JP5781943B2 - 炎症性疾患、自己免疫疾患または増殖性疾患の治療に有用なｎ２−（３−ピリジルまたはフェニル）−ｎ４−（４−ピペリジル）−２，４−ピリミジンジアミン誘導体 - Google Patents
炎症性疾患、自己免疫疾患または増殖性疾患の治療に有用なｎ２−（３−ピリジルまたはフェニル）−ｎ４−（４−ピペリジル）−２，４−ピリミジンジアミン誘導体 Download PDFInfo
- Publication number
- JP5781943B2 JP5781943B2 JP2011546451A JP2011546451A JP5781943B2 JP 5781943 B2 JP5781943 B2 JP 5781943B2 JP 2011546451 A JP2011546451 A JP 2011546451A JP 2011546451 A JP2011546451 A JP 2011546451A JP 5781943 B2 JP5781943 B2 JP 5781943B2
- Authority
- JP
- Japan
- Prior art keywords
- substituted
- alkyl
- fluoro
- phenyl
- cycloalkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 98
- 201000010099 disease Diseases 0.000 title claims description 51
- 208000023275 Autoimmune disease Diseases 0.000 title claims description 13
- 238000011282 treatment Methods 0.000 title claims description 11
- 208000027866 inflammatory disease Diseases 0.000 title claims description 8
- 230000002062 proliferating effect Effects 0.000 title description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title description 5
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 title 1
- -1 amino, substituted amino, carboxyl Chemical group 0.000 claims description 478
- 125000000217 alkyl group Chemical group 0.000 claims description 356
- 150000001875 compounds Chemical class 0.000 claims description 267
- 229910052739 hydrogen Inorganic materials 0.000 claims description 224
- 239000001257 hydrogen Substances 0.000 claims description 223
- 125000000623 heterocyclic group Chemical group 0.000 claims description 220
- 125000001072 heteroaryl group Chemical group 0.000 claims description 206
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 187
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 156
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 148
- 125000003118 aryl group Chemical group 0.000 claims description 129
- 125000002252 acyl group Chemical group 0.000 claims description 115
- 125000003545 alkoxy group Chemical group 0.000 claims description 95
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 89
- 229910052736 halogen Inorganic materials 0.000 claims description 77
- 125000003342 alkenyl group Chemical group 0.000 claims description 76
- 150000002367 halogens Chemical class 0.000 claims description 76
- 125000000304 alkynyl group Chemical group 0.000 claims description 73
- 150000003839 salts Chemical class 0.000 claims description 73
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 73
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 72
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 71
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 69
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 67
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 62
- 125000003107 substituted aryl group Chemical group 0.000 claims description 53
- 125000004442 acylamino group Chemical group 0.000 claims description 50
- 208000035475 disorder Diseases 0.000 claims description 47
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 43
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 42
- 229910052757 nitrogen Inorganic materials 0.000 claims description 42
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 40
- 230000001404 mediated effect Effects 0.000 claims description 36
- 206010028980 Neoplasm Diseases 0.000 claims description 35
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 33
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 32
- 125000001153 fluoro group Chemical group F* 0.000 claims description 30
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 23
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 21
- 230000002757 inflammatory effect Effects 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 15
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- 208000015181 infectious disease Diseases 0.000 claims description 14
- 125000004414 alkyl thio group Chemical group 0.000 claims description 13
- TVNUWQIRTYYTNN-UHFFFAOYSA-N 5-fluoro-4-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)-6-phenylpyrimidine-2,4-diamine Chemical compound C1(=CC=CC=C1)C1=C(C(=NC(=N1)N)NC1CC(N(C(C1)(C)C)C)(C)C)F TVNUWQIRTYYTNN-UHFFFAOYSA-N 0.000 claims description 11
- 201000011510 cancer Diseases 0.000 claims description 10
- 150000001721 carbon Chemical group 0.000 claims description 10
- 206010061218 Inflammation Diseases 0.000 claims description 9
- 230000004054 inflammatory process Effects 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims description 9
- 201000004624 Dermatitis Diseases 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- PCJSQXQRMJJBBS-UHFFFAOYSA-N 4-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)-5-phenylpyrimidine-2,4-diamine Chemical compound C1(=CC=CC=C1)C=1C(=NC(=NC=1)N)NC1CC(N(C(C1)(C)C)C)(C)C PCJSQXQRMJJBBS-UHFFFAOYSA-N 0.000 claims description 7
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 7
- 230000001154 acute effect Effects 0.000 claims description 7
- 230000002491 angiogenic effect Effects 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 208000011580 syndromic disease Diseases 0.000 claims description 7
- 206010019280 Heart failures Diseases 0.000 claims description 6
- 201000004681 Psoriasis Diseases 0.000 claims description 6
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
- 230000033115 angiogenesis Effects 0.000 claims description 6
- 208000006673 asthma Diseases 0.000 claims description 6
- 125000002837 carbocyclic group Chemical group 0.000 claims description 6
- 208000037976 chronic inflammation Diseases 0.000 claims description 6
- 208000028867 ischemia Diseases 0.000 claims description 6
- 201000006417 multiple sclerosis Diseases 0.000 claims description 6
- 208000010125 myocardial infarction Diseases 0.000 claims description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 6
- 208000011231 Crohn disease Diseases 0.000 claims description 5
- 206010012442 Dermatitis contact Diseases 0.000 claims description 5
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 5
- 208000035895 Guillain-Barré syndrome Diseases 0.000 claims description 5
- 206010020751 Hypersensitivity Diseases 0.000 claims description 5
- 206010049567 Miller Fisher syndrome Diseases 0.000 claims description 5
- 208000006011 Stroke Diseases 0.000 claims description 5
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 5
- 206010046851 Uveitis Diseases 0.000 claims description 5
- 230000007815 allergy Effects 0.000 claims description 5
- 208000030533 eye disease Diseases 0.000 claims description 5
- 208000024908 graft versus host disease Diseases 0.000 claims description 5
- 230000003463 hyperproliferative effect Effects 0.000 claims description 5
- 206010023332 keratitis Diseases 0.000 claims description 5
- 201000010666 keratoconjunctivitis Diseases 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- 238000002054 transplantation Methods 0.000 claims description 5
- BFMGOJBQXYYXLG-UHFFFAOYSA-N 2-n-[3-(2,5-dimethylpyrrol-1-yl)-4-(2-morpholin-4-ylethoxy)phenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(OCCN3CCOCC3)=CC=2)N2C(=CC=C2C)C)=NC=C1F BFMGOJBQXYYXLG-UHFFFAOYSA-N 0.000 claims description 4
- YKFGBWVAVVOOQP-UHFFFAOYSA-N 2-n-[3-(2,5-dimethylpyrrol-1-yl)-4-(2-morpholin-4-ylethoxy)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound CC1=CC=C(C)N1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC=C1OCCN1CCOCC1 YKFGBWVAVVOOQP-UHFFFAOYSA-N 0.000 claims description 4
- QIPDYHFWFMMPQM-UHFFFAOYSA-N 2-n-[3-(2,5-dimethylpyrrol-1-yl)-4-(2-pyrrolidin-1-ylethoxy)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound CC1=CC=C(C)N1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC=C1OCCN1CCCC1 QIPDYHFWFMMPQM-UHFFFAOYSA-N 0.000 claims description 4
- DFVSXLDAJLVVLH-UHFFFAOYSA-N 5-fluoro-2-n-[3-methoxy-5-(2-morpholin-4-ylethoxy)phenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C=1C(OCCN2CCOCC2)=CC(OC)=CC=1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)N(C)C(C)(C)C1 DFVSXLDAJLVVLH-UHFFFAOYSA-N 0.000 claims description 4
- JAUBLXVJBSZVSH-UHFFFAOYSA-N 5-fluoro-2-n-[3-methoxy-5-(2-morpholin-4-ylethoxy)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C=1C(OCCN2CCOCC2)=CC(OC)=CC=1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 JAUBLXVJBSZVSH-UHFFFAOYSA-N 0.000 claims description 4
- VTKJXOMDTPRGOL-UHFFFAOYSA-N 5-fluoro-2-n-[3-methoxy-5-(2-pyrrol-1-ylethoxy)phenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C=1C(OCCN2C=CC=C2)=CC(OC)=CC=1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)N(C)C(C)(C)C1 VTKJXOMDTPRGOL-UHFFFAOYSA-N 0.000 claims description 4
- BUUNPQCCBUNUSR-UHFFFAOYSA-N 5-fluoro-2-n-[3-methoxy-5-(2-pyrrol-1-ylethoxy)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C=1C(OCCN2C=CC=C2)=CC(OC)=CC=1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 BUUNPQCCBUNUSR-UHFFFAOYSA-N 0.000 claims description 4
- HTGWTCFYVDIVPK-UHFFFAOYSA-N 5-fluoro-2-n-[3-methoxy-5-(2-pyrrolidin-1-ylethoxy)phenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C=1C(OCCN2CCCC2)=CC(OC)=CC=1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)N(C)C(C)(C)C1 HTGWTCFYVDIVPK-UHFFFAOYSA-N 0.000 claims description 4
- BFCNQMNRCLSWEV-UHFFFAOYSA-N 5-fluoro-2-n-[3-methoxy-5-(2-pyrrolidin-1-ylethoxy)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C=1C(OCCN2CCCC2)=CC(OC)=CC=1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 BFCNQMNRCLSWEV-UHFFFAOYSA-N 0.000 claims description 4
- 208000030507 AIDS Diseases 0.000 claims description 4
- 208000030090 Acute Disease Diseases 0.000 claims description 4
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 4
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 4
- 208000030836 Hashimoto thyroiditis Diseases 0.000 claims description 4
- 208000032456 Hemorrhagic Shock Diseases 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 206010022680 Intestinal ischaemia Diseases 0.000 claims description 4
- 208000019693 Lung disease Diseases 0.000 claims description 4
- 208000013901 Nephropathies and tubular disease Diseases 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 4
- 206010039793 Seborrhoeic dermatitis Diseases 0.000 claims description 4
- 206010040070 Septic Shock Diseases 0.000 claims description 4
- 206010049771 Shock haemorrhagic Diseases 0.000 claims description 4
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 4
- 208000031709 Skin Manifestations Diseases 0.000 claims description 4
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 4
- 206010044541 Traumatic shock Diseases 0.000 claims description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
- 208000024248 Vascular System injury Diseases 0.000 claims description 4
- 208000012339 Vascular injury Diseases 0.000 claims description 4
- 206010053648 Vascular occlusion Diseases 0.000 claims description 4
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 4
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 4
- 208000002029 allergic contact dermatitis Diseases 0.000 claims description 4
- 201000008937 atopic dermatitis Diseases 0.000 claims description 4
- 208000010668 atopic eczema Diseases 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 208000015114 central nervous system disease Diseases 0.000 claims description 4
- 208000037893 chronic inflammatory disorder Diseases 0.000 claims description 4
- 208000001875 irritant dermatitis Diseases 0.000 claims description 4
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 4
- 208000019423 liver disease Diseases 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 201000008482 osteoarthritis Diseases 0.000 claims description 4
- 201000009104 prediabetes syndrome Diseases 0.000 claims description 4
- 208000023504 respiratory system disease Diseases 0.000 claims description 4
- 208000037803 restenosis Diseases 0.000 claims description 4
- 208000008742 seborrheic dermatitis Diseases 0.000 claims description 4
- 230000036303 septic shock Effects 0.000 claims description 4
- 208000017520 skin disease Diseases 0.000 claims description 4
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 4
- 230000009529 traumatic brain injury Effects 0.000 claims description 4
- 208000021331 vascular occlusion disease Diseases 0.000 claims description 4
- SYYSBZOSEAUMEY-UHFFFAOYSA-N 1,1,1-trifluoro-2-$l^{1}-sulfanylethane Chemical group FC(F)(F)C[S] SYYSBZOSEAUMEY-UHFFFAOYSA-N 0.000 claims description 3
- RQHZHEIDLQGEFL-UHFFFAOYSA-N 2-n-[3-(2,5-dimethylpyrrol-1-yl)-4-(2-pyrrolidin-1-ylethoxy)phenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(OCCN3CCCC3)=CC=2)N2C(=CC=C2C)C)=NC=C1F RQHZHEIDLQGEFL-UHFFFAOYSA-N 0.000 claims description 3
- 208000022461 Glomerular disease Diseases 0.000 claims description 3
- 241001465754 Metazoa Species 0.000 claims description 3
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 3
- 206010063837 Reperfusion injury Diseases 0.000 claims description 3
- 201000006370 kidney failure Diseases 0.000 claims description 3
- 206010028417 myasthenia gravis Diseases 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 201000010065 polycystic ovary syndrome Diseases 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 208000026935 allergic disease Diseases 0.000 claims description 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 2
- 206010028289 Muscle atrophy Diseases 0.000 claims 2
- 201000010901 lateral sclerosis Diseases 0.000 claims 2
- 208000005264 motor neuron disease Diseases 0.000 claims 2
- 230000020763 muscle atrophy Effects 0.000 claims 2
- 201000000585 muscular atrophy Diseases 0.000 claims 2
- 125000001845 4 membered carbocyclic group Chemical group 0.000 claims 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims 1
- 102000003923 Protein Kinase C Human genes 0.000 description 67
- 108090000315 Protein Kinase C Proteins 0.000 description 67
- 238000000034 method Methods 0.000 description 66
- 125000001424 substituent group Chemical group 0.000 description 61
- 210000004027 cell Anatomy 0.000 description 53
- 125000000392 cycloalkenyl group Chemical group 0.000 description 51
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 51
- 239000000203 mixture Substances 0.000 description 37
- 230000000694 effects Effects 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 31
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 30
- 125000005843 halogen group Chemical group 0.000 description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 28
- YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical compound NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 description 28
- 238000003556 assay Methods 0.000 description 27
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 27
- 238000006467 substitution reaction Methods 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Natural products CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 24
- 241000700605 Viruses Species 0.000 description 24
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 24
- 125000003277 amino group Chemical group 0.000 description 23
- 239000012453 solvate Substances 0.000 description 23
- 238000003786 synthesis reaction Methods 0.000 description 22
- 108010029485 Protein Isoforms Proteins 0.000 description 21
- 102000001708 Protein Isoforms Human genes 0.000 description 21
- 238000005859 coupling reaction Methods 0.000 description 21
- 230000015572 biosynthetic process Effects 0.000 description 19
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 18
- 150000003536 tetrazoles Chemical class 0.000 description 18
- 125000005309 thioalkoxy group Chemical group 0.000 description 18
- 150000001412 amines Chemical class 0.000 description 17
- 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 17
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 16
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 16
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 16
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 16
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 16
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 16
- 238000009472 formulation Methods 0.000 description 16
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 235000019441 ethanol Nutrition 0.000 description 15
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 14
- 125000002947 alkylene group Chemical group 0.000 description 14
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- 239000003112 inhibitor Substances 0.000 description 14
- 125000006239 protecting group Chemical group 0.000 description 14
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 13
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 239000007858 starting material Substances 0.000 description 13
- YCBKWEWWGGPBAM-UHFFFAOYSA-N 5-phenyl-4-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1(=CC=CC=C1)C=1C(=NC(=NC=1)N)NC1CC(NC(C1)(C)C)(C)C YCBKWEWWGGPBAM-UHFFFAOYSA-N 0.000 description 12
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 12
- 239000005977 Ethylene Substances 0.000 description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 12
- 125000002577 pseudohalo group Chemical group 0.000 description 12
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 11
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 11
- 239000002953 phosphate buffered saline Substances 0.000 description 11
- 108010044467 Isoenzymes Proteins 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 125000004181 carboxyalkyl group Chemical group 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 10
- 150000004820 halides Chemical class 0.000 description 10
- 208000032839 leukemia Diseases 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 10
- 229940002612 prodrug Drugs 0.000 description 10
- 239000000651 prodrug Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 9
- 208000017604 Hodgkin disease Diseases 0.000 description 9
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 9
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 9
- 125000004423 acyloxy group Chemical group 0.000 description 9
- 125000004429 atom Chemical group 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 125000000524 functional group Chemical group 0.000 description 9
- 125000005553 heteroaryloxy group Chemical group 0.000 description 9
- 125000005842 heteroatom Chemical group 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 125000003386 piperidinyl group Chemical group 0.000 description 9
- 125000005296 thioaryloxy group Chemical group 0.000 description 9
- 150000003573 thiols Chemical class 0.000 description 9
- 125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 description 8
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 8
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 8
- VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 8
- VLRSADZEDXVUPG-UHFFFAOYSA-N 2-naphthalen-1-ylpyridine Chemical compound N1=CC=CC=C1C1=CC=CC2=CC=CC=C12 VLRSADZEDXVUPG-UHFFFAOYSA-N 0.000 description 8
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 8
- 208000012526 B-cell neoplasm Diseases 0.000 description 8
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 125000004104 aryloxy group Chemical group 0.000 description 8
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 8
- 150000001540 azides Chemical class 0.000 description 8
- 239000011575 calcium Substances 0.000 description 8
- 125000002541 furyl group Chemical group 0.000 description 8
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 8
- 125000004470 heterocyclooxy group Chemical group 0.000 description 8
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 8
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 8
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 8
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 8
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 8
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 8
- 229910052751 metal Inorganic materials 0.000 description 8
- 239000002184 metal Substances 0.000 description 8
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 8
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 8
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 8
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 8
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 8
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 8
- 210000000130 stem cell Anatomy 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 125000005404 thioheteroaryloxy group Chemical group 0.000 description 8
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 8
- 229930192474 thiophene Natural products 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 150000003852 triazoles Chemical class 0.000 description 8
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 7
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 7
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 7
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 7
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 7
- 102100024924 Protein kinase C alpha type Human genes 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 125000000033 alkoxyamino group Chemical group 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 239000002552 dosage form Substances 0.000 description 7
- 230000014509 gene expression Effects 0.000 description 7
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 7
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 7
- 125000004043 oxo group Chemical group O=* 0.000 description 7
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 7
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 7
- 125000005323 thioketone group Chemical group 0.000 description 7
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 6
- FUFZNHHSSMCXCZ-UHFFFAOYSA-N 5-piperidin-4-yl-3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C1=CC=CC(C=2N=C(ON=2)C2CCNCC2)=C1 FUFZNHHSSMCXCZ-UHFFFAOYSA-N 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- 101001051777 Homo sapiens Protein kinase C alpha type Proteins 0.000 description 6
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 6
- 108010002350 Interleukin-2 Proteins 0.000 description 6
- 102000000588 Interleukin-2 Human genes 0.000 description 6
- 208000022873 Ocular disease Diseases 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 102000001253 Protein Kinase Human genes 0.000 description 6
- 230000006044 T cell activation Effects 0.000 description 6
- 208000025317 T-cell and NK-cell neoplasm Diseases 0.000 description 6
- 230000002159 abnormal effect Effects 0.000 description 6
- 125000003725 azepanyl group Chemical group 0.000 description 6
- 125000002393 azetidinyl group Chemical group 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 6
- 125000001033 ether group Chemical group 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 210000004698 lymphocyte Anatomy 0.000 description 6
- 125000005255 oxyaminoacyl group Chemical group 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 210000004986 primary T-cell Anatomy 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- 108060006633 protein kinase Proteins 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000010561 standard procedure Methods 0.000 description 6
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 6
- 229910052717 sulfur Chemical group 0.000 description 6
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 125000004953 trihalomethyl group Chemical group 0.000 description 6
- 229940035893 uracil Drugs 0.000 description 6
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
- 206010006187 Breast cancer Diseases 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 5
- 206010061187 Haematopoietic neoplasm Diseases 0.000 description 5
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 5
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 5
- 208000014767 Myeloproliferative disease Diseases 0.000 description 5
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 5
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- 108091008874 T cell receptors Proteins 0.000 description 5
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 5
- 206010042971 T-cell lymphoma Diseases 0.000 description 5
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 229910052791 calcium Inorganic materials 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 235000019253 formic acid Nutrition 0.000 description 5
- 201000005787 hematologic cancer Diseases 0.000 description 5
- 150000002391 heterocyclic compounds Chemical class 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 208000003747 lymphoid leukemia Diseases 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 5
- 150000003230 pyrimidines Chemical class 0.000 description 5
- 230000009257 reactivity Effects 0.000 description 5
- 239000000829 suppository Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical group CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical compound ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 4
- QRUXQNJTEVLAJM-UHFFFAOYSA-N 5-fluoro-6-phenyl-4-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1(=CC=CC=C1)C1=C(C(=NC(=N1)N)NC1CC(NC(C1)(C)C)(C)C)F QRUXQNJTEVLAJM-UHFFFAOYSA-N 0.000 description 4
- 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 4
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 4
- 208000007766 Kaposi sarcoma Diseases 0.000 description 4
- 108060001084 Luciferase Proteins 0.000 description 4
- 206010025323 Lymphomas Diseases 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 101100335081 Mus musculus Flt3 gene Proteins 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- 101150077555 Ret gene Proteins 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 238000006069 Suzuki reaction reaction Methods 0.000 description 4
- 102000000551 Syk Kinase Human genes 0.000 description 4
- 108010016672 Syk Kinase Proteins 0.000 description 4
- 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 description 4
- 101710112791 Tyrosine-protein kinase JAK2 Proteins 0.000 description 4
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 4
- 201000006966 adult T-cell leukemia Diseases 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 150000004982 aromatic amines Chemical class 0.000 description 4
- 150000001502 aryl halides Chemical class 0.000 description 4
- 229940098773 bovine serum albumin Drugs 0.000 description 4
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
- 239000008120 corn starch Substances 0.000 description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- 208000037765 diseases and disorders Diseases 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 125000001183 hydrocarbyl group Chemical group 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 150000007522 mineralic acids Chemical class 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 239000012038 nucleophile Substances 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 230000002093 peripheral effect Effects 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 150000003141 primary amines Chemical class 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000003586 protic polar solvent Substances 0.000 description 4
- 125000006413 ring segment Chemical group 0.000 description 4
- 150000003335 secondary amines Chemical class 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000011593 sulfur Chemical group 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 3
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 3
- JVQIKJMSUIMUDI-UHFFFAOYSA-N 3-pyrroline Chemical compound C1NCC=C1 JVQIKJMSUIMUDI-UHFFFAOYSA-N 0.000 description 3
- GMMWNTHAIOJBSD-UHFFFAOYSA-N 6-chloro-4-n-(2,3-dimethylphenyl)-2-n,2-n-dimethylpyrimidine-2,4-diamine Chemical compound CN(C)C1=NC(Cl)=CC(NC=2C(=C(C)C=CC=2)C)=N1 GMMWNTHAIOJBSD-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 208000011691 Burkitt lymphomas Diseases 0.000 description 3
- 208000031404 Chromosome Aberrations Diseases 0.000 description 3
- 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 3
- 238000002965 ELISA Methods 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 229920001917 Ficoll Polymers 0.000 description 3
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 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
- 239000005089 Luciferase Substances 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 208000033833 Myelomonocytic Chronic Leukemia Diseases 0.000 description 3
- 108700020796 Oncogene Proteins 0.000 description 3
- 108091000080 Phosphotransferase Proteins 0.000 description 3
- 108010015499 Protein Kinase C-theta Proteins 0.000 description 3
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 3
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 3
- 239000007868 Raney catalyst Substances 0.000 description 3
- 229910000564 Raney nickel Inorganic materials 0.000 description 3
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 3
- 208000017442 Retinal disease Diseases 0.000 description 3
- 238000006619 Stille reaction Methods 0.000 description 3
- 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 3
- 206010052779 Transplant rejections Diseases 0.000 description 3
- 208000036142 Viral infection Diseases 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 3
- 125000002877 alkyl aryl group Chemical group 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 201000010902 chronic myelomonocytic leukemia Diseases 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 238000002875 fluorescence polarization Methods 0.000 description 3
- 229960002949 fluorouracil Drugs 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 230000003394 haemopoietic effect Effects 0.000 description 3
- 125000004438 haloalkoxy group Chemical group 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 3
- PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 206010025135 lupus erythematosus Diseases 0.000 description 3
- 208000019420 lymphoid neoplasm Diseases 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 125000002757 morpholinyl group Chemical group 0.000 description 3
- 201000000050 myeloid neoplasm Diseases 0.000 description 3
- 235000005985 organic acids Nutrition 0.000 description 3
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 102000020233 phosphotransferase Human genes 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 229910003446 platinum oxide Inorganic materials 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229920001592 potato starch Polymers 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 3
- 125000003226 pyrazolyl group Chemical group 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- UAWABSHMGXMCRK-UHFFFAOYSA-L samarium(ii) iodide Chemical compound I[Sm]I UAWABSHMGXMCRK-UHFFFAOYSA-L 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 239000013589 supplement Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 125000003831 tetrazolyl group Chemical group 0.000 description 3
- 230000005945 translocation Effects 0.000 description 3
- 125000001425 triazolyl group Chemical group 0.000 description 3
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 3
- 230000009385 viral infection Effects 0.000 description 3
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- WHPFEQUEHBULBW-UHFFFAOYSA-N 2,4-dichloro-5-fluoropyrimidine Chemical compound FC1=CN=C(Cl)N=C1Cl WHPFEQUEHBULBW-UHFFFAOYSA-N 0.000 description 2
- 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 2
- ASSKVPFEZFQQNQ-UHFFFAOYSA-N 2-benzoxazolinone Chemical compound C1=CC=C2OC(O)=NC2=C1 ASSKVPFEZFQQNQ-UHFFFAOYSA-N 0.000 description 2
- UOWWJSZPWAQBQK-UHFFFAOYSA-N 2-n-[3-cyclopropyl-5-(1-methyltetrazol-5-yl)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound CN1N=NN=C1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC(C2CC2)=C1 UOWWJSZPWAQBQK-UHFFFAOYSA-N 0.000 description 2
- DFYIBNINAOPFOZ-UHFFFAOYSA-N 2-n-[3-cyclopropyl-5-(tetrazol-1-yl)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(C=C(C=2)C2CC2)N2N=NN=C2)=NC=C1F DFYIBNINAOPFOZ-UHFFFAOYSA-N 0.000 description 2
- PNZLGDLGWOXSRK-UHFFFAOYSA-N 2-n-[4-cyclopropyl-3-(1-methyltetrazol-5-yl)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound CN1N=NN=C1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC=C1C1CC1 PNZLGDLGWOXSRK-UHFFFAOYSA-N 0.000 description 2
- MQQIZFQCEPINDF-UHFFFAOYSA-N 2-n-[4-cyclopropyl-3-(tetrazol-1-yl)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(C(C3CC3)=CC=2)N2N=NN=C2)=NC=C1F MQQIZFQCEPINDF-UHFFFAOYSA-N 0.000 description 2
- ZPNJUMTXEAFJGY-UHFFFAOYSA-N 4-(2-fluoroethyl)-7-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2,2-dimethyl-1,4-benzoxazin-3-one Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C3OC(C)(C)C(=O)N(CCF)C3=CC=2)=NC=C1F ZPNJUMTXEAFJGY-UHFFFAOYSA-N 0.000 description 2
- VLTYEUQYWCEFPP-UHFFFAOYSA-N 5-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1C1=CN=C(N)N=C1N VLTYEUQYWCEFPP-UHFFFAOYSA-N 0.000 description 2
- LMNPKIOZMGYQIU-UHFFFAOYSA-N 5-(trifluoromethyl)-1h-pyrimidine-2,4-dione Chemical compound FC(F)(F)C1=CNC(=O)NC1=O LMNPKIOZMGYQIU-UHFFFAOYSA-N 0.000 description 2
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 2
- ZQHUSSZHUXEYEL-UHFFFAOYSA-N 5-fluoro-2-n-[3-(1-methyltetrazol-5-yl)-5-(oxetan-3-yloxy)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound CN1N=NN=C1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC(OC2COC2)=C1 ZQHUSSZHUXEYEL-UHFFFAOYSA-N 0.000 description 2
- KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical compound IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 description 2
- TUARVSWVPPVUGS-UHFFFAOYSA-N 5-nitrouracil Chemical compound [O-][N+](=O)C1=CNC(=O)NC1=O TUARVSWVPPVUGS-UHFFFAOYSA-N 0.000 description 2
- 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 2
- WXCANTMDWFNTEE-UHFFFAOYSA-N 9-fluoro-8-phenyl-9a-n-(2,2,6,6-tetramethylpiperidin-4-yl)-2,3-dihydropyrimido[1,6-b][1,4,2]dioxazine-6,9a-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1(C(=C(N=C2N)C=3C=CC=CC=3)F)N2OCCO1 WXCANTMDWFNTEE-UHFFFAOYSA-N 0.000 description 2
- 208000033496 Acute myeloid leukaemia with myelodysplasia-related features Diseases 0.000 description 2
- 208000009746 Adult T-Cell Leukemia-Lymphoma Diseases 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 240000006108 Allium ampeloprasum Species 0.000 description 2
- 235000005254 Allium ampeloprasum Nutrition 0.000 description 2
- 206010073478 Anaplastic large-cell lymphoma Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 2
- 208000006029 Cardiomegaly Diseases 0.000 description 2
- 206010008805 Chromosomal abnormalities Diseases 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 206010058314 Dysplasia Diseases 0.000 description 2
- 102000015212 Fas Ligand Protein Human genes 0.000 description 2
- 108010039471 Fas Ligand Protein Proteins 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 206010017533 Fungal infection Diseases 0.000 description 2
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 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 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 2
- 101001026864 Homo sapiens Protein kinase C gamma type Proteins 0.000 description 2
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 208000032004 Large-Cell Anaplastic Lymphoma Diseases 0.000 description 2
- 208000001344 Macular Edema Diseases 0.000 description 2
- 206010025415 Macular oedema Diseases 0.000 description 2
- 206010027906 Monocytosis Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 2
- 150000001204 N-oxides Chemical class 0.000 description 2
- SEQKRHFRPICQDD-UHFFFAOYSA-N N-tris(hydroxymethyl)methylglycine Chemical compound OCC(CO)(CO)[NH2+]CC([O-])=O SEQKRHFRPICQDD-UHFFFAOYSA-N 0.000 description 2
- 102000043276 Oncogene Human genes 0.000 description 2
- 208000003435 Optic Neuritis Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 102000001892 Protein Kinase C-theta Human genes 0.000 description 2
- 102100037314 Protein kinase C gamma type Human genes 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 208000009527 Refractory anemia Diseases 0.000 description 2
- 206010072684 Refractory cytopenia with unilineage dysplasia Diseases 0.000 description 2
- 206010038389 Renal cancer Diseases 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- 208000007014 Retinitis pigmentosa Diseases 0.000 description 2
- 206010038933 Retinopathy of prematurity Diseases 0.000 description 2
- 229940124639 Selective inhibitor Drugs 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 108700005077 Viral Genes Proteins 0.000 description 2
- 102000007624 ZAP-70 Protein-Tyrosine Kinase Human genes 0.000 description 2
- 108010046882 ZAP-70 Protein-Tyrosine Kinase Proteins 0.000 description 2
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 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 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 208000038016 acute inflammation Diseases 0.000 description 2
- 230000006022 acute inflammation Effects 0.000 description 2
- 208000016544 acute myeloid leukemia with multilineage dysplasia Diseases 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 150000001345 alkine derivatives Chemical class 0.000 description 2
- 125000005133 alkynyloxy group Chemical group 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 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 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 208000035269 cancer or benign tumor Diseases 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 239000002771 cell marker Substances 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000010307 cell transformation Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000006020 chronic inflammation Effects 0.000 description 2
- 229940110456 cocoa butter Drugs 0.000 description 2
- 235000019868 cocoa butter Nutrition 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000006880 cross-coupling reaction Methods 0.000 description 2
- 125000006165 cyclic alkyl group Chemical group 0.000 description 2
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 2
- 230000002559 cytogenic effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 150000001982 diacylglycerols Chemical class 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 231100000676 disease causative agent Toxicity 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 230000001804 emulsifying effect Effects 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 108700004025 env Genes Proteins 0.000 description 2
- 101150030339 env gene Proteins 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 208000024386 fungal infectious disease Diseases 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
- 239000008187 granular material Substances 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 125000004404 heteroalkyl group Chemical group 0.000 description 2
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 2
- 208000026278 immune system disease Diseases 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 201000010982 kidney cancer Diseases 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 210000002751 lymph Anatomy 0.000 description 2
- 201000010230 macular retinal edema Diseases 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 2
- 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 2
- 210000004287 null lymphocyte Anatomy 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 231100000590 oncogenic Toxicity 0.000 description 2
- 230000002246 oncogenic effect Effects 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 description 2
- 239000002644 phorbol ester Substances 0.000 description 2
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- XVIAPHVAGFEFFN-UHFFFAOYSA-N pyrimidine-5-carbonitrile Chemical compound N#CC1=CN=CN=C1 XVIAPHVAGFEFFN-UHFFFAOYSA-N 0.000 description 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- 210000002027 skeletal muscle Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 230000000638 stimulation Effects 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
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 108091005703 transmembrane proteins Proteins 0.000 description 2
- 102000035160 transmembrane proteins Human genes 0.000 description 2
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 241001529453 unidentified herpesvirus Species 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- KKVZONPEMODBBG-UHFFFAOYSA-N (1-hydroxydodecane-1,1-diyl)bis(phosphonic acid) Chemical compound CCCCCCCCCCCC(O)(P(O)(O)=O)P(O)(O)=O KKVZONPEMODBBG-UHFFFAOYSA-N 0.000 description 1
- 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 1
- FZXIGEWNUBLAFD-WNQIDUERSA-N (2s)-2-aminobutanedioic acid;benzenesulfonic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O.OS(=O)(=O)C1=CC=CC=C1 FZXIGEWNUBLAFD-WNQIDUERSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- KOFLVDBWRHFSAB-UHFFFAOYSA-N 1,2,4,5-tetrahydro-1-(phenylmethyl)-5,9b(1',2')-benzeno-9bh-benz(g)indol-3(3ah)-one Chemical compound C1C(C=2C3=CC=CC=2)C2=CC=CC=C2C23C1C(=O)CN2CC1=CC=CC=C1 KOFLVDBWRHFSAB-UHFFFAOYSA-N 0.000 description 1
- ALEDRWLOYABIEJ-UHFFFAOYSA-N 1-[2-[2-(difluoromethoxy)-4-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenoxy]ethyl]imidazolidin-2-one Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OCCN3C(NCC3)=O)=CC=2)=NC=C1F ALEDRWLOYABIEJ-UHFFFAOYSA-N 0.000 description 1
- UYEDYXMQUJKUNJ-UHFFFAOYSA-N 1-[2-[2-(difluoromethoxy)-4-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenoxy]ethyl]pyrrolidin-2-one Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OCCN3C(CCC3)=O)=CC=2)=NC=C1F UYEDYXMQUJKUNJ-UHFFFAOYSA-N 0.000 description 1
- HDVTXVHIZHHXPA-UHFFFAOYSA-N 1-[2-[3-(difluoromethoxy)-5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]pyridin-2-yl]oxyethyl]pyrrolidin-2-one Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OCCN3C(CCC3)=O)=NC=2)=NC=C1F HDVTXVHIZHHXPA-UHFFFAOYSA-N 0.000 description 1
- MVACJJHBZWEXDS-UHFFFAOYSA-N 1-[2-[3-fluoro-5-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenoxy]ethyl]pyrrolidin-2-one Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OCCN3C(CCC3)=O)C=C(F)C=2)=NC=C1F MVACJJHBZWEXDS-UHFFFAOYSA-N 0.000 description 1
- XUUAVUSUJJZXOP-UHFFFAOYSA-N 1-[2-[3-fluoro-5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenoxy]ethyl]pyrrolidin-2-one Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OCCN3C(CCC3)=O)C=C(F)C=2)=NC=C1F XUUAVUSUJJZXOP-UHFFFAOYSA-N 0.000 description 1
- YRDJHSOGHAPLCQ-UHFFFAOYSA-N 1-[2-[4-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-(trifluoromethyl)phenoxy]ethyl]pyrrolidin-2-one Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(OCCN3C(CCC3)=O)=CC=2)C(F)(F)F)=NC=C1F YRDJHSOGHAPLCQ-UHFFFAOYSA-N 0.000 description 1
- DXZHHOUBIMETLX-UHFFFAOYSA-N 1-[2-[4-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-(trifluoromethyl)phenoxy]ethyl]pyrrolidin-2-one Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(C(OCCN3C(CCC3)=O)=CC=2)C(F)(F)F)=NC=C1F DXZHHOUBIMETLX-UHFFFAOYSA-N 0.000 description 1
- POQLTEKWVSCSDJ-UHFFFAOYSA-N 1-[4-[2,6-difluoro-4-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenoxy]azepan-1-yl]ethanone Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC3CCN(CCC3)C(C)=O)=C(F)C=2)=NC=C1F POQLTEKWVSCSDJ-UHFFFAOYSA-N 0.000 description 1
- XDOIKXPCLTYDEB-UHFFFAOYSA-N 1-[4-[2,6-difluoro-4-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenoxy]piperidin-1-yl]ethanone Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC3CCN(CC3)C(C)=O)=C(F)C=2)=NC=C1F XDOIKXPCLTYDEB-UHFFFAOYSA-N 0.000 description 1
- VHHGYYXZSDZWAJ-UHFFFAOYSA-N 1-[4-[2,6-difluoro-4-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenoxy]azepan-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCCC1OC(C(=C1)F)=C(F)C=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 VHHGYYXZSDZWAJ-UHFFFAOYSA-N 0.000 description 1
- YKFDVPIMXKQRET-UHFFFAOYSA-N 1-[4-[2,6-difluoro-4-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenoxy]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1OC(C(=C1)F)=C(F)C=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 YKFDVPIMXKQRET-UHFFFAOYSA-N 0.000 description 1
- BSBITNIZHSNSGQ-UHFFFAOYSA-N 1-[4-[2-(difluoromethoxy)-4-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenoxy]azepan-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCCC1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 BSBITNIZHSNSGQ-UHFFFAOYSA-N 0.000 description 1
- JPSIHRQABRKJNC-UHFFFAOYSA-N 1-[4-[2-(difluoromethoxy)-4-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenoxy]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 JPSIHRQABRKJNC-UHFFFAOYSA-N 0.000 description 1
- NCIHFDDUSYSCHO-UHFFFAOYSA-N 1-[4-[2-fluoro-4-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenoxy]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1OC(C(=C1)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 NCIHFDDUSYSCHO-UHFFFAOYSA-N 0.000 description 1
- OLULHLFHCXUFPA-UHFFFAOYSA-N 1-[4-[[2-[3-(difluoromethoxy)-4-(1-propan-2-ylpiperidin-4-yl)oxyanilino]-5-fluoropyrimidin-4-yl]amino]-2,2,6,6-tetramethylpiperidin-1-yl]ethanone Chemical compound C1CN(C(C)C)CCC1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)N(C(C)=O)C(C)(C)C2)=N1 OLULHLFHCXUFPA-UHFFFAOYSA-N 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 1
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical class O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 1
- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 1
- INXPAZBYOONEGE-UHFFFAOYSA-N 2-[3-(difluoromethoxy)-4-[2-(1,2,4-triazol-1-yl)ethoxy]anilino]-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OCCN3N=CN=C3)=CC=2)=NC=C1C#N INXPAZBYOONEGE-UHFFFAOYSA-N 0.000 description 1
- SKZUWSDFQBFIDW-UHFFFAOYSA-N 2-[3-(difluoromethoxy)-4-[2-(triazol-1-yl)ethoxy]anilino]-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OCCN3N=NC=C3)=CC=2)=NC=C1C#N SKZUWSDFQBFIDW-UHFFFAOYSA-N 0.000 description 1
- RETATRAGONWZGO-UHFFFAOYSA-N 2-[3-(difluoromethoxy)-4-[2-(triazol-1-yl)ethoxy]anilino]-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OCCN3N=NC=C3)=CC=2)=NC=C1C#N RETATRAGONWZGO-UHFFFAOYSA-N 0.000 description 1
- LHVNCSDSTOQUIF-UHFFFAOYSA-N 2-[3-(difluoromethoxy)-4-pyridin-3-yloxyanilino]-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OC=3C=NC=CC=3)=CC=2)=NC=C1C#N LHVNCSDSTOQUIF-UHFFFAOYSA-N 0.000 description 1
- UQIJVPKQGGSTQQ-UHFFFAOYSA-N 2-[3-(difluoromethoxy)-4-pyridin-4-yloxyanilino]-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OC=3C=CN=CC=3)=CC=2)=NC=C1C#N UQIJVPKQGGSTQQ-UHFFFAOYSA-N 0.000 description 1
- ALFOVQMLADJVHU-UHFFFAOYSA-N 2-[3-(difluoromethoxy)-4-pyridin-4-yloxyanilino]-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OC=3C=CN=CC=3)=CC=2)=NC=C1C#N ALFOVQMLADJVHU-UHFFFAOYSA-N 0.000 description 1
- UMULDROISPPMFA-UHFFFAOYSA-N 2-[3-fluoro-5-[2-(triazol-1-yl)ethoxy]anilino]-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OCCN3N=NC=C3)C=C(F)C=2)=NC=C1C#N UMULDROISPPMFA-UHFFFAOYSA-N 0.000 description 1
- OSFIUCJPGDHBSO-UHFFFAOYSA-N 2-[4-[2,6-difluoro-4-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenoxy]piperidin-1-yl]ethanol Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC3CCN(CCO)CC3)=C(F)C=2)=NC=C1F OSFIUCJPGDHBSO-UHFFFAOYSA-N 0.000 description 1
- OKLIVFOMONMCFM-UHFFFAOYSA-N 2-[4-[2,6-difluoro-4-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenoxy]piperidin-1-yl]ethanol Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC3CCN(CCO)CC3)=C(F)C=2)=NC=C1F OKLIVFOMONMCFM-UHFFFAOYSA-N 0.000 description 1
- MPPNJSMGUZOVKW-UHFFFAOYSA-N 2-[4-[2-(difluoromethoxy)-4-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenoxy]piperidin-1-yl]ethanol Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OC3CCN(CCO)CC3)=CC=2)=NC=C1F MPPNJSMGUZOVKW-UHFFFAOYSA-N 0.000 description 1
- YRZOTZBKXJMHQC-UHFFFAOYSA-N 2-[4-[2-fluoro-4-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenoxy]piperidin-1-yl]ethanol Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC3CCN(CCO)CC3)=CC=2)=NC=C1F YRZOTZBKXJMHQC-UHFFFAOYSA-N 0.000 description 1
- RVTZKNPKYHZZPC-UHFFFAOYSA-N 2-[4-[2-fluoro-4-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenoxy]piperidin-1-yl]ethanol Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC3CCN(CCO)CC3)=CC=2)=NC=C1F RVTZKNPKYHZZPC-UHFFFAOYSA-N 0.000 description 1
- FHPOARWPEVYWGX-UHFFFAOYSA-N 2-[4-fluoro-3-(5-methyltetrazol-1-yl)anilino]-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound CC1=NN=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(C#N)=CN=2)=CC=C1F FHPOARWPEVYWGX-UHFFFAOYSA-N 0.000 description 1
- RHXAVTDUVRRMJI-UHFFFAOYSA-N 2-[[5-(1-cyclopropyltetrazol-5-yl)-6-propan-2-yloxypyridin-3-yl]amino]-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound C1=C(C=2N(N=NN=2)C2CC2)C(OC(C)C)=NC=C1NC(N=1)=NC=C(C#N)C=1NC1CC(C)(C)N(C)C(C)(C)C1 RHXAVTDUVRRMJI-UHFFFAOYSA-N 0.000 description 1
- XXKHVGGPICESIT-UHFFFAOYSA-N 2-[[5-(1-cyclopropyltetrazol-5-yl)-6-propan-2-yloxypyridin-3-yl]amino]-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound C1=C(C=2N(N=NN=2)C2CC2)C(OC(C)C)=NC=C1NC(N=1)=NC=C(C#N)C=1NC1CC(C)(C)NC(C)(C)C1 XXKHVGGPICESIT-UHFFFAOYSA-N 0.000 description 1
- XPEIRWDYVPJEPV-UHFFFAOYSA-N 2-[[5-(1-methyltetrazol-5-yl)-6-propan-2-yloxypyridin-3-yl]amino]-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound C1=C(C=2N(N=NN=2)C)C(OC(C)C)=NC=C1NC(N=1)=NC=C(C#N)C=1NC1CC(C)(C)N(C)C(C)(C)C1 XPEIRWDYVPJEPV-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- SCVJRXQHFJXZFZ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SCVJRXQHFJXZFZ-KVQBGUIXSA-N 0.000 description 1
- GDYDHLRWGXMBEG-UHFFFAOYSA-N 2-n-[3,4-difluoro-5-(1-methyltetrazol-5-yl)phenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(F)=C(F)C=2)C=2N(N=NN=2)C)=NC=C1F GDYDHLRWGXMBEG-UHFFFAOYSA-N 0.000 description 1
- PFBFIHMAUYXBBT-UHFFFAOYSA-N 2-n-[3,4-difluoro-5-(1-methyltetrazol-5-yl)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound CN1N=NN=C1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC(F)=C1F PFBFIHMAUYXBBT-UHFFFAOYSA-N 0.000 description 1
- GIJFUUMKEFBLKC-UHFFFAOYSA-N 2-n-[3,5-difluoro-4-(1-methylsulfonylazepan-4-yl)oxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC3CCN(CCC3)S(C)(=O)=O)=C(F)C=2)=NC=C1F GIJFUUMKEFBLKC-UHFFFAOYSA-N 0.000 description 1
- WNSSCJNAGRXFFN-UHFFFAOYSA-N 2-n-[3,5-difluoro-4-(1-methylsulfonylazepan-4-yl)oxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC3CCN(CCC3)S(C)(=O)=O)=C(F)C=2)=NC=C1F WNSSCJNAGRXFFN-UHFFFAOYSA-N 0.000 description 1
- LBBZIRJBQWBNPX-UHFFFAOYSA-N 2-n-[3,5-difluoro-4-(1-methylsulfonylpiperidin-4-yl)oxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC3CCN(CC3)S(C)(=O)=O)=C(F)C=2)=NC=C1F LBBZIRJBQWBNPX-UHFFFAOYSA-N 0.000 description 1
- XTHYNPFATMIPLE-UHFFFAOYSA-N 2-n-[3,5-difluoro-4-(1-methylsulfonylpiperidin-4-yl)oxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC3CCN(CC3)S(C)(=O)=O)=C(F)C=2)=NC=C1F XTHYNPFATMIPLE-UHFFFAOYSA-N 0.000 description 1
- ZQIYAOVRMYXIBX-UHFFFAOYSA-N 2-n-[3,5-difluoro-4-(2-methyl-4-pyrrolidin-1-ylbutan-2-yl)oxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC(C)(C)CCN3CCCC3)=C(F)C=2)=NC=C1F ZQIYAOVRMYXIBX-UHFFFAOYSA-N 0.000 description 1
- BSAGBBCLRPIKEC-UHFFFAOYSA-N 2-n-[3,5-difluoro-4-(2-methyl-4-pyrrolidin-1-ylbutan-2-yl)oxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound FC=1C=C(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)C=C(F)C=1OC(C)(C)CCN1CCCC1 BSAGBBCLRPIKEC-UHFFFAOYSA-N 0.000 description 1
- SVXQQNNDSPKLRR-UHFFFAOYSA-N 2-n-[3,5-difluoro-4-(oxan-4-yloxy)phenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC3CCOCC3)=C(F)C=2)=NC=C1F SVXQQNNDSPKLRR-UHFFFAOYSA-N 0.000 description 1
- SAVJRCXOOKWLDV-UHFFFAOYSA-N 2-n-[3,5-difluoro-4-(oxan-4-yloxy)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC3CCOCC3)=C(F)C=2)=NC=C1F SAVJRCXOOKWLDV-UHFFFAOYSA-N 0.000 description 1
- FBRPENHXGMIIFY-UHFFFAOYSA-N 2-n-[3,5-difluoro-4-[1-(2-phenylmethoxyethyl)piperidin-4-yl]oxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC3CCN(CCOCC=4C=CC=CC=4)CC3)=C(F)C=2)=NC=C1F FBRPENHXGMIIFY-UHFFFAOYSA-N 0.000 description 1
- XSMPGXVGTASUPM-UHFFFAOYSA-N 2-n-[3,5-difluoro-4-[1-(2-phenylmethoxyethyl)piperidin-4-yl]oxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC3CCN(CCOCC=4C=CC=CC=4)CC3)=C(F)C=2)=NC=C1F XSMPGXVGTASUPM-UHFFFAOYSA-N 0.000 description 1
- GWFZJRLEUAMBJA-UHFFFAOYSA-N 2-n-[3-(1-cyclopropyltetrazol-5-yl)phenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=CC=2)C=2N(N=NN=2)C2CC2)=NC=C1F GWFZJRLEUAMBJA-UHFFFAOYSA-N 0.000 description 1
- VFWMSNXVWUFXQG-UHFFFAOYSA-N 2-n-[3-(1-cyclopropyltetrazol-5-yl)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(C=CC=2)C=2N(N=NN=2)C2CC2)=NC=C1F VFWMSNXVWUFXQG-UHFFFAOYSA-N 0.000 description 1
- UZPYTUFWNCKTRJ-UHFFFAOYSA-N 2-n-[3-(2,5-dimethylpyrrol-1-yl)-4-ethoxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(N2C(=CC=C2C)C)C(OCC)=CC=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)N(C)C(C)(C)C1 UZPYTUFWNCKTRJ-UHFFFAOYSA-N 0.000 description 1
- CPCMAMCOIMDHLT-UHFFFAOYSA-N 2-n-[3-(2,5-dimethylpyrrol-1-yl)-4-ethoxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(N2C(=CC=C2C)C)C(OCC)=CC=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 CPCMAMCOIMDHLT-UHFFFAOYSA-N 0.000 description 1
- AXWIHNGEEVGHGE-UHFFFAOYSA-N 2-n-[3-(2,5-dimethylpyrrol-1-yl)-4-propan-2-yloxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(N2C(=CC=C2C)C)C(OC(C)C)=CC=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)N(C)C(C)(C)C1 AXWIHNGEEVGHGE-UHFFFAOYSA-N 0.000 description 1
- WYQPUPQSYVSISB-UHFFFAOYSA-N 2-n-[3-(2,5-dimethylpyrrol-1-yl)-4-propan-2-yloxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(N2C(=CC=C2C)C)C(OC(C)C)=CC=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 WYQPUPQSYVSISB-UHFFFAOYSA-N 0.000 description 1
- CMAYWAYKGFRPDP-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(1,1-dioxothian-4-yl)oxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OC3CCS(=O)(=O)CC3)=CC=2)=NC=C1F CMAYWAYKGFRPDP-UHFFFAOYSA-N 0.000 description 1
- SOTLQFBEAPZAER-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(1-methylsulfonylazepan-4-yl)oxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OC3CCN(CCC3)S(C)(=O)=O)=CC=2)=NC=C1F SOTLQFBEAPZAER-UHFFFAOYSA-N 0.000 description 1
- XTZGGOFDTQCYKA-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(1-methylsulfonylazepan-4-yl)oxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OC3CCN(CCC3)S(C)(=O)=O)=CC=2)=NC=C1F XTZGGOFDTQCYKA-UHFFFAOYSA-N 0.000 description 1
- GJAOBLPXNGWPPG-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(1-methylsulfonylpiperidin-4-yl)oxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OC3CCN(CC3)S(C)(=O)=O)=CC=2)=NC=C1F GJAOBLPXNGWPPG-UHFFFAOYSA-N 0.000 description 1
- YPJYEINEDOBZAY-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(1-methylsulfonylpiperidin-4-yl)oxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OC3CCN(CC3)S(C)(=O)=O)=CC=2)=NC=C1F YPJYEINEDOBZAY-UHFFFAOYSA-N 0.000 description 1
- CVGSPFRIBUUPQL-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(1-propan-2-ylazepan-4-yl)oxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1CN(C(C)C)CCCC1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)N(C)C(C)(C)C2)=N1 CVGSPFRIBUUPQL-UHFFFAOYSA-N 0.000 description 1
- VRVVVNTWLYLBBN-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(1-propan-2-ylazepan-4-yl)oxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1CN(C(C)C)CCCC1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 VRVVVNTWLYLBBN-UHFFFAOYSA-N 0.000 description 1
- XQEGYZDLOFKWMV-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(1-propan-2-ylazetidin-3-yl)oxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1N(C(C)C)CC1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 XQEGYZDLOFKWMV-UHFFFAOYSA-N 0.000 description 1
- KCWPQKINGRRATP-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(1-propan-2-ylpiperidin-4-yl)oxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1CN(C(C)C)CCC1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)N(C)C(C)(C)C2)=N1 KCWPQKINGRRATP-UHFFFAOYSA-N 0.000 description 1
- PVPQEUHWPXELPH-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(1-propan-2-ylpiperidin-4-yl)oxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1CN(C(C)C)CCC1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 PVPQEUHWPXELPH-UHFFFAOYSA-N 0.000 description 1
- BWYGDLIVAUCLPD-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(1-propan-2-ylpiperidin-4-yl)oxyphenyl]-5-fluoro-4-n-[2,2,6,6-tetramethyl-1-(2,2,2-trifluoroethyl)piperidin-4-yl]pyrimidine-2,4-diamine Chemical compound C1CN(C(C)C)CCC1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)N(CC(F)(F)F)C(C)(C)C2)=N1 BWYGDLIVAUCLPD-UHFFFAOYSA-N 0.000 description 1
- UOCVZJXHKZJCAS-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(2-methyl-1-morpholin-4-ylpropan-2-yl)oxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OC(C)(C)CN3CCOCC3)=CC=2)=NC=C1F UOCVZJXHKZJCAS-UHFFFAOYSA-N 0.000 description 1
- YHDUTCGAGYMCSM-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(2-methyl-1-pyrrolidin-1-ylpropan-2-yl)oxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C=1C=C(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)C=C(OC(F)F)C=1OC(C)(C)CN1CCCC1 YHDUTCGAGYMCSM-UHFFFAOYSA-N 0.000 description 1
- ITKINQRQWSJGML-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(2-morpholin-4-ylethoxy)phenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OCCN3CCOCC3)=CC=2)=NC=C1F ITKINQRQWSJGML-UHFFFAOYSA-N 0.000 description 1
- JACPSOKSEWHINU-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(2-morpholin-4-ylethoxy)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OCCN3CCOCC3)=CC=2)=NC=C1F JACPSOKSEWHINU-UHFFFAOYSA-N 0.000 description 1
- YVKLHMWGXZRYPV-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(2-pyrrolidin-1-ylethoxy)phenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OCCN3CCCC3)=CC=2)=NC=C1F YVKLHMWGXZRYPV-UHFFFAOYSA-N 0.000 description 1
- GTUKAHCINSBOLK-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(2-pyrrolidin-1-ylethoxy)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OCCN3CCCC3)=CC=2)=NC=C1F GTUKAHCINSBOLK-UHFFFAOYSA-N 0.000 description 1
- KVICMTHNCXAPGT-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(3,3-difluoro-1-propan-2-ylpiperidin-4-yl)oxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound FC1(F)CN(C(C)C)CCC1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 KVICMTHNCXAPGT-UHFFFAOYSA-N 0.000 description 1
- FYDJUBRCIZMMFU-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(3-fluoro-1-propan-2-ylpiperidin-4-yl)oxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound FC1CN(C(C)C)CCC1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)N(C)C(C)(C)C2)=N1 FYDJUBRCIZMMFU-UHFFFAOYSA-N 0.000 description 1
- NVLMKHJYYWUWHB-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(3-fluoro-1-propan-2-ylpiperidin-4-yl)oxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.FC1CN(C(C)C)CCC1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)N(C)C(C)(C)C2)=N1 NVLMKHJYYWUWHB-UHFFFAOYSA-N 0.000 description 1
- DGDFWBXKBJTJKO-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(3-fluoro-1-propan-2-ylpiperidin-4-yl)oxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound FC1CN(C(C)C)CCC1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 DGDFWBXKBJTJKO-UHFFFAOYSA-N 0.000 description 1
- DSZLZCSKYWHXAY-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(3-fluoro-1-propan-2-ylpiperidin-4-yl)oxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.FC1CN(C(C)C)CCC1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 DSZLZCSKYWHXAY-UHFFFAOYSA-N 0.000 description 1
- FYDJUBRCIZMMFU-UKDQJQFQSA-N 2-n-[3-(difluoromethoxy)-4-(3-fluoro-1-propan-2-ylpiperidin-4-yl)oxyphenyl]-5-fluoro-4-n-[2,2,6,6-tetramethyl-1-(trideuteriomethyl)piperidin-4-yl]pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C([2H])([2H])[2H])C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OC3C(CN(CC3)C(C)C)F)=CC=2)=NC=C1F FYDJUBRCIZMMFU-UKDQJQFQSA-N 0.000 description 1
- FWTWGUUIXWNVJB-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(3-morpholin-4-ylpropoxy)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OCCCN3CCOCC3)=CC=2)=NC=C1F FWTWGUUIXWNVJB-UHFFFAOYSA-N 0.000 description 1
- XZDQNRBQJLSZTA-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(3-morpholin-4-ylpropoxy)phenyl]-5-fluoro-4-n-[2,2,6,6-tetramethyl-1-(2,2,2-trifluoroethyl)piperidin-4-yl]pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(CC(F)(F)F)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OCCCN3CCOCC3)=CC=2)=NC=C1F XZDQNRBQJLSZTA-UHFFFAOYSA-N 0.000 description 1
- IMMMHXPXNUPIRG-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(3-pyrrol-1-ylpropoxy)phenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OCCCN3C=CC=C3)=CC=2)=NC=C1F IMMMHXPXNUPIRG-UHFFFAOYSA-N 0.000 description 1
- PJIQDHIUFBNWAF-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(3-pyrrol-1-ylpropoxy)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OCCCN3C=CC=C3)=CC=2)=NC=C1F PJIQDHIUFBNWAF-UHFFFAOYSA-N 0.000 description 1
- ZQEYPOXTLSZPOD-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-(oxan-4-yloxy)phenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OC3CCOCC3)=CC=2)=NC=C1F ZQEYPOXTLSZPOD-UHFFFAOYSA-N 0.000 description 1
- ZIPOMNVLVCSMPD-HXUWFJFHSA-N 2-n-[3-(difluoromethoxy)-4-[(3r)-1-propan-2-ylpyrrolidin-3-yl]oxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1N(C(C)C)CC[C@H]1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)N(C)C(C)(C)C2)=N1 ZIPOMNVLVCSMPD-HXUWFJFHSA-N 0.000 description 1
- URZMQNQGYSLCPJ-LJQANCHMSA-N 2-n-[3-(difluoromethoxy)-4-[(3r)-1-propan-2-ylpyrrolidin-3-yl]oxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1N(C(C)C)CC[C@H]1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 URZMQNQGYSLCPJ-LJQANCHMSA-N 0.000 description 1
- ZIPOMNVLVCSMPD-FQEVSTJZSA-N 2-n-[3-(difluoromethoxy)-4-[(3s)-1-propan-2-ylpyrrolidin-3-yl]oxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1N(C(C)C)CC[C@@H]1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)N(C)C(C)(C)C2)=N1 ZIPOMNVLVCSMPD-FQEVSTJZSA-N 0.000 description 1
- URZMQNQGYSLCPJ-IBGZPJMESA-N 2-n-[3-(difluoromethoxy)-4-[(3s)-1-propan-2-ylpyrrolidin-3-yl]oxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1N(C(C)C)CC[C@@H]1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 URZMQNQGYSLCPJ-IBGZPJMESA-N 0.000 description 1
- BUCXQPNZXSSISI-KRWDZBQOSA-N 2-n-[3-(difluoromethoxy)-4-[(3s)-oxolan-3-yl]oxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(O[C@@H]3COCC3)=CC=2)=NC=C1F BUCXQPNZXSSISI-KRWDZBQOSA-N 0.000 description 1
- ALHCNISMMUZTEZ-INIZCTEOSA-N 2-n-[3-(difluoromethoxy)-4-[(3s)-oxolan-3-yl]oxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(O[C@@H]3COCC3)=CC=2)=NC=C1F ALHCNISMMUZTEZ-INIZCTEOSA-N 0.000 description 1
- PDHZMLWAWUKJJA-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]oxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OC3CCN(CC(F)(F)F)CC3)=CC=2)=NC=C1F PDHZMLWAWUKJJA-UHFFFAOYSA-N 0.000 description 1
- UQCAEASUCFFTRN-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-[1-(2-fluoroethyl)piperidin-4-yl]oxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OC3CCN(CCF)CC3)=CC=2)=NC=C1F UQCAEASUCFFTRN-UHFFFAOYSA-N 0.000 description 1
- CHKPKYFHYZEZBS-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-[2-(1,2,4-triazol-1-yl)ethoxy]phenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OCCN3N=CN=C3)=CC=2)=NC=C1F CHKPKYFHYZEZBS-UHFFFAOYSA-N 0.000 description 1
- LHGNDYJLIILNDE-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-[2-(triazol-1-yl)ethoxy]phenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OCCN3N=NC=C3)=CC=2)=NC=C1F LHGNDYJLIILNDE-UHFFFAOYSA-N 0.000 description 1
- RIQRUHSXWDAHSM-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-[2-(triazol-1-yl)ethoxy]phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OCCN3N=NC=C3)=CC=2)=NC=C1F RIQRUHSXWDAHSM-UHFFFAOYSA-N 0.000 description 1
- RDEPHPJSWCVVSB-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-ethoxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(OC(F)F)C(OCC)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)N(C)C(C)(C)C2)=N1 RDEPHPJSWCVVSB-UHFFFAOYSA-N 0.000 description 1
- OEDNHDNVMPBPPV-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-ethoxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(OC(F)F)C(OCC)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 OEDNHDNVMPBPPV-UHFFFAOYSA-N 0.000 description 1
- MHFZCUODIPYLKB-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-piperidin-4-yloxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OC3CCNCC3)=CC=2)=NC=C1F MHFZCUODIPYLKB-UHFFFAOYSA-N 0.000 description 1
- TUOCNUSJSCUNSL-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-piperidin-4-yloxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OC3CCNCC3)=CC=2)=NC=C1F TUOCNUSJSCUNSL-UHFFFAOYSA-N 0.000 description 1
- NBRWWENLOKHRES-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-pyridin-3-yloxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OC=3C=NC=CC=3)=CC=2)=NC=C1F NBRWWENLOKHRES-UHFFFAOYSA-N 0.000 description 1
- XCAZCAJSYYQQQW-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-pyridin-3-yloxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OC=3C=NC=CC=3)=CC=2)=NC=C1F XCAZCAJSYYQQQW-UHFFFAOYSA-N 0.000 description 1
- FHOJXZSIYSOYEZ-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-pyridin-3-ylphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(=CC=2)C=2C=NC=CC=2)=NC=C1F FHOJXZSIYSOYEZ-UHFFFAOYSA-N 0.000 description 1
- KGJAFPGUFSZUGC-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-pyridin-3-ylphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(=CC=2)C=2C=NC=CC=2)=NC=C1F KGJAFPGUFSZUGC-UHFFFAOYSA-N 0.000 description 1
- WAVPQRUTBAAZTM-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-4-pyridin-4-yloxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OC=3C=CN=CC=3)=CC=2)=NC=C1F WAVPQRUTBAAZTM-UHFFFAOYSA-N 0.000 description 1
- GLJCSAKMZLXXIC-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-5-(trifluoromethyl)phenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=C(OC(F)F)C=2)C(F)(F)F)=NC=C1F GLJCSAKMZLXXIC-UHFFFAOYSA-N 0.000 description 1
- VJODGRXVLZVMJR-UHFFFAOYSA-N 2-n-[3-(difluoromethoxy)-5-(trifluoromethyl)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(C=C(OC(F)F)C=2)C(F)(F)F)=NC=C1F VJODGRXVLZVMJR-UHFFFAOYSA-N 0.000 description 1
- JEOIAKRCEJLQBB-UHFFFAOYSA-N 2-n-[3-chloro-4-(1-propan-2-ylpiperidin-4-yl)oxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1CN(C(C)C)CCC1OC(C(=C1)Cl)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)N(C)C(C)(C)C2)=N1 JEOIAKRCEJLQBB-UHFFFAOYSA-N 0.000 description 1
- ZBFQCISVGWRTKE-UHFFFAOYSA-N 2-n-[3-chloro-4-(1-propan-2-ylpiperidin-4-yl)oxyphenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1CN(C(C)C)CCC1OC(C(=C1)Cl)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 ZBFQCISVGWRTKE-UHFFFAOYSA-N 0.000 description 1
- JEOIAKRCEJLQBB-UKDQJQFQSA-N 2-n-[3-chloro-4-(1-propan-2-ylpiperidin-4-yl)oxyphenyl]-5-fluoro-4-n-[2,2,6,6-tetramethyl-1-(trideuteriomethyl)piperidin-4-yl]pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C([2H])([2H])[2H])C(C)(C)CC1NC1=NC(NC=2C=C(Cl)C(OC3CCN(CC3)C(C)C)=CC=2)=NC=C1F JEOIAKRCEJLQBB-UKDQJQFQSA-N 0.000 description 1
- APSMLZZRYNNCCI-UHFFFAOYSA-N 2-n-[3-chloro-4-[1-(2-fluoroethyl)piperidin-4-yl]oxyphenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(Cl)C(OC3CCN(CCF)CC3)=CC=2)=NC=C1F APSMLZZRYNNCCI-UHFFFAOYSA-N 0.000 description 1
- HOJSSXNCMRIXHD-UHFFFAOYSA-N 2-n-[3-chloro-5-(1-methyltetrazol-5-yl)phenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=C(Cl)C=2)C=2N(N=NN=2)C)=NC=C1F HOJSSXNCMRIXHD-UHFFFAOYSA-N 0.000 description 1
- YNLSCEYLGAUVAT-UHFFFAOYSA-N 2-n-[3-chloro-5-(1-methyltetrazol-5-yl)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound CN1N=NN=C1C1=CC(Cl)=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=C1 YNLSCEYLGAUVAT-UHFFFAOYSA-N 0.000 description 1
- FZRMGRLNTVBMDA-UHFFFAOYSA-N 2-n-[4-(1,1-dioxothian-4-yl)oxy-3-fluorophenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC3CCS(=O)(=O)CC3)=CC=2)=NC=C1F FZRMGRLNTVBMDA-UHFFFAOYSA-N 0.000 description 1
- MYDBITBKPFSCII-UHFFFAOYSA-N 2-n-[4-(1-benzylpiperidin-4-yl)oxy-3-(difluoromethoxy)phenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OC3CCN(CC=4C=CC=CC=4)CC3)=CC=2)=NC=C1F MYDBITBKPFSCII-UHFFFAOYSA-N 0.000 description 1
- PQOPSLXNZPKPML-UHFFFAOYSA-N 2-n-[4-(difluoromethoxy)-3-(2,5-dimethylpyrrol-1-yl)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound CC1=CC=C(C)N1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC=C1OC(F)F PQOPSLXNZPKPML-UHFFFAOYSA-N 0.000 description 1
- AOCQNVBZTTXWAW-UHFFFAOYSA-N 2-n-[4-(difluoromethoxy)-3-(5-ethyltetrazol-1-yl)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound CCC1=NN=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC=C1OC(F)F AOCQNVBZTTXWAW-UHFFFAOYSA-N 0.000 description 1
- WZGSSEBZFIRTTD-UHFFFAOYSA-N 2-n-[4-chloro-3-(1-methyltetrazol-5-yl)phenyl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(Cl)=CC=2)C=2N(N=NN=2)C)=NC=C1F WZGSSEBZFIRTTD-UHFFFAOYSA-N 0.000 description 1
- OCQGDWMILSFCEE-UHFFFAOYSA-N 2-n-[4-chloro-3-(1-methyltetrazol-5-yl)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound CN1N=NN=C1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC=C1Cl OCQGDWMILSFCEE-UHFFFAOYSA-N 0.000 description 1
- RPXQQCJEAILWCK-UHFFFAOYSA-N 2-n-[5-(1-cyclopropyltetrazol-5-yl)-6-propan-2-yloxypyridin-3-yl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(C=2N(N=NN=2)C2CC2)C(OC(C)C)=NC=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 RPXQQCJEAILWCK-UHFFFAOYSA-N 0.000 description 1
- JBYRTYYQMUSURM-UHFFFAOYSA-N 2-n-[5-(2,5-dimethylpyrrol-1-yl)-6-propan-2-yloxypyridin-3-yl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(N2C(=CC=C2C)C)C(OC(C)C)=NC=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)N(C)C(C)(C)C1 JBYRTYYQMUSURM-UHFFFAOYSA-N 0.000 description 1
- MMXQORJJCOEHSV-UHFFFAOYSA-N 2-n-[5-(2,5-dimethylpyrrol-1-yl)-6-propan-2-yloxypyridin-3-yl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(N2C(=CC=C2C)C)C(OC(C)C)=NC=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 MMXQORJJCOEHSV-UHFFFAOYSA-N 0.000 description 1
- SDYNMBGVBWWBGV-UHFFFAOYSA-N 2-n-[5-(difluoromethoxy)-6-(2-pyrrolidin-1-ylethoxy)pyridin-3-yl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OCCN3CCCC3)=NC=2)=NC=C1F SDYNMBGVBWWBGV-UHFFFAOYSA-N 0.000 description 1
- PMOHCMVZCQAZOA-UHFFFAOYSA-N 2-n-[5-(difluoromethoxy)-6-(2-pyrrolidin-1-ylethoxy)pyridin-3-yl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OC(F)F)C(OCCN3CCCC3)=NC=2)=NC=C1F PMOHCMVZCQAZOA-UHFFFAOYSA-N 0.000 description 1
- MNFBFIVNSPVVSX-UHFFFAOYSA-N 2-n-[5-(difluoromethoxy)-6-ethoxypyridin-3-yl]-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(OC(F)F)C(OCC)=NC=C1NC1=NC=C(F)C(NC2CC(C)(C)N(C)C(C)(C)C2)=N1 MNFBFIVNSPVVSX-UHFFFAOYSA-N 0.000 description 1
- NLEONFOSGAEYLN-UHFFFAOYSA-N 2-n-[5-(difluoromethoxy)-6-ethoxypyridin-3-yl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(OC(F)F)C(OCC)=NC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 NLEONFOSGAEYLN-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- PEIZWDDUHJKWEC-UHFFFAOYSA-N 3-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-5-(1-methyltetrazol-5-yl)benzonitrile Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=C(C=2)C#N)C=2N(N=NN=2)C)=NC=C1F PEIZWDDUHJKWEC-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
- UGOVYDCWBUVFSE-UHFFFAOYSA-N 4-(1-cyclopropyl-2,6-dimethylpiperidin-4-yl)-5-fluoro-2-N-[3-(5-methylsulfanyltetrazol-1-yl)phenyl]-1H-pyrimidine-2,4-diamine Chemical compound C1(CC1)N1C(CC(CC1C)C1(NC(=NC=C1F)NC1=CC(=CC=C1)N1N=NN=C1SC)N)C UGOVYDCWBUVFSE-UHFFFAOYSA-N 0.000 description 1
- UDQRMEJHOCDORF-UHFFFAOYSA-N 4-(1-cyclopropyl-2,6-dimethylpiperidin-4-yl)-5-fluoro-2-N-[3-(5-methyltetrazol-1-yl)phenyl]-1H-pyrimidine-2,4-diamine Chemical compound C1(CC1)N1C(CC(CC1C)C1(NC(=NC=C1F)NC1=CC(=CC=C1)N1N=NN=C1C)N)C UDQRMEJHOCDORF-UHFFFAOYSA-N 0.000 description 1
- NKVOMOVIJHAORM-UHFFFAOYSA-N 4-(1-cyclopropyl-2,6-dimethylpiperidin-4-yl)-5-fluoro-2-N-[3-[5-(2,2,2-trifluoroethylsulfanyl)tetrazol-1-yl]phenyl]-1H-pyrimidine-2,4-diamine Chemical compound C1(CC1)N1C(CC(CC1C)C1(NC(=NC=C1F)NC1=CC(=CC=C1)N1N=NN=C1SCC(F)(F)F)N)C NKVOMOVIJHAORM-UHFFFAOYSA-N 0.000 description 1
- XSCUQPRJBPDYIU-UHFFFAOYSA-N 4-(1-cyclopropyl-2,6-dimethylpiperidin-4-yl)-5-fluoro-2-N-[3-methoxy-5-(tetrazol-1-yl)phenyl]-1H-pyrimidine-2,4-diamine Chemical compound C1(CC1)N1C(CC(CC1C)C1(NC(=NC=C1F)NC1=CC(=CC(=C1)N1N=NN=C1)OC)N)C XSCUQPRJBPDYIU-UHFFFAOYSA-N 0.000 description 1
- XLMPZBSNMCWXHB-UHFFFAOYSA-N 4-(1-cyclopropyl-2,6-dimethylpiperidin-4-yl)-5-fluoro-2-N-[4-fluoro-3-(tetrazol-1-yl)phenyl]-1H-pyrimidine-2,4-diamine Chemical compound C1(CC1)N1C(CC(CC1C)C1(NC(=NC=C1F)NC1=CC(=C(C=C1)F)N1N=NN=C1)N)C XLMPZBSNMCWXHB-UHFFFAOYSA-N 0.000 description 1
- QDFCHIFPPIMOQK-UHFFFAOYSA-N 4-(1-cyclopropyl-2,6-dimethylpiperidin-4-yl)-5-fluoro-2-N-[4-methyl-3-(tetrazol-1-yl)phenyl]-1H-pyrimidine-2,4-diamine Chemical compound C1(CC1)N1C(CC(CC1C)C1(NC(=NC=C1F)NC1=CC(=C(C=C1)C)N1N=NN=C1)N)C QDFCHIFPPIMOQK-UHFFFAOYSA-N 0.000 description 1
- IAUDULOWARJXQS-UHFFFAOYSA-N 4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]-2-[[6-propan-2-yloxy-5-(1-propan-2-yltetrazol-5-yl)pyridin-3-yl]amino]pyrimidine-5-carbonitrile Chemical compound C1=C(C=2N(N=NN=2)C(C)C)C(OC(C)C)=NC=C1NC(N=1)=NC=C(C#N)C=1NC1CC(C)(C)N(C)C(C)(C)C1 IAUDULOWARJXQS-UHFFFAOYSA-N 0.000 description 1
- SNJWQJOUYBWUGH-UHFFFAOYSA-N 4-[2,6-difluoro-4-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenoxy]-n-ethylazepane-1-carboxamide Chemical compound C1CN(C(=O)NCC)CCCC1OC(C(=C1)F)=C(F)C=C1NC1=NC=C(F)C(NC2CC(C)(C)N(C)C(C)(C)C2)=N1 SNJWQJOUYBWUGH-UHFFFAOYSA-N 0.000 description 1
- OBMORCIPXCYDHP-UHFFFAOYSA-N 4-[2-(difluoromethoxy)-4-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenoxy]-n-ethylazepane-1-carboxamide Chemical compound C1CN(C(=O)NCC)CCCC1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)N(C)C(C)(C)C2)=N1 OBMORCIPXCYDHP-UHFFFAOYSA-N 0.000 description 1
- QELZCXZWTOYAND-UHFFFAOYSA-N 4-[2-(difluoromethoxy)-4-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenoxy]-n-ethylazepane-1-carboxamide Chemical compound C1CN(C(=O)NCC)CCCC1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 QELZCXZWTOYAND-UHFFFAOYSA-N 0.000 description 1
- UJDMIMBRWIFURI-UHFFFAOYSA-N 4-[2-(difluoromethoxy)-4-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenoxy]-n-ethylpiperidine-1-carboxamide Chemical compound C1CN(C(=O)NCC)CCC1OC(C(=C1)OC(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 UJDMIMBRWIFURI-UHFFFAOYSA-N 0.000 description 1
- GYXSAYLBNLVPRZ-UHFFFAOYSA-N 5-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1C1=CN=C(N)N=C1N GYXSAYLBNLVPRZ-UHFFFAOYSA-N 0.000 description 1
- BBJGFURFGXIVDP-UHFFFAOYSA-N 5-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-(1-propan-2-ylpiperidin-4-yl)oxybenzonitrile Chemical compound C1CN(C(C)C)CCC1OC(C(=C1)C#N)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)N(C)C(C)(C)C2)=N1 BBJGFURFGXIVDP-UHFFFAOYSA-N 0.000 description 1
- ATCDVMXIJOIUAQ-UHFFFAOYSA-N 5-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-3-(5-methyltetrazol-1-yl)-1h-pyridin-2-one Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(O)=NC=2)N2C(=NN=N2)C)=NC=C1F ATCDVMXIJOIUAQ-UHFFFAOYSA-N 0.000 description 1
- NLSSWERTDMEZJD-UHFFFAOYSA-N 5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-(1-propan-2-ylpiperidin-4-yl)oxybenzonitrile Chemical compound C1CN(C(C)C)CCC1OC(C(=C1)C#N)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 NLSSWERTDMEZJD-UHFFFAOYSA-N 0.000 description 1
- VBJAWEPFTBXDRJ-UHFFFAOYSA-N 5-fluoro-2-n-(3-pyrazol-1-ylphenyl)-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(C=CC=2)N2N=CC=C2)=NC=C1F VBJAWEPFTBXDRJ-UHFFFAOYSA-N 0.000 description 1
- GZKKEQJGOMVLKN-UHFFFAOYSA-N 5-fluoro-2-n-[2-(morpholin-4-ylmethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C3OCC(CN4CCOCC4)OC3=CC=2)=NC=C1F GZKKEQJGOMVLKN-UHFFFAOYSA-N 0.000 description 1
- BCLNSGSUHFAZJB-UHFFFAOYSA-N 5-fluoro-2-n-[2-(piperidin-1-ylmethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C3OCC(CN4CCCCC4)OC3=CC=2)=NC=C1F BCLNSGSUHFAZJB-UHFFFAOYSA-N 0.000 description 1
- UIWBWHSIEMALIC-UHFFFAOYSA-N 5-fluoro-2-n-[3-(1-methyltetrazol-5-yl)-4-(oxan-4-yloxy)phenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(OC3CCOCC3)=CC=2)C=2N(N=NN=2)C)=NC=C1F UIWBWHSIEMALIC-UHFFFAOYSA-N 0.000 description 1
- OLRYHFKNIPDSAL-UHFFFAOYSA-N 5-fluoro-2-n-[3-(1-methyltetrazol-5-yl)-4-(oxan-4-yloxy)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound CN1N=NN=C1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC=C1OC1CCOCC1 OLRYHFKNIPDSAL-UHFFFAOYSA-N 0.000 description 1
- CGMXOENYWQMNNY-UHFFFAOYSA-N 5-fluoro-2-n-[3-(1-methyltetrazol-5-yl)-4-(oxetan-3-yloxy)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound CN1N=NN=C1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC=C1OC1COC1 CGMXOENYWQMNNY-UHFFFAOYSA-N 0.000 description 1
- SBPHRJQEMWDFGY-UHFFFAOYSA-N 5-fluoro-2-n-[3-(1-methyltetrazol-5-yl)-4-propan-2-yloxyphenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(C=2N(N=NN=2)C)C(OC(C)C)=CC=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)N(C)C(C)(C)C1 SBPHRJQEMWDFGY-UHFFFAOYSA-N 0.000 description 1
- KCSZTSIBFKIPCT-UHFFFAOYSA-N 5-fluoro-2-n-[3-(1-methyltetrazol-5-yl)-4-propan-2-yloxyphenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(C=2N(N=NN=2)C)C(OC(C)C)=CC=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 KCSZTSIBFKIPCT-UHFFFAOYSA-N 0.000 description 1
- NPGFBLIZXRRTPO-UHFFFAOYSA-N 5-fluoro-2-n-[3-(1-methyltetrazol-5-yl)-5-(oxetan-3-yloxy)phenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=C(OC3COC3)C=2)C=2N(N=NN=2)C)=NC=C1F NPGFBLIZXRRTPO-UHFFFAOYSA-N 0.000 description 1
- NWTTYSJNYFTOSH-UHFFFAOYSA-N 5-fluoro-2-n-[3-(1-methyltetrazol-5-yl)-5-(trifluoromethyl)phenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=C(C=2)C=2N(N=NN=2)C)C(F)(F)F)=NC=C1F NWTTYSJNYFTOSH-UHFFFAOYSA-N 0.000 description 1
- ZIJNYRKIWIPIOC-UHFFFAOYSA-N 5-fluoro-2-n-[3-(1-methyltetrazol-5-yl)-5-(trifluoromethyl)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound CN1N=NN=C1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC(C(F)(F)F)=C1 ZIJNYRKIWIPIOC-UHFFFAOYSA-N 0.000 description 1
- VBOUMFNJWKVSQI-UHFFFAOYSA-N 5-fluoro-2-n-[3-(1-propan-2-yltetrazol-5-yl)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound CC(C)N1N=NN=C1C1=CC=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=C1 VBOUMFNJWKVSQI-UHFFFAOYSA-N 0.000 description 1
- YMIAFDWEICWOCD-UHFFFAOYSA-N 5-fluoro-2-n-[3-(3-methylpyrazol-1-yl)phenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=CC=2)N2N=C(C)C=C2)=NC=C1F YMIAFDWEICWOCD-UHFFFAOYSA-N 0.000 description 1
- ILJAMAOKAOJSGW-UHFFFAOYSA-N 5-fluoro-2-n-[3-(3-methylpyrazol-1-yl)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound N1=C(C)C=CN1C1=CC=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=C1 ILJAMAOKAOJSGW-UHFFFAOYSA-N 0.000 description 1
- SFNGYEUADMMAKN-UHFFFAOYSA-N 5-fluoro-2-n-[3-(5-methyltetrazol-1-yl)-4-(1-propan-2-ylpiperidin-4-yl)oxyphenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1CN(C(C)C)CCC1OC(C(=C1)N2C(=NN=N2)C)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)N(C)C(C)(C)C2)=N1 SFNGYEUADMMAKN-UHFFFAOYSA-N 0.000 description 1
- MUWJCLSMRWEVQH-UHFFFAOYSA-N 5-fluoro-2-n-[3-(5-methyltetrazol-1-yl)-4-(1-propan-2-ylpiperidin-4-yl)oxyphenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1CN(C(C)C)CCC1OC(C(=C1)N2C(=NN=N2)C)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 MUWJCLSMRWEVQH-UHFFFAOYSA-N 0.000 description 1
- PCVSGIZJLDBIFT-UHFFFAOYSA-N 5-fluoro-2-n-[3-(5-methyltetrazol-1-yl)-4-(trifluoromethoxy)phenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(OC(F)(F)F)=CC=2)N2C(=NN=N2)C)=NC=C1F PCVSGIZJLDBIFT-UHFFFAOYSA-N 0.000 description 1
- TVLMIZKNMVBJHM-UHFFFAOYSA-N 5-fluoro-2-n-[3-(5-methyltetrazol-1-yl)-4-(trifluoromethoxy)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound CC1=NN=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC=C1OC(F)(F)F TVLMIZKNMVBJHM-UHFFFAOYSA-N 0.000 description 1
- LOCVVLRTHDQLIE-UNLAWSRZSA-N 5-fluoro-2-n-[3-(5-methyltetrazol-1-yl)phenyl]-4-n-[2,2,6,6-tetramethyl-1-(trideuteriomethyl)piperidin-4-yl]pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C([2H])([2H])[2H])C(C)(C)CC1NC1=NC(NC=2C=C(C=CC=2)N2C(=NN=N2)C)=NC=C1F LOCVVLRTHDQLIE-UNLAWSRZSA-N 0.000 description 1
- GSGLBWLYOPLOHY-UHFFFAOYSA-N 5-fluoro-2-n-[3-(propan-2-ylamino)-4-propan-2-yloxyphenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(OC(C)C)C(NC(C)C)=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=C1 GSGLBWLYOPLOHY-UHFFFAOYSA-N 0.000 description 1
- LWXLVJOXSSKHBH-UHFFFAOYSA-N 5-fluoro-2-n-[3-[1-(2-fluoroethyl)tetrazol-5-yl]phenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=CC=2)C=2N(N=NN=2)CCF)=NC=C1F LWXLVJOXSSKHBH-UHFFFAOYSA-N 0.000 description 1
- PZYHOXXERKKJAG-UHFFFAOYSA-N 5-fluoro-2-n-[3-[1-(2-fluoroethyl)tetrazol-5-yl]phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(C=CC=2)C=2N(N=NN=2)CCF)=NC=C1F PZYHOXXERKKJAG-UHFFFAOYSA-N 0.000 description 1
- SZDJHXDETRQXLE-UHFFFAOYSA-N 5-fluoro-2-n-[3-[1-(2-morpholin-4-ylethyl)tetrazol-5-yl]phenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=CC=2)C=2N(N=NN=2)CCN2CCOCC2)=NC=C1F SZDJHXDETRQXLE-UHFFFAOYSA-N 0.000 description 1
- SZLSAUBXTWLNHH-UHFFFAOYSA-N 5-fluoro-2-n-[3-[1-(2-morpholin-4-ylethyl)tetrazol-5-yl]phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(C=CC=2)C=2N(N=NN=2)CCN2CCOCC2)=NC=C1F SZLSAUBXTWLNHH-UHFFFAOYSA-N 0.000 description 1
- YWMDVILICRPLOW-UHFFFAOYSA-N 5-fluoro-2-n-[3-[methyl(propan-2-yl)amino]-4-propan-2-yloxyphenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(N(C)C(C)C)C(OC(C)C)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)N(C)C(C)(C)C2)=N1 YWMDVILICRPLOW-UHFFFAOYSA-N 0.000 description 1
- NKNMCFRPDHQVNU-UHFFFAOYSA-N 5-fluoro-2-n-[3-[methyl(propan-2-yl)amino]-4-propan-2-yloxyphenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(N(C)C(C)C)C(OC(C)C)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 NKNMCFRPDHQVNU-UHFFFAOYSA-N 0.000 description 1
- HFDFUMOUGPYHSR-UHFFFAOYSA-N 5-fluoro-2-n-[3-fluoro-4-(1-methylsulfonylpiperidin-4-yl)oxyphenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC3CCN(CC3)S(C)(=O)=O)=CC=2)=NC=C1F HFDFUMOUGPYHSR-UHFFFAOYSA-N 0.000 description 1
- LZSGPYRQPLYDFM-UHFFFAOYSA-N 5-fluoro-2-n-[3-fluoro-4-(1-methylsulfonylpiperidin-4-yl)oxyphenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC3CCN(CC3)S(C)(=O)=O)=CC=2)=NC=C1F LZSGPYRQPLYDFM-UHFFFAOYSA-N 0.000 description 1
- IMGDJJMTLSKBPQ-UHFFFAOYSA-N 5-fluoro-2-n-[3-fluoro-4-(1-propan-2-ylpiperidin-4-yl)oxyphenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1CN(C(C)C)CCC1OC(C(=C1)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)N(C)C(C)(C)C2)=N1 IMGDJJMTLSKBPQ-UHFFFAOYSA-N 0.000 description 1
- LQRCWGXKTVBTSN-UHFFFAOYSA-N 5-fluoro-2-n-[3-fluoro-4-(1-propan-2-ylpiperidin-4-yl)oxyphenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1CN(C(C)C)CCC1OC(C(=C1)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 LQRCWGXKTVBTSN-UHFFFAOYSA-N 0.000 description 1
- WGJPLXKVGWCGER-UHFFFAOYSA-N 5-fluoro-2-n-[3-fluoro-4-(2-methyl-4-pyrrolidin-1-ylbutan-2-yl)oxyphenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC(C)(C)CCN3CCCC3)=CC=2)=NC=C1F WGJPLXKVGWCGER-UHFFFAOYSA-N 0.000 description 1
- QXLFYOFKKPTKAI-UHFFFAOYSA-N 5-fluoro-2-n-[3-fluoro-4-(oxan-4-yloxy)phenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC3CCOCC3)=CC=2)=NC=C1F QXLFYOFKKPTKAI-UHFFFAOYSA-N 0.000 description 1
- WYCDCAZRHBYFJG-UHFFFAOYSA-N 5-fluoro-2-n-[3-fluoro-4-(oxan-4-yloxy)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC3CCOCC3)=CC=2)=NC=C1F WYCDCAZRHBYFJG-UHFFFAOYSA-N 0.000 description 1
- WJTKDJJLZCCXEQ-UHFFFAOYSA-N 5-fluoro-2-n-[3-fluoro-4-[1-(2-phenylmethoxyethyl)piperidin-4-yl]oxyphenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(F)C(OC3CCN(CCOCC=4C=CC=CC=4)CC3)=CC=2)=NC=C1F WJTKDJJLZCCXEQ-UHFFFAOYSA-N 0.000 description 1
- JOPPFWKYAZKZNT-UHFFFAOYSA-N 5-fluoro-2-n-[3-fluoro-5-(1-methyltetrazol-5-yl)phenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=C(F)C=2)C=2N(N=NN=2)C)=NC=C1F JOPPFWKYAZKZNT-UHFFFAOYSA-N 0.000 description 1
- JWUQDIYXGAAFNI-UHFFFAOYSA-N 5-fluoro-2-n-[3-fluoro-5-(1-methyltetrazol-5-yl)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound CN1N=NN=C1C1=CC(F)=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=C1 JWUQDIYXGAAFNI-UHFFFAOYSA-N 0.000 description 1
- IVCDHJWWOSOWHO-UHFFFAOYSA-N 5-fluoro-2-n-[3-fluoro-5-[2-(1,2,4-triazol-1-yl)ethoxy]phenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OCCN3N=CN=C3)C=C(F)C=2)=NC=C1F IVCDHJWWOSOWHO-UHFFFAOYSA-N 0.000 description 1
- XNEZKPCZNMSPDN-UHFFFAOYSA-N 5-fluoro-2-n-[3-fluoro-5-[2-(1,2,4-triazol-1-yl)ethoxy]phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(OCCN3N=CN=C3)C=C(F)C=2)=NC=C1F XNEZKPCZNMSPDN-UHFFFAOYSA-N 0.000 description 1
- TUSJZEBOXBMDCL-UHFFFAOYSA-N 5-fluoro-2-n-[3-fluoro-5-[2-(triazol-1-yl)ethoxy]phenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(OCCN3N=NC=C3)C=C(F)C=2)=NC=C1F TUSJZEBOXBMDCL-UHFFFAOYSA-N 0.000 description 1
- AUXRKSMPVODGNH-UHFFFAOYSA-N 5-fluoro-2-n-[3-methyl-5-(1-methyltetrazol-5-yl)phenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=C(C)C=2)C=2N(N=NN=2)C)=NC=C1F AUXRKSMPVODGNH-UHFFFAOYSA-N 0.000 description 1
- DHYFEZJQNVLUCK-UHFFFAOYSA-N 5-fluoro-2-n-[3-methyl-5-(1-methyltetrazol-5-yl)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C=1C(C=2N(N=NN=2)C)=CC(C)=CC=1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 DHYFEZJQNVLUCK-UHFFFAOYSA-N 0.000 description 1
- VZJNKUDBRFLNPO-UHFFFAOYSA-N 5-fluoro-2-n-[4-(1-propan-2-ylpiperidin-4-yl)oxy-3-(trifluoromethyl)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1CN(C(C)C)CCC1OC(C(=C1)C(F)(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)NC(C)(C)C2)=N1 VZJNKUDBRFLNPO-UHFFFAOYSA-N 0.000 description 1
- CIIWIZSCAADTHF-UHFFFAOYSA-N 5-fluoro-2-n-[4-(2-morpholin-4-ylethoxy)-3-(trifluoromethyl)phenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(OCCN3CCOCC3)=CC=2)C(F)(F)F)=NC=C1F CIIWIZSCAADTHF-UHFFFAOYSA-N 0.000 description 1
- IRYXCBDMVHTDJO-UHFFFAOYSA-N 5-fluoro-2-n-[4-(2-morpholin-4-ylethoxy)-3-(trifluoromethyl)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(C(OCCN3CCOCC3)=CC=2)C(F)(F)F)=NC=C1F IRYXCBDMVHTDJO-UHFFFAOYSA-N 0.000 description 1
- SPFGSOXILCBJIP-UHFFFAOYSA-N 5-fluoro-2-n-[4-fluoro-3-(1-methyltetrazol-5-yl)phenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(F)=CC=2)C=2N(N=NN=2)C)=NC=C1F SPFGSOXILCBJIP-UHFFFAOYSA-N 0.000 description 1
- ZMVCHUHMWDGSDV-UHFFFAOYSA-N 5-fluoro-2-n-[4-fluoro-3-(1-methyltetrazol-5-yl)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound CN1N=NN=C1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC=C1F ZMVCHUHMWDGSDV-UHFFFAOYSA-N 0.000 description 1
- ASYZWGNAKMKJLR-UHFFFAOYSA-N 5-fluoro-2-n-[4-fluoro-3-(5-methyltetrazol-1-yl)phenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(F)=CC=2)N2C(=NN=N2)C)=NC=C1F ASYZWGNAKMKJLR-UHFFFAOYSA-N 0.000 description 1
- GIEBENJCMRPTHD-UHFFFAOYSA-N 5-fluoro-2-n-[4-fluoro-3-(5-methyltetrazol-1-yl)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound CC1=NN=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC=C1F GIEBENJCMRPTHD-UHFFFAOYSA-N 0.000 description 1
- RLCLWKUPUSPLJW-UHFFFAOYSA-N 5-fluoro-2-n-[4-fluoro-3-[1-(2-methoxyethyl)tetrazol-5-yl]phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound COCCN1N=NN=C1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC=C1F RLCLWKUPUSPLJW-UHFFFAOYSA-N 0.000 description 1
- ZBLGOWBRCYYQCE-UHFFFAOYSA-N 5-fluoro-2-n-[4-methyl-3-(1-methyltetrazol-5-yl)phenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(C)=CC=2)C=2N(N=NN=2)C)=NC=C1F ZBLGOWBRCYYQCE-UHFFFAOYSA-N 0.000 description 1
- VWPAUYXZZLLCRL-UHFFFAOYSA-N 5-fluoro-2-n-[4-methyl-3-(1-methyltetrazol-5-yl)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(C=2N(N=NN=2)C)C(C)=CC=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 VWPAUYXZZLLCRL-UHFFFAOYSA-N 0.000 description 1
- XDUXOLSAASADLN-UNLAWSRZSA-N 5-fluoro-2-n-[4-methyl-3-(tetrazol-1-yl)phenyl]-4-n-[2,2,6,6-tetramethyl-1-(trideuteriomethyl)piperidin-4-yl]pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C([2H])([2H])[2H])C(C)(C)CC1NC1=NC(NC=2C=C(C(C)=CC=2)N2N=NN=C2)=NC=C1F XDUXOLSAASADLN-UNLAWSRZSA-N 0.000 description 1
- ZGCXVBFATJOZQB-UHFFFAOYSA-N 5-fluoro-2-n-[4-pyridin-3-yloxy-3-(trifluoromethyl)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(C(OC=3C=NC=CC=3)=CC=2)C(F)(F)F)=NC=C1F ZGCXVBFATJOZQB-UHFFFAOYSA-N 0.000 description 1
- JOEFJLALSPDQPJ-UHFFFAOYSA-N 5-fluoro-2-n-[5-(1-methyltetrazol-5-yl)-6-propan-2-yloxypyridin-3-yl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(C=2N(N=NN=2)C)C(OC(C)C)=NC=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 JOEFJLALSPDQPJ-UHFFFAOYSA-N 0.000 description 1
- XIRJEEMPNDRTIS-UHFFFAOYSA-N 5-fluoro-2-n-[5-(5-methyltetrazol-1-yl)-6-propan-2-yloxypyridin-3-yl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(N2C(=NN=N2)C)C(OC(C)C)=NC=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 XIRJEEMPNDRTIS-UHFFFAOYSA-N 0.000 description 1
- BGVQRGJSTLFNDU-UHFFFAOYSA-N 5-fluoro-2-n-[6-propan-2-yloxy-5-(1-propan-2-yltetrazol-5-yl)pyridin-3-yl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(C=2N(N=NN=2)C(C)C)C(OC(C)C)=NC=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 BGVQRGJSTLFNDU-UHFFFAOYSA-N 0.000 description 1
- XURYHERHHHFJHC-UHFFFAOYSA-N 5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2-n-(3-pyrazol-1-ylphenyl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=CC=2)N2N=CC=C2)=NC=C1F XURYHERHHHFJHC-UHFFFAOYSA-N 0.000 description 1
- SYKOAICHCJYUFW-UHFFFAOYSA-N 5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2-n-[2-(piperidin-1-ylmethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C3OCC(CN4CCCCC4)OC3=CC=2)=NC=C1F SYKOAICHCJYUFW-UHFFFAOYSA-N 0.000 description 1
- QBZSOGOWQWDRRZ-UHFFFAOYSA-N 5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2-n-[3-(1,2,4-triazol-1-yl)phenyl]pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=CC=2)N2N=CN=C2)=NC=C1F QBZSOGOWQWDRRZ-UHFFFAOYSA-N 0.000 description 1
- RFHQZPCANISSGD-UHFFFAOYSA-N 5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2-n-[3-(2h-tetrazol-5-yl)phenyl]pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=CC=2)C2=NNN=N2)=NC=C1F RFHQZPCANISSGD-UHFFFAOYSA-N 0.000 description 1
- SOJBMHUPWNCNRZ-UHFFFAOYSA-N 5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2-n-[3-(propan-2-ylamino)-4-propan-2-yloxyphenyl]pyrimidine-2,4-diamine Chemical compound C1=C(OC(C)C)C(NC(C)C)=CC(NC=2N=C(NC3CC(C)(C)N(C)C(C)(C)C3)C(F)=CN=2)=C1 SOJBMHUPWNCNRZ-UHFFFAOYSA-N 0.000 description 1
- RZDPORSYVCGPCE-UHFFFAOYSA-N 5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2-n-[3-[2-(1,2,4-triazol-1-yl)ethoxy]-5-(trifluoromethyl)phenyl]pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=C(OCCN3N=CN=C3)C=2)C(F)(F)F)=NC=C1F RZDPORSYVCGPCE-UHFFFAOYSA-N 0.000 description 1
- BFNZODSBTZCLFV-UHFFFAOYSA-N 5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2-n-[3-[2-(triazol-1-yl)ethoxy]-5-(trifluoromethyl)phenyl]pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=C(OCCN3N=NC=C3)C=2)C(F)(F)F)=NC=C1F BFNZODSBTZCLFV-UHFFFAOYSA-N 0.000 description 1
- CFUJOJABSDQHIT-UHFFFAOYSA-N 5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2-n-[3-[3-(trifluoromethyl)pyrazol-1-yl]phenyl]pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=CC=2)N2N=C(C=C2)C(F)(F)F)=NC=C1F CFUJOJABSDQHIT-UHFFFAOYSA-N 0.000 description 1
- YRWVJOWLFISLAV-UHFFFAOYSA-N 5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2-n-[4-(1-propan-2-ylpiperidin-4-yl)oxy-3-(trifluoromethyl)phenyl]pyrimidine-2,4-diamine Chemical compound C1CN(C(C)C)CCC1OC(C(=C1)C(F)(F)F)=CC=C1NC1=NC=C(F)C(NC2CC(C)(C)N(C)C(C)(C)C2)=N1 YRWVJOWLFISLAV-UHFFFAOYSA-N 0.000 description 1
- BPLCVFFNKBIXAX-UHFFFAOYSA-N 5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2-n-[4-pyridin-3-yloxy-3-(trifluoromethyl)phenyl]pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(OC=3C=NC=CC=3)=CC=2)C(F)(F)F)=NC=C1F BPLCVFFNKBIXAX-UHFFFAOYSA-N 0.000 description 1
- ODCYNECTZSMANN-UHFFFAOYSA-N 5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2-n-[4-pyridin-4-yloxy-3-(trifluoromethyl)phenyl]pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(OC=3C=CN=CC=3)=CC=2)C(F)(F)F)=NC=C1F ODCYNECTZSMANN-UHFFFAOYSA-N 0.000 description 1
- VCWBGAFUAUNFPF-UHFFFAOYSA-N 5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)-2-n-[3-(1,2,4-triazol-1-yl)phenyl]pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(C=CC=2)N2N=CN=C2)=NC=C1F VCWBGAFUAUNFPF-UHFFFAOYSA-N 0.000 description 1
- XLBNRLLIIWBAOL-UHFFFAOYSA-N 5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)-2-n-[3-(2h-tetrazol-5-yl)phenyl]pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(C=CC=2)C2=NNN=N2)=NC=C1F XLBNRLLIIWBAOL-UHFFFAOYSA-N 0.000 description 1
- BLCIJUJRFYLCRK-UHFFFAOYSA-N 5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)-2-n-[3-[2-(1,2,4-triazol-1-yl)ethoxy]-5-(trifluoromethyl)phenyl]pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(C=C(OCCN3N=CN=C3)C=2)C(F)(F)F)=NC=C1F BLCIJUJRFYLCRK-UHFFFAOYSA-N 0.000 description 1
- MJJNADVBNQDBBI-UHFFFAOYSA-N 5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)-2-n-[3-[2-(triazol-1-yl)ethoxy]-5-(trifluoromethyl)phenyl]pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(C=C(OCCN3N=NC=C3)C=2)C(F)(F)F)=NC=C1F MJJNADVBNQDBBI-UHFFFAOYSA-N 0.000 description 1
- BUSLDYWQGYBCLF-UHFFFAOYSA-N 5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)-2-n-[3-[3-(trifluoromethyl)pyrazol-1-yl]phenyl]pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(C=CC=2)N2N=C(C=C2)C(F)(F)F)=NC=C1F BUSLDYWQGYBCLF-UHFFFAOYSA-N 0.000 description 1
- APOWNHQIYOIWDU-VPYROQPTSA-N 5-fluoro-4-n-[2,2,6,6-tetramethyl-1-(trideuteriomethyl)piperidin-4-yl]-2-n-[3-(tetrazol-1-yl)phenyl]pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C([2H])([2H])[2H])C(C)(C)CC1NC1=NC(NC=2C=C(C=CC=2)N2N=NN=C2)=NC=C1F APOWNHQIYOIWDU-VPYROQPTSA-N 0.000 description 1
- 206010068532 5q minus syndrome Diseases 0.000 description 1
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
- 208000016557 Acute basophilic leukemia Diseases 0.000 description 1
- 206010000890 Acute myelomonocytic leukaemia Diseases 0.000 description 1
- 208000016585 Acute panmyelosis with myelofibrosis Diseases 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 206010001413 Adult T-cell lymphoma/leukaemia Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 101000719121 Arabidopsis thaliana Protein MEI2-like 1 Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 108091008875 B cell receptors Proteins 0.000 description 1
- 208000036170 B-Cell Marginal Zone Lymphoma Diseases 0.000 description 1
- 208000025324 B-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 102100035634 B-cell linker protein Human genes 0.000 description 1
- 208000032568 B-cell prolymphocytic leukaemia Diseases 0.000 description 1
- 208000033775 Basophilic Acute Leukemia Diseases 0.000 description 1
- 102000051485 Bcl-2 family Human genes 0.000 description 1
- 108700038897 Bcl-2 family Proteins 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 208000008720 Bone Marrow Neoplasms Diseases 0.000 description 1
- 206010048396 Bone marrow transplant rejection Diseases 0.000 description 1
- YXISUWIRPNTSLS-UHFFFAOYSA-N C(C)N1CCC(CC1)OC1=C(C=C(C=C1)NC1=NC=C(C(=N1)NC1CC(NC(C1)(C)C)(C)C)F)F Chemical compound C(C)N1CCC(CC1)OC1=C(C=C(C=C1)NC1=NC=C(C(=N1)NC1CC(NC(C1)(C)C)(C)C)F)F YXISUWIRPNTSLS-UHFFFAOYSA-N 0.000 description 1
- ZVCOXCUZSUFORZ-UHFFFAOYSA-N C1(CC1)C1=C(C=C(C=C1)C1(NC=C(C(=N1)NC1CC(N(C(C1)(C)C)C)(C)C)F)N)N1N=NN=C1 Chemical compound C1(CC1)C1=C(C=C(C=C1)C1(NC=C(C(=N1)NC1CC(N(C(C1)(C)C)C)(C)C)F)N)N1N=NN=C1 ZVCOXCUZSUFORZ-UHFFFAOYSA-N 0.000 description 1
- GOXLMUZKDOQLHX-UHFFFAOYSA-N C1(CC1)C=1C=C(C=C(C=1)N1N=NN=C1)C1(NC=C(C(=N1)NC1CC(N(C(C1)(C)C)C)(C)C)F)N Chemical compound C1(CC1)C=1C=C(C=C(C=1)N1N=NN=C1)C1(NC=C(C(=N1)NC1CC(N(C(C1)(C)C)C)(C)C)F)N GOXLMUZKDOQLHX-UHFFFAOYSA-N 0.000 description 1
- GKNPKXFVTWKXJJ-UHFFFAOYSA-N CC(C)(C1)N(C)C(C)(C)CC1NC1=NC(N)=NC(C(C=C2)=CC(N3C(C)=CC=C3C)=C2OCCN2CCCC2)=C1F Chemical compound CC(C)(C1)N(C)C(C)(C)CC1NC1=NC(N)=NC(C(C=C2)=CC(N3C(C)=CC=C3C)=C2OCCN2CCCC2)=C1F GKNPKXFVTWKXJJ-UHFFFAOYSA-N 0.000 description 1
- IRBOLMQSADHEIN-UHFFFAOYSA-N CC(C)(C1)NC(C)(C)CC1NC1=NC(N)=NC(C(C=C2)=CC(Cl)=C2OC2CCN(CCF)CC2)=C1F Chemical compound CC(C)(C1)NC(C)(C)CC1NC1=NC(N)=NC(C(C=C2)=CC(Cl)=C2OC2CCN(CCF)CC2)=C1F IRBOLMQSADHEIN-UHFFFAOYSA-N 0.000 description 1
- NFLRFINQSXAPID-UHFFFAOYSA-N CC(C)(C1)NC(C)(C)CC1NC1=NC(N)=NC(C(C=C2)=CC(OC(F)F)=C2OCCN2N=CN=C2)=C1F Chemical compound CC(C)(C1)NC(C)(C)CC1NC1=NC(N)=NC(C(C=C2)=CC(OC(F)F)=C2OCCN2N=CN=C2)=C1F NFLRFINQSXAPID-UHFFFAOYSA-N 0.000 description 1
- NIBSEGCCXQECFC-UHFFFAOYSA-N CC(C)(CN1CCOCC1)OC(C=CC(C(N=C(N)N=C1NC2CC(C)(C)NC(C)(C)C2)=C1F)=C1)=C1OC(F)F Chemical compound CC(C)(CN1CCOCC1)OC(C=CC(C(N=C(N)N=C1NC2CC(C)(C)NC(C)(C)C2)=C1F)=C1)=C1OC(F)F NIBSEGCCXQECFC-UHFFFAOYSA-N 0.000 description 1
- LMEQDNJQGKDUEF-UHFFFAOYSA-N CC(C)OC(C(C1=NN=NN1C)=CC(C1=CN=C(N)N=C1NC1CC(C)(C)NC(C)(C)C1)=C1)=C1F Chemical compound CC(C)OC(C(C1=NN=NN1C)=CC(C1=CN=C(N)N=C1NC1CC(C)(C)NC(C)(C)C1)=C1)=C1F LMEQDNJQGKDUEF-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
- SMDCNRBQSZTVPM-UHFFFAOYSA-N Cl[SiH3].[N-]=[N+]=[N-].[N-]=[N+]=[N-].[N-]=[N+]=[N-] Chemical compound Cl[SiH3].[N-]=[N+]=[N-].[N-]=[N+]=[N-].[N-]=[N+]=[N-] SMDCNRBQSZTVPM-UHFFFAOYSA-N 0.000 description 1
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 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
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-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-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 1
- 108700020911 DNA-Binding Proteins Proteins 0.000 description 1
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
- 208000010837 Diabetic eye disease Diseases 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 1
- 206010013774 Dry eye Diseases 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 206010015108 Epstein-Barr virus infection Diseases 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 208000032027 Essential Thrombocythemia Diseases 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 208000016937 Extranodal nasal NK/T cell lymphoma Diseases 0.000 description 1
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 208000001204 Hashimoto Disease Diseases 0.000 description 1
- 208000032087 Hereditary Leber Optic Atrophy Diseases 0.000 description 1
- 241000700586 Herpesviridae Species 0.000 description 1
- 101000803266 Homo sapiens B-cell linker protein Proteins 0.000 description 1
- 101100166600 Homo sapiens CD28 gene Proteins 0.000 description 1
- 101100456320 Homo sapiens NR3C2 gene Proteins 0.000 description 1
- 101000573199 Homo sapiens Protein PML Proteins 0.000 description 1
- 101000944909 Homo sapiens Ribosomal protein S6 kinase alpha-1 Proteins 0.000 description 1
- 101000857677 Homo sapiens Runt-related transcription factor 1 Proteins 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 102000009438 IgE Receptors Human genes 0.000 description 1
- 108010073816 IgE Receptors Proteins 0.000 description 1
- 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 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 208000010038 Ischemic Optic Neuropathy Diseases 0.000 description 1
- 229930194542 Keto Natural products 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
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 1
- 208000006404 Large Granular Lymphocytic Leukemia Diseases 0.000 description 1
- 201000000639 Leber hereditary optic neuropathy Diseases 0.000 description 1
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
- 208000030289 Lymphoproliferative disease Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 1
- 208000035490 Megakaryoblastic Acute Leukemia Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100351501 Mus musculus Cbfb gene Proteins 0.000 description 1
- 101100456322 Mus musculus Nr3c2 gene Proteins 0.000 description 1
- 101100268066 Mus musculus Zap70 gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 208000033835 Myelomonocytic Acute Leukemia Diseases 0.000 description 1
- KEAAKVIGEVELAQ-UHFFFAOYSA-N N1(N=NN=C1)C=1C=C(C=CC=1)C1(NC=C(C(=N1)NC1CC(N(C(C1)C)C1CC1)C)F)N Chemical compound N1(N=NN=C1)C=1C=C(C=CC=1)C1(NC=C(C(=N1)NC1CC(N(C(C1)C)C1CC1)C)F)N KEAAKVIGEVELAQ-UHFFFAOYSA-N 0.000 description 1
- 208000033755 Neutrophilic Chronic Leukemia Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- 206010029461 Nodal marginal zone B-cell lymphomas Diseases 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 1
- 102000011931 Nucleoproteins Human genes 0.000 description 1
- 108010061100 Nucleoproteins Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010030924 Optic ischaemic neuropathy Diseases 0.000 description 1
- 206010061323 Optic neuropathy Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 102000042846 PKC family Human genes 0.000 description 1
- 108091082203 PKC family Proteins 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 206010033661 Pancytopenia Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 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
- 208000027190 Peripheral T-cell lymphomas Diseases 0.000 description 1
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 1
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 1
- 102000015439 Phospholipases Human genes 0.000 description 1
- 108010064785 Phospholipases Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 208000007452 Plasmacytoma Diseases 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000017414 Precursor T-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000032758 Precursor T-lymphoblastic lymphoma/leukaemia Diseases 0.000 description 1
- 206010036711 Primary mediastinal large B-cell lymphomas Diseases 0.000 description 1
- 208000035416 Prolymphocytic B-Cell Leukemia Diseases 0.000 description 1
- 208000033759 Prolymphocytic T-Cell Leukemia Diseases 0.000 description 1
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- 108010024526 Protein Kinase C beta Proteins 0.000 description 1
- 102000015766 Protein Kinase C beta Human genes 0.000 description 1
- 108010050276 Protein Kinase C-alpha Proteins 0.000 description 1
- 108010039230 Protein Kinase C-delta Proteins 0.000 description 1
- 108010078137 Protein Kinase C-epsilon Proteins 0.000 description 1
- 102100026375 Protein PML Human genes 0.000 description 1
- 102100037340 Protein kinase C delta type Human genes 0.000 description 1
- 102100037339 Protein kinase C epsilon type Human genes 0.000 description 1
- 102100021556 Protein kinase C eta type Human genes 0.000 description 1
- 102100021566 Protein kinase C theta type Human genes 0.000 description 1
- 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 1
- 201000007737 Retinal degeneration Diseases 0.000 description 1
- 206010038848 Retinal detachment Diseases 0.000 description 1
- 102100023606 Retinoic acid receptor alpha Human genes 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 102100033536 Ribosomal protein S6 kinase alpha-1 Human genes 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 102100025373 Runt-related transcription factor 1 Human genes 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 208000009359 Sezary Syndrome Diseases 0.000 description 1
- 208000021388 Sezary disease Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000027073 Stargardt disease Diseases 0.000 description 1
- 108010090804 Streptavidin Proteins 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
- UZMAPBJVXOGOFT-UHFFFAOYSA-N Syringetin Natural products COC1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UZMAPBJVXOGOFT-UHFFFAOYSA-N 0.000 description 1
- 230000033540 T cell apoptotic process Effects 0.000 description 1
- 208000031672 T-Cell Peripheral Lymphoma Diseases 0.000 description 1
- 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000026651 T-cell prolymphocytic leukemia Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 239000007997 Tricine buffer Substances 0.000 description 1
- 208000026911 Tuberous sclerosis complex Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- ZTYIHYYQPGGIOZ-UHFFFAOYSA-N [6-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2,3-dihydro-1,4-benzodioxin-2-yl]-morpholin-4-ylmethanone Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C3OCC(OC3=CC=2)C(=O)N2CCOCC2)=NC=C1F ZTYIHYYQPGGIOZ-UHFFFAOYSA-N 0.000 description 1
- WDMCTSZKZGRYLW-UHFFFAOYSA-N [6-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2,3-dihydro-1,4-benzodioxin-2-yl]-piperidin-1-ylmethanone Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C3OCC(OC3=CC=2)C(=O)N2CCCCC2)=NC=C1F WDMCTSZKZGRYLW-UHFFFAOYSA-N 0.000 description 1
- JCCKPSCOGUKODR-UHFFFAOYSA-N [6-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2,3-dihydro-1,4-benzodioxin-2-yl]-morpholin-4-ylmethanone Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C3OCC(OC3=CC=2)C(=O)N2CCOCC2)=NC=C1F JCCKPSCOGUKODR-UHFFFAOYSA-N 0.000 description 1
- OECSLONGNGZWJV-UHFFFAOYSA-N [6-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2,3-dihydro-1,4-benzodioxin-2-yl]-piperidin-1-ylmethanone Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C3OCC(OC3=CC=2)C(=O)N2CCCCC2)=NC=C1F OECSLONGNGZWJV-UHFFFAOYSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 208000017733 acquired polycythemia vera Diseases 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 208000013593 acute megakaryoblastic leukemia Diseases 0.000 description 1
- 208000020700 acute megakaryocytic leukemia Diseases 0.000 description 1
- 208000026784 acute myeloblastic leukemia with maturation Diseases 0.000 description 1
- 208000010816 acute myeloblastic leukemia without maturation Diseases 0.000 description 1
- 208000011912 acute myelomonocytic leukemia M4 Diseases 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 208000015230 aggressive NK-cell leukemia Diseases 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 125000005055 alkyl alkoxy group Chemical group 0.000 description 1
- 125000000278 alkyl amino alkyl group Chemical group 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 125000005275 alkylenearyl group Chemical class 0.000 description 1
- 125000004419 alkynylene group Chemical group 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 201000007058 anterior ischemic optic neuropathy Diseases 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 239000012911 assay medium Substances 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 239000003855 balanced salt solution Substances 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000029918 bioluminescence Effects 0.000 description 1
- 238000005415 bioluminescence Methods 0.000 description 1
- 210000003969 blast cell Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 201000006491 bone marrow cancer Diseases 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000872 buffer 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
- 239000003560 cancer drug Substances 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000023549 cell-cell signaling Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000021668 chronic eosinophilic leukemia Diseases 0.000 description 1
- 201000010903 chronic neutrophilic leukemia Diseases 0.000 description 1
- 235000017803 cinnamon Nutrition 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 1
- 239000005516 coenzyme A Substances 0.000 description 1
- 229940093530 coenzyme a Drugs 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 108010010201 core binding factor alpha Proteins 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 150000001925 cycloalkenes Chemical class 0.000 description 1
- 125000004465 cycloalkenyloxy group Chemical group 0.000 description 1
- 125000000000 cycloalkoxy group Chemical group 0.000 description 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 208000024389 cytopenia Diseases 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 208000001309 degenerative myopia Diseases 0.000 description 1
- 230000004340 degenerative myopia Effects 0.000 description 1
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
- 238000006251 dihalogenation reaction Methods 0.000 description 1
- KCFYHBSOLOXZIF-UHFFFAOYSA-N dihydrochrysin Natural products COC1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 KCFYHBSOLOXZIF-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- CWHBCTLVWOCMPQ-UHFFFAOYSA-L disodium;2-[(3,5-diiodo-4-oxidophenyl)-(3,5-diiodo-4-oxocyclohexa-2,5-dien-1-ylidene)methyl]benzoate Chemical group [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C(C=1C=C(I)C([O-])=C(I)C=1)=C1C=C(I)C(=O)C(I)=C1 CWHBCTLVWOCMPQ-UHFFFAOYSA-L 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 125000005290 ethynyloxy group Chemical group C(#C)O* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 125000003709 fluoroalkyl group Chemical group 0.000 description 1
- 201000003444 follicular lymphoma Diseases 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 201000006321 fundus dystrophy Diseases 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 210000004475 gamma-delta t lymphocyte Anatomy 0.000 description 1
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000006377 glucose transport Effects 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 201000009277 hairy cell leukemia Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000009033 hematopoietic malignancy Effects 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 125000004475 heteroaralkyl group Chemical group 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 description 1
- 125000005844 heterocyclyloxy group Chemical group 0.000 description 1
- 125000004468 heterocyclylthio group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 102000055277 human IL2 Human genes 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 125000006301 indolyl methyl group Chemical group 0.000 description 1
- 201000006747 infectious mononucleosis Diseases 0.000 description 1
- 208000017532 inherited retinal dystrophy Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- FBAFATDZDUQKNH-UHFFFAOYSA-M iron chloride Chemical compound [Cl-].[Fe] FBAFATDZDUQKNH-UHFFFAOYSA-M 0.000 description 1
- 230000000302 ischemic effect Effects 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
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000011649 lymphoblastic lymphoma Diseases 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 208000037652 lymphocytic-histiocytic predominance Hodgkin lymphoma Diseases 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 201000001268 lymphoproliferative syndrome Diseases 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 201000007924 marginal zone B-cell lymphoma Diseases 0.000 description 1
- 208000021937 marginal zone lymphoma Diseases 0.000 description 1
- 208000020968 mature T-cell and NK-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 125000005322 morpholin-1-yl group Chemical group 0.000 description 1
- 230000036473 myasthenia Effects 0.000 description 1
- 201000005962 mycosis fungoides Diseases 0.000 description 1
- 208000017869 myelodysplastic/myeloproliferative disease Diseases 0.000 description 1
- 210000003643 myeloid progenitor cell Anatomy 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- PWUHMCHBJHWECV-UHFFFAOYSA-N n-[3-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-5-methoxyphenyl]acetamide Chemical compound COC1=CC(NC(C)=O)=CC(NC=2N=C(NC3CC(C)(C)N(C)C(C)(C)C3)C(F)=CN=2)=C1 PWUHMCHBJHWECV-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
- 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
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 230000000683 nonmetastatic effect Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000008266 oncogenic mechanism Effects 0.000 description 1
- 208000020911 optic nerve disease Diseases 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002892 organic cations Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 230000037324 pain perception Effects 0.000 description 1
- 230000008058 pain sensation Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical group [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000037361 pathway 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
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229950000688 phenothiazine Drugs 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Chemical group O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 210000004214 philadelphia chromosome Anatomy 0.000 description 1
- 150000004633 phorbol derivatives Chemical class 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 210000001778 pluripotent stem cell Anatomy 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 208000037244 polycythemia vera Diseases 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 208000017426 precursor B-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 150000003140 primary amides Chemical class 0.000 description 1
- 208000003476 primary myelofibrosis Diseases 0.000 description 1
- 210000001948 pro-b lymphocyte Anatomy 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- TURAMGVWNUTQKH-UHFFFAOYSA-N propa-1,2-dien-1-one Chemical group C=C=C=O TURAMGVWNUTQKH-UHFFFAOYSA-N 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 108010027883 protein kinase C eta Proteins 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- CSNFMBGHUOSBFU-UHFFFAOYSA-N pyrimidine-2,4,5-triamine Chemical compound NC1=NC=C(N)C(N)=N1 CSNFMBGHUOSBFU-UHFFFAOYSA-N 0.000 description 1
- QDXGKRWDQCEABB-UHFFFAOYSA-N pyrimidine-5-carboxamide Chemical compound NC(=O)C1=CN=CN=C1 QDXGKRWDQCEABB-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 238000010791 quenching Methods 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
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 230000003134 recirculating effect Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 210000000486 refractive cornea Anatomy 0.000 description 1
- 230000009703 regulation of cell differentiation Effects 0.000 description 1
- 230000021014 regulation of cell growth Effects 0.000 description 1
- 230000014493 regulation of gene expression Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000004258 retinal degeneration Effects 0.000 description 1
- 230000004264 retinal detachment Effects 0.000 description 1
- 108091008726 retinoic acid receptors α Proteins 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 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
- 210000002966 serum Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 102000034285 signal transducing proteins Human genes 0.000 description 1
- 108091006024 signal transducing proteins Proteins 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 230000036555 skin type Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 206010062113 splenic marginal zone lymphoma Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 125000000464 thioxo group Chemical group S=* 0.000 description 1
- IUTCEZPPWBHGIX-UHFFFAOYSA-N tin(2+) Chemical compound [Sn+2] IUTCEZPPWBHGIX-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000006208 topical dosage form Substances 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 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
- 230000009466 transformation Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- JLEXUIVKURIPFI-UHFFFAOYSA-N tris phosphate Chemical compound OP(O)(O)=O.OCC(N)(CO)CO JLEXUIVKURIPFI-UHFFFAOYSA-N 0.000 description 1
- 208000009999 tuberous sclerosis Diseases 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000007733 viral latency Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000001238 wet grinding Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/538—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Diabetes (AREA)
- Neurology (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Virology (AREA)
- Rheumatology (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Dermatology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Molecular Biology (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14627309P | 2009-01-21 | 2009-01-21 | |
| US61/146,273 | 2009-01-21 | ||
| US26416509P | 2009-11-24 | 2009-11-24 | |
| US61/264,165 | 2009-11-24 | ||
| PCT/US2010/021662 WO2010090875A1 (en) | 2009-01-21 | 2010-01-21 | Derivatives of n2-(3-pyridil or phenyl)-n4-(4-piperidyl)-2,4-pyrimidinediamine useful in the treatment of inflammatory, autoimmune or proliferative diseases |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015018931A Division JP2015110629A (ja) | 2009-01-21 | 2015-02-03 | 炎症性疾患、自己免疫疾患または増殖性疾患の治療に有用なｎ２−（３−ピリジルまたはフェニル）−ｎ４−（４−ピペリジル）−２，４−ピリミジンジアミン誘導体 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2012515724A JP2012515724A (ja) | 2012-07-12 |
| JP2012515724A5 JP2012515724A5 (https=) | 2013-03-07 |
| JP5781943B2 true JP5781943B2 (ja) | 2015-09-24 |
Family
ID=42272042
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011546451A Expired - Fee Related JP5781943B2 (ja) | 2009-01-21 | 2010-01-21 | 炎症性疾患、自己免疫疾患または増殖性疾患の治療に有用なｎ２−（３−ピリジルまたはフェニル）−ｎ４−（４−ピペリジル）−２，４−ピリミジンジアミン誘導体 |
| JP2015018931A Withdrawn JP2015110629A (ja) | 2009-01-21 | 2015-02-03 | 炎症性疾患、自己免疫疾患または増殖性疾患の治療に有用なｎ２−（３−ピリジルまたはフェニル）−ｎ４−（４−ピペリジル）−２，４−ピリミジンジアミン誘導体 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015018931A Withdrawn JP2015110629A (ja) | 2009-01-21 | 2015-02-03 | 炎症性疾患、自己免疫疾患または増殖性疾患の治療に有用なｎ２−（３−ピリジルまたはフェニル）−ｎ４−（４−ピペリジル）−２，４−ピリミジンジアミン誘導体 |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US8377924B2 (https=) |
| EP (1) | EP2389373B1 (https=) |
| JP (2) | JP5781943B2 (https=) |
| CA (1) | CA2749837C (https=) |
| ES (1) | ES2635504T3 (https=) |
| WO (1) | WO2010090875A1 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013531074A (ja) * | 2010-07-21 | 2013-08-01 | ライジェル ファーマシューティカルズ， インコーポレイテッド | プロテインキナーゼｃ阻害剤およびその使用 |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005013996A2 (en) * | 2003-08-07 | 2005-02-17 | Rigel Pharmaceuticals, Inc. | 2,4-pyrimidinediamine compounds and uses as anti-proliferative agents |
| US20110130415A1 (en) | 2009-12-01 | 2011-06-02 | Rajinder Singh | Protein kinase c inhibitors and uses thereof |
| SG10201509157QA (en) * | 2010-11-09 | 2015-12-30 | Fujian Haixi Pharmaceuticals Inc | Compound for increasing kinase active and application thereof |
| SMT202400031T1 (it) | 2011-04-22 | 2024-03-13 | Signal Pharm Llc | Diamminocarbossammide e diamminocarbonitrile pirimidine sostituite, loro composizioni e metodi di trattamento con esse |
| ES2658395T3 (es) | 2012-04-04 | 2018-03-09 | Rigel Pharmaceuticals, Inc. | Inhibidores de proteína cinasa C y usos de los mismos |
| EP2928891B1 (en) | 2012-12-04 | 2019-02-20 | Rigel Pharmaceuticals, Inc. | Protein kinase c inhibitors and uses thereof |
| CA2904610A1 (en) | 2013-03-14 | 2014-09-25 | Rigel Pharmaceuticals, Inc. | Protein kinase c inhibitors and uses thereof |
| EP3082819B1 (en) | 2013-12-20 | 2020-06-17 | Signal Pharmaceuticals, LLC | Substituted diaminopyrimidyl compounds, compositions thereof, and methods of treatment therewith |
| NZ715903A (en) | 2014-01-30 | 2017-06-30 | Signal Pharm Llc | Solid forms of 2-(tert-butylamino)-4-((1r,3r,4r)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide, compositions thereof and methods of their use |
| MX2016012574A (es) | 2014-03-28 | 2017-09-26 | Calitor Sciences Llc | Compuestos heteroarilo sustituidos y metodos de uso. |
| EP3206691B1 (en) | 2014-10-14 | 2018-09-19 | Sunshine Lake Pharma Co., Ltd. | Substituted heteroaryl compounds and methods of use |
| BR112017012795A2 (pt) | 2014-12-16 | 2018-01-02 | Signal Pharmaceuticals, Llc | Formulações de 2-(terc-butilamino)-4-((1r,3r,4r)-3- hidroxi-4-metilciclo-hexilamino)-pirimidina-5- carboxamida |
| EP3233808B1 (en) | 2014-12-16 | 2021-07-14 | Signal Pharmaceuticals, LLC | Medical uses comprising methods for measurement of inhibition of c-jun n-terminal kinase in skin |
| WO2016123291A1 (en) | 2015-01-29 | 2016-08-04 | Signal Pharmaceuticals, Llc | Isotopologues of 2-(tert-butylamino)-4-((1r,3r,4r)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide |
| CN108137559B (zh) * | 2015-07-09 | 2021-11-02 | 默克专利有限公司 | 用作btk抑制剂的嘧啶衍生物及其用途 |
| CA3208587A1 (en) | 2015-07-24 | 2017-02-02 | Celgene Corporation | Methods of synthesis of (1r,2r,5r)-5-amino-2-methylcyclohexanol hydrochloride and intermediates useful therein |
| WO2017044434A1 (en) | 2015-09-11 | 2017-03-16 | Sunshine Lake Pharma Co., Ltd. | Substituted heteroaryl compounds and methods of use |
| WO2017075418A1 (en) | 2015-10-30 | 2017-05-04 | Board Of Trustees Of The University Of Arkansas | Inhibitors of oxidized low-density lipoprotein receptor 1 and methods of use thereof |
| CN110621316B (zh) | 2017-04-21 | 2024-01-26 | Epizyme股份有限公司 | 用ehmt2抑制剂进行的组合疗法 |
| CN110869017B (zh) | 2017-05-12 | 2023-05-05 | 英安塔制药有限公司 | 细胞凋亡信号调节激酶1抑制剂及其使用方法 |
| WO2018218051A1 (en) | 2017-05-25 | 2018-11-29 | Enanta Pharmaceuticals, Inc. | Apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof |
| WO2018218044A2 (en) | 2017-05-25 | 2018-11-29 | Enanta Pharmaceuticals Inc | Apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof |
| US10253018B2 (en) | 2017-05-25 | 2019-04-09 | Enanta Pharmaceuticals, Inc. | Apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof |
| WO2019046186A1 (en) * | 2017-08-28 | 2019-03-07 | Enanta Pharmaceuticals, Inc. | INHIBITORS OF KINASE 1 REGULATING THE APOPTOTIC SIGNAL CONTAINING TETRAZOLES AND METHODS OF USE THEREOF |
| EP3697419A4 (en) * | 2017-10-17 | 2021-08-18 | Epizyme, Inc. | AMINE SUBSTITUTION HETEROCYCLIC COMPOUNDS USED AS AND DERIVATIVES OF EHMT2 |
| US10683297B2 (en) | 2017-11-19 | 2020-06-16 | Calitor Sciences, Llc | Substituted heteroaryl compounds and methods of use |
| EP3787621B1 (en) | 2018-05-02 | 2024-12-18 | Enanta Pharmaceuticals, Inc. | Tetrazole containing apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof |
| WO2019213239A1 (en) | 2018-05-02 | 2019-11-07 | Enanta Pharmaceuticals Inc. | Apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof |
| US10968199B2 (en) | 2018-08-22 | 2021-04-06 | Enanta Pharmaceuticals, Inc. | Cycloalkyl-containing apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof |
| WO2020106707A1 (en) | 2018-11-19 | 2020-05-28 | Enanta Pharmaceuticals, Inc. | Apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof |
| US11466033B2 (en) | 2019-03-25 | 2022-10-11 | Enanta Pharmaceuticals, Inc. | Substituted pyridines as apoptosis signal-regulating kinase 1 inhibitors |
| WO2022147622A1 (en) * | 2021-01-07 | 2022-07-14 | Ontario Institute For Cancer Research (Oicr) | Isoindolinone aminopyrimidine compounds as inhibitors of nuak kinases, compositions and uses thereof |
| WO2023043630A1 (en) * | 2021-09-16 | 2023-03-23 | Lomond Therapeutics, Inc. | Compounds having n-arylpyrimidin-2-amine derivatives as therapeutic agents |
| CN119462522A (zh) * | 2023-08-08 | 2025-02-18 | 浙江大学 | N2-3-氟-5-取代苯基-2-氨基嘧啶类衍生物、其制备方法及医药用途 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9523675D0 (en) | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
| ATE407678T1 (de) * | 2001-10-17 | 2008-09-15 | Boehringer Ingelheim Pharma | Pyrimidinderivate, arzneimittel enthaltend diese verbindungen, deren verwendung und verfahren zu ihrer herstellung |
| TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| ES2445208T3 (es) | 2002-07-29 | 2014-02-28 | Rigel Pharmaceuticals, Inc. | Compuestos de 2,4-pirimidindiamina para uso en métodos para tratar o prevenir enfermedades autoinmunitarias |
| CA2505546A1 (en) | 2002-11-08 | 2004-05-27 | Tolerrx, Inc. | Molecules preferentially associated with effector t cells and methods of their use |
| UA80767C2 (en) * | 2002-12-20 | 2007-10-25 | Pfizer Prod Inc | Pyrimidine derivatives for the treatment of abnormal cell growth |
| US7603542B2 (en) | 2003-06-25 | 2009-10-13 | Nec Corporation | Reconfigurable electric computer, semiconductor integrated circuit and control method, program generation method, and program for creating a logic circuit from an application program |
| BRPI0413018B8 (pt) * | 2003-07-30 | 2021-05-25 | Rigel Pharmaceuticals Inc | composto, e, uso de um composto |
| WO2005013996A2 (en) | 2003-08-07 | 2005-02-17 | Rigel Pharmaceuticals, Inc. | 2,4-pyrimidinediamine compounds and uses as anti-proliferative agents |
| CN1863773A (zh) | 2003-10-09 | 2006-11-15 | 埃科特莱茵药品有限公司 | 四氢吡啶衍生物 |
| US20050164323A1 (en) | 2003-12-24 | 2005-07-28 | Wyeth | Methods of treating asthma |
| JP2007532506A (ja) * | 2004-04-08 | 2007-11-15 | ノバルティス アクチエンゲゼルシャフト | 自己免疫疾患および拒絶反応の処置のためのタンパク質キナーゼｃ阻害剤 |
| EP1883302A4 (en) * | 2005-05-03 | 2009-05-20 | Rigel Pharmaceuticals Inc | JAK KINASE HEMMER AND ITS USE |
| US20100144751A1 (en) | 2007-03-28 | 2010-06-10 | Array Biopharma Inc. | IMIDAZO[1,2-a]PYRIDINE COMPOUNDS AS RECEPTOR TYROSINE KINASE INHIBITORS |
| CA2693594A1 (en) * | 2007-07-17 | 2009-01-22 | Rigel Pharmaceuticals, Inc. | Cyclic amine substituted pyrimidinediamines as pkc inhibitors |
| TWI546290B (zh) * | 2008-06-27 | 2016-08-21 | 賽基艾維洛米斯研究股份有限公司 | 雜芳基化合物及其用途 |
| EP2595982B1 (en) * | 2010-07-21 | 2018-06-13 | Rigel Pharmaceuticals, Inc. | Protein kinase c inhibitors and uses thereof |
-
2010
- 2010-01-21 CA CA2749837A patent/CA2749837C/en active Active
- 2010-01-21 US US12/691,607 patent/US8377924B2/en not_active Expired - Fee Related
- 2010-01-21 EP EP10701773.3A patent/EP2389373B1/en not_active Not-in-force
- 2010-01-21 WO PCT/US2010/021662 patent/WO2010090875A1/en not_active Ceased
- 2010-01-21 ES ES10701773.3T patent/ES2635504T3/es active Active
- 2010-01-21 JP JP2011546451A patent/JP5781943B2/ja not_active Expired - Fee Related
-
2012
- 2012-12-18 US US13/718,632 patent/US9149475B2/en not_active Expired - Fee Related
-
2015
- 2015-02-03 JP JP2015018931A patent/JP2015110629A/ja not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013531074A (ja) * | 2010-07-21 | 2013-08-01 | ライジェル ファーマシューティカルズ， インコーポレイテッド | プロテインキナーゼｃ阻害剤およびその使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2389373A1 (en) | 2011-11-30 |
| CA2749837C (en) | 2017-07-11 |
| US20100204208A1 (en) | 2010-08-12 |
| US20130210810A1 (en) | 2013-08-15 |
| EP2389373B1 (en) | 2017-05-17 |
| US9149475B2 (en) | 2015-10-06 |
| CA2749837A1 (en) | 2010-08-12 |
| ES2635504T3 (es) | 2017-10-04 |
| JP2015110629A (ja) | 2015-06-18 |
| US8377924B2 (en) | 2013-02-19 |
| JP2012515724A (ja) | 2012-07-12 |
| WO2010090875A1 (en) | 2010-08-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5781943B2 (ja) | 炎症性疾患、自己免疫疾患または増殖性疾患の治療に有用なｎ２−（３−ピリジルまたはフェニル）−ｎ４−（４−ピペリジル）−２，４−ピリミジンジアミン誘導体 | |
| EP2507227B1 (en) | Tetrazolones as protein kinase c inhibitors and uses thereof | |
| JP6035238B2 (ja) | プロテインキナーゼｃ阻害剤およびその使用 | |
| JP6113828B2 (ja) | プロテインキナーゼｃ阻害剤およびその使用 | |
| JP5603881B2 (ja) | プロテインキナーゼｃ阻害剤とその使用 | |
| JP6357167B2 (ja) | プロテインキナーゼｃ阻害剤およびそれらの用途 | |
| JP6421170B2 (ja) | プロテインキナーゼｃ阻害剤およびその使用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130118 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130118 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140425 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140724 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140731 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140822 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20141003 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150203 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20150206 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20150305 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A132 Effective date: 20150515 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150603 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20150626 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150716 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5781943 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |