0.000 claims description 3
• QVFRZHXKIZTYEZ-UHFFFAOYSA-N 7-cycloheptyl-2-[[5-(2,5-diazabicyclo[2.2.1]heptane-2-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3C4CC(NC4)C3)N=C2N1C1CCCCCC1 QVFRZHXKIZTYEZ-UHFFFAOYSA-N 0.000 claims description 3
• MGVGOHXTHDTWHQ-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)-4-methylpyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=C(C)C=3)C(=O)N3CC4CCC(N4)C3)N=C2N1C1CCCC1 MGVGOHXTHDTWHQ-UHFFFAOYSA-N 0.000 claims description 3
• IUMNOHMCVRQIFR-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-(3,9-diazabicyclo[3.3.1]nonane-3-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCCC(N4)C3)N=C2N1C1CCCC1 IUMNOHMCVRQIFR-UHFFFAOYSA-N 0.000 claims description 3
• JMYHPWJJCGPKPL-UXHICEINSA-N 7-cyclopentyl-2-[[5-[(1r,6s)-4,9-diazabicyclo[4.2.1]nonane-4-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@@]1(CC[C@](CC2)(N1)[H])[H])N2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 JMYHPWJJCGPKPL-UXHICEINSA-N 0.000 claims description 3
• ZRGKDHUMYRDLNI-WMZOPIPTSA-N 7-cyclopentyl-2-[[5-[(1s,4s)-2,5-diazabicyclo[2.2.1]heptane-2-carbonyl]pyridin-2-yl]amino]-n-methylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@]1(NC[C@]2([H])C1)[H])N2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)NC)N2C1CCCC1 ZRGKDHUMYRDLNI-WMZOPIPTSA-N 0.000 claims description 3
• HHXHYZMMRQQXRI-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(2-oxo-1-oxa-3,8-diazaspiro[4.5]decan-3-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C(O1)=O)CC21CCNCC2 HHXHYZMMRQQXRI-UHFFFAOYSA-N 0.000 claims description 3
• UJVHIJSYEJNERA-DLBZAZTESA-N 7-cyclopentyl-n-methyl-2-[[5-[(1s,6r)-3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@@]1(CC[C@](C2)(N1)[H])[H])C(=O)N2C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)NC)N2C1CCCC1 UJVHIJSYEJNERA-DLBZAZTESA-N 0.000 claims description 3
• GVALVDSUZAFNAA-AZUAARDMSA-N 7-cyclopentyl-n-methyl-2-[[5-[(1s,6r)-9-methyl-3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@@]1(CC[C@](C2)(N1C)[H])[H])C(=O)N2C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)NC)N2C1CCCC1 GVALVDSUZAFNAA-AZUAARDMSA-N 0.000 claims description 3
• 208000003950 B-cell lymphoma Diseases 0.000 claims description 3
• 229910052736 halogen Inorganic materials 0.000 claims description 3
• 150000002367 halogens Chemical class 0.000 claims description 3
• 125000004043 oxo group Chemical group O=* 0.000 claims description 3
• 238000002560 therapeutic procedure Methods 0.000 claims description 3
• PUNCJUFFXSLLLA-VQIMIIECSA-N 2-[[5-[(3as,6ar)-4-oxo-1,2,3,3a,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C([C@@H]4CNC[C@@H]4C3)=O)N=C2N1C1CCCC1 PUNCJUFFXSLLLA-VQIMIIECSA-N 0.000 claims description 2
• VMHOCSPSLUBLHE-LPHOPBHVSA-N 7-cyclopentyl-2-[[5-[(1s,5s)-3,6-diazabicyclo[3.2.1]octane-3-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@@]1([H])NC[C@](C1)(C1)[H])N1C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 VMHOCSPSLUBLHE-LPHOPBHVSA-N 0.000 claims description 2
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 2
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 2
• 206010003571 Astrocytoma Diseases 0.000 claims description 2
• 201000008808 Fibrosarcoma Diseases 0.000 claims description 2
• 208000032612 Glial tumor Diseases 0.000 claims description 2
• 201000010915 Glioblastoma multiforme Diseases 0.000 claims description 2
• 206010018338 Glioma Diseases 0.000 claims description 2
• 208000017604 Hodgkin disease Diseases 0.000 claims description 2
• 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 2
• 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 2
• 206010029260 Neuroblastoma Diseases 0.000 claims description 2
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 2
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 2
• 201000000582 Retinoblastoma Diseases 0.000 claims description 2
• 206010039491 Sarcoma Diseases 0.000 claims description 2
• 201000010208 Seminoma Diseases 0.000 claims description 2
• 201000006083 Xeroderma Pigmentosum Diseases 0.000 claims description 2
• 210000003169 central nervous system Anatomy 0.000 claims description 2
• 210000003679 cervix uteri Anatomy 0.000 claims description 2
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 2
• 210000001072 colon Anatomy 0.000 claims description 2
• 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 210000002615 epidermis Anatomy 0.000 claims description 2
• 201000000497 familial melanoma Diseases 0.000 claims description 2
• 210000000232 gallbladder Anatomy 0.000 claims description 2
• 208000005017 glioblastoma Diseases 0.000 claims description 2
• 210000003128 head Anatomy 0.000 claims description 2
• 210000003734 kidney Anatomy 0.000 claims description 2
• 208000032839 leukemia Diseases 0.000 claims description 2
• 210000004185 liver Anatomy 0.000 claims description 2
• 210000004072 lung Anatomy 0.000 claims description 2
• 210000003739 neck Anatomy 0.000 claims description 2
• 208000007538 neurilemmoma Diseases 0.000 claims description 2
• 210000001331 nose Anatomy 0.000 claims description 2
• 201000008968 osteosarcoma Diseases 0.000 claims description 2
• 210000001672 ovary Anatomy 0.000 claims description 2
• 210000000496 pancreas Anatomy 0.000 claims description 2
• 210000001428 peripheral nervous system Anatomy 0.000 claims description 2
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
• 125000003386 piperidinyl group Chemical group 0.000 claims description 2
• 210000002307 prostate Anatomy 0.000 claims description 2
• 206010039667 schwannoma Diseases 0.000 claims description 2
• 210000002784 stomach Anatomy 0.000 claims description 2
• 208000001608 teratocarcinoma Diseases 0.000 claims description 2
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 4
• PUNCJUFFXSLLLA-LPHOPBHVSA-N 2-[[5-[(3ar,6as)-4-oxo-1,2,3,3a,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C([C@H]4CNC[C@H]4C3)=O)N=C2N1C1CCCC1 PUNCJUFFXSLLLA-LPHOPBHVSA-N 0.000 claims 1
• FYCONNCGUQHMRE-UHFFFAOYSA-N 5h-pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C1=NC=C2CC(C(=O)N)=NC2=N1 FYCONNCGUQHMRE-UHFFFAOYSA-N 0.000 claims 1
• KSBSIXFKBIRVML-RBUKOAKNSA-N 7-cyclohexyl-n,n-dimethyl-2-[[5-[(1s,6r)-3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@@]1(CC[C@](C2)(N1)[H])[H])C(=O)N2C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCCC1 KSBSIXFKBIRVML-RBUKOAKNSA-N 0.000 claims 1
• PBGMYLLXSOFMTR-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(CC4CCC(N4)C3)=O)N=C2N1C1CCCC1 PBGMYLLXSOFMTR-UHFFFAOYSA-N 0.000 claims 1
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims 1
• 206010016935 Follicular thyroid cancer Diseases 0.000 claims 1
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 1
• 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 claims 1
• BVCRERJDOOBZOH-UHFFFAOYSA-N bicyclo[2.2.1]heptanyl Chemical group C1C[C+]2CC[C-]1C2 BVCRERJDOOBZOH-UHFFFAOYSA-N 0.000 claims 1
• 210000003238 esophagus Anatomy 0.000 claims 1
• 210000002768 hair cell Anatomy 0.000 claims 1
• 201000003445 large cell neuroendocrine carcinoma Diseases 0.000 claims 1
• HKSQZEGSMBFHGC-UHFFFAOYSA-N pyrimidine-4-carboxamide Chemical compound NC(=O)C1=CC=NC=N1 HKSQZEGSMBFHGC-UHFFFAOYSA-N 0.000 claims 1
• 201000009410 rhabdomyosarcoma Diseases 0.000 claims 1
• 208000030901 thyroid gland follicular carcinoma Diseases 0.000 claims 1
• 238000000034 method Methods 0.000 description 274
• 238000002360 preparation method Methods 0.000 description 267
• 238000005160 1H NMR spectroscopy Methods 0.000 description 194
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 163
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 134
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 130
• 239000000203 mixture Substances 0.000 description 100
• QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 description 97
• 239000007787 solid Substances 0.000 description 81
• 239000002253 acid Substances 0.000 description 77
• 230000008878 coupling Effects 0.000 description 75
• 238000010168 coupling process Methods 0.000 description 75
• 238000005859 coupling reaction Methods 0.000 description 75
• 238000010511 deprotection reaction Methods 0.000 description 75
• 239000000243 solution Substances 0.000 description 71
• 238000006243 chemical reaction Methods 0.000 description 63
• 235000019439 ethyl acetate Nutrition 0.000 description 62
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 56
• 238000010640 amide synthesis reaction Methods 0.000 description 55
• 238000005481 NMR spectroscopy Methods 0.000 description 54
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 54
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 50
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 49
• 239000011541 reaction mixture Substances 0.000 description 48
• 101000715943 Caenorhabditis elegans Cyclin-dependent kinase 4 homolog Proteins 0.000 description 45
• 238000004896 high resolution mass spectrometry Methods 0.000 description 42
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 40
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 37
• 201000010099 disease Diseases 0.000 description 34
• 239000003112 inhibitor Substances 0.000 description 33
• 238000000746 purification Methods 0.000 description 32
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 30
• KBWFQCHPVFOJEU-UHFFFAOYSA-N 6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carboxylic acid Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC1=CC=C(C(O)=O)C=N1 KBWFQCHPVFOJEU-UHFFFAOYSA-N 0.000 description 29
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 28
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 26
• 239000012267 brine Substances 0.000 description 26
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 26
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 26
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 26
• PMDDQOHZLBZUSO-UHFFFAOYSA-N 2-chloro-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(Cl)N=C2N1C1CCCC1 PMDDQOHZLBZUSO-UHFFFAOYSA-N 0.000 description 25
• 239000000543 intermediate Substances 0.000 description 25
• 239000000725 suspension Substances 0.000 description 25
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 23
• 239000012044 organic layer Substances 0.000 description 23
• 239000011664 nicotinic acid Substances 0.000 description 22
• 230000009467 reduction Effects 0.000 description 21
• 238000006722 reduction reaction Methods 0.000 description 21
• 238000010898 silica gel chromatography Methods 0.000 description 21
• 239000002904 solvent Substances 0.000 description 21
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
• 208000035475 disorder Diseases 0.000 description 20
• 230000000694 effects Effects 0.000 description 20
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 20
• ATXXLNCPVSUCNK-UHFFFAOYSA-N 5-bromo-2-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Br)C=N1 ATXXLNCPVSUCNK-UHFFFAOYSA-N 0.000 description 19
• CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 19
• 230000001404 mediated effect Effects 0.000 description 19
• 238000003756 stirring Methods 0.000 description 19
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 18
• 235000001968 nicotinic acid Nutrition 0.000 description 18
• 238000003199 nucleic acid amplification method Methods 0.000 description 18
• 239000012071 phase Substances 0.000 description 18
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 17
• 230000003321 amplification Effects 0.000 description 17
• 102100038042 Retinoblastoma-associated protein Human genes 0.000 description 16
• 239000003795 chemical substances by application Substances 0.000 description 16
• 229960003512 nicotinic acid Drugs 0.000 description 16
• 238000004809 thin layer chromatography Methods 0.000 description 16
• 102000013701 Cyclin-Dependent Kinase 4 Human genes 0.000 description 15
• 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 15
• 239000000706 filtrate Substances 0.000 description 15
• 239000000047 product Substances 0.000 description 15
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 14
• 150000001412 amines Chemical class 0.000 description 14
• OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 14
• 238000012552 review Methods 0.000 description 14
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 13
• 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 13
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
• 230000014759 maintenance of location Effects 0.000 description 13
• MKURCZPZTZGDIX-UHFFFAOYSA-N tert-butyl 3-(6-aminopyridine-3-carbonyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCC1CN2C(=O)C1=CC=C(N)N=C1 MKURCZPZTZGDIX-UHFFFAOYSA-N 0.000 description 13
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• 230000005764 inhibitory process Effects 0.000 description 12
• 239000011734 sodium Substances 0.000 description 12
• CQOIEJVFQVQPKE-UHFFFAOYSA-N 6-[[7-cycloheptyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carboxylic acid Chemical compound N1=C2N(C3CCCCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC1=CC=C(C(O)=O)C=N1 CQOIEJVFQVQPKE-UHFFFAOYSA-N 0.000 description 11
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 11
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
• 238000003556 assay Methods 0.000 description 11
• 125000004429 atom Chemical group 0.000 description 11
• 238000004587 chromatography analysis Methods 0.000 description 11
• NFNVBMMKAPKBEG-UHFFFAOYSA-N 2-chloro-7-cyclohexyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(Cl)N=C2N1C1CCCCC1 NFNVBMMKAPKBEG-UHFFFAOYSA-N 0.000 description 10
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
• 239000004480 active ingredient Substances 0.000 description 10
• 238000004440 column chromatography Methods 0.000 description 10
• 238000010348 incorporation Methods 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• 239000011369 resultant mixture Substances 0.000 description 10
• 229910052938 sodium sulfate Inorganic materials 0.000 description 10
• 235000011152 sodium sulphate Nutrition 0.000 description 10
• HNINFCBLGHCFOJ-UHFFFAOYSA-N tert-butyl 3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound C1NCC2CCC1N2C(=O)OC(C)(C)C HNINFCBLGHCFOJ-UHFFFAOYSA-N 0.000 description 10
• BLJHSWAMPJGQPT-UHFFFAOYSA-N 2-chloro-7-cycloheptyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(Cl)N=C2N1C1CCCCCC1 BLJHSWAMPJGQPT-UHFFFAOYSA-N 0.000 description 9
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 9
• 239000002552 dosage form Substances 0.000 description 9
• 238000011534 incubation Methods 0.000 description 9
• 239000010410 layer Substances 0.000 description 9
• 230000002018 overexpression Effects 0.000 description 9
• 230000007170 pathology Effects 0.000 description 9
• 238000005932 reductive alkylation reaction Methods 0.000 description 9
• 238000003786 synthesis reaction Methods 0.000 description 9
• 239000003826 tablet Substances 0.000 description 9
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
• 102000006311 Cyclin D1 Human genes 0.000 description 8
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
• 239000000872 buffer Substances 0.000 description 8
• 230000002401 inhibitory effect Effects 0.000 description 8
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
• 229960000649 oxyphenbutazone Drugs 0.000 description 8
• 230000026731 phosphorylation Effects 0.000 description 8
• 238000006366 phosphorylation reaction Methods 0.000 description 8
• 239000002244 precipitate Substances 0.000 description 8
• 108090000623 proteins and genes Proteins 0.000 description 8
• 230000002829 reductive effect Effects 0.000 description 8
• 238000000926 separation method Methods 0.000 description 8
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
• 102000016736 Cyclin Human genes 0.000 description 7
• 108050006400 Cyclin Proteins 0.000 description 7
• 108010058546 Cyclin D1 Proteins 0.000 description 7
• 108010025468 Cyclin-Dependent Kinase 6 Proteins 0.000 description 7
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
• 230000015572 biosynthetic process Effects 0.000 description 7
• 125000004432 carbon atom Chemical group C* 0.000 description 7
• 238000012512 characterization method Methods 0.000 description 7
• 239000012043 crude product Substances 0.000 description 7
• 238000001914 filtration Methods 0.000 description 7
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
• 239000000463 material Substances 0.000 description 7
• 239000003921 oil Substances 0.000 description 7
• 235000019198 oils Nutrition 0.000 description 7
• 230000037361 pathway Effects 0.000 description 7
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
• 239000007858 starting material Substances 0.000 description 7
• WHBATQQKHRALJP-NSBMVTJDSA-N tert-butyl 3-[6-[[7-[(1s,3r,4r)-3-bicyclo[2.2.1]heptanyl]-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound C1C(N2C(=O)OC(C)(C)C)CCC2CN1C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C2C=C(C(=O)N(C)C)N1[C@H](C1)[C@]2([H])CC[C@@]1([H])C2 WHBATQQKHRALJP-NSBMVTJDSA-N 0.000 description 7
• RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 7
• 230000005945 translocation Effects 0.000 description 7
• JHEJQKUXSYTVIK-UHFFFAOYSA-N 7-cyclopentyl-2-[[6-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridazin-3-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=NC(=CC=3)C(=O)N3CC4CCC(N4)C3)N=C2N1C1CCCC1 JHEJQKUXSYTVIK-UHFFFAOYSA-N 0.000 description 6
• 102100032857 Cyclin-dependent kinase 1 Human genes 0.000 description 6
• 101710106279 Cyclin-dependent kinase 1 Proteins 0.000 description 6
• 102100026804 Cyclin-dependent kinase 6 Human genes 0.000 description 6
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 6
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 6
• 239000007864 aqueous solution Substances 0.000 description 6
• 239000012298 atmosphere Substances 0.000 description 6
• 229910052799 carbon Inorganic materials 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 238000001816 cooling Methods 0.000 description 6
• 229940079593 drug Drugs 0.000 description 6
• 201000004101 esophageal cancer Diseases 0.000 description 6
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 6
• MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 6
• 230000035772 mutation Effects 0.000 description 6
• 239000002953 phosphate buffered saline Substances 0.000 description 6
• 239000000843 powder Substances 0.000 description 6
• VZYLYBFAMLPQPL-UHFFFAOYSA-N tert-butyl 4-(6-aminopyridin-3-yl)-3-oxo-4,9-diazabicyclo[4.2.1]nonane-9-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCC1CC(=O)N2C1=CC=C(N)N=C1 VZYLYBFAMLPQPL-UHFFFAOYSA-N 0.000 description 6
• 239000003039 volatile agent Substances 0.000 description 6
• CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 6
• LQPPBDSKWIFZOF-UHFFFAOYSA-N 2-(6-aminopyridin-3-yl)-4,6,7,8,9,9a-hexahydro-3h-pyrido[1,2-a]pyrazin-1-one Chemical compound C1=NC(N)=CC=C1N1C(=O)C2CCCCN2CC1 LQPPBDSKWIFZOF-UHFFFAOYSA-N 0.000 description 5
• ZSEKPRGGCJNABQ-UHFFFAOYSA-N 2-amino-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(N)N=C2N1C1CCCC1 ZSEKPRGGCJNABQ-UHFFFAOYSA-N 0.000 description 5
• HJALFAPIHMNNHZ-UHFFFAOYSA-N 2-chloro-n,n-dimethyl-7-(oxan-3-yl)pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(Cl)N=C2N1C1CCCOC1 HJALFAPIHMNNHZ-UHFFFAOYSA-N 0.000 description 5
• KDYZIBQFKOKQRM-MEKIYTOJSA-N 7-cycloheptyl-2-[[5-[(1r,4r,7r)-7-hydroxy-3-azabicyclo[2.2.1]heptane-3-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1([C@]2([H])CC[C@@]([C@H]2O)(C1)[H])C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCCCC1 KDYZIBQFKOKQRM-MEKIYTOJSA-N 0.000 description 5
• GYRXBFNBHPDFOA-KEVCNVLYSA-N 7-cycloheptyl-2-[[5-[(1r,5s)-9-hydroxy-3,7-diazabicyclo[3.3.1]nonane-3-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@]1(CNC[C@@](C2)(C1O)[H])[H])N2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCCCC1 GYRXBFNBHPDFOA-KEVCNVLYSA-N 0.000 description 5
• HYLVNBXAOJUSTK-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-(2,6-diazaspiro[3.3]heptane-2-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1C(=O)N(C1)CC21CNC2 HYLVNBXAOJUSTK-UHFFFAOYSA-N 0.000 description 5
• JMYHPWJJCGPKPL-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-(4,9-diazabicyclo[4.2.1]nonane-4-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4)CC3)N=C2N1C1CCCC1 JMYHPWJJCGPKPL-UHFFFAOYSA-N 0.000 description 5
• 102100024458 Cyclin-dependent kinase inhibitor 2A Human genes 0.000 description 5
• 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 5
• 108091000080 Phosphotransferase Proteins 0.000 description 5
• 230000003213 activating effect Effects 0.000 description 5
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 5
• 239000003153 chemical reaction reagent Substances 0.000 description 5
• 238000001514 detection method Methods 0.000 description 5
• 238000011161 development Methods 0.000 description 5
• 230000018109 developmental process Effects 0.000 description 5
• 230000004077 genetic alteration Effects 0.000 description 5
• 230000002779 inactivation Effects 0.000 description 5
• 230000001965 increasing effect Effects 0.000 description 5
• 235000019341 magnesium sulphate Nutrition 0.000 description 5
• JACPDLJUQLKABC-UHFFFAOYSA-N methyl 6-aminopyridine-3-carboxylate Chemical compound COC(=O)C1=CC=C(N)N=C1 JACPDLJUQLKABC-UHFFFAOYSA-N 0.000 description 5
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 5
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 5
• 102000020233 phosphotransferase Human genes 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• 102000004169 proteins and genes Human genes 0.000 description 5
• 229920006395 saturated elastomer Polymers 0.000 description 5
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 5
• 239000000126 substance Substances 0.000 description 5
• IOGXIKSQPQGQJJ-UHFFFAOYSA-N tert-butyl 3-(6-aminopyridazine-3-carbonyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCC1CN2C(=O)C1=CC=C(N)N=N1 IOGXIKSQPQGQJJ-UHFFFAOYSA-N 0.000 description 5
• SHYDBHUNMBIOAI-UHFFFAOYSA-N tert-butyl 3-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridazine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=NC(=CC=3)C(=O)N3CC4CCC(N4C(=O)OC(C)(C)C)C3)N=C2N1C1CCCC1 SHYDBHUNMBIOAI-UHFFFAOYSA-N 0.000 description 5
• FPIVTVPLBXUJRR-UHFFFAOYSA-N 2-(6-aminopyridin-3-yl)-3,4,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-1-one Chemical compound C1=NC(N)=CC=C1N1C(=O)C2CCCN2CC1 FPIVTVPLBXUJRR-UHFFFAOYSA-N 0.000 description 4
• LYVPWDUVRNOERF-UHFFFAOYSA-N 2-(6-nitropyridin-3-yl)-3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazine Chemical compound C1=NC([N+](=O)[O-])=CC=C1N1CC2CCCN2CC1 LYVPWDUVRNOERF-UHFFFAOYSA-N 0.000 description 4
• GOBAXMJYGDOAFA-UHFFFAOYSA-N 2-[[5-(2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[3,4-c]pyrrole-5-carbonyl)pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CNCC4C3)N=C2N1C1CCCC1 GOBAXMJYGDOAFA-UHFFFAOYSA-N 0.000 description 4
• BRHFAHGYEGQNOI-UHFFFAOYSA-N 2-[[5-(3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazin-2-yl)pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3CC4CCCN4CC3)N=C2N1C1CCCC1 BRHFAHGYEGQNOI-UHFFFAOYSA-N 0.000 description 4
• ABAXEAIRGMFJEO-UHFFFAOYSA-N 2-[[5-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]-n,n-dimethyl-7-(oxan-3-yl)pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4)C3)N=C2N1C1CCCOC1 ABAXEAIRGMFJEO-UHFFFAOYSA-N 0.000 description 4
• OPVSAEYAWVWOLS-KXTRFFEISA-N 2-[[5-[8-[(2r)-2-amino-4-methylsulfanylbutanoyl]-3,8-diazabicyclo[3.2.1]octane-3-carbonyl]pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CSCC[C@@H](N)C(=O)N1C(C2)CCC1CN2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 OPVSAEYAWVWOLS-KXTRFFEISA-N 0.000 description 4
• SQNHUZOPPRVLDH-UHFFFAOYSA-N 3-[2-chloro-4-(cycloheptylamino)pyrimidin-5-yl]prop-2-yn-1-ol Chemical compound OCC#CC1=CN=C(Cl)N=C1NC1CCCCCC1 SQNHUZOPPRVLDH-UHFFFAOYSA-N 0.000 description 4
• SPWTXMHCNCTDOK-UHFFFAOYSA-N 4-(6-aminopyridin-3-yl)-1,4-diazabicyclo[3.2.2]nonan-3-one Chemical compound C1=NC(N)=CC=C1N1C(=O)CN2CCC1CC2 SPWTXMHCNCTDOK-UHFFFAOYSA-N 0.000 description 4
• BPNSZQIMYKUVMU-CMXYPTAGSA-N 7-[(1r,3s)-3-bicyclo[2.2.1]heptanyl]-2-[[5-[(5s)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C1C(N2)CC[C@@]2([H])CN1C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C2C=C(C(=O)N(C)C)N1[C@@H](C1)C2CC[C@]1([H])C2 BPNSZQIMYKUVMU-CMXYPTAGSA-N 0.000 description 4
• BQSBBSHVTKCVKT-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-(3,8-diazabicyclo[3.2.1]octan-3-yl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3CC4CCC(N4)C3)N=C2N1C1CCCC1 BQSBBSHVTKCVKT-UHFFFAOYSA-N 0.000 description 4
• YLGIETSDTZJGEB-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]-n-methylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CNC(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4)C3)N=C2N1C1CCCC1 YLGIETSDTZJGEB-UHFFFAOYSA-N 0.000 description 4
• MUTDVTPBZIPMQD-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-[8-(dimethylamino)-3-azabicyclo[3.2.1]octane-3-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C1C(C2)CCC1CN2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 MUTDVTPBZIPMQD-UHFFFAOYSA-N 0.000 description 4
• CPPBJYRMEXUZEP-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(8-oxa-4,10-diazabicyclo[4.3.1]decane-4-carbonyl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4COCC(N4)CC3)N=C2N1C1CCCC1 CPPBJYRMEXUZEP-UHFFFAOYSA-N 0.000 description 4
• SBXGKKOSDIUNGQ-HHHXNRCGSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-[(5r)-2-oxo-1-oxa-3,9-diazaspiro[4.6]undecan-3-yl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C(O1)=O)C[C@@]21CCCNCC2 SBXGKKOSDIUNGQ-HHHXNRCGSA-N 0.000 description 4
• SBXGKKOSDIUNGQ-MHZLTWQESA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-[(5s)-2-oxo-1-oxa-3,9-diazaspiro[4.6]undecan-3-yl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C(O1)=O)C[C@]21CCCNCC2 SBXGKKOSDIUNGQ-MHZLTWQESA-N 0.000 description 4
• 101150013553 CD40 gene Proteins 0.000 description 4
• 102100032937 CD40 ligand Human genes 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
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• 101000759376 Escherichia phage Mu Tail sheath protein Proteins 0.000 description 4
• 101000868215 Homo sapiens CD40 ligand Proteins 0.000 description 4
• NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 4
• 108700020796 Oncogene Proteins 0.000 description 4
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
• 230000018199 S phase Effects 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
• 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 4
• JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 4
• 230000004913 activation Effects 0.000 description 4
• 230000001028 anti-proliverative effect Effects 0.000 description 4
• 239000002585 base Substances 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
• 230000001413 cellular effect Effects 0.000 description 4
• 229940127089 cytotoxic agent Drugs 0.000 description 4
• 238000010790 dilution Methods 0.000 description 4
• 239000012895 dilution Substances 0.000 description 4
• 238000003821 enantio-separation Methods 0.000 description 4
• 238000005516 engineering process Methods 0.000 description 4
• 230000002255 enzymatic effect Effects 0.000 description 4
• PHBSBYLCZSNQDA-UHFFFAOYSA-N ethyl 3-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CCOC(=O)N1C(C2)CCC1CN2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 PHBSBYLCZSNQDA-UHFFFAOYSA-N 0.000 description 4
• 230000014509 gene expression Effects 0.000 description 4
• 150000002430 hydrocarbons Chemical group 0.000 description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 4
• 238000000338 in vitro Methods 0.000 description 4
• 238000001727 in vivo Methods 0.000 description 4
• 230000000155 isotopic effect Effects 0.000 description 4
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
• 239000002609 medium Substances 0.000 description 4
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 4
• 230000003287 optical effect Effects 0.000 description 4
• 235000011181 potassium carbonates Nutrition 0.000 description 4
• 239000003755 preservative agent Substances 0.000 description 4
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• 239000002002 slurry Substances 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• 239000012453 solvate Substances 0.000 description 4
• 239000003381 stabilizer Substances 0.000 description 4
• 238000006467 substitution reaction Methods 0.000 description 4
• 238000004808 supercritical fluid chromatography Methods 0.000 description 4
• LJAZEXDLXJQPIL-SFTDATJTSA-N tert-butyl (1s,4s)-5-[6-[[7-cyclopentyl-6-(methylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C([C@]1(N(C[C@]2([H])C1)C(=O)OC(C)(C)C)[H])N2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)NC)N2C1CCCC1 LJAZEXDLXJQPIL-SFTDATJTSA-N 0.000 description 4
• SMVSPLNEEXXVEA-WJOKGBTCSA-N tert-butyl (5r)-3-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-2-oxo-1-oxa-3,9-diazaspiro[4.5]decane-9-carboxylate Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C(O1)=O)C[C@@]21CCCN(C(=O)OC(C)(C)C)C2 SMVSPLNEEXXVEA-WJOKGBTCSA-N 0.000 description 4
• DRVSRTCIXTVMPA-JGCGQSQUSA-N tert-butyl (5r)-3-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-2-oxo-1-oxa-3,9-diazaspiro[4.6]undecane-9-carboxylate Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C(O1)=O)C[C@@]21CCCN(C(=O)OC(C)(C)C)CC2 DRVSRTCIXTVMPA-JGCGQSQUSA-N 0.000 description 4
• PSHHHKJQKVFITC-UHFFFAOYSA-N tert-butyl 2-(6-aminopyridin-3-yl)-3-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC11CC(=O)N(C=2C=NC(N)=CC=2)C1 PSHHHKJQKVFITC-UHFFFAOYSA-N 0.000 description 4
• FOXOGTVFDAPELR-UHFFFAOYSA-N tert-butyl 2-[3-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carbonyl]pyrrolidine-1-carboxylate Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1C(=O)N(C1)CC2CCC1N2C(=O)C1CCCN1C(=O)OC(C)(C)C FOXOGTVFDAPELR-UHFFFAOYSA-N 0.000 description 4
• NPGKNJHMTARXBF-UHFFFAOYSA-N tert-butyl 2-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CN(CC4C3)C(=O)OC(C)(C)C)N=C2N1C1CCCC1 NPGKNJHMTARXBF-UHFFFAOYSA-N 0.000 description 4
• JYWJGLHBWRDOQT-UHFFFAOYSA-N tert-butyl 3-(6-aminopyridin-3-yl)-2-oxo-1-oxa-3,9-diazaspiro[4.5]decane-9-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11OC(=O)N(C=2C=NC(N)=CC=2)C1 JYWJGLHBWRDOQT-UHFFFAOYSA-N 0.000 description 4
• MBKGDJKXYKTWSP-UHFFFAOYSA-N tert-butyl 3-(6-aminopyridin-3-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCC1CN2C1=CC=C(N)N=C1 MBKGDJKXYKTWSP-UHFFFAOYSA-N 0.000 description 4
• FLXREXLQKHCCLX-UHFFFAOYSA-N tert-butyl 3-[6-[[7-(4-tert-butylcyclohexyl)-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4C(=O)OC(C)(C)C)C3)N=C2N1C1CCC(C(C)(C)C)CC1 FLXREXLQKHCCLX-UHFFFAOYSA-N 0.000 description 4
• WHBATQQKHRALJP-ZIZQGDGQSA-N tert-butyl 3-[6-[[7-[(1r,3s,4s)-3-bicyclo[2.2.1]heptanyl]-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound C1C(N2C(=O)OC(C)(C)C)CCC2CN1C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C2C=C(C(=O)N(C)C)N1[C@@H](C1)[C@@]2([H])CC[C@]1([H])C2 WHBATQQKHRALJP-ZIZQGDGQSA-N 0.000 description 4
• ZBUOPRZQJQUEQC-UHFFFAOYSA-N tert-butyl 3-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4C(=O)OC(C)(C)C)C3)N=C2N1C1CCCC1 ZBUOPRZQJQUEQC-UHFFFAOYSA-N 0.000 description 4
• CRRRWZXXIKUITG-UHFFFAOYSA-N tert-butyl 3-[6-[[7-cyclopentyl-6-(methylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CNC(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4C(=O)OC(C)(C)C)C3)N=C2N1C1CCCC1 CRRRWZXXIKUITG-UHFFFAOYSA-N 0.000 description 4
• GGHIWYYHMKZSRN-UHFFFAOYSA-N tert-butyl 4-(6-nitropyridin-3-yl)-3-oxo-4,9-diazabicyclo[4.2.1]nonane-9-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCC1CC(=O)N2C1=CC=C([N+]([O-])=O)N=C1 GGHIWYYHMKZSRN-UHFFFAOYSA-N 0.000 description 4
• MSVYEFFEDVTRIZ-UHFFFAOYSA-N tert-butyl 4-[6-[[7-cyclobutyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-3-oxo-4,9-diazabicyclo[4.2.1]nonane-9-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(CC4CCC(N4C(=O)OC(C)(C)C)C3)=O)N=C2N1C1CCC1 MSVYEFFEDVTRIZ-UHFFFAOYSA-N 0.000 description 4
• AZZTYYSIMWGXSZ-UHFFFAOYSA-N tert-butyl 4-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-3-oxo-8-oxa-4,10-diazabicyclo[4.3.1]decane-10-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(CC4COCC(N4C(=O)OC(C)(C)C)C3)=O)N=C2N1C1CCCC1 AZZTYYSIMWGXSZ-UHFFFAOYSA-N 0.000 description 4
• ZCVCEBXWRPIXKX-UHFFFAOYSA-N tert-butyl 4-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]piperazine-1-carboxylate Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N1CCN(C(=O)OC(C)(C)C)CC1 ZCVCEBXWRPIXKX-UHFFFAOYSA-N 0.000 description 4
• ARLBCNLMIRASHJ-UHFFFAOYSA-N tert-butyl 4-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-8-oxa-4,10-diazabicyclo[4.3.1]decane-10-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4COCC(N4C(=O)OC(C)(C)C)CC3)N=C2N1C1CCCC1 ARLBCNLMIRASHJ-UHFFFAOYSA-N 0.000 description 4
• YZVLRNXVKXHOJF-UHFFFAOYSA-N tert-butyl 5-[2-[[7-cyclohexyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyrimidine-5-carbonyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CN=3)C(=O)N3C4CC(N(C4)C(=O)OC(C)(C)C)C3)N=C2N1C1CCCCC1 YZVLRNXVKXHOJF-UHFFFAOYSA-N 0.000 description 4
• CMZXFIOKKKFFMN-UHFFFAOYSA-N tert-butyl 7-(6-aminopyridin-3-yl)-6-oxo-1,7-diazaspiro[4.4]nonane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC11C(=O)N(C=2C=NC(N)=CC=2)CC1 CMZXFIOKKKFFMN-UHFFFAOYSA-N 0.000 description 4
• RWSQMCASCMQYKE-UHFFFAOYSA-N tert-butyl 7-(6-nitropyridin-3-yl)-6-oxo-1,7-diazaspiro[4.4]nonane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC11C(=O)N(C=2C=NC(=CC=2)[N+]([O-])=O)CC1 RWSQMCASCMQYKE-UHFFFAOYSA-N 0.000 description 4
• WLFUHAQDTLFPCV-UHFFFAOYSA-N tert-butyl 7-[6-[[7-cycloheptyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-2,7-diazaspiro[3.5]nonane-2-carboxylate Chemical compound N1=C2N(C3CCCCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1C(=O)N(CC1)CCC21CN(C(=O)OC(C)(C)C)C2 WLFUHAQDTLFPCV-UHFFFAOYSA-N 0.000 description 4
• DEYGBQWMQSSWNK-YITPRAEKSA-N tert-butyl n-[(2r)-1-[3-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](C(C)C)C(=O)N1C(C2)CCC1CN2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 DEYGBQWMQSSWNK-YITPRAEKSA-N 0.000 description 4
• 238000012360 testing method Methods 0.000 description 4
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
• 210000001519 tissue Anatomy 0.000 description 4
• 230000000699 topical effect Effects 0.000 description 4
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
• 238000001665 trituration Methods 0.000 description 4
• XKEPSNVFDIZRKX-UHFFFAOYSA-N (2-chloro-7-cycloheptylpyrrolo[2,3-d]pyrimidin-6-yl)methanol Chemical compound OCC1=CC2=CN=C(Cl)N=C2N1C1CCCCCC1 XKEPSNVFDIZRKX-UHFFFAOYSA-N 0.000 description 3
• QYIFCHNVUKGBOZ-UHFFFAOYSA-N 2-(6-nitropyridin-3-yl)-4,6,7,8,9,9a-hexahydro-3h-pyrido[1,2-a]pyrazin-1-one Chemical compound C1=NC([N+](=O)[O-])=CC=C1N1C(=O)C2CCCCN2CC1 QYIFCHNVUKGBOZ-UHFFFAOYSA-N 0.000 description 3
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
• MUAJELARGSOWPS-UHFFFAOYSA-N 2-[[5-(1-amino-3-azabicyclo[3.1.0]hexane-3-carbonyl)pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4(N)CC4C3)N=C2N1C1CCCC1 MUAJELARGSOWPS-UHFFFAOYSA-N 0.000 description 3
• JCRUSEOGJUANIE-UHFFFAOYSA-N 2-[[5-(3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazine-2-carbonyl)pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCCN4CC3)N=C2N1C1CCCC1 JCRUSEOGJUANIE-UHFFFAOYSA-N 0.000 description 3
• DAWYEQMUEUOGPC-UHFFFAOYSA-N 2-[[5-(7-benzyl-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carbonyl)pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1C(=O)N(CC(C1)O2)CC2CN1CC1=CC=CC=C1 DAWYEQMUEUOGPC-UHFFFAOYSA-N 0.000 description 3
• HUUBVFPRGOZUJY-UHFFFAOYSA-N 2-[[5-(8-acetyl-3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]-7-cycloheptyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4C(C)=O)C3)N=C2N1C1CCCCCC1 HUUBVFPRGOZUJY-UHFFFAOYSA-N 0.000 description 3
• DJBWBDGQYXKFQN-UHFFFAOYSA-N 2-[[5-(8-acetyl-3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4C(C)=O)C3)N=C2N1C1CCCC1 DJBWBDGQYXKFQN-UHFFFAOYSA-N 0.000 description 3
• IKEVOTQKDVGATP-IRLDBZIGSA-N 2-[[5-[(1r,6s)-9-acetyl-3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl]pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@]1(CC[C@@](C2)(N1C(C)=O)[H])[H])C(=O)N2C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 IKEVOTQKDVGATP-IRLDBZIGSA-N 0.000 description 3
• VLUJHZWOUOZYQQ-WIYYLYMNSA-N 2-[[5-[(3as,6ar)-4-oxo-1,2,3,3a,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]pyridin-2-yl]amino]-7-cycloheptyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C([C@@H]4CNC[C@@H]4C3)=O)N=C2N1C1CCCCCC1 VLUJHZWOUOZYQQ-WIYYLYMNSA-N 0.000 description 3
• QDMFIGBWXRJFHJ-UHFFFAOYSA-N 2-[[5-[8-(2-aminoacetyl)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl]pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4C(=O)CN)C3)N=C2N1C1CCCC1 QDMFIGBWXRJFHJ-UHFFFAOYSA-N 0.000 description 3
• LAUNQECSFQRQEV-QGPIEZSZSA-N 2-[[5-[8-[(2r)-2-amino-3-methylbutanoyl]-3,8-diazabicyclo[3.2.1]octane-3-carbonyl]pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CC(C)[C@@H](N)C(=O)N1C(C2)CCC1CN2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 LAUNQECSFQRQEV-QGPIEZSZSA-N 0.000 description 3
• PSQCBIKUVQQSOV-UHFFFAOYSA-N 2-chloro-7-[4-(2-cyanopropan-2-yl)phenyl]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(Cl)N=C2N1C1=CC=C(C(C)(C)C#N)C=C1 PSQCBIKUVQQSOV-UHFFFAOYSA-N 0.000 description 3
• IKMVALRMRGIPIJ-UHFFFAOYSA-N 5-(3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazin-2-yl)pyridin-2-amine Chemical compound C1=NC(N)=CC=C1N1CC2CCCN2CC1 IKMVALRMRGIPIJ-UHFFFAOYSA-N 0.000 description 3
• PHTLRNZYQLSKBH-UHFFFAOYSA-N 6-[[7-cyclohexyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carboxylic acid Chemical compound N1=C2N(C3CCCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC1=CC=C(C(O)=O)C=N1 PHTLRNZYQLSKBH-UHFFFAOYSA-N 0.000 description 3
• WOZPHGMYKYVQOK-XZZNXKJUSA-N 7-(4-tert-butylcyclohexyl)-2-[[5-[(1S,5S)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl]pyridin-2-yl]amino]-N,N-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@@]1(CC[C@@](C2)(N1)[H])[H])N2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCC(C(C)(C)C)CC1 WOZPHGMYKYVQOK-XZZNXKJUSA-N 0.000 description 3
• OJGXDWSQHNTLDP-UHFFFAOYSA-N 7-[4-(2-cyanopropan-2-yl)phenyl]-n,n-dimethyl-2-[[5-(3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(CC4CCC(N4)C3)=O)N=C2N1C1=CC=C(C(C)(C)C#N)C=C1 OJGXDWSQHNTLDP-UHFFFAOYSA-N 0.000 description 3
• BNXVQCFHGPTGJT-UHFFFAOYSA-N 7-cycloheptyl-2-[[5-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4)C3)N=C2N1C1CCCCCC1 BNXVQCFHGPTGJT-UHFFFAOYSA-N 0.000 description 3
• WCKGPGTXDGDKMB-UHFFFAOYSA-N 7-cycloheptyl-2-[[5-(8-hydroxy-8-methyl-3-azabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(C4(C)O)C3)N=C2N1C1CCCCCC1 WCKGPGTXDGDKMB-UHFFFAOYSA-N 0.000 description 3
• DSCMBIMDDPKUCE-UHFFFAOYSA-N 7-cycloheptyl-n,n-dimethyl-2-[[5-(3-oxo-1,4-diazabicyclo[3.2.2]nonan-4-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(CN4CCC3CC4)=O)N=C2N1C1CCCCCC1 DSCMBIMDDPKUCE-UHFFFAOYSA-N 0.000 description 3
• JHQYYYTZAIFSNA-UHFFFAOYSA-N 7-cycloheptyl-n,n-dimethyl-2-[[5-(4-oxo-3,8-diazabicyclo[3.2.1]octan-3-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(C4CCC(N4)C3)=O)N=C2N1C1CCCCCC1 JHQYYYTZAIFSNA-UHFFFAOYSA-N 0.000 description 3
• GYESOKVQMVWQTH-UHFFFAOYSA-N 7-cyclohexyl-2-[[5-(2,5-diazabicyclo[2.2.1]heptane-2-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3C4CC(NC4)C3)N=C2N1C1CCCCC1 GYESOKVQMVWQTH-UHFFFAOYSA-N 0.000 description 3
• PGOVADJXEQVJAD-UHFFFAOYSA-N 7-cyclohexyl-2-[[5-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4)C3)N=C2N1C1CCCCC1 PGOVADJXEQVJAD-UHFFFAOYSA-N 0.000 description 3
• BXXWHFGJPHSCSJ-UHFFFAOYSA-N 7-cyclohexyl-n,n-dimethyl-2-[[5-(1-oxo-3,4,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-2-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(C4CCCN4CC3)=O)N=C2N1C1CCCCC1 BXXWHFGJPHSCSJ-UHFFFAOYSA-N 0.000 description 3
• KSBSIXFKBIRVML-UHFFFAOYSA-N 7-cyclohexyl-n,n-dimethyl-2-[[5-(3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(CC4CCC(N4)C3)=O)N=C2N1C1CCCCC1 KSBSIXFKBIRVML-UHFFFAOYSA-N 0.000 description 3
• QLCJAUXNJZCIOB-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-(1,4-diazabicyclo[3.2.2]nonane-4-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3C4CCN(CC4)CC3)N=C2N1C1CCCC1 QLCJAUXNJZCIOB-UHFFFAOYSA-N 0.000 description 3
• LCQFIXPBRDGHGG-IEBWSBKVSA-N 7-cyclopentyl-2-[[5-[(1r,4r)-2,5-diazabicyclo[2.2.1]heptane-2-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@@]1(NC[C@@]2([H])C1)[H])N2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 LCQFIXPBRDGHGG-IEBWSBKVSA-N 0.000 description 3
• DGHUARQKUGEORR-HFSMHLIXSA-N 7-cyclopentyl-2-[[5-[(1s,4s,5r)-5-hydroxy-2-azabicyclo[2.2.1]heptane-2-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@]1([C@@H](C[C@]2([H])C1)O)[H])N2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 DGHUARQKUGEORR-HFSMHLIXSA-N 0.000 description 3
• DGHUARQKUGEORR-CUWPLCDZSA-N 7-cyclopentyl-2-[[5-[(1s,4s,5s)-5-hydroxy-2-azabicyclo[2.2.1]heptane-2-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@]1([C@H](C[C@]2([H])C1)O)[H])N2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 DGHUARQKUGEORR-CUWPLCDZSA-N 0.000 description 3
• GIGBBCAIXDPDLD-LIMIJEPZSA-N 7-cyclopentyl-2-[[5-[(1s,5r)-9-hydroxy-3,7-diazabicyclo[3.3.1]nonane-3-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@]1(CNC[C@@](C2)(C1O)[H])[H])N2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 GIGBBCAIXDPDLD-LIMIJEPZSA-N 0.000 description 3
• YFTHNXLMZZSIID-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-[8-(2-hydroxyethyl)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4CCO)C3)N=C2N1C1CCCC1 YFTHNXLMZZSIID-UHFFFAOYSA-N 0.000 description 3
• QGOHDQPMIZUYRB-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(3-oxa-7,9-diazabicyclo[3.3.1]nonane-7-carbonyl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4COCC(N4)C3)N=C2N1C1CCCC1 QGOHDQPMIZUYRB-UHFFFAOYSA-N 0.000 description 3
• LKIMOMLBYIKHGV-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(8-propan-2-yl-3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CC(C)N1C(C2)CCC1CN2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 LKIMOMLBYIKHGV-UHFFFAOYSA-N 0.000 description 3
• NTRHKDRQXZZCSB-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(9-methyl-2-oxo-1-oxa-3,9-diazaspiro[4.5]decan-3-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C(O1)=O)CC21CCCN(C)C2 NTRHKDRQXZZCSB-UHFFFAOYSA-N 0.000 description 3
• LBAZDXGDLBZRAG-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carbonyl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CNCC(O4)C3)N=C2N1C1CCCC1 LBAZDXGDLBZRAG-UHFFFAOYSA-N 0.000 description 3
• FIMQVRFSGKERNW-CTNGQTDRSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-[(1r,6s)-9-methyl-3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@]1(CC[C@@](C2)(N1C)[H])[H])C(=O)N2C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 FIMQVRFSGKERNW-CTNGQTDRSA-N 0.000 description 3
• CKPSHUDUTFOEGY-CTNGQTDRSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-[(1r,6s)-9-methylsulfonyl-3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@]1(CC[C@@](C2)(N1S(C)(=O)=O)[H])[H])C(=O)N2C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 CKPSHUDUTFOEGY-CTNGQTDRSA-N 0.000 description 3
• MUMDMEZSCDFPES-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-[6-(2,2,2-trifluoroethyl)-3,6-diazabicyclo[3.2.1]octane-3-carbonyl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CC(CN4CC(F)(F)F)C3)N=C2N1C1CCCC1 MUMDMEZSCDFPES-UHFFFAOYSA-N 0.000 description 3
• AZLGBASLSPFZCV-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-[8-(pyrrolidine-2-carbonyl)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1C(=O)N(C1)CC2CCC1N2C(=O)C1CCCN1 AZLGBASLSPFZCV-UHFFFAOYSA-N 0.000 description 3
• KJFCFCHNCRQNSA-UHFFFAOYSA-N 7-tert-butyl-2-[[5-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C1C(N2)CCC2CN1C(=O)C(C=N1)=CC=C1NC1=NC=C2C=C(C(=O)N(C)C)N(C(C)(C)C)C2=N1 KJFCFCHNCRQNSA-UHFFFAOYSA-N 0.000 description 3
• LSXZDFSMECALBQ-UHFFFAOYSA-N 8-methyl-3-azabicyclo[3.2.1]octan-8-ol Chemical compound C1NCC2CCC1C2(O)C LSXZDFSMECALBQ-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
• 108091007914 CDKs Proteins 0.000 description 3
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
• 102000002427 Cyclin B Human genes 0.000 description 3
• 108010068150 Cyclin B Proteins 0.000 description 3
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 3
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
• 238000002965 ELISA Methods 0.000 description 3
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
• 239000007995 HEPES buffer Substances 0.000 description 3
• 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 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
• 229920002472 Starch Polymers 0.000 description 3
• 239000006180 TBST buffer Substances 0.000 description 3
• 239000012317 TBTU Substances 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• 102000004142 Trypsin Human genes 0.000 description 3
• 108090000631 Trypsin Proteins 0.000 description 3
• CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 230000004075 alteration Effects 0.000 description 3
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
• SPVCUIHUEABWQP-HUUCEWRRSA-N benzyl (3ar,8as)-3,3a,4,5,6,7,8,8a-octahydro-2h-pyrrolo[2,3-c]azepine-1-carboxylate Chemical compound N1([C@@H]2CNCCC[C@@H]2CC1)C(=O)OCC1=CC=CC=C1 SPVCUIHUEABWQP-HUUCEWRRSA-N 0.000 description 3
• STKMRMGRDHAZIX-DHIUTWEWSA-N benzyl (3ar,8as)-7-(2-phenylethyl)-2,3,3a,4,5,6,8,8a-octahydropyrrolo[2,3-c]azepine-1-carboxylate Chemical compound N1([C@@H]2CN(CCC=3C=CC=CC=3)CCC[C@@H]2CC1)C(=O)OCC1=CC=CC=C1 STKMRMGRDHAZIX-DHIUTWEWSA-N 0.000 description 3
• VGXXXFKDUJTTOC-UHFFFAOYSA-N benzyl 7-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3-oxa-7,9-diazabicyclo[3.3.1]nonane-9-carboxylate Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1C(=O)N(C1)CC2COCC1N2C(=O)OCC1=CC=CC=C1 VGXXXFKDUJTTOC-UHFFFAOYSA-N 0.000 description 3
• BTNYOFYWGYYTFI-UHFFFAOYSA-N benzyl 8-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-3-carboxylate Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1C(=O)N1C(C2)CCC1CN2C(=O)OCC1=CC=CC=C1 BTNYOFYWGYYTFI-UHFFFAOYSA-N 0.000 description 3
• 230000000903 blocking effect Effects 0.000 description 3
• 239000011575 calcium Substances 0.000 description 3
• 229910052791 calcium Inorganic materials 0.000 description 3
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
• 238000000423 cell based assay Methods 0.000 description 3
• 239000013592 cell lysate Substances 0.000 description 3
• 230000004663 cell proliferation Effects 0.000 description 3
• 208000029742 colonic neoplasm Diseases 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 239000000839 emulsion Substances 0.000 description 3
• 239000000284 extract Substances 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 239000007903 gelatin capsule Substances 0.000 description 3
• 125000005843 halogen group Chemical group 0.000 description 3
• 238000004128 high performance liquid chromatography Methods 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
• 229940043355 kinase inhibitor Drugs 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 239000000314 lubricant Substances 0.000 description 3
• 239000011777 magnesium Substances 0.000 description 3
• 229910052749 magnesium Inorganic materials 0.000 description 3
• PKBRZAFDKREFAY-UHFFFAOYSA-N methyl 6-[[7-cyclohexyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1NC1=NC=C(C=C(C(=O)N(C)C)N2C3CCCCC3)C2=N1 PKBRZAFDKREFAY-UHFFFAOYSA-N 0.000 description 3
• LEBODWHKBJKGMM-UHFFFAOYSA-N methyl 6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1NC1=NC=C(C=C(C(=O)N(C)C)N2C3CCCC3)C2=N1 LEBODWHKBJKGMM-UHFFFAOYSA-N 0.000 description 3
• YWBICKVWQPKKHN-UHFFFAOYSA-N n,n-dimethyl-3-azabicyclo[3.2.1]octan-8-amine Chemical compound C1NCC2CCC1C2N(C)C YWBICKVWQPKKHN-UHFFFAOYSA-N 0.000 description 3
• YDHOISKQRAMMCI-UHFFFAOYSA-N n,n-dimethyl-7-(oxan-3-yl)-2-[[5-(6-oxo-1,7-diazaspiro[4.4]nonan-7-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3COCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C1=O)CCC21CCCN2 YDHOISKQRAMMCI-UHFFFAOYSA-N 0.000 description 3
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
• 239000012074 organic phase Substances 0.000 description 3
• 229920001223 polyethylene glycol Polymers 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• 108090000765 processed proteins & peptides Proteins 0.000 description 3
• 150000004944 pyrrolopyrimidines Chemical class 0.000 description 3
• 108020003175 receptors Proteins 0.000 description 3
• 102000005962 receptors Human genes 0.000 description 3
• 239000000741 silica gel Substances 0.000 description 3
• 229910002027 silica gel Inorganic materials 0.000 description 3
• 239000000377 silicon dioxide Substances 0.000 description 3
• 235000015424 sodium Nutrition 0.000 description 3
• 239000007921 spray Substances 0.000 description 3
• 235000019698 starch Nutrition 0.000 description 3
• 238000003860 storage Methods 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• IXKNPSLHUPHNQK-VXGBXAGGSA-N tert-butyl (1r,4r)-5-(6-aminopyridine-3-carbonyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C([C@@]1(N(C[C@@]2([H])C1)C(=O)OC(C)(C)C)[H])N2C(=O)C1=CC=C(N)N=C1 IXKNPSLHUPHNQK-VXGBXAGGSA-N 0.000 description 3
• VZYLYBFAMLPQPL-WCQYABFASA-N tert-butyl (1s,6r)-4-(6-aminopyridin-3-yl)-3-oxo-4,9-diazabicyclo[4.2.1]nonane-9-carboxylate Chemical compound C([C@@]1(CC[C@](C2)(N1C(=O)OC(C)(C)C)[H])[H])C(=O)N2C1=CC=C(N)N=C1 VZYLYBFAMLPQPL-WCQYABFASA-N 0.000 description 3
• YTBCHPDGWSPJOH-JTHBVZDNSA-N tert-butyl (1s,6r)-4-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-3-oxo-4,9-diazabicyclo[4.2.1]nonane-9-carboxylate Chemical compound C([C@@]1(CC[C@](C2)(N1C(=O)OC(C)(C)C)[H])[H])C(=O)N2C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 YTBCHPDGWSPJOH-JTHBVZDNSA-N 0.000 description 3
• SMVSPLNEEXXVEA-HKBQPEDESA-N tert-butyl (5s)-3-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-2-oxo-1-oxa-3,9-diazaspiro[4.5]decane-9-carboxylate Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C(O1)=O)C[C@]21CCCN(C(=O)OC(C)(C)C)C2 SMVSPLNEEXXVEA-HKBQPEDESA-N 0.000 description 3
• YRXVJTUEVWRIER-UHFFFAOYSA-N tert-butyl 1'-(6-aminopyridin-3-yl)-2'-oxospiro[8-azabicyclo[3.2.1]octane-3,4'-pyrrolidine]-8-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCC1CC2(CC1=O)CN1C1=CC=C(N)N=C1 YRXVJTUEVWRIER-UHFFFAOYSA-N 0.000 description 3
• GAFIPFHPWOEZCF-UHFFFAOYSA-N tert-butyl 2-(6-aminopyridin-3-yl)-1-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC11C(=O)N(C=2C=NC(N)=CC=2)CCC1 GAFIPFHPWOEZCF-UHFFFAOYSA-N 0.000 description 3
• QOQHXJPJXOPAQH-UHFFFAOYSA-N tert-butyl 2-(6-nitropyridin-3-yl)-1-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC11C(=O)N(C=2C=NC(=CC=2)[N+]([O-])=O)CCC1 QOQHXJPJXOPAQH-UHFFFAOYSA-N 0.000 description 3
• HSQJVHKGXUOVHD-UHFFFAOYSA-N tert-butyl 2-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-1-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylate Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C1=O)CCCC21CCN(C(=O)OC(C)(C)C)CC2 HSQJVHKGXUOVHD-UHFFFAOYSA-N 0.000 description 3
• IZLGOGRHBJIRNU-UHFFFAOYSA-N tert-butyl 3,9-diazabicyclo[3.3.1]nonane-9-carboxylate Chemical compound C1CCC2CNCC1N2C(=O)OC(C)(C)C IZLGOGRHBJIRNU-UHFFFAOYSA-N 0.000 description 3
• BAWOGNNTLNPQKC-UHFFFAOYSA-N tert-butyl 3-(6-amino-2-methylpyridine-3-carbonyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC1=NC(N)=CC=C1C(=O)N1CC(N2C(=O)OC(C)(C)C)CCC2C1 BAWOGNNTLNPQKC-UHFFFAOYSA-N 0.000 description 3
• RLFUBOGBOXTLSZ-UHFFFAOYSA-N tert-butyl 3-(6-amino-4-methylpyridine-3-carbonyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC1=CC(N)=NC=C1C(=O)N1CC(N2C(=O)OC(C)(C)C)CCC2C1 RLFUBOGBOXTLSZ-UHFFFAOYSA-N 0.000 description 3
• ITLAOIAVPZAUSP-UHFFFAOYSA-N tert-butyl 3-(6-aminopyridin-3-yl)-2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC11OC(=O)N(C=2C=NC(N)=CC=2)C1 ITLAOIAVPZAUSP-UHFFFAOYSA-N 0.000 description 3
• WOJHEUJHISCHAZ-UHFFFAOYSA-N tert-butyl 3-(6-aminopyridin-3-yl)-2-oxo-1-oxa-3,9-diazaspiro[4.6]undecane-9-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCCC11OC(=O)N(C=2C=NC(N)=CC=2)C1 WOJHEUJHISCHAZ-UHFFFAOYSA-N 0.000 description 3
• ADCPOMUTWQVQMI-UHFFFAOYSA-N tert-butyl 3-(6-aminopyridin-3-yl)-4-oxo-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCC1C(=O)N2C1=CC=C(N)N=C1 ADCPOMUTWQVQMI-UHFFFAOYSA-N 0.000 description 3
• RDVDMXBLFVLYIR-UHFFFAOYSA-N tert-butyl 3-(6-aminopyridine-3-carbonyl)-3,9-diazabicyclo[3.3.1]nonane-9-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCCC1CN2C(=O)C1=CC=C(N)N=C1 RDVDMXBLFVLYIR-UHFFFAOYSA-N 0.000 description 3
• BDIXUHNCFZLZFF-UHFFFAOYSA-N tert-butyl 3-(6-nitropyridin-3-yl)-2-oxo-1-oxa-3,9-diazaspiro[4.6]undecane-9-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCCC11OC(=O)N(C=2C=NC(=CC=2)[N+]([O-])=O)C1 BDIXUHNCFZLZFF-UHFFFAOYSA-N 0.000 description 3
• JSNNSBUDVLWJNA-UHFFFAOYSA-N tert-butyl 3-(6-nitropyridin-3-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCC1CN2C1=CC=C([N+]([O-])=O)N=C1 JSNNSBUDVLWJNA-UHFFFAOYSA-N 0.000 description 3
• QHRVCXOXWDSBKY-UHFFFAOYSA-N tert-butyl 3-(6-nitropyridin-3-yl)-4-oxo-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCC1C(=O)N2C1=CC=C([N+]([O-])=O)N=C1 QHRVCXOXWDSBKY-UHFFFAOYSA-N 0.000 description 3
• YWLHIVFNZSPILF-UHFFFAOYSA-N tert-butyl 3-[6-[[6-(dimethylcarbamoyl)-7-(oxan-3-yl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4C(=O)OC(C)(C)C)C3)N=C2N1C1CCCOC1 YWLHIVFNZSPILF-UHFFFAOYSA-N 0.000 description 3
• YRXKUGSGCZLXRN-UHFFFAOYSA-N tert-butyl 3-[6-[[7-(1-cyclopropylpiperidin-4-yl)-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4C(=O)OC(C)(C)C)C3)N=C2N1C(CC1)CCN1C1CC1 YRXKUGSGCZLXRN-UHFFFAOYSA-N 0.000 description 3
• IZOOGDVQMRBMKF-UHFFFAOYSA-N tert-butyl 3-[6-[[7-[4-(2-cyanopropan-2-yl)phenyl]-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4C(=O)OC(C)(C)C)C3)N=C2N1C1=CC=C(C(C)(C)C#N)C=C1 IZOOGDVQMRBMKF-UHFFFAOYSA-N 0.000 description 3
• YSOSTEATDSFSFU-UHFFFAOYSA-N tert-butyl 3-[6-[[7-cyclobutyl-6-(methylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CNC(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4C(=O)OC(C)(C)C)C3)N=C2N1C1CCC1 YSOSTEATDSFSFU-UHFFFAOYSA-N 0.000 description 3
• NTQVRXBWTSJKQT-UHFFFAOYSA-N tert-butyl 4-(6-nitropyridin-3-yl)-3-oxo-8-oxa-4,10-diazabicyclo[4.3.1]decane-10-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)COCC1CC(=O)N2C1=CC=C([N+]([O-])=O)N=C1 NTQVRXBWTSJKQT-UHFFFAOYSA-N 0.000 description 3
• NYHXHWWVJFOYPV-UHFFFAOYSA-N tert-butyl 4-[6-[[6-(dimethylcarbamoyl)-7-phenylpyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-3-oxo-4,9-diazabicyclo[4.2.1]nonane-9-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(CC4CCC(N4C(=O)OC(C)(C)C)C3)=O)N=C2N1C1=CC=CC=C1 NYHXHWWVJFOYPV-UHFFFAOYSA-N 0.000 description 3
• YIAAHSUQCQCEAR-UHFFFAOYSA-N tert-butyl 4-[6-[[7-[4-(2-cyanopropan-2-yl)phenyl]-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-3-oxo-4,9-diazabicyclo[4.2.1]nonane-9-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(CC4CCC(N4C(=O)OC(C)(C)C)C3)=O)N=C2N1C1=CC=C(C(C)(C)C#N)C=C1 YIAAHSUQCQCEAR-UHFFFAOYSA-N 0.000 description 3
• WXNFDCNYOSGJFA-UHFFFAOYSA-N tert-butyl 4-[6-[[7-cyclohexyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-3-oxo-4,9-diazabicyclo[4.2.1]nonane-9-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(CC4CCC(N4C(=O)OC(C)(C)C)C3)=O)N=C2N1C1CCCCC1 WXNFDCNYOSGJFA-UHFFFAOYSA-N 0.000 description 3
• PZBAINDBOCMSMM-UHFFFAOYSA-N tert-butyl 4-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-4,9-diazabicyclo[4.2.1]nonane-9-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4C(=O)OC(C)(C)C)CC3)N=C2N1C1CCCC1 PZBAINDBOCMSMM-UHFFFAOYSA-N 0.000 description 3
• YXVQFQBJUDOWAS-UHFFFAOYSA-N tert-butyl 5-[6-[[7-cycloheptyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3C4CC(N(C4)C(=O)OC(C)(C)C)C3)N=C2N1C1CCCCCC1 YXVQFQBJUDOWAS-UHFFFAOYSA-N 0.000 description 3
• JXDVMKQFPSVLBZ-UHFFFAOYSA-N tert-butyl 6-oxo-1,7-diazaspiro[4.4]nonane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC11C(=O)NCC1 JXDVMKQFPSVLBZ-UHFFFAOYSA-N 0.000 description 3
• IKAKDWFKIFQQJU-UHFFFAOYSA-N tert-butyl 7-[6-[[6-(dimethylcarbamoyl)-7-(oxan-3-yl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-6-oxo-1,7-diazaspiro[4.4]nonane-1-carboxylate Chemical compound N1=C2N(C3COCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C1=O)CCC21CCCN2C(=O)OC(C)(C)C IKAKDWFKIFQQJU-UHFFFAOYSA-N 0.000 description 3
• IZUZIVIUDTZPFE-UHFFFAOYSA-N tert-butyl decanoate Chemical compound CCCCCCCCCC(=O)OC(C)(C)C IZUZIVIUDTZPFE-UHFFFAOYSA-N 0.000 description 3
• VSXMITILSPGKNW-WZDPVOGJSA-N tert-butyl n-[(2r)-1-[3-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-4-methylsulfanyl-1-oxobutan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](CCSC)C(=O)N1C(C2)CCC1CN2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 VSXMITILSPGKNW-WZDPVOGJSA-N 0.000 description 3
• VZDRRBLDTAXSEI-UHFFFAOYSA-N tert-butyl n-[2-[3-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-oxoethyl]carbamate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4C(=O)CNC(=O)OC(C)(C)C)C3)N=C2N1C1CCCC1 VZDRRBLDTAXSEI-UHFFFAOYSA-N 0.000 description 3
• VRAAJHHBWRUEPD-UHFFFAOYSA-N tert-butyl n-[3-(6-nitropyridin-3-yl)-3-azabicyclo[3.1.0]hexan-1-yl]carbamate Chemical compound C1C2(NC(=O)OC(C)(C)C)CC2CN1C1=CC=C([N+]([O-])=O)N=C1 VRAAJHHBWRUEPD-UHFFFAOYSA-N 0.000 description 3
• FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 3
• CPTSUMQCVSZIEN-UHFFFAOYSA-N tert-butyl n-[3-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3-azabicyclo[3.1.0]hexan-1-yl]carbamate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4(CC4C3)NC(=O)OC(C)(C)C)N=C2N1C1CCCC1 CPTSUMQCVSZIEN-UHFFFAOYSA-N 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• 239000012588 trypsin Substances 0.000 description 3
• 238000010626 work up procedure Methods 0.000 description 3
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
• MNTXVNZRTFTVKM-HSUXUTPPSA-N (1r,4r,7r)-3-azabicyclo[2.2.1]heptan-7-ol Chemical compound C1C[C@@]2([H])NC[C@]1([H])[C@H]2O MNTXVNZRTFTVKM-HSUXUTPPSA-N 0.000 description 2
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 2
• 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 description 2
• 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 2
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
• BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
• AQUCDZZCANBRFO-UHFFFAOYSA-N 1-(3,8-diazabicyclo[3.2.1]octan-8-yl)ethanone Chemical compound C1NCC2CCC1N2C(=O)C AQUCDZZCANBRFO-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• KKVYYGGCHJGEFJ-UHFFFAOYSA-N 1-n-(4-chlorophenyl)-6-methyl-5-n-[3-(7h-purin-6-yl)pyridin-2-yl]isoquinoline-1,5-diamine Chemical compound N=1C=CC2=C(NC=3C(=CC=CN=3)C=3C=4N=CNC=4N=CN=3)C(C)=CC=C2C=1NC1=CC=C(Cl)C=C1 KKVYYGGCHJGEFJ-UHFFFAOYSA-N 0.000 description 2
• RTMMSCJWQYWMNK-UHFFFAOYSA-N 2,2,2-trifluoroethyl trifluoromethanesulfonate Chemical compound FC(F)(F)COS(=O)(=O)C(F)(F)F RTMMSCJWQYWMNK-UHFFFAOYSA-N 0.000 description 2
• SCTLMBLBWIVUFW-UHFFFAOYSA-N 2-(6-nitropyridin-3-yl)-3,4,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-1-one Chemical compound C1=NC([N+](=O)[O-])=CC=C1N1C(=O)C2CCCN2CC1 SCTLMBLBWIVUFW-UHFFFAOYSA-N 0.000 description 2
• REABZMYOYCYIEG-UHFFFAOYSA-N 2-(benzhydrylideneamino)-7-hexan-3-yl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C(CC)CCC)C(C(=O)N(C)C)=CC2=CN=C1N=C(C=1C=CC=CC=1)C1=CC=CC=C1 REABZMYOYCYIEG-UHFFFAOYSA-N 0.000 description 2
• OWQADRXHCRCSAM-UHFFFAOYSA-N 2-[4-[(5-bromo-2-chloropyrimidin-4-yl)amino]phenyl]-2-methylpropanenitrile Chemical compound C1=CC(C(C)(C#N)C)=CC=C1NC1=NC(Cl)=NC=C1Br OWQADRXHCRCSAM-UHFFFAOYSA-N 0.000 description 2
• HWMBWZMRKAEGHV-UHFFFAOYSA-N 2-[4-[2-chloro-6-(hydroxymethyl)pyrrolo[2,3-d]pyrimidin-7-yl]phenyl]-2-methylpropanenitrile Chemical compound C1=CC(C(C)(C#N)C)=CC=C1N1C2=NC(Cl)=NC=C2C=C1CO HWMBWZMRKAEGHV-UHFFFAOYSA-N 0.000 description 2
• DROFPQWMEFHUCZ-UHFFFAOYSA-N 2-[4-[[2-chloro-5-(3-hydroxyprop-1-ynyl)pyrimidin-4-yl]amino]phenyl]-2-methylpropanenitrile Chemical compound C1=CC(C(C)(C#N)C)=CC=C1NC1=NC(Cl)=NC=C1C#CCO DROFPQWMEFHUCZ-UHFFFAOYSA-N 0.000 description 2
• IDEHOUYXOQLYHG-UHFFFAOYSA-N 2-[[5-(1-amino-3-azabicyclo[3.1.0]hexan-3-yl)pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3CC4(N)CC4C3)N=C2N1C1CCCC1 IDEHOUYXOQLYHG-UHFFFAOYSA-N 0.000 description 2
• OZMLSQPQQQPPRJ-UHFFFAOYSA-N 2-[[5-(1-amino-3-azabicyclo[3.1.0]hexane-3-carbonyl)pyridin-2-yl]amino]-7-cyclopentylpyrrolo[2,3-d]pyrimidine-6-carboxylic acid Chemical compound NC12CN(CC2C1)C(=O)C=1C=CC(=NC=1)NC=1N=CC2=C(N=1)N(C(=C2)C(=O)O)C1CCCC1 OZMLSQPQQQPPRJ-UHFFFAOYSA-N 0.000 description 2
• MUAJELARGSOWPS-HHPDBAQJSA-N 2-[[5-[(1r)-1-amino-3-azabicyclo[3.1.0]hexane-3-carbonyl]pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3C[C@@]4(N)CC4C3)N=C2N1C1CCCC1 MUAJELARGSOWPS-HHPDBAQJSA-N 0.000 description 2
• BRQKQTKOGULFRA-GGAORHGYSA-N 2-[[5-[(1r,6s)-9-(2-acetamidoacetyl)-3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl]pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@]1(CC[C@@](C2)(N1C(=O)CNC(C)=O)[H])[H])C(=O)N2C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 BRQKQTKOGULFRA-GGAORHGYSA-N 0.000 description 2
• MUAJELARGSOWPS-DNIBEGIYSA-N 2-[[5-[(1s)-1-amino-3-azabicyclo[3.1.0]hexane-3-carbonyl]pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3C[C@]4(N)CC4C3)N=C2N1C1CCCC1 MUAJELARGSOWPS-DNIBEGIYSA-N 0.000 description 2
• BXXWHFGJPHSCSJ-OAQYLSRUSA-N 2-[[5-[(8ar)-1-oxo-3,4,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-2-yl]pyridin-2-yl]amino]-7-cyclohexyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C([C@H]4CCCN4CC3)=O)N=C2N1C1CCCCC1 BXXWHFGJPHSCSJ-OAQYLSRUSA-N 0.000 description 2
• JCRUSEOGJUANIE-OAQYLSRUSA-N 2-[[5-[(8ar)-3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazine-2-carbonyl]pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3C[C@H]4CCCN4CC3)N=C2N1C1CCCC1 JCRUSEOGJUANIE-OAQYLSRUSA-N 0.000 description 2
• HUJZYYLVDRDEEX-UHFFFAOYSA-N 2-chloro-7-cyclobutyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(Cl)N=C2N1C1CCC1 HUJZYYLVDRDEEX-UHFFFAOYSA-N 0.000 description 2
• JATZKXQRAAGTGK-UHFFFAOYSA-N 2-chloro-7-cyclopentyl-n-methylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CNC(=O)C1=CC2=CN=C(Cl)N=C2N1C1CCCC1 JATZKXQRAAGTGK-UHFFFAOYSA-N 0.000 description 2
• LXCZVGKSFJMLRO-UHFFFAOYSA-N 2-chloro-7-cyclopentylpyrrolo[2,3-d]pyrimidine-6-carboxylic acid Chemical compound OC(=O)C1=CC2=CN=C(Cl)N=C2N1C1CCCC1 LXCZVGKSFJMLRO-UHFFFAOYSA-N 0.000 description 2
• IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
• JBIHMFNMKHDTEE-UHFFFAOYSA-N 3,4,6,7,8,8a-hexahydro-2h-pyrrolo[1,2-a]pyrazin-1-one Chemical compound O=C1NCCN2CCCC12 JBIHMFNMKHDTEE-UHFFFAOYSA-N 0.000 description 2
• NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 2
• IRGRGNINMVLGBC-UHFFFAOYSA-N 3-benzyl-8-methyl-3-azabicyclo[3.2.1]octan-8-ol Chemical compound CC1(O)C(C2)CCC1CN2CC1=CC=CC=C1 IRGRGNINMVLGBC-UHFFFAOYSA-N 0.000 description 2
• WXGZUFRQPHLTJQ-UHFFFAOYSA-N 3-benzyl-n,n-dimethyl-3-azabicyclo[3.2.1]octan-8-amine Chemical compound CN(C)C1C(C2)CCC1CN2CC1=CC=CC=C1 WXGZUFRQPHLTJQ-UHFFFAOYSA-N 0.000 description 2
• WYSIBBZMXWMIGU-UHFFFAOYSA-N 4-(6-nitropyridin-3-yl)-1,4-diazabicyclo[3.2.2]nonan-3-one Chemical compound C1=NC([N+](=O)[O-])=CC=C1N1C(=O)CN2CCC1CC2 WYSIBBZMXWMIGU-UHFFFAOYSA-N 0.000 description 2
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
• TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 2
• WUMXKZAJMDXRLG-UHFFFAOYSA-N 4-oxo-3,9-diazabicyclo[4.2.1]nonane-9-carboxylic acid Chemical compound O=C1NCC2CCC(C1)N2C(=O)O WUMXKZAJMDXRLG-UHFFFAOYSA-N 0.000 description 2
• SIKXIUWKPGWBBF-UHFFFAOYSA-N 5-bromo-2,4-dichloropyrimidine Chemical compound ClC1=NC=C(Br)C(Cl)=N1 SIKXIUWKPGWBBF-UHFFFAOYSA-N 0.000 description 2
• ZCIFWRHIEBXBOY-UHFFFAOYSA-N 6-aminonicotinic acid Chemical compound NC1=CC=C(C(O)=O)C=N1 ZCIFWRHIEBXBOY-UHFFFAOYSA-N 0.000 description 2
• OTXZCRCTNZCHKJ-UHFFFAOYSA-N 6-aminopyridazine-3-carboxylic acid Chemical compound NC1=CC=C(C(O)=O)N=N1 OTXZCRCTNZCHKJ-UHFFFAOYSA-N 0.000 description 2
• OPRDAHHLGNDNTD-UHFFFAOYSA-N 7-(1-cyclopropylpiperidin-4-yl)-2-[[5-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4)C3)N=C2N1C(CC1)CCN1C1CC1 OPRDAHHLGNDNTD-UHFFFAOYSA-N 0.000 description 2
• UARIJLGMVQNUGV-UHFFFAOYSA-N 7-(1-tert-butylpiperidin-4-yl)-2-[[5-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4)C3)N=C2N1C1CCN(C(C)(C)C)CC1 UARIJLGMVQNUGV-UHFFFAOYSA-N 0.000 description 2
• STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 2
• IYNVGJVJNFJVRB-SCVCMEIPSA-N 7-[(1r,3s,4s)-3-bicyclo[2.2.1]heptanyl]-2-chloro-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(Cl)N=C2N1[C@@H](C1)[C@@]2([H])CC[C@]1([H])C2 IYNVGJVJNFJVRB-SCVCMEIPSA-N 0.000 description 2
• IHOIYKXHMJYFFS-UHFFFAOYSA-N 7-cyclobutyl-2-[[5-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4)C3)N=C2N1C1CCC1 IHOIYKXHMJYFFS-UHFFFAOYSA-N 0.000 description 2
• HBBBOMMFSYNTJJ-UHFFFAOYSA-N 7-cyclobutyl-n,n-dimethyl-2-[[5-(3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(CC4CCC(N4)C3)=O)N=C2N1C1CCC1 HBBBOMMFSYNTJJ-UHFFFAOYSA-N 0.000 description 2
• HBBBOMMFSYNTJJ-DLBZAZTESA-N 7-cyclobutyl-n,n-dimethyl-2-[[5-[(1s,6r)-3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical class C([C@@]1(CC[C@](C2)(N1)[H])[H])C(=O)N2C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCC1 HBBBOMMFSYNTJJ-DLBZAZTESA-N 0.000 description 2
• LLBZJTXVEQULEW-UHFFFAOYSA-N 7-cyclohexyl-2-[[6-(3,8-diazabicyclo[3.2.1]octan-3-yl)pyridazin-3-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=NC(=CC=3)N3CC4CCC(N4)C3)N=C2N1C1CCCCC1 LLBZJTXVEQULEW-UHFFFAOYSA-N 0.000 description 2
• SRXMHCDCBDEWCA-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-[1-(dimethylamino)-3-azabicyclo[3.1.0]hexane-3-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4(CC4C3)N(C)C)N=C2N1C1CCCC1 SRXMHCDCBDEWCA-UHFFFAOYSA-N 0.000 description 2
• OEACICXLKCZAIY-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-[8-(1-hydroxypropan-2-yl)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound OCC(C)N1C(C2)CCC1CN2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 OEACICXLKCZAIY-UHFFFAOYSA-N 0.000 description 2
• VOCUQDNMILJPDL-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(1-oxo-2,9-diazaspiro[5.5]undecan-2-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C1=O)CCCC21CCNCC2 VOCUQDNMILJPDL-UHFFFAOYSA-N 0.000 description 2
• RDCPBWXKGPRFPR-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(3-oxo-8-oxa-4,10-diazabicyclo[4.3.1]decan-4-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(CC4COCC(N4)C3)=O)N=C2N1C1CCCC1 RDCPBWXKGPRFPR-UHFFFAOYSA-N 0.000 description 2
• MTUFQVABLFTRJX-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(6-methyl-3,6-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CC(CN4C)C3)N=C2N1C1CCCC1 MTUFQVABLFTRJX-UHFFFAOYSA-N 0.000 description 2
• NWPCVRCQSLMEDM-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(6-oxo-1,7-diazaspiro[4.4]nonan-7-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C1=O)CCC21CCCN2 NWPCVRCQSLMEDM-UHFFFAOYSA-N 0.000 description 2
• PQXREXAVKNZBOV-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(8-oxa-3-azabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(O4)C3)N=C2N1C1CCCC1 PQXREXAVKNZBOV-UHFFFAOYSA-N 0.000 description 2
• ALPLOEBOODOLJY-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(9-methyl-2-oxo-1-oxa-3,9-diazaspiro[4.6]undecan-3-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C(O1)=O)CC21CCCN(C)CC2 ALPLOEBOODOLJY-UHFFFAOYSA-N 0.000 description 2
• FIMQVRFSGKERNW-WVAOCEFKSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-[(1r,6s)-3-oxo-9-(trideuteriomethyl)-4,9-diazabicyclo[4.2.1]nonan-4-yl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@H]1CC[C@@H](C2)N1C([2H])([2H])[2H])C(=O)N2C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 FIMQVRFSGKERNW-WVAOCEFKSA-N 0.000 description 2
• ZHVBXFKYWPNMKT-GGAORHGYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-[(1r,6s)-3-oxo-9-propan-2-yl-4,9-diazabicyclo[4.2.1]nonan-4-yl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@]1(CC[C@@](C2)(N1C(C)C)[H])[H])C(=O)N2C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 ZHVBXFKYWPNMKT-GGAORHGYSA-N 0.000 description 2
• HWRMTGWTJWAFOT-PZJWPPBQSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-[(1s,6r)-3-oxo-9-(2,2,2-trifluoroethyl)-4,9-diazabicyclo[4.2.1]nonan-4-yl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@@]1(CC[C@](C2)(N1CC(F)(F)F)[H])[H])C(=O)N2C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 HWRMTGWTJWAFOT-PZJWPPBQSA-N 0.000 description 2
• RGGRAERHROXLKH-HPRDVNIFSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-[8-(trideuteriomethyl)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound [2H]C([2H])([2H])N1C(C2)CCC1CN2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 RGGRAERHROXLKH-HPRDVNIFSA-N 0.000 description 2
• SXPGTBVNJDSEPQ-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[6-(3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl)pyridazin-3-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=NC(=CC=3)N3C(CC4CCC(N4)C3)=O)N=C2N1C1CCCC1 SXPGTBVNJDSEPQ-UHFFFAOYSA-N 0.000 description 2
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
• 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 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 201000001320 Atherosclerosis Diseases 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• 241000282472 Canis lupus familiaris Species 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
• 108010058545 Cyclin D3 Proteins 0.000 description 2
• 102000003903 Cyclin-dependent kinases Human genes 0.000 description 2
• 108090000266 Cyclin-dependent kinases Proteins 0.000 description 2
• 229930105110 Cyclosporin A Natural products 0.000 description 2
• 108010036949 Cyclosporine Proteins 0.000 description 2
• UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 2
• 102000004127 Cytokines Human genes 0.000 description 2
• 108090000695 Cytokines Proteins 0.000 description 2
• 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 2
• 101150029707 ERBB2 gene Proteins 0.000 description 2
• XXPXYPLPSDPERN-UHFFFAOYSA-N Ecteinascidin 743 Natural products COc1cc2C(NCCc2cc1O)C(=O)OCC3N4C(O)C5Cc6cc(C)c(OC)c(O)c6C(C4C(S)c7c(OC(=O)C)c(C)c8OCOc8c37)N5C XXPXYPLPSDPERN-UHFFFAOYSA-N 0.000 description 2
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
• 102100037859 G1/S-specific cyclin-D3 Human genes 0.000 description 2
• 101710113436 GTPase KRas Proteins 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• 206010018364 Glomerulonephritis Diseases 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 108010009202 Growth Factor Receptors Proteins 0.000 description 2
• 102000009465 Growth Factor Receptors Human genes 0.000 description 2
• 239000007821 HATU Substances 0.000 description 2
• 102000006947 Histones Human genes 0.000 description 2
• 108010033040 Histones Proteins 0.000 description 2
• 101000932478 Homo sapiens Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 description 2
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
• 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 2
• JXLYSJRDGCGARV-PJXZDTQASA-N Leurosidine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-PJXZDTQASA-N 0.000 description 2
• LPGWZGMPDKDHEP-HLTPFJCJSA-N Leurosine Chemical compound C([C@]1([C@@H]2O1)CC)N(CCC=1C3=CC=CC=C3NC=11)C[C@H]2C[C@]1(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC LPGWZGMPDKDHEP-HLTPFJCJSA-N 0.000 description 2
• LPGWZGMPDKDHEP-GKWAKPNHSA-N Leurosine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@]6(CC)O[C@@H]6[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C LPGWZGMPDKDHEP-GKWAKPNHSA-N 0.000 description 2
• 108091054455 MAP kinase family Proteins 0.000 description 2
• 102000043136 MAP kinase family Human genes 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• HRHKSTOGXBBQCB-UHFFFAOYSA-N Mitomycin E Natural products O=C1C(N)=C(C)C(=O)C2=C1C(COC(N)=O)C1(OC)C3N(C)C3CN12 HRHKSTOGXBBQCB-UHFFFAOYSA-N 0.000 description 2
• 101100381978 Mus musculus Braf gene Proteins 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
• XCUAIINAJCDIPM-XVFCMESISA-N N(4)-hydroxycytidine Chemical group O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=NO)C=C1 XCUAIINAJCDIPM-XVFCMESISA-N 0.000 description 2
• 108010057466 NF-kappa B Proteins 0.000 description 2
• 102000003945 NF-kappa B Human genes 0.000 description 2
• 229930012538 Paclitaxel Natural products 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 239000004793 Polystyrene Substances 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• 241000288906 Primates Species 0.000 description 2
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
• 102100037787 Protein-tyrosine kinase 2-beta Human genes 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 description 2
• 108050002653 Retinoblastoma protein Proteins 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• 235000021355 Stearic acid Nutrition 0.000 description 2
• 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 2
• 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 2
• 102000013814 Wnt Human genes 0.000 description 2
• 108050003627 Wnt Proteins 0.000 description 2
• JXLYSJRDGCGARV-KSNABSRWSA-N ac1l29ym Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-KSNABSRWSA-N 0.000 description 2
• 208000009956 adenocarcinoma Diseases 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 235000010443 alginic acid Nutrition 0.000 description 2
• 239000000783 alginic acid Substances 0.000 description 2
• 229920000615 alginic acid Polymers 0.000 description 2
• 229960001126 alginic acid Drugs 0.000 description 2
• 150000004781 alginic acids Chemical class 0.000 description 2
• 150000001408 amides Chemical class 0.000 description 2
• 229960003896 aminopterin Drugs 0.000 description 2
• 230000001093 anti-cancer Effects 0.000 description 2
• 230000003110 anti-inflammatory effect Effects 0.000 description 2
• 239000002246 antineoplastic agent Substances 0.000 description 2
• 239000008346 aqueous phase Substances 0.000 description 2
• VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 2
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
• 125000002619 bicyclic group Chemical group 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
• 229910000024 caesium carbonate Inorganic materials 0.000 description 2
• 229910000019 calcium carbonate Inorganic materials 0.000 description 2
• 235000010216 calcium carbonate Nutrition 0.000 description 2
• 239000001506 calcium phosphate Substances 0.000 description 2
• 229910000389 calcium phosphate Inorganic materials 0.000 description 2
• 235000011010 calcium phosphates Nutrition 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 150000001721 carbon Chemical group 0.000 description 2
• 229960004562 carboplatin Drugs 0.000 description 2
• XREUEWVEMYWFFA-CSKJXFQVSA-N carminomycin 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=C(O)C=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XREUEWVEMYWFFA-CSKJXFQVSA-N 0.000 description 2
• 229930188550 carminomycin Natural products 0.000 description 2
• XREUEWVEMYWFFA-UHFFFAOYSA-N carminomycin I Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XREUEWVEMYWFFA-UHFFFAOYSA-N 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 229950001725 carubicin Drugs 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 239000013553 cell monolayer Substances 0.000 description 2
• 239000006285 cell suspension Substances 0.000 description 2
• 230000005754 cellular signaling Effects 0.000 description 2
• 229960001265 ciclosporin Drugs 0.000 description 2
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
• 229960004316 cisplatin Drugs 0.000 description 2
• 235000015165 citric acid Nutrition 0.000 description 2
• 239000003086 colorant Substances 0.000 description 2
• 239000012230 colorless oil Substances 0.000 description 2
• 238000002648 combination therapy Methods 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• 239000013058 crude material Substances 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• 231100000433 cytotoxic Toxicity 0.000 description 2
• 239000002254 cytotoxic agent Substances 0.000 description 2
• 231100000599 cytotoxic agent Toxicity 0.000 description 2
• 230000001472 cytotoxic effect Effects 0.000 description 2
• STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 2
• 229960000975 daunorubicin Drugs 0.000 description 2
• DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
• 150000001975 deuterium Chemical group 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 229960004679 doxorubicin Drugs 0.000 description 2
• 230000007831 electrophysiology Effects 0.000 description 2
• 238000002001 electrophysiology Methods 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
• YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 description 2
• 229930013356 epothilone Natural products 0.000 description 2
• 150000003883 epothilone derivatives Chemical class 0.000 description 2
• DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 2
• DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
• 229960005420 etoposide Drugs 0.000 description 2
• VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 2
• 229960000752 etoposide phosphate Drugs 0.000 description 2
• LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 125000001153 fluoro group Chemical group F* 0.000 description 2
• 229960002949 fluorouracil Drugs 0.000 description 2
• 239000011888 foil Substances 0.000 description 2
• 230000003325 follicular Effects 0.000 description 2
• 235000003599 food sweetener Nutrition 0.000 description 2
• 238000001640 fractional crystallisation Methods 0.000 description 2
• 239000012458 free base Substances 0.000 description 2
• 108020001507 fusion proteins Proteins 0.000 description 2
• 102000037865 fusion proteins Human genes 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 2
• 229960005277 gemcitabine Drugs 0.000 description 2
• BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
• 150000002344 gold compounds Chemical class 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 239000003102 growth factor Substances 0.000 description 2
• 229940093915 gynecological organic acid Drugs 0.000 description 2
• 230000003394 haemopoietic effect Effects 0.000 description 2
• 125000001188 haloalkyl group Chemical group 0.000 description 2
• 150000004677 hydrates Chemical class 0.000 description 2
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
• XLSMFKSTNGKWQX-UHFFFAOYSA-N hydroxyacetone Chemical compound CC(=O)CO XLSMFKSTNGKWQX-UHFFFAOYSA-N 0.000 description 2
• 230000001900 immune effect Effects 0.000 description 2
• 229960003444 immunosuppressant agent Drugs 0.000 description 2
• 230000001861 immunosuppressant effect Effects 0.000 description 2
• 239000003018 immunosuppressive agent Substances 0.000 description 2
• 239000003701 inert diluent Substances 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 229940124302 mTOR inhibitor Drugs 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
• 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 2
• 229960002510 mandelic acid Drugs 0.000 description 2
• SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 2
• 229960001924 melphalan Drugs 0.000 description 2
• 229960001428 mercaptopurine Drugs 0.000 description 2
• 230000002503 metabolic effect Effects 0.000 description 2
• 229910052751 metal Inorganic materials 0.000 description 2
• 239000002184 metal Substances 0.000 description 2
• FBOZXECLQNJBKD-UHFFFAOYSA-N methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-UHFFFAOYSA-N 0.000 description 2
• 229960000485 methotrexate Drugs 0.000 description 2
• BJLKWQHSAVRZLX-UHFFFAOYSA-N methyl 6-[[7-cycloheptyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1NC1=NC=C(C=C(C(=O)N(C)C)N2C3CCCCCC3)C2=N1 BJLKWQHSAVRZLX-UHFFFAOYSA-N 0.000 description 2
• HRHKSTOGXBBQCB-VFWICMBZSA-N methylmitomycin Chemical compound O=C1C(N)=C(C)C(=O)C2=C1[C@@H](COC(N)=O)[C@@]1(OC)[C@H]3N(C)[C@H]3CN12 HRHKSTOGXBBQCB-VFWICMBZSA-N 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 239000003226 mitogen Substances 0.000 description 2
• 229960004857 mitomycin Drugs 0.000 description 2
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
• 239000012452 mother liquor Substances 0.000 description 2
• RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 2
• 229960004866 mycophenolate mofetil Drugs 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
• MWDCCRWZGLSKGS-UHFFFAOYSA-N n-methylmethanamine;dihydrochloride Chemical compound Cl.Cl.CNC MWDCCRWZGLSKGS-UHFFFAOYSA-N 0.000 description 2
• 208000015122 neurodegenerative disease Diseases 0.000 description 2
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 238000004806 packaging method and process Methods 0.000 description 2
• 229960001592 paclitaxel Drugs 0.000 description 2
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 2
• QJPQVXSHYBGQGM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 2
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
• YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 description 2
• 229960001237 podophyllotoxin Drugs 0.000 description 2
• YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 description 2
• 229950004406 porfiromycin Drugs 0.000 description 2
• 238000002600 positron emission tomography Methods 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 2
• TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 2
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 2
• 230000002285 radioactive effect Effects 0.000 description 2
• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 2
• 239000011535 reaction buffer Substances 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 150000003335 secondary amines Chemical class 0.000 description 2
• 230000011664 signaling Effects 0.000 description 2
• XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 2
• 238000002603 single-photon emission computed tomography Methods 0.000 description 2
• 229960002930 sirolimus Drugs 0.000 description 2
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 2
• 238000000527 sonication Methods 0.000 description 2
• 230000006641 stabilisation Effects 0.000 description 2
• 238000011105 stabilization Methods 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 239000008117 stearic acid Substances 0.000 description 2
• 150000003431 steroids Chemical class 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• 229960005322 streptomycin Drugs 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 239000003765 sweetening agent Substances 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 239000011975 tartaric acid Substances 0.000 description 2
• 235000002906 tartaric acid Nutrition 0.000 description 2
• 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 2
• NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 2
• 229960001278 teniposide Drugs 0.000 description 2
• UXAWXZDXVOYLII-HTQZYQBOSA-N tert-butyl (1r,4r)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1[C@H]2N(C(=O)OC(C)(C)C)C[C@@H]1NC2 UXAWXZDXVOYLII-HTQZYQBOSA-N 0.000 description 2
• SOQIWANRSPAFOH-FGZHOGPDSA-N tert-butyl (1r,4r)-5-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C([C@@]1(N(C[C@@]2([H])C1)C(=O)OC(C)(C)C)[H])N2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 SOQIWANRSPAFOH-FGZHOGPDSA-N 0.000 description 2
• OKOKEVUXUPQMJW-ZRZAMGCNSA-N tert-butyl (1r,5s)-9-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3-oxa-7,9-diazabicyclo[3.3.1]nonane-7-carboxylate Chemical compound N1([C@]2([H])COC[C@]1(CN(C2)C(=O)OC(C)(C)C)[H])C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 OKOKEVUXUPQMJW-ZRZAMGCNSA-N 0.000 description 2
• UXAWXZDXVOYLII-YUMQZZPRSA-N tert-butyl (1s,4s)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1[C@@H]2N(C(=O)OC(C)(C)C)C[C@H]1NC2 UXAWXZDXVOYLII-YUMQZZPRSA-N 0.000 description 2
• IXKNPSLHUPHNQK-RYUDHWBXSA-N tert-butyl (1s,4s)-5-(6-aminopyridine-3-carbonyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C([C@]1(N(C[C@]2([H])C1)C(=O)OC(C)(C)C)[H])N2C(=O)C1=CC=C(N)N=C1 IXKNPSLHUPHNQK-RYUDHWBXSA-N 0.000 description 2
• SOQIWANRSPAFOH-VXKWHMMOSA-N tert-butyl (1s,4s)-5-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C([C@]1(N(C[C@]2([H])C1)C(=O)OC(C)(C)C)[H])N2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 SOQIWANRSPAFOH-VXKWHMMOSA-N 0.000 description 2
• GGHIWYYHMKZSRN-WCQYABFASA-N tert-butyl (1s,6r)-4-(6-nitropyridin-3-yl)-3-oxo-4,9-diazabicyclo[4.2.1]nonane-9-carboxylate Chemical compound C([C@@]1(CC[C@](C2)(N1C(=O)OC(C)(C)C)[H])[H])C(=O)N2C1=CC=C([N+]([O-])=O)N=C1 GGHIWYYHMKZSRN-WCQYABFASA-N 0.000 description 2
• DRVSRTCIXTVMPA-YTTGMZPUSA-N tert-butyl (5s)-3-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-2-oxo-1-oxa-3,9-diazaspiro[4.6]undecane-9-carboxylate Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C(O1)=O)C[C@]21CCCN(C(=O)OC(C)(C)C)CC2 DRVSRTCIXTVMPA-YTTGMZPUSA-N 0.000 description 2
• UXAWXZDXVOYLII-UHFFFAOYSA-N tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1C2N(C(=O)OC(C)(C)C)CC1NC2 UXAWXZDXVOYLII-UHFFFAOYSA-N 0.000 description 2
• XMFOMYFSOLKHBH-UHFFFAOYSA-N tert-butyl 2-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C1=O)CCC21CCN(C(=O)OC(C)(C)C)CC2 XMFOMYFSOLKHBH-UHFFFAOYSA-N 0.000 description 2
• FQCAMCMQMJHPOU-UHFFFAOYSA-N tert-butyl 3-(6-aminopyridazin-3-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCC1CN2C1=CC=C(N)N=N1 FQCAMCMQMJHPOU-UHFFFAOYSA-N 0.000 description 2
• PRWMMXMZIKZLBB-UHFFFAOYSA-N tert-butyl 3-(6-nitropyridin-3-yl)-2-oxo-1-oxa-3,9-diazaspiro[4.5]decane-9-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11OC(=O)N(C=2C=NC(=CC=2)[N+]([O-])=O)C1 PRWMMXMZIKZLBB-UHFFFAOYSA-N 0.000 description 2
• KNHYHIILHGOPBR-UHFFFAOYSA-N tert-butyl 3-[6-[[7-(1-tert-butylpiperidin-4-yl)-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4C(=O)OC(C)(C)C)C3)N=C2N1C1CCN(C(C)(C)C)CC1 KNHYHIILHGOPBR-UHFFFAOYSA-N 0.000 description 2
• GXAINMWIXRIJEK-UHFFFAOYSA-N tert-butyl 3-[6-[[7-(3-tert-butylphenyl)-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4C(=O)OC(C)(C)C)C3)N=C2N1C1=CC=CC(C(C)(C)C)=C1 GXAINMWIXRIJEK-UHFFFAOYSA-N 0.000 description 2
• LLHMNXRQBFGBJJ-UHFFFAOYSA-N tert-butyl 3-[6-[[7-(4-tert-butylphenyl)-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4C(=O)OC(C)(C)C)C3)N=C2N1C1=CC=C(C(C)(C)C)C=C1 LLHMNXRQBFGBJJ-UHFFFAOYSA-N 0.000 description 2
• LSVBLSYBAFIKTK-UHFFFAOYSA-N tert-butyl 3-[6-[[7-cyclohexyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridazin-3-yl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=NC(=CC=3)N3CC4CCC(N4C(=O)OC(C)(C)C)C3)N=C2N1C1CCCCC1 LSVBLSYBAFIKTK-UHFFFAOYSA-N 0.000 description 2
• YMEVSJZKGHLIQK-UHFFFAOYSA-N tert-butyl 3-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]-2-methylpyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=C(C)C(C(=O)N4CC5CCC(N5C(=O)OC(C)(C)C)C4)=CC=3)N=C2N1C1CCCC1 YMEVSJZKGHLIQK-UHFFFAOYSA-N 0.000 description 2
• JLTXPLBWMVQWFN-UHFFFAOYSA-N tert-butyl 3-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylate Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C(O1)=O)CC21CCN(C(=O)OC(C)(C)C)CC2 JLTXPLBWMVQWFN-UHFFFAOYSA-N 0.000 description 2
• HPNYPBQOJOQPEB-UHFFFAOYSA-N tert-butyl 3-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3CC4CCC(N4C(=O)OC(C)(C)C)C3)N=C2N1C1CCCC1 HPNYPBQOJOQPEB-UHFFFAOYSA-N 0.000 description 2
• NQMRDBGNPRMWFX-UHFFFAOYSA-N tert-butyl 3-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,6-diazabicyclo[3.2.1]octane-6-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CC(CN4C(=O)OC(C)(C)C)C3)N=C2N1C1CCCC1 NQMRDBGNPRMWFX-UHFFFAOYSA-N 0.000 description 2
• LTEKXFDSTWJVCX-UHFFFAOYSA-N tert-butyl 3-[6-[[7-tert-butyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound C1C(N2C(=O)OC(C)(C)C)CCC2CN1C(=O)C(C=N1)=CC=C1NC1=NC=C2C=C(C(=O)N(C)C)N(C(C)(C)C)C2=N1 LTEKXFDSTWJVCX-UHFFFAOYSA-N 0.000 description 2
• YTBCHPDGWSPJOH-UHFFFAOYSA-N tert-butyl 4-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-3-oxo-4,9-diazabicyclo[4.2.1]nonane-9-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(CC4CCC(N4C(=O)OC(C)(C)C)C3)=O)N=C2N1C1CCCC1 YTBCHPDGWSPJOH-UHFFFAOYSA-N 0.000 description 2
• RKWHXYAMXGVBMO-UHFFFAOYSA-N tert-butyl 5-(6-nitropyridin-3-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC2CC1CN2C1=CC=C([N+]([O-])=O)N=C1 RKWHXYAMXGVBMO-UHFFFAOYSA-N 0.000 description 2
• QBKSUZDJAQEKJB-UHFFFAOYSA-N tert-butyl 6-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-2,6-diazaspiro[3.3]heptane-2-carboxylate Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1C(=O)N(C1)CC21CN(C(=O)OC(C)(C)C)C2 QBKSUZDJAQEKJB-UHFFFAOYSA-N 0.000 description 2
• IJHTZGBRXSYOMG-UHFFFAOYSA-N tert-butyl n-(3-azabicyclo[3.1.0]hexan-1-yl)carbamate Chemical compound C1NCC2(NC(=O)OC(C)(C)C)C1C2 IJHTZGBRXSYOMG-UHFFFAOYSA-N 0.000 description 2
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• PKVRCIRHQMSYJX-AIFWHQITSA-N trabectedin Chemical compound C([C@@]1(C(OC2)=O)NCCC3=C1C=C(C(=C3)O)OC)S[C@@H]1C3=C(OC(C)=O)C(C)=C4OCOC4=C3[C@H]2N2[C@@H](O)[C@H](CC=3C4=C(O)C(OC)=C(C)C=3)N(C)[C@H]4[C@@H]21 PKVRCIRHQMSYJX-AIFWHQITSA-N 0.000 description 2
• 229960000977 trabectedin Drugs 0.000 description 2
• 230000007704 transition Effects 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
• 102000003298 tumor necrosis factor receptor Human genes 0.000 description 2
• 229960003048 vinblastine Drugs 0.000 description 2
• JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 2
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
• 229960004528 vincristine Drugs 0.000 description 2
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
• UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 2
• 229960004355 vindesine Drugs 0.000 description 2
• 238000010792 warming Methods 0.000 description 2
• 239000000080 wetting agent Substances 0.000 description 2
• DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical group C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 1
• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
• XQDSUPZEXMHXIE-ZLUOBGJFSA-N (1s,4s,5s)-2-azabicyclo[2.2.1]heptan-5-ol Chemical compound C1[C@H](O)[C@]2([H])CN[C@@]1([H])C2 XQDSUPZEXMHXIE-ZLUOBGJFSA-N 0.000 description 1
• IMUSLIHRIYOHEV-SSDOTTSWSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-methylsulfanylbutanoic acid Chemical compound CSCC[C@H](C(O)=O)NC(=O)OC(C)(C)C IMUSLIHRIYOHEV-SSDOTTSWSA-N 0.000 description 1
• SZXBQTSZISFIAO-SSDOTTSWSA-N (2r)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)[C@H](C(O)=O)NC(=O)OC(C)(C)C SZXBQTSZISFIAO-SSDOTTSWSA-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
• ZQEBQGAAWMOMAI-ZETCQYMHSA-N (2s)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C(O)=O ZQEBQGAAWMOMAI-ZETCQYMHSA-N 0.000 description 1
• HIJHWAJALGSHLA-HZPDHXFCSA-N (3ar,8as)-7-(2-phenylethyl)-2,3,3a,4,5,6,8,8a-octahydro-1h-pyrrolo[2,3-c]azepine Chemical compound C([C@H]1NCC[C@H]1CCC1)N1CCC1=CC=CC=C1 HIJHWAJALGSHLA-HZPDHXFCSA-N 0.000 description 1
• FTTATHOUSOIFOQ-SSDOTTSWSA-N (8ar)-1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazine Chemical compound C1NCCN2CCC[C@@H]21 FTTATHOUSOIFOQ-SSDOTTSWSA-N 0.000 description 1
• 125000004178 (C1-C4) alkyl group Chemical group 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
• MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
• FTTATHOUSOIFOQ-UHFFFAOYSA-N 1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazine Chemical compound C1NCCN2CCCC21 FTTATHOUSOIFOQ-UHFFFAOYSA-N 0.000 description 1
• HDNDFGNEEKOHMW-UHFFFAOYSA-N 1,3,5-trimethyl-3,7-diazabicyclo[3.3.1]nonan-9-ol Chemical compound C1NCC2(C)CN(C)CC1(C)C2O HDNDFGNEEKOHMW-UHFFFAOYSA-N 0.000 description 1
• CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 1
• VCIKVHACZDLJCT-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-3-one Chemical compound N1C(=O)CN2CCC1CC2 VCIKVHACZDLJCT-UHFFFAOYSA-N 0.000 description 1
• XJKNACDCUAFDHD-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonane Chemical compound C1CC2CCN1CCN2 XJKNACDCUAFDHD-UHFFFAOYSA-N 0.000 description 1
• JSJBFUIXXKBVPA-UHFFFAOYSA-N 1,7-diazaspiro[4.4]nonan-6-one;hydrochloride Chemical compound Cl.O=C1NCCC11NCCC1 JSJBFUIXXKBVPA-UHFFFAOYSA-N 0.000 description 1
• ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
• LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 1
• HBRSWIOISCOVNK-UHFFFAOYSA-N 2,3,4,6,7,8-hexahydropyrido[1,2-a]pyrazin-1-one Chemical compound C1CCC=C2C(=O)NCCN21 HBRSWIOISCOVNK-UHFFFAOYSA-N 0.000 description 1
• GYUGNUWAXQXAHX-UHFFFAOYSA-N 2,4-dimethyl-7h-pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CC1=NC(C)=C2C=C(C(N)=O)NC2=N1 GYUGNUWAXQXAHX-UHFFFAOYSA-N 0.000 description 1
• FUPZCCAUPTZBGB-UHFFFAOYSA-N 2-(3,8-diazabicyclo[3.2.1]octan-8-yl)ethanol Chemical compound C1NCC2CCC1N2CCO FUPZCCAUPTZBGB-UHFFFAOYSA-N 0.000 description 1
• VXDPOGVDHHJTDY-UHFFFAOYSA-N 2-(4-aminophenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)C1=CC=C(N)C=C1 VXDPOGVDHHJTDY-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
• NKBWMBRPILTCRD-UHFFFAOYSA-N 2-Methylheptanoic acid Chemical compound CCCCCC(C)C(O)=O NKBWMBRPILTCRD-UHFFFAOYSA-N 0.000 description 1
• VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 1
• NGJPQECPPQEKSH-PXNSSMCTSA-N 2-[[5-[(3ar,6as)-2-methyl-4-oxo-3,3a,6,6a-tetrahydro-1h-pyrrolo[3,4-c]pyrrol-5-yl]pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C([C@H]4CN(C)C[C@H]4C3)=O)N=C2N1C1CCCC1 NGJPQECPPQEKSH-PXNSSMCTSA-N 0.000 description 1
• NDHWUUBJAUPCBT-XMSQKQJNSA-N 2-[[5-[(3ar,8as)-2,3,3a,4,5,6,8,8a-octahydro-1h-pyrrolo[2,3-c]azepine-7-carbonyl]pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3C[C@H]4NCC[C@H]4CCC3)N=C2N1C1CCCC1 NDHWUUBJAUPCBT-XMSQKQJNSA-N 0.000 description 1
• QHKSOUNRROAMGU-SFTDATJTSA-N 2-[[5-[(3as,7ar)-2-methyl-6-oxo-1,3,3a,4,7,7a-hexahydropyrrolo[3,4-c]pyridin-5-yl]pyridin-2-yl]amino]-7-cycloheptyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(C[C@H]4CN(C)C[C@H]4C3)=O)N=C2N1C1CCCCCC1 QHKSOUNRROAMGU-SFTDATJTSA-N 0.000 description 1
• APVMMXISFUOGOQ-LJQANCHMSA-N 2-[[5-[(8aR)-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine-2-carbonyl]pyridin-2-yl]amino]-7-cyclopentylpyrrolo[2,3-d]pyrimidine-6-carboxylic acid Chemical compound C1(CCCC1)N1C(=CC2=C1N=C(N=C2)NC1=NC=C(C=C1)C(=O)N1C[C@@H]2N(CC1)CCC2)C(=O)O APVMMXISFUOGOQ-LJQANCHMSA-N 0.000 description 1
• BXXWHFGJPHSCSJ-NRFANRHFSA-N 2-[[5-[(8as)-1-oxo-3,4,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-2-yl]pyridin-2-yl]amino]-7-cyclohexyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C([C@@H]4CCCN4CC3)=O)N=C2N1C1CCCCC1 BXXWHFGJPHSCSJ-NRFANRHFSA-N 0.000 description 1
• WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
• KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
• HUUFTVUBFFESEN-UHFFFAOYSA-N 2-bromo-5-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Br)N=C1 HUUFTVUBFFESEN-UHFFFAOYSA-N 0.000 description 1
• WKVJHRUZNRNEKH-UHFFFAOYSA-N 2-chloro-7-(1-cyclopropylpiperidin-4-yl)-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(Cl)N=C2N1C(CC1)CCN1C1CC1 WKVJHRUZNRNEKH-UHFFFAOYSA-N 0.000 description 1
• FJZKZOVTHDPRDX-UHFFFAOYSA-N 2-chloro-n,n-dimethyl-7-phenylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(Cl)N=C2N1C1=CC=CC=C1 FJZKZOVTHDPRDX-UHFFFAOYSA-N 0.000 description 1
• 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
• 125000005916 2-methylpentyl group Chemical group 0.000 description 1
• DTXVKPOKPFWSFF-UHFFFAOYSA-N 3(S)-hydroxy-13-cis-eicosenoyl-CoA Chemical compound NC1=CC=C(Cl)N=N1 DTXVKPOKPFWSFF-UHFFFAOYSA-N 0.000 description 1
• VQAFMTSSCUETHA-UHFFFAOYSA-N 3,6-dibromopyridazine Chemical compound BrC1=CC=C(Br)N=N1 VQAFMTSSCUETHA-UHFFFAOYSA-N 0.000 description 1
• JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
• OPXGIXNXHJHPLP-UHFFFAOYSA-N 3,8-diazabicyclo[3.2.1]octane-8-carboxylic acid Chemical compound C1NCC2CCC1N2C(=O)O OPXGIXNXHJHPLP-UHFFFAOYSA-N 0.000 description 1
• HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
• BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
• CFTAUIXBYCXJDL-UHFFFAOYSA-N 3-(6-aminopyridin-3-yl)-1-oxa-3,9-diazaspiro[4.6]undecan-2-one Chemical compound C1=NC(N)=CC=C1N1C(=O)OC2(CCNCCC2)C1 CFTAUIXBYCXJDL-UHFFFAOYSA-N 0.000 description 1
• WUIZVLNIOZIQGK-UHFFFAOYSA-N 3-(6-nitropyridin-3-yl)-1-oxa-3,9-diazaspiro[4.6]undecan-2-one Chemical compound C1=NC([N+](=O)[O-])=CC=C1N1C(=O)OC2(CCNCCC2)C1 WUIZVLNIOZIQGK-UHFFFAOYSA-N 0.000 description 1
• ZESPHSZFZSEKKX-UHFFFAOYSA-N 3-[2-chloro-4-(oxan-3-ylamino)pyrimidin-5-yl]prop-2-yn-1-ol Chemical compound OCC#CC1=CN=C(Cl)N=C1NC1COCCC1 ZESPHSZFZSEKKX-UHFFFAOYSA-N 0.000 description 1
• WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
• XPZYBFOYRKOKPL-UHFFFAOYSA-N 3-azabicyclo[3.2.1]octan-8-ol Chemical compound C1NCC2CCC1C2O XPZYBFOYRKOKPL-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
• FYSCXTRDKBSUBL-UHFFFAOYSA-N 3-benzyl-3,9-diazabicyclo[3.3.1]nonane Chemical compound C1C(N2)CCCC2CN1CC1=CC=CC=C1 FYSCXTRDKBSUBL-UHFFFAOYSA-N 0.000 description 1
• DCDAOVIVXGHHHU-UHFFFAOYSA-N 3-benzyl-3-azabicyclo[3.2.1]octan-8-one Chemical compound O=C1C(C2)CCC1CN2CC1=CC=CC=C1 DCDAOVIVXGHHHU-UHFFFAOYSA-N 0.000 description 1
• SLFJZMKCBPIOSE-UHFFFAOYSA-N 3-benzyl-9-oxa-3,7-diazabicyclo[3.3.1]nonane Chemical compound C1C(O2)CNCC2CN1CC1=CC=CC=C1 SLFJZMKCBPIOSE-UHFFFAOYSA-N 0.000 description 1
• XHTSIDJPECQAJD-UHFFFAOYSA-N 3-benzyl-N,N-dimethyl-3-azabicyclo[3.2.1]octan-1-amine Chemical compound C(C1=CC=CC=C1)N1CC2(CCC(C1)C2)N(C)C XHTSIDJPECQAJD-UHFFFAOYSA-N 0.000 description 1
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
• VQFUVYCIMPUROE-UHFFFAOYSA-N 5-bromo-2-chloro-n-(oxan-3-yl)pyrimidin-4-amine Chemical compound ClC1=NC=C(Br)C(NC2COCCC2)=N1 VQFUVYCIMPUROE-UHFFFAOYSA-N 0.000 description 1
• KHXNGFJREJNACT-UHFFFAOYSA-N 5-bromo-2-chloro-n-cycloheptylpyrimidin-4-amine Chemical compound ClC1=NC=C(Br)C(NC2CCCCCC2)=N1 KHXNGFJREJNACT-UHFFFAOYSA-N 0.000 description 1
• HXFLZWAZSSPLCO-UHFFFAOYSA-N 6,6-dimethylbicyclo[3.1.1]heptyl Chemical group C1[C-]2C([CH2+])([CH2-])[C+]1CCC2 HXFLZWAZSSPLCO-UHFFFAOYSA-N 0.000 description 1
• KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
• TZZLIARCVQOPQS-UHFFFAOYSA-N 6-amino-2-methylpyridine-3-carboxylic acid Chemical compound CC1=NC(N)=CC=C1C(O)=O TZZLIARCVQOPQS-UHFFFAOYSA-N 0.000 description 1
• FBKFFOOSODQYPO-UHFFFAOYSA-N 6-amino-4-methylpyridine-3-carboxylic acid Chemical compound CC1=CC(N)=NC=C1C(O)=O FBKFFOOSODQYPO-UHFFFAOYSA-N 0.000 description 1
• XTLFMTAOHREREO-UHFFFAOYSA-N 7-(1-tert-butylpiperidin-4-yl)-2-[[5-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]-N,N-dimethyl-1,2-dihydropyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C(=O)C1=CC2=C(NC(N=C2)NC2=NC=C(C=C2)C(=O)N2CC3CCC(C2)N3)N1C1CCN(CC1)C(C)(C)C)C XTLFMTAOHREREO-UHFFFAOYSA-N 0.000 description 1
• CDEFBKQNDIPXQA-UHFFFAOYSA-N 7-(1-tert-butylpiperidin-4-yl)-2-chloro-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(Cl)N=C2N1C1CCN(C(C)(C)C)CC1 CDEFBKQNDIPXQA-UHFFFAOYSA-N 0.000 description 1
• PTIRVLFOZGEFPK-UHFFFAOYSA-N 7-(3-tert-butylphenyl)-2-chloro-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(Cl)N=C2N1C1=CC=CC(C(C)(C)C)=C1 PTIRVLFOZGEFPK-UHFFFAOYSA-N 0.000 description 1
• WOZPHGMYKYVQOK-UHFFFAOYSA-N 7-(4-tert-butylcyclohexyl)-2-[[5-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4)C3)N=C2N1C1CCC(C(C)(C)C)CC1 WOZPHGMYKYVQOK-UHFFFAOYSA-N 0.000 description 1
• BULDWUVRCZKADX-UHFFFAOYSA-N 7-(4-tert-butylphenyl)-2-chloro-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(Cl)N=C2N1C1=CC=C(C(C)(C)C)C=C1 BULDWUVRCZKADX-UHFFFAOYSA-N 0.000 description 1
• BPNSZQIMYKUVMU-KQUCSHIGSA-N 7-[(1s,3r)-3-bicyclo[2.2.1]heptanyl]-2-[[5-[(5r)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C1C(N2)CC[C@]2([H])CN1C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C2C=C(C(=O)N(C)C)N1[C@H](C1)C2CC[C@@]1([H])C2 BPNSZQIMYKUVMU-KQUCSHIGSA-N 0.000 description 1
• IYNVGJVJNFJVRB-HOSYDEDBSA-N 7-[(1s,3r,4r)-3-bicyclo[2.2.1]heptanyl]-2-chloro-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(Cl)N=C2N1[C@H](C1)[C@]2([H])CC[C@@]1([H])C2 IYNVGJVJNFJVRB-HOSYDEDBSA-N 0.000 description 1
• OZXBZQSURNMZDJ-UHFFFAOYSA-N 7-cycloheptyl-2-[[5-(2,5-diazabicyclo[2.2.1]heptane-2-carbonyl)pyridin-2-yl]amino]-N,N-dimethylpyrrolo[2,3-d]pyrimidine-5-carboxamide Chemical compound CN(C(=O)C1=CN(C=2N=C(N=CC=21)NC1=NC=C(C=C1)C(=O)N1C2CNC(C1)C2)C1CCCCCC1)C OZXBZQSURNMZDJ-UHFFFAOYSA-N 0.000 description 1
• ASHICYVUPHFNCK-UHFFFAOYSA-N 7-cycloheptyl-2-[[5-(2-oxo-3,8-diazabicyclo[3.2.1]octan-3-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxylic acid Chemical compound C1(CCCCCC1)N1C(=CC2=C1N=C(N=C2)NC1=NC=C(C=C1)N1C(C2CCC(C1)N2)=O)C(=O)O ASHICYVUPHFNCK-UHFFFAOYSA-N 0.000 description 1
• VLUJHZWOUOZYQQ-UHFFFAOYSA-N 7-cycloheptyl-n,n-dimethyl-2-[[5-(4-oxo-1,2,3,3a,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(C4CNCC4C3)=O)N=C2N1C1CCCCCC1 VLUJHZWOUOZYQQ-UHFFFAOYSA-N 0.000 description 1
• XGEJQZNPNALCEX-UHFFFAOYSA-N 7-cyclohexyl-n,n-dimethyl-2-[[5-(1-oxo-4,6,7,8,9,9a-hexahydro-3h-pyrido[1,2-a]pyrazin-2-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(C4CCCCN4CC3)=O)N=C2N1C1CCCCC1 XGEJQZNPNALCEX-UHFFFAOYSA-N 0.000 description 1
• JHHINTVZHOALDI-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C4CC(NC4)C3)N=C2N1C1CCCC1 JHHINTVZHOALDI-UHFFFAOYSA-N 0.000 description 1
• OHXJTIXQHDUXMS-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-(3,6-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxylic acid Chemical compound C1(CCCC1)N1C(=CC2=C1N=C(N=C2)NC1=NC=C(C=C1)C(=O)N1CC2CNC(C1)C2)C(=O)O OHXJTIXQHDUXMS-UHFFFAOYSA-N 0.000 description 1
• OGKCNYUNQLOOHJ-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-(3,8-diazabicyclo[3.2.1]oct-1-ene-3-carbonyl)pyridin-2-yl]amino]-N,N-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C(=O)C1=CC2=C(N=C(N=C2)NC2=NC=C(C=C2)C(=O)N2C=C3CCC(C2)N3)N1C1CCCC1)C OGKCNYUNQLOOHJ-UHFFFAOYSA-N 0.000 description 1
• ZRZLHPNOJFIXLH-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-(3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxylic acid Chemical compound OC(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(CC4CCC(N4)C3)=O)N=C2N1C1CCCC1 ZRZLHPNOJFIXLH-UHFFFAOYSA-N 0.000 description 1
• VMHOCSPSLUBLHE-VQIMIIECSA-N 7-cyclopentyl-2-[[5-[(1r,5r)-3,6-diazabicyclo[3.2.1]octane-3-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@]1([H])NC[C@@](C1)(C1)[H])N1C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 VMHOCSPSLUBLHE-VQIMIIECSA-N 0.000 description 1
• ZRZLHPNOJFIXLH-JKSUJKDBSA-N 7-cyclopentyl-2-[[5-[(1s,6r)-3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxylic acid Chemical compound C([C@@]1(CC[C@](C2)(N1)[H])[H])C(=O)N2C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(O)=O)N2C1CCCC1 ZRZLHPNOJFIXLH-JKSUJKDBSA-N 0.000 description 1
• HZSGWPUAJDJNKG-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(1-oxo-2,8-diazaspiro[4.5]decan-2-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C1=O)CCC21CCNCC2 HZSGWPUAJDJNKG-UHFFFAOYSA-N 0.000 description 1
• SWMRYZWSHCYJGG-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(1-oxo-4,6,7,8,9,9a-hexahydro-3h-pyrido[1,2-a]pyrazin-2-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(C4CCCCN4CC3)=O)N=C2N1C1CCCC1 SWMRYZWSHCYJGG-UHFFFAOYSA-N 0.000 description 1
• BWRSHZDVVSAUGM-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(2'-oxospiro[8-azabicyclo[3.2.1]octane-3,4'-pyrrolidine]-1'-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(CC4(C3)CC3CCC(N3)C4)=O)N=C2N1C1CCCC1 BWRSHZDVVSAUGM-UHFFFAOYSA-N 0.000 description 1
• WXTIRKWPZHCCIM-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide;dihydrochloride Chemical compound Cl.Cl.CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(CC4CCC(N4)C3)=O)N=C2N1C1CCCC1 WXTIRKWPZHCCIM-UHFFFAOYSA-N 0.000 description 1
• OHOGKSHNJOSNJQ-BGYRXZFFSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-[(1r,5s)-3-oxa-7,9-diazabicyclo[3.3.1]nonane-9-carbonyl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1([C@]2([H])CNC[C@]1(COC2)[H])C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 OHOGKSHNJOSNJQ-BGYRXZFFSA-N 0.000 description 1
• KYCXJULIXGIISB-UHFFFAOYSA-N 7-tert-butyl-2-chloro-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C(Cl)N=C2N(C(C)(C)C)C(C(=O)N(C)C)=CC2=C1 KYCXJULIXGIISB-UHFFFAOYSA-N 0.000 description 1
• CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
• OFNWMZRPXFBZPX-UHFFFAOYSA-N 8-methyl-3,8-diazabicyclo[3.2.1]octane Chemical compound C1NCC2CCC1N2C OFNWMZRPXFBZPX-UHFFFAOYSA-N 0.000 description 1
• POOPWPIOIMBTOH-UHFFFAOYSA-N 8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C1NCC2CCC1O2 POOPWPIOIMBTOH-UHFFFAOYSA-N 0.000 description 1
• IZTSYUBBKNSBJC-UHFFFAOYSA-N 9-benzyl-4,9-diazabicyclo[4.2.1]nonan-3-one Chemical compound C1NC(=O)CC2CCC1N2CC1=CC=CC=C1 IZTSYUBBKNSBJC-UHFFFAOYSA-N 0.000 description 1
• 208000030507 AIDS Diseases 0.000 description 1
• 206010065040 AIDS dementia complex Diseases 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 241000251468 Actinopterygii Species 0.000 description 1
• 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• 208000032467 Aplastic anaemia Diseases 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 241000271566 Aves Species 0.000 description 1
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• 101150108519 CDK4 gene Proteins 0.000 description 1
• 229940125888 CDK7 inhibitor Drugs 0.000 description 1
• SUIPBOVXBCFUCE-HDJSIYSDSA-N CN(C)C(=O)c1cc2cnc(Cl)nc2n1[C@H]1CC[C@@H](CC1)C(C)(C)C Chemical compound CN(C)C(=O)c1cc2cnc(Cl)nc2n1[C@H]1CC[C@@H](CC1)C(C)(C)C SUIPBOVXBCFUCE-HDJSIYSDSA-N 0.000 description 1
• 101100101413 Caenorhabditis elegans ubh-4 gene Proteins 0.000 description 1
• 206010058019 Cancer Pain Diseases 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
• 208000006029 Cardiomegaly Diseases 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 206010048832 Colon adenoma Diseases 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 description 1
• 108010025454 Cyclin-Dependent Kinase 5 Proteins 0.000 description 1
• 102000000578 Cyclin-Dependent Kinase Inhibitor p21 Human genes 0.000 description 1
• 108010016788 Cyclin-Dependent Kinase Inhibitor p21 Proteins 0.000 description 1
• 102100036239 Cyclin-dependent kinase 2 Human genes 0.000 description 1
• 102100024456 Cyclin-dependent kinase 8 Human genes 0.000 description 1
• 102100024457 Cyclin-dependent kinase 9 Human genes 0.000 description 1
• 102100026805 Cyclin-dependent-like kinase 5 Human genes 0.000 description 1
• 201000003883 Cystic fibrosis Diseases 0.000 description 1
• 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 1
• 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 1
• 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 1
• RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
• AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
• KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
• 206010061818 Disease progression Diseases 0.000 description 1
• 108010093502 E2F Transcription Factors Proteins 0.000 description 1
• 102000001388 E2F Transcription Factors Human genes 0.000 description 1
• 108050002772 E3 ubiquitin-protein ligase Mdm2 Proteins 0.000 description 1
• 238000008157 ELISA kit Methods 0.000 description 1
• 206010014759 Endometrial neoplasm Diseases 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
• 244000068988 Glycine max Species 0.000 description 1
• 235000010469 Glycine max Nutrition 0.000 description 1
• 208000023661 Haematological disease Diseases 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000715942 Homo sapiens Cyclin-dependent kinase 4 Proteins 0.000 description 1
• 101000980937 Homo sapiens Cyclin-dependent kinase 8 Proteins 0.000 description 1
• 101000980930 Homo sapiens Cyclin-dependent kinase 9 Proteins 0.000 description 1
• 101000980756 Homo sapiens G1/S-specific cyclin-D1 Proteins 0.000 description 1
• 101000736088 Homo sapiens PC4 and SFRS1-interacting protein Proteins 0.000 description 1
• 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 1
• 101000733249 Homo sapiens Tumor suppressor ARF Proteins 0.000 description 1
• 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
• 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
• 208000007766 Kaposi sarcoma Diseases 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
• 229930182816 L-glutamine Natural products 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 description 1
• YEJCDKJIEMIWRQ-UHFFFAOYSA-N Linopirdine Chemical compound O=C1N(C=2C=CC=CC=2)C2=CC=CC=C2C1(CC=1C=CN=CC=1)CC1=CC=NC=C1 YEJCDKJIEMIWRQ-UHFFFAOYSA-N 0.000 description 1
• 239000012448 Lithium borohydride Substances 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 229940083338 MDM2 inhibitor Drugs 0.000 description 1
• 239000012819 MDM2-Inhibitor Substances 0.000 description 1
• 229940124647 MEK inhibitor Drugs 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
• OKJIRPAQVSHGFK-UHFFFAOYSA-N N-acetylglycine Chemical compound CC(=O)NCC(O)=O OKJIRPAQVSHGFK-UHFFFAOYSA-N 0.000 description 1
• QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 102100036220 PC4 and SFRS1-interacting protein Human genes 0.000 description 1
• 239000012828 PI3K inhibitor Substances 0.000 description 1
• 102000038030 PI3Ks Human genes 0.000 description 1
• 108091007960 PI3Ks Proteins 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 1
• 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
• 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
• 229920001213 Polysorbate 20 Polymers 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 239000012980 RPMI-1640 medium Substances 0.000 description 1
• 206010063837 Reperfusion injury Diseases 0.000 description 1
• 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
• BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
• 241000580858 Simian-Human immunodeficiency virus Species 0.000 description 1
• 241000710960 Sindbis virus Species 0.000 description 1
• 208000000453 Skin Neoplasms Diseases 0.000 description 1
• 206010041067 Small cell lung cancer Diseases 0.000 description 1
• 108010090804 Streptavidin Proteins 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• 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 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 210000001744 T-lymphocyte Anatomy 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 239000013504 Triton X-100 Substances 0.000 description 1
• 229920004890 Triton X-100 Polymers 0.000 description 1
• 229940122618 Trypsin inhibitor Drugs 0.000 description 1
• 101710162629 Trypsin inhibitor Proteins 0.000 description 1
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
• 102100040247 Tumor necrosis factor Human genes 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 206010046851 Uveitis Diseases 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
• JIWFQJBKRNPDLQ-UHFFFAOYSA-N [2-chloro-7-(oxan-3-yl)pyrrolo[2,3-d]pyrimidin-6-yl]methanol Chemical compound OCC1=CC2=CN=C(Cl)N=C2N1C1CCCOC1 JIWFQJBKRNPDLQ-UHFFFAOYSA-N 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• 239000002250 absorbent Substances 0.000 description 1
• 230000002745 absorbent Effects 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 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 1
• 150000007513 acids Chemical class 0.000 description 1
• YBCVMFKXIKNREZ-UHFFFAOYSA-N acoh acetic acid Chemical compound CC(O)=O.CC(O)=O YBCVMFKXIKNREZ-UHFFFAOYSA-N 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• 239000003463 adsorbent Substances 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 235000010419 agar Nutrition 0.000 description 1
• 206010064930 age-related macular degeneration Diseases 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
• KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 1
• 229960000836 amitriptyline Drugs 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 239000003098 androgen Substances 0.000 description 1
• 208000007502 anemia Diseases 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 230000006793 arrhythmia Effects 0.000 description 1
• 206010003119 arrhythmia Diseases 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 239000012131 assay buffer Substances 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 150000007514 bases Chemical class 0.000 description 1
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• KFKJACLLRKRWJE-UHFFFAOYSA-N benzyl 3,8-diazabicyclo[3.2.1]octane-3-carboxylate Chemical compound C1C(N2)CCC2CN1C(=O)OCC1=CC=CC=C1 KFKJACLLRKRWJE-UHFFFAOYSA-N 0.000 description 1
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 239000012148 binding buffer Substances 0.000 description 1
• 238000004166 bioassay Methods 0.000 description 1
• 239000012620 biological material Substances 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 239000011616 biotin Substances 0.000 description 1
• 230000002051 biphasic effect Effects 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• 229940045348 brown mixture Drugs 0.000 description 1
• 239000006172 buffering agent Substances 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
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 150000003857 carboxamides Chemical class 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 230000022131 cell cycle Effects 0.000 description 1
• 230000006369 cell cycle progression Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 208000025434 cerebellar degeneration Diseases 0.000 description 1
• KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
• 239000012069 chiral reagent Substances 0.000 description 1
• 239000000460 chlorine Chemical group 0.000 description 1
• 229910052801 chlorine Chemical group 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 1
• WGXZDYPGLJYBJW-UHFFFAOYSA-N chloroform;propan-2-ol Chemical compound CC(C)O.ClC(Cl)Cl WGXZDYPGLJYBJW-UHFFFAOYSA-N 0.000 description 1
• 208000037976 chronic inflammation Diseases 0.000 description 1
• 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
• 238000011278 co-treatment Methods 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 201000010897 colon adenocarcinoma Diseases 0.000 description 1
• 239000013066 combination product Substances 0.000 description 1
• 229940127555 combination product Drugs 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 239000002537 cosmetic Substances 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• VXVVUHQULXCUPF-UHFFFAOYSA-N cycloheptanamine Chemical compound NC1CCCCCC1 VXVVUHQULXCUPF-UHFFFAOYSA-N 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 238000007405 data analysis Methods 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• 230000009849 deactivation Effects 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 230000036576 dermal application Effects 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
• 239000013024 dilution buffer Substances 0.000 description 1
• SXZIXHOMFPUIRK-UHFFFAOYSA-N diphenylmethanimine Chemical compound C=1C=CC=CC=1C(=N)C1=CC=CC=C1 SXZIXHOMFPUIRK-UHFFFAOYSA-N 0.000 description 1
• WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 1
• 230000005750 disease progression Effects 0.000 description 1
• 208000037765 diseases and disorders Diseases 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• ODCCJTMPMUFERV-UHFFFAOYSA-N ditert-butyl carbonate Chemical compound CC(C)(C)OC(=O)OC(C)(C)C ODCCJTMPMUFERV-UHFFFAOYSA-N 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
• 229940043264 dodecyl sulfate Drugs 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 229940112141 dry powder inhaler Drugs 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 229940121647 egfr inhibitor Drugs 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 238000003366 endpoint assay Methods 0.000 description 1
• 238000007824 enzymatic assay Methods 0.000 description 1
• AFAXGSQYZLGZPG-UHFFFAOYSA-L ethanedisulfonate group Chemical group C(CS(=O)(=O)[O-])S(=O)(=O)[O-] AFAXGSQYZLGZPG-UHFFFAOYSA-L 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
• 239000002024 ethyl acetate extract Substances 0.000 description 1
• UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
• 229960005167 everolimus Drugs 0.000 description 1
• 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 229940125829 fibroblast growth factor receptor inhibitor Drugs 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 239000011737 fluorine Chemical group 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 229940050411 fumarate Drugs 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 230000009395 genetic defect Effects 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 229960001731 gluceptate Drugs 0.000 description 1
• 239000003862 glucocorticoid Substances 0.000 description 1
• KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
• 229940050410 gluconate Drugs 0.000 description 1
• 229940097042 glucuronate Drugs 0.000 description 1
• 229940074045 glyceryl distearate Drugs 0.000 description 1
• 229940075507 glyceryl monostearate Drugs 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 239000007902 hard capsule Substances 0.000 description 1
• 239000003481 heat shock protein 90 inhibitor Substances 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
• GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
• 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
• 102000048992 human CDK4 Human genes 0.000 description 1
• BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical group [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• QYRFJLLXPINATB-UHFFFAOYSA-N hydron;2,4,5,6-tetrafluorobenzene-1,3-diamine;dichloride Chemical class Cl.Cl.NC1=C(F)C(N)=C(F)C(F)=C1F QYRFJLLXPINATB-UHFFFAOYSA-N 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• 230000003463 hyperproliferative effect Effects 0.000 description 1
• 238000003384 imaging method Methods 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 208000037906 ischaemic injury Diseases 0.000 description 1
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• 239000000644 isotonic solution Substances 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
• 150000002576 ketones Chemical class 0.000 description 1
• 208000017169 kidney disease Diseases 0.000 description 1
• 238000012933 kinetic analysis Methods 0.000 description 1
• 229940001447 lactate Drugs 0.000 description 1
• 229940099584 lactobionate Drugs 0.000 description 1
• JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[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 JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
• 201000010901 lateral sclerosis Diseases 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 238000002514 liquid chromatography mass spectrum Methods 0.000 description 1
• 229940057995 liquid paraffin Drugs 0.000 description 1
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
• OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 1
• 208000019423 liver disease Diseases 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• 229960003646 lysine Drugs 0.000 description 1
• 239000012139 lysis buffer Substances 0.000 description 1
• 208000002780 macular degeneration Diseases 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
• 229940049920 malate Drugs 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
• 210000004962 mammalian cell Anatomy 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
• 229960003194 meglumine Drugs 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 239000002808 molecular sieve Substances 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 239000004570 mortar (masonry) Substances 0.000 description 1
• 208000005264 motor neuron disease Diseases 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 230000003387 muscular Effects 0.000 description 1
• 210000002346 musculoskeletal system Anatomy 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• WXCGPYFNDWQWHG-RBUKOAKNSA-N n,n-dimethyl-2-[[5-[(1s,6r)-3-oxo-4,9-diazabicyclo[4.2.1]nonan-4-yl]pyridin-2-yl]amino]-7-phenylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@@]1(CC[C@](C2)(N1)[H])[H])C(=O)N2C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1=CC=CC=C1 WXCGPYFNDWQWHG-RBUKOAKNSA-N 0.000 description 1
• LHEWYMHUYHCYSK-UHFFFAOYSA-N n,n-dimethyl-7-(oxan-3-yl)-2-[[5-(2'-oxospiro[8-azabicyclo[3.2.1]octane-3,4'-pyrrolidine]-1'-yl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(CC4(C3)CC3CCC(N3)C4)=O)N=C2N1C1CCCOC1 LHEWYMHUYHCYSK-UHFFFAOYSA-N 0.000 description 1
• PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
• IFYDWYVPVAMGRO-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]tetradecanamide Chemical compound CCCCCCCCCCCCCC(=O)NCCCN(C)C IFYDWYVPVAMGRO-UHFFFAOYSA-N 0.000 description 1
• OBJNFLYHUXWUPF-IZZDOVSWSA-N n-[3-[[5-chloro-4-(1h-indol-3-yl)pyrimidin-2-yl]amino]phenyl]-4-[[(e)-4-(dimethylamino)but-2-enoyl]amino]benzamide Chemical compound C1=CC(NC(=O)/C=C/CN(C)C)=CC=C1C(=O)NC1=CC=CC(NC=2N=C(C(Cl)=CN=2)C=2C3=CC=CC=C3NC=2)=C1 OBJNFLYHUXWUPF-IZZDOVSWSA-N 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-M octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC([O-])=O QIQXTHQIDYTFRH-UHFFFAOYSA-M 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-M oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC([O-])=O ZQPPMHVWECSIRJ-KTKRTIGZSA-M 0.000 description 1
• 229940049964 oleate Drugs 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 231100000590 oncogenic Toxicity 0.000 description 1
• 230000002246 oncogenic effect Effects 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 239000001301 oxygen Chemical group 0.000 description 1
• 239000006174 pH buffer Substances 0.000 description 1
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 235000019371 penicillin G benzathine Nutrition 0.000 description 1
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 229940021222 peritoneal dialysis isotonic solution 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
• 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 229960005141 piperazine Drugs 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 229920003023 plastic Polymers 0.000 description 1
• 230000010287 polarization Effects 0.000 description 1
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
• 229920002223 polystyrene Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000015320 potassium carbonate Nutrition 0.000 description 1
• 230000001376 precipitating effect Effects 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 230000036278 prepulse Effects 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• 230000002062 proliferating effect Effects 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 230000004952 protein activity Effects 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 239000003909 protein kinase inhibitor Substances 0.000 description 1
• 235000021251 pulses Nutrition 0.000 description 1
• 230000001696 purinergic effect Effects 0.000 description 1
• 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 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
• 230000008707 rearrangement Effects 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 239000013643 reference control Substances 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 230000002336 repolarization Effects 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 208000037803 restenosis Diseases 0.000 description 1
• 230000036390 resting membrane potential Effects 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 238000007363 ring formation reaction Methods 0.000 description 1
• 238000010079 rubber tapping Methods 0.000 description 1
• MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 238000013207 serial dilution Methods 0.000 description 1
• 229910052709 silver Inorganic materials 0.000 description 1
• 239000004332 silver Substances 0.000 description 1
• 201000009890 sinusitis Diseases 0.000 description 1
• 201000000849 skin cancer Diseases 0.000 description 1
• 208000000587 small cell lung carcinoma Diseases 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 239000004071 soot Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 206010041823 squamous cell carcinoma Diseases 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 229940114926 stearate Drugs 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 239000011550 stock solution Substances 0.000 description 1
• 239000012089 stop solution Substances 0.000 description 1
• 229940086735 succinate Drugs 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 229940071103 sulfosalicylate Drugs 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
• NCVKNBTUOGQKLP-XUEDKKMFSA-N tert-butyl (1r,5s)-7-[6-[[7-cycloheptyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-9-hydroxy-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C([C@]1(CN(C[C@@](C2)(C1O)[H])C(=O)OC(C)(C)C)[H])N2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCCCC1 NCVKNBTUOGQKLP-XUEDKKMFSA-N 0.000 description 1
• JKNPIKNTQGYBSJ-KMXBQNHCSA-N tert-butyl (1r,5s)-7-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-9-hydroxy-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C([C@]1(CN(C[C@@](C2)(C1O)[H])C(=O)OC(C)(C)C)[H])N2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 JKNPIKNTQGYBSJ-KMXBQNHCSA-N 0.000 description 1
• NXIZCOXUZZYOOJ-ULKQDVFKSA-N tert-butyl (1r,5s)-9-hydroxy-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1NC[C@]2([H])CN(C(=O)OC(C)(C)C)C[C@@]1([H])C2O NXIZCOXUZZYOOJ-ULKQDVFKSA-N 0.000 description 1
• GGHIWYYHMKZSRN-YPMHNXCESA-N tert-butyl (1r,6s)-4-(6-nitropyridin-3-yl)-3-oxo-4,9-diazabicyclo[4.2.1]nonane-9-carboxylate Chemical compound C([C@]1(CC[C@@](C2)(N1C(=O)OC(C)(C)C)[H])[H])C(=O)N2C1=CC=C([N+]([O-])=O)N=C1 GGHIWYYHMKZSRN-YPMHNXCESA-N 0.000 description 1
• SYYVJJWPPNEPGD-DTORHVGOSA-N tert-butyl (1s,5r)-3-oxa-7,9-diazabicyclo[3.3.1]nonane-7-carboxylate Chemical compound C1OC[C@]2([H])CN(C(=O)OC(C)(C)C)C[C@@]1([H])N2 SYYVJJWPPNEPGD-DTORHVGOSA-N 0.000 description 1
• LIMIYNARSUPELM-RBBKRZOGSA-N tert-butyl (1s,6r)-4-[6-[[7-cyclopentyl-6-(methylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-3-oxo-4,9-diazabicyclo[4.2.1]nonane-9-carboxylate Chemical compound C([C@@]1(CC[C@](C2)(N1C(=O)OC(C)(C)C)[H])[H])C(=O)N2C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)NC)N2C1CCCC1 LIMIYNARSUPELM-RBBKRZOGSA-N 0.000 description 1
• BQFMMOCNINXPIC-JGVFFNPUSA-N tert-butyl (3as,6as)-3-oxo-1,2,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound C1NC(=O)[C@@H]2CN(C(=O)OC(C)(C)C)C[C@@H]21 BQFMMOCNINXPIC-JGVFFNPUSA-N 0.000 description 1
• WOJHEUJHISCHAZ-GOSISDBHSA-N tert-butyl (5r)-3-(6-aminopyridin-3-yl)-2-oxo-1-oxa-3,9-diazaspiro[4.6]undecane-9-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC[C@@]11OC(=O)N(C=2C=NC(N)=CC=2)C1 WOJHEUJHISCHAZ-GOSISDBHSA-N 0.000 description 1
• JYWJGLHBWRDOQT-KRWDZBQOSA-N tert-butyl (5s)-3-(6-aminopyridin-3-yl)-2-oxo-1-oxa-3,9-diazaspiro[4.5]decane-9-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC[C@]11OC(=O)N(C=2C=NC(N)=CC=2)C1 JYWJGLHBWRDOQT-KRWDZBQOSA-N 0.000 description 1
• WOJHEUJHISCHAZ-SFHVURJKSA-N tert-butyl (5s)-3-(6-aminopyridin-3-yl)-2-oxo-1-oxa-3,9-diazaspiro[4.6]undecane-9-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC[C@]11OC(=O)N(C=2C=NC(N)=CC=2)C1 WOJHEUJHISCHAZ-SFHVURJKSA-N 0.000 description 1
• XXEUMFFRQBTVIP-UHFFFAOYSA-N tert-butyl 1'-(6-nitropyridin-3-yl)-2'-oxospiro[8-azabicyclo[3.2.1]octane-3,4'-pyrrolidine]-8-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCC1CC2(CC1=O)CN1C1=CC=C([N+]([O-])=O)N=C1 XXEUMFFRQBTVIP-UHFFFAOYSA-N 0.000 description 1
• SYOGSWOEAYVNNO-UHFFFAOYSA-N tert-butyl 1'-[6-[[6-(dimethylcarbamoyl)-7-(oxan-3-yl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-2'-oxospiro[8-azabicyclo[3.2.1]octane-3,4'-pyrrolidine]-8-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(CC4(C3)CC3CCC(N3C(=O)OC(C)(C)C)C4)=O)N=C2N1C1CCCOC1 SYOGSWOEAYVNNO-UHFFFAOYSA-N 0.000 description 1
• ASQYESNEKNOSJZ-UHFFFAOYSA-N tert-butyl 1'-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-2'-oxospiro[8-azabicyclo[3.2.1]octane-3,4'-pyrrolidine]-8-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(CC4(C3)CC3CCC(N3C(=O)OC(C)(C)C)C4)=O)N=C2N1C1CCCC1 ASQYESNEKNOSJZ-UHFFFAOYSA-N 0.000 description 1
• FYUVLZRRIRGSTE-UHFFFAOYSA-N tert-butyl 2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound C1NCC2CN(C(=O)OC(C)(C)C)CC21 FYUVLZRRIRGSTE-UHFFFAOYSA-N 0.000 description 1
• KVOUHLVOTMOJBS-UHFFFAOYSA-N tert-butyl 2,6-diazaspiro[3.3]heptane-2-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC11CNC1 KVOUHLVOTMOJBS-UHFFFAOYSA-N 0.000 description 1
• HWLNKJXLGQVMJH-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[3.5]nonane-2-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC21CCNCC2 HWLNKJXLGQVMJH-UHFFFAOYSA-N 0.000 description 1
• WEEMVXIMHUFIHA-UHFFFAOYSA-N tert-butyl 2-(6-nitropyridin-3-yl)-3-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC11CC(=O)N(C=2C=NC(=CC=2)[N+]([O-])=O)C1 WEEMVXIMHUFIHA-UHFFFAOYSA-N 0.000 description 1
• OBOAAUFXVIQOAA-UHFFFAOYSA-N tert-butyl 2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-6-carboxylate Chemical compound O=C1OC2(CN1)C(CNCC2)C(=O)OC(C)(C)C OBOAAUFXVIQOAA-UHFFFAOYSA-N 0.000 description 1
• XMXWDVORJLWWCH-UHFFFAOYSA-N tert-butyl 2-oxo-1-oxa-3,9-diazaspiro[4.5]decane-9-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11OC(=O)NC1 XMXWDVORJLWWCH-UHFFFAOYSA-N 0.000 description 1
• HLWBAHUDEBFOOU-UHFFFAOYSA-N tert-butyl 2-oxo-1-oxa-3,9-diazaspiro[4.6]undecane-9-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCCC11OC(=O)NC1 HLWBAHUDEBFOOU-UHFFFAOYSA-N 0.000 description 1
• CSQBUSQTOWHXLW-UHFFFAOYSA-N tert-butyl 3,6-diazabicyclo[3.2.1]octane-6-carboxylate Chemical compound C1C2N(C(=O)OC(C)(C)C)CC1CNC2 CSQBUSQTOWHXLW-UHFFFAOYSA-N 0.000 description 1
• WFFPBJQQZGNFCW-UHFFFAOYSA-N tert-butyl 3-[6-[[7-(1-tert-butylpiperidin-4-yl)-6-(dimethylcarbamoyl)-1,2-dihydropyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound C(C)(C)(C)OC(=O)N1C2CN(CC1CC2)C(=O)C=1C=NC(=CC=1)NC1N=CC2=C(N1)N(C(=C2)C(N(C)C)=O)C1CCN(CC1)C(C)(C)C WFFPBJQQZGNFCW-UHFFFAOYSA-N 0.000 description 1
• CILGQNZXZZOHET-UHFFFAOYSA-N tert-butyl 3-[6-[[7-cycloheptyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4C(=O)OC(C)(C)C)C3)N=C2N1C1CCCCCC1 CILGQNZXZZOHET-UHFFFAOYSA-N 0.000 description 1
• ADIHYABTTDWDQJ-UHFFFAOYSA-N tert-butyl 3-[6-[[7-cyclohexyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4C(=O)OC(C)(C)C)C3)N=C2N1C1CCCCC1 ADIHYABTTDWDQJ-UHFFFAOYSA-N 0.000 description 1
• RRRVXJPOMODHGI-UHFFFAOYSA-N tert-butyl 3-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]-4-methylpyridine-3-carbonyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=C(C)C=3)C(=O)N3CC4CCC(N4C(=O)OC(C)(C)C)C3)N=C2N1C1CCCC1 RRRVXJPOMODHGI-UHFFFAOYSA-N 0.000 description 1
• SMVSPLNEEXXVEA-UHFFFAOYSA-N tert-butyl 3-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-2-oxo-1-oxa-3,9-diazaspiro[4.5]decane-9-carboxylate Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N(C(O1)=O)CC21CCCN(C(=O)OC(C)(C)C)C2 SMVSPLNEEXXVEA-UHFFFAOYSA-N 0.000 description 1
• NEKXRMIVDZGVOF-UHFFFAOYSA-N tert-butyl 3-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-3,9-diazabicyclo[3.3.1]nonane-9-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCCC(N4C(=O)OC(C)(C)C)C3)N=C2N1C1CCCC1 NEKXRMIVDZGVOF-UHFFFAOYSA-N 0.000 description 1
• MASXHWHKDFQBHX-UHFFFAOYSA-N tert-butyl 3-benzyl-3,9-diazabicyclo[3.3.1]nonane-9-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCCC1CN2CC1=CC=CC=C1 MASXHWHKDFQBHX-UHFFFAOYSA-N 0.000 description 1
• FZDUEORZXQGBEC-UHFFFAOYSA-N tert-butyl 3-oxo-4,9-diazabicyclo[4.2.1]nonane-9-carboxylate Chemical compound C1NC(=O)CC2CCC1N2C(=O)OC(C)(C)C FZDUEORZXQGBEC-UHFFFAOYSA-N 0.000 description 1
• IDJDDPDWYRVJPF-UHFFFAOYSA-N tert-butyl 4,9-diazabicyclo[4.2.1]nonane-9-carboxylate Chemical compound C1CNCC2CCC1N2C(=O)OC(C)(C)C IDJDDPDWYRVJPF-UHFFFAOYSA-N 0.000 description 1
• NLQYXKVXZFENMF-UHFFFAOYSA-N tert-butyl 4-(6-aminopyridin-3-yl)-3-oxo-8-oxa-4,10-diazabicyclo[4.3.1]decane-10-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)COCC1CC(=O)N2C1=CC=C(N)N=C1 NLQYXKVXZFENMF-UHFFFAOYSA-N 0.000 description 1
• PEDGODRBOPTSAI-UHFFFAOYSA-N tert-butyl 5-(6-aminopyridin-3-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC2CC1CN2C1=CC=C(N)N=C1 PEDGODRBOPTSAI-UHFFFAOYSA-N 0.000 description 1
• FRRJOGZKKTXZQC-UHFFFAOYSA-N tert-butyl 5-(6-aminopyridin-3-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate;tert-butyl 5-(6-nitropyridin-3-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC2CC1CN2C1=CC=C(N)N=C1.CC(C)(C)OC(=O)N1CC2CC1CN2C1=CC=C([N+]([O-])=O)N=C1 FRRJOGZKKTXZQC-UHFFFAOYSA-N 0.000 description 1
• IXKNPSLHUPHNQK-UHFFFAOYSA-N tert-butyl 5-(6-aminopyridine-3-carbonyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC2CC1CN2C(=O)C1=CC=C(N)N=C1 IXKNPSLHUPHNQK-UHFFFAOYSA-N 0.000 description 1
• BBCMXUSDDGEGQP-UHFFFAOYSA-N tert-butyl 5-benzyl-3,9-diazabicyclo[3.3.1]nonane-9-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(CNC2)CCCC12CC1=CC=CC=C1 BBCMXUSDDGEGQP-UHFFFAOYSA-N 0.000 description 1
• QLGXGUMGAGRXGT-UHFFFAOYSA-N tert-butyl 7-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CN(CC(O4)C3)C(=O)OC(C)(C)C)N=C2N1C1CCCC1 QLGXGUMGAGRXGT-UHFFFAOYSA-N 0.000 description 1
• FQECAYIXVHVQPO-UHFFFAOYSA-N tert-butyl 8-oxa-4,10-diazabicyclo[4.3.1]decane-10-carboxylate Chemical compound C1CNCC2COCC1N2C(=O)OC(C)(C)C FQECAYIXVHVQPO-UHFFFAOYSA-N 0.000 description 1
• MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
• QIYOMZXJQAKHEK-DHBOJHSNSA-N tert-butyl n-[(1r,5s)-3-azabicyclo[3.1.0]hexan-6-yl]carbamate Chemical compound C1NC[C@H]2C(NC(=O)OC(C)(C)C)[C@H]21 QIYOMZXJQAKHEK-DHBOJHSNSA-N 0.000 description 1
• YSQUMWRBEUYICX-UHFFFAOYSA-N tert-butyl n-[3-(6-aminopyridin-3-yl)-3-azabicyclo[3.1.0]hexan-1-yl]carbamate Chemical compound C1C2(NC(=O)OC(C)(C)C)CC2CN1C1=CC=C(N)N=C1 YSQUMWRBEUYICX-UHFFFAOYSA-N 0.000 description 1
• NJAZHDRMYRUBKM-UHFFFAOYSA-N tert-butyl n-[3-[6-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]-3-azabicyclo[3.1.0]hexan-1-yl]carbamate Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3CC4(CC4C3)NC(=O)OC(C)(C)C)N=C2N1C1CCCC1 NJAZHDRMYRUBKM-UHFFFAOYSA-N 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 125000006337 tetrafluoro ethyl group Chemical group 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 231100001274 therapeutic index Toxicity 0.000 description 1
• 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 1
• 238000003354 tissue distribution assay Methods 0.000 description 1
• 238000004448 titration Methods 0.000 description 1
• 238000000954 titration curve Methods 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
• 239000012443 tonicity enhancing agent Substances 0.000 description 1
• 239000003053 toxin Substances 0.000 description 1
• 231100000765 toxin Toxicity 0.000 description 1
• 108700012359 toxins Proteins 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 230000037317 transdermal delivery Effects 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
• 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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
• 239000002753 trypsin inhibitor Substances 0.000 description 1
• 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 1
• 239000002452 tumor necrosis factor alpha inhibitor Substances 0.000 description 1
• 241000701161 unidentified adenovirus Species 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1
• 241001529453 unidentified herpesvirus Species 0.000 description 1
• 238000011144 upstream manufacturing Methods 0.000 description 1
• 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
• 229940099039 velcade Drugs 0.000 description 1
• 230000035899 viability Effects 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 239000011534 wash buffer Substances 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1