TWI242559B - Chemical compounds - Google Patents

Info

Publication number

TWI242559B

TWI242559B TW090122494A TW90122494A TWI242559B TW I242559 B TWI242559 B TW I242559B TW 090122494 A TW090122494 A TW 090122494A TW 90122494 A TW90122494 A TW 90122494A TW I242559 B TWI242559 B TW I242559B

Authority

TW

Taiwan

Prior art keywords

sulfamidino

group

alkyl

compound

formula

Prior art date

2000-09-05

Links

• Espacenet
• Global Dossier
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• 150000001875 compounds Chemical class 0.000 title claims abstract description 241
• 238000000034 method Methods 0.000 claims abstract description 153
• 150000003839 salts Chemical class 0.000 claims abstract description 53
• 238000001727 in vivo Methods 0.000 claims abstract description 51
• 150000002148 esters Chemical class 0.000 claims abstract description 41
• 239000003814 drug Substances 0.000 claims abstract description 22
• 241001465754 Metazoa Species 0.000 claims abstract description 20
• 230000000694 effects Effects 0.000 claims abstract description 19
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 18
• 230000022131 cell cycle Effects 0.000 claims abstract description 16
• 238000002360 preparation method Methods 0.000 claims abstract description 7
• -1 cyano, hydroxyl Chemical group 0.000 claims description 423
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 214
• 125000000217 alkyl group Chemical group 0.000 claims description 133
• 239000000203 mixture Substances 0.000 claims description 92
• 239000007787 solid Substances 0.000 claims description 66
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 63
• 125000000623 heterocyclic group Chemical group 0.000 claims description 54
• 125000003545 alkoxy group Chemical group 0.000 claims description 52
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 51
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 51
• 229910052799 carbon Inorganic materials 0.000 claims description 49
• 229910052757 nitrogen Inorganic materials 0.000 claims description 49
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 47
• 239000001257 hydrogen Substances 0.000 claims description 46
• 229910052739 hydrogen Inorganic materials 0.000 claims description 46
• 150000001412 amines Chemical class 0.000 claims description 40
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 37
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
• 206010028980 Neoplasm Diseases 0.000 claims description 32
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 30
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 27
• 238000011282 treatment Methods 0.000 claims description 24
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 23
• 229910052736 halogen Inorganic materials 0.000 claims description 22
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 22
• 125000005843 halogen group Chemical group 0.000 claims description 20
• 150000002431 hydrogen Chemical group 0.000 claims description 20
• 229920006395 saturated elastomer Polymers 0.000 claims description 20
• 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 19
• 125000003277 amino group Chemical group 0.000 claims description 18
• 201000010099 disease Diseases 0.000 claims description 17
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 17
• 229940079593 drug Drugs 0.000 claims description 14
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 13
• 201000011510 cancer Diseases 0.000 claims description 12
• 239000000460 chlorine Chemical group 0.000 claims description 12
• 150000002367 halogens Chemical group 0.000 claims description 12
• 125000006239 protecting group Chemical group 0.000 claims description 12
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 11
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
• 125000000304 alkynyl group Chemical group 0.000 claims description 10
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
• 230000005764 inhibitory process Effects 0.000 claims description 10
• 210000002307 prostate Anatomy 0.000 claims description 10
• 239000000126 substance Substances 0.000 claims description 10
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 9
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 9
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
• 230000035755 proliferation Effects 0.000 claims description 9
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 8
• 125000003342 alkenyl group Chemical group 0.000 claims description 8
• 229910052717 sulfur Inorganic materials 0.000 claims description 8
• 239000000052 vinegar Substances 0.000 claims description 8
• 235000021419 vinegar Nutrition 0.000 claims description 8
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 7
• CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 claims description 7
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
• 210000000481 breast Anatomy 0.000 claims description 7
• 239000003085 diluting agent Substances 0.000 claims description 7
• 208000032839 leukemia Diseases 0.000 claims description 7
• 210000004072 lung Anatomy 0.000 claims description 7
• 125000003396 thiol group Chemical group [H]S* 0.000 claims description 7
• 201000001320 Atherosclerosis Diseases 0.000 claims description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
• 208000007766 Kaposi sarcoma Diseases 0.000 claims description 6
• 201000004681 Psoriasis Diseases 0.000 claims description 6
• 208000038016 acute inflammation Diseases 0.000 claims description 6
• 230000006022 acute inflammation Effects 0.000 claims description 6
• 230000015572 biosynthetic process Effects 0.000 claims description 6
• 208000037976 chronic inflammation Diseases 0.000 claims description 6
• 230000006020 chronic inflammation Effects 0.000 claims description 6
• 230000004069 differentiation Effects 0.000 claims description 6
• 208000035475 disorder Diseases 0.000 claims description 6
• 230000000893 fibroproliferative effect Effects 0.000 claims description 6
• 201000011066 hemangioma Diseases 0.000 claims description 6
• 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 6
• 239000011593 sulfur Substances 0.000 claims description 6
• 230000002792 vascular Effects 0.000 claims description 6
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 5
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 5
• 208000030090 Acute Disease Diseases 0.000 claims description 5
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 5
• 230000001154 acute effect Effects 0.000 claims description 5
• 125000003282 alkyl amino group Chemical group 0.000 claims description 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
• 229910052801 chlorine Chemical group 0.000 claims description 5
• 208000020832 chronic kidney disease Diseases 0.000 claims description 5
• 210000001072 colon Anatomy 0.000 claims description 5
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 5
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
• 210000003491 skin Anatomy 0.000 claims description 5
• 125000004434 sulfur atom Chemical group 0.000 claims description 5
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 4
• 208000023275 Autoimmune disease Diseases 0.000 claims description 4
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
• 150000001335 aliphatic alkanes Chemical class 0.000 claims description 4
• 125000002619 bicyclic group Chemical group 0.000 claims description 4
• 125000002950 monocyclic group Chemical group 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
• 229910052760 oxygen Inorganic materials 0.000 claims description 4
• 239000001301 oxygen Substances 0.000 claims description 4
• 210000000496 pancreas Anatomy 0.000 claims description 4
• 239000004575 stone Substances 0.000 claims description 4
• 230000001225 therapeutic effect Effects 0.000 claims description 4
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
• 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 claims description 3
• QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical group ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 claims description 3
• 150000001204 N-oxides Chemical class 0.000 claims description 3
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 3
• 210000003905 vulva Anatomy 0.000 claims description 3
• 206010051113 Arterial restenosis Diseases 0.000 claims description 2
• 206010003210 Arteriosclerosis Diseases 0.000 claims description 2
• 208000037260 Atherosclerotic Plaque Diseases 0.000 claims description 2
• 206010005003 Bladder cancer Diseases 0.000 claims description 2
• 208000026310 Breast neoplasm Diseases 0.000 claims description 2
• 208000008771 Lymphadenopathy Diseases 0.000 claims description 2
• ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical group [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 claims description 2
• 206010033128 Ovarian cancer Diseases 0.000 claims description 2
• 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
• 206010060862 Prostate cancer Diseases 0.000 claims description 2
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
• 206010039491 Sarcoma Diseases 0.000 claims description 2
• 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
• 125000004429 atom Chemical group 0.000 claims description 2
• 208000029742 colonic neoplasm Diseases 0.000 claims description 2
• 206010017758 gastric cancer Diseases 0.000 claims description 2
• RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 claims description 2
• 210000004185 liver Anatomy 0.000 claims description 2
• 208000018555 lymphatic system disease Diseases 0.000 claims description 2
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
• 229910052750 molybdenum Inorganic materials 0.000 claims description 2
• 239000011733 molybdenum Substances 0.000 claims description 2
• 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
• 210000002784 stomach Anatomy 0.000 claims description 2
• 201000011549 stomach cancer Diseases 0.000 claims description 2
• 210000003932 urinary bladder Anatomy 0.000 claims description 2
• 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
• PCTMTFRHKVHKIS-BMFZQQSSSA-N (1s,3r,4e,6e,8e,10e,12e,14e,16e,18s,19r,20r,21s,25r,27r,30r,31r,33s,35r,37s,38r)-3-[(2r,3s,4s,5s,6r)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-19,25,27,30,31,33,35,37-octahydroxy-18,20,21-trimethyl-23-oxo-22,39-dioxabicyclo[33.3.1]nonatriaconta-4,6,8,10 Chemical compound C1C=C2C[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2.O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 PCTMTFRHKVHKIS-BMFZQQSSSA-N 0.000 claims 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims 2
• 206010029098 Neoplasm skin Diseases 0.000 claims 1
• 208000000453 Skin Neoplasms Diseases 0.000 claims 1
• 208000004354 Vulvar Neoplasms Diseases 0.000 claims 1
• GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims 1
• 210000000988 bone and bone Anatomy 0.000 claims 1
• GPSINNCBFURFNQ-UHFFFAOYSA-N cyclopropylhydrazine Chemical compound NNC1CC1 GPSINNCBFURFNQ-UHFFFAOYSA-N 0.000 claims 1
• 230000003301 hydrolyzing effect Effects 0.000 claims 1
• 208000037841 lung tumor Diseases 0.000 claims 1
• DROIHSMGGKKIJT-UHFFFAOYSA-N propane-1-sulfonamide Chemical compound CCCS(N)(=O)=O DROIHSMGGKKIJT-UHFFFAOYSA-N 0.000 claims 1
• 208000023958 prostate neoplasm Diseases 0.000 claims 1
• 229940126589 solid medicine Drugs 0.000 claims 1
• 230000008961 swelling Effects 0.000 claims 1
• 230000008569 process Effects 0.000 abstract description 3
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 156
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 144
• MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 117
• 238000005481 NMR spectroscopy Methods 0.000 description 91
• 239000000243 solution Substances 0.000 description 74
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 64
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 55
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 48
• 229910001868 water Inorganic materials 0.000 description 48
• 238000001704 evaporation Methods 0.000 description 46
• 230000008020 evaporation Effects 0.000 description 45
• 239000003039 volatile agent Substances 0.000 description 33
• 235000019439 ethyl acetate Nutrition 0.000 description 32
• 239000002904 solvent Substances 0.000 description 32
• 238000006243 chemical reaction Methods 0.000 description 28
• 238000003818 flash chromatography Methods 0.000 description 28
• 239000011541 reaction mixture Substances 0.000 description 28
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 27
• 210000004027 cell Anatomy 0.000 description 27
• 238000001914 filtration Methods 0.000 description 26
• CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 25
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 24
• 239000012267 brine Substances 0.000 description 22
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 21
• 239000007858 starting material Substances 0.000 description 21
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
• 239000000741 silica gel Substances 0.000 description 20
• 229910002027 silica gel Inorganic materials 0.000 description 20
• 239000000284 extract Substances 0.000 description 18
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
• 238000004440 column chromatography Methods 0.000 description 17
• 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 description 16
• 102100036239 Cyclin-dependent kinase 2 Human genes 0.000 description 16
• 239000007789 gas Substances 0.000 description 16
• 238000010992 reflux Methods 0.000 description 16
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 15
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 14
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
• 235000017557 sodium bicarbonate Nutrition 0.000 description 13
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
• 239000002253 acid Substances 0.000 description 12
• QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
• 239000000725 suspension Substances 0.000 description 12
• 238000012360 testing method Methods 0.000 description 12
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 11
• 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 description 11
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
• 229960000583 acetic acid Drugs 0.000 description 10
• 239000002585 base Substances 0.000 description 10
• 239000003112 inhibitor Substances 0.000 description 10
• 239000003921 oil Substances 0.000 description 10
• 239000000047 product Substances 0.000 description 10
• 238000003756 stirring Methods 0.000 description 10
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• 239000007853 buffer solution Substances 0.000 description 9
• 239000000706 filtrate Substances 0.000 description 9
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 9
• 108090000623 proteins and genes Proteins 0.000 description 9
• 238000000746 purification Methods 0.000 description 9
• 229940124530 sulfonamide Drugs 0.000 description 9
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
• 101150041968 CDC13 gene Proteins 0.000 description 8
• 102000003909 Cyclin E Human genes 0.000 description 8
• 108090000257 Cyclin E Proteins 0.000 description 8
• 241000282412 Homo Species 0.000 description 8
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
• 239000007937 lozenge Substances 0.000 description 8
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
• 230000003211 malignant effect Effects 0.000 description 8
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 8
• 239000012265 solid product Substances 0.000 description 8
• 125000001424 substituent group Chemical group 0.000 description 8
• 201000004384 Alopecia Diseases 0.000 description 7
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
• 235000011114 ammonium hydroxide Nutrition 0.000 description 7
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 7
• 238000000605 extraction Methods 0.000 description 7
• 239000011737 fluorine Substances 0.000 description 7
• 229910052731 fluorine Inorganic materials 0.000 description 7
• 239000000499 gel Substances 0.000 description 7
• 230000003676 hair loss Effects 0.000 description 7
• 208000024963 hair loss Diseases 0.000 description 7
• BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 7
• 239000012071 phase Substances 0.000 description 7
• 102000004169 proteins and genes Human genes 0.000 description 7
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
• 239000007983 Tris buffer Substances 0.000 description 6
• 238000004458 analytical method Methods 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• 238000004587 chromatography analysis Methods 0.000 description 6
• 238000010494 dissociation reaction Methods 0.000 description 6
• 230000005593 dissociations Effects 0.000 description 6
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