CA2735048A1

CA2735048A1 - 6-substituted 2-(benzimidazolyl)purine and purinone derivatives and 6-substituted 2-(imidazolo[4,5- c]pyridinyl)purine and purinone derivatives for immunosuppression

6-substituted 2-(benzimidazolyl)purine and purinone derivatives and 6-substituted 2-(imidazolo[4,5- c]pyridinyl)purine and purinone derivatives for immunosuppression Download PDF

Info

Publication number: CA2735048A1
Authority: CA; Canada
Prior art keywords: substituted; alkyl; mmol; chosen; aryl
Prior art date: 2008-08-22
Legal status : Abandoned

Application number

CA2735048A

Other languages

English (en)

French (fr)

Inventor

Irina Neagu

David Diller

Celia Kingsbury

Adolph C. Bohnstedt

Michael J. Ohlmeyer

Vidyadhar Paradkar

Nasrin Ansari

Current Assignee

Wyeth LLC

Original Assignee

Wyeth LLC

Priority date

2008-08-22

Filing date

2009-08-21

Publication date

2010-02-25

2009-08-21 Application filed by Wyeth LLC filed Critical Wyeth LLC

2010-02-25 Publication of CA2735048A1 publication Critical patent/CA2735048A1/en

Status Abandoned legal-status Critical Current

Links

-1 6-substituted 2-(benzimidazolyl)purine Chemical class 0.000 title claims description 81
UFZNZKGKBWOSJG-UHFFFAOYSA-N purin-2-one Chemical class O=C1N=CC2=NC=NC2=N1 UFZNZKGKBWOSJG-UHFFFAOYSA-N 0.000 title abstract description 15
206010062016 Immunosuppression Diseases 0.000 title description 4
230000001506 immunosuppresive effect Effects 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims abstract description 97
125000000623 heterocyclic group Chemical group 0.000 claims description 47
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 46
229910052739 hydrogen Inorganic materials 0.000 claims description 41
239000001257 hydrogen Substances 0.000 claims description 38
125000003118 aryl group Chemical group 0.000 claims description 33
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 30
125000000217 alkyl group Chemical group 0.000 claims description 30
229910052736 halogen Inorganic materials 0.000 claims description 29
150000002367 halogens Chemical group 0.000 claims description 29
229910052757 nitrogen Inorganic materials 0.000 claims description 28
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 19
125000003107 substituted aryl group Chemical group 0.000 claims description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
125000003545 alkoxy group Chemical group 0.000 claims description 14
125000004093 cyano group Chemical group *C#N 0.000 claims description 13
229910052731 fluorine Chemical group 0.000 claims description 13
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
125000001072 heteroaryl group Chemical group 0.000 claims description 11
125000000547 substituted alkyl group Chemical group 0.000 claims description 10
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
125000006528 (C2-C6) alkyl group Chemical group 0.000 claims description 8
239000001301 oxygen Substances 0.000 claims description 8
229910052760 oxygen Inorganic materials 0.000 claims description 8
239000008194 pharmaceutical composition Substances 0.000 claims description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
229910052799 carbon Inorganic materials 0.000 claims description 7
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
125000003725 azepanyl group Chemical group 0.000 claims description 6
125000002393 azetidinyl group Chemical group 0.000 claims description 6
QYJXLKYOBNZROU-UHFFFAOYSA-N carboxysulfonylformic acid Chemical group OC(=O)S(=O)(=O)C(O)=O QYJXLKYOBNZROU-UHFFFAOYSA-N 0.000 claims description 6
125000005959 diazepanyl group Chemical group 0.000 claims description 6
239000011737 fluorine Chemical group 0.000 claims description 6
125000002757 morpholinyl group Chemical group 0.000 claims description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
125000003386 piperidinyl group Chemical group 0.000 claims description 6
125000003226 pyrazolyl group Chemical group 0.000 claims description 6
125000004076 pyridyl group Chemical group 0.000 claims description 6
125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
125000002252 acyl group Chemical group 0.000 claims description 5
239000000039 congener Substances 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
125000006575 electron-withdrawing group Chemical group 0.000 claims description 4
125000005415 substituted alkoxy group Chemical group 0.000 claims description 4
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 claims description 4
JAAJQSRLGAYGKZ-UHFFFAOYSA-N 1,2,3,4-tetrahydronaphthalen-1-ol Chemical compound C1=CC=C2C(O)CCCC2=C1 JAAJQSRLGAYGKZ-UHFFFAOYSA-N 0.000 claims description 3
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 3
125000000676 alkoxyimino group Chemical group 0.000 claims description 3
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 claims description 3
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 3
HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 3
125000004438 haloalkoxy group Chemical group 0.000 claims description 3
125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 claims description 2
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
UHHKSVZZTYJVEG-UHFFFAOYSA-N oxepane Chemical compound C1CCCOCC1 UHHKSVZZTYJVEG-UHFFFAOYSA-N 0.000 claims description 2
125000003551 oxepanyl group Chemical group 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 2
150000002431 hydrogen Chemical group 0.000 claims 7
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
208000023275 Autoimmune disease Diseases 0.000 abstract description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 9
210000003630 histaminocyte Anatomy 0.000 abstract description 9
208000027866 inflammatory disease Diseases 0.000 abstract description 6
230000001404 mediated effect Effects 0.000 abstract description 6
201000010099 disease Diseases 0.000 abstract description 5
150000003212 purines Chemical class 0.000 abstract description 5
206010052779 Transplant rejections Diseases 0.000 abstract description 2
230000002265 prevention Effects 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 164
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 159
YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 123
239000007787 solid Substances 0.000 description 122
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 112
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 92
239000011541 reaction mixture Substances 0.000 description 88
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 75
238000005481 NMR spectroscopy Methods 0.000 description 71
239000000203 mixture Substances 0.000 description 68
239000000047 product Substances 0.000 description 68
238000000034 method Methods 0.000 description 65
239000000243 solution Substances 0.000 description 64
239000002904 solvent Substances 0.000 description 62
235000019439 ethyl acetate Nutrition 0.000 description 58
229910052740 iodine Inorganic materials 0.000 description 58
238000006243 chemical reaction Methods 0.000 description 56
229910001868 water Inorganic materials 0.000 description 54
101150041968 CDC13 gene Proteins 0.000 description 53
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 53
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 42
238000000746 purification Methods 0.000 description 37
238000004128 high performance liquid chromatography Methods 0.000 description 34
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 32
239000000460 chlorine Substances 0.000 description 32
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 31
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 31
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 30
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 29
101150069380 JAK3 gene Proteins 0.000 description 29
PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 28
238000003756 stirring Methods 0.000 description 27
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 26
239000000741 silica gel Substances 0.000 description 26
229910002027 silica gel Inorganic materials 0.000 description 26
238000001035 drying Methods 0.000 description 25
238000012544 monitoring process Methods 0.000 description 24
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 23
229910000024 caesium carbonate Inorganic materials 0.000 description 22
238000010828 elution Methods 0.000 description 22
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 21
238000001704 evaporation Methods 0.000 description 21
230000008020 evaporation Effects 0.000 description 21
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 21
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 18
239000012044 organic layer Substances 0.000 description 18
238000004440 column chromatography Methods 0.000 description 17
238000002953 preparative HPLC Methods 0.000 description 17
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 16
239000000706 filtrate Substances 0.000 description 16
239000010410 layer Substances 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
235000017557 sodium bicarbonate Nutrition 0.000 description 15
229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
150000003839 salts Chemical class 0.000 description 14
YLKYOEVXPMJDQM-UHFFFAOYSA-N 6-chloropurin-2-one Chemical class ClC1=NC(=O)N=C2N=CN=C12 YLKYOEVXPMJDQM-UHFFFAOYSA-N 0.000 description 13
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 13
239000007832 Na2SO4 Substances 0.000 description 13
239000004677 Nylon Substances 0.000 description 13
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
239000007864 aqueous solution Substances 0.000 description 13
229920001778 nylon Polymers 0.000 description 13
210000000056 organ Anatomy 0.000 description 13
229910052938 sodium sulfate Inorganic materials 0.000 description 13
235000011152 sodium sulphate Nutrition 0.000 description 13
238000005160 1H NMR spectroscopy Methods 0.000 description 12
239000012267 brine Substances 0.000 description 12
210000004027 cell Anatomy 0.000 description 12
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 12
229920006395 saturated elastomer Polymers 0.000 description 12
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 11
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 11
238000005406 washing Methods 0.000 description 11
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
229960000583 acetic acid Drugs 0.000 description 10
238000006073 displacement reaction Methods 0.000 description 10
238000001914 filtration Methods 0.000 description 10
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
238000002360 preparation method Methods 0.000 description 10
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
229940123241 Janus kinase 3 inhibitor Drugs 0.000 description 9
NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 9
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 9
238000006880 cross-coupling reaction Methods 0.000 description 9
239000012362 glacial acetic acid Substances 0.000 description 9
125000005842 heteroatom Chemical group 0.000 description 9
238000010992 reflux Methods 0.000 description 9
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
229910052786 argon Inorganic materials 0.000 description 8
239000003153 chemical reaction reagent Substances 0.000 description 8
229910052801 chlorine Inorganic materials 0.000 description 8
238000001816 cooling Methods 0.000 description 8
125000000753 cycloalkyl group Chemical group 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
239000000725 suspension Substances 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
208000009329 Graft vs Host Disease Diseases 0.000 description 7
235000011114 ammonium hydroxide Nutrition 0.000 description 7
230000000694 effects Effects 0.000 description 7
238000003818 flash chromatography Methods 0.000 description 7
208000024908 graft versus host disease Diseases 0.000 description 7
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
238000003786 synthesis reaction Methods 0.000 description 7
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 7
VSCBATMPTLKTOV-UHFFFAOYSA-N 2-tert-butylimino-n,n-diethyl-1,3-dimethyl-1,3,2$l^{5}-diazaphosphinan-2-amine Chemical compound CCN(CC)P1(=NC(C)(C)C)N(C)CCCN1C VSCBATMPTLKTOV-UHFFFAOYSA-N 0.000 description 6
ZVXRYABVTWAFCX-UHFFFAOYSA-N 6-chloro-4-n-(oxan-4-yl)pyrimidine-2,4,5-triamine Chemical compound NC1=NC(Cl)=C(N)C(NC2CCOCC2)=N1 ZVXRYABVTWAFCX-UHFFFAOYSA-N 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
239000003018 immunosuppressive agent Substances 0.000 description 6
239000000463 material Substances 0.000 description 6
229940098779 methanesulfonic acid Drugs 0.000 description 6
238000012746 preparative thin layer chromatography Methods 0.000 description 6
239000012453 solvate Substances 0.000 description 6
239000000126 substance Substances 0.000 description 6
125000001424 substituent group Chemical group 0.000 description 6
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 5
LILACARBFWKAIR-UHFFFAOYSA-N 2-amino-6-chloro-9-(oxan-4-yl)-7h-purin-8-one Chemical compound C12=NC(N)=NC(Cl)=C2NC(=O)N1C1CCOCC1 LILACARBFWKAIR-UHFFFAOYSA-N 0.000 description 5
HFHFGHLXUCOHLN-UHFFFAOYSA-N 2-fluorophenol Chemical compound OC1=CC=CC=C1F HFHFGHLXUCOHLN-UHFFFAOYSA-N 0.000 description 5
ZXWGHENZKVQKPX-UHFFFAOYSA-N 4,6-dichloropyrimidine-2,5-diamine Chemical compound NC1=NC(Cl)=C(N)C(Cl)=N1 ZXWGHENZKVQKPX-UHFFFAOYSA-N 0.000 description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
108090000695 Cytokines Proteins 0.000 description 5
102000004127 Cytokines Human genes 0.000 description 5
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 5
239000000908 ammonium hydroxide Substances 0.000 description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
239000002585 base Substances 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
239000002775 capsule Substances 0.000 description 5
125000004432 carbon atom Chemical group C* 0.000 description 5
239000003054 catalyst Substances 0.000 description 5
230000003197 catalytic effect Effects 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
229960003444 immunosuppressant agent Drugs 0.000 description 5
208000032839 leukemia Diseases 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
230000009467 reduction Effects 0.000 description 5
239000011347 resin Substances 0.000 description 5
229920005989 resin Polymers 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
235000017550 sodium carbonate Nutrition 0.000 description 5
229910052717 sulfur Inorganic materials 0.000 description 5
BBIJXSGGWSAYRZ-UHFFFAOYSA-N 4-[(2,5-diamino-6-chloropyrimidin-4-yl)amino]cyclohexan-1-ol Chemical compound NC1=NC(Cl)=C(N)C(NC2CCC(O)CC2)=N1 BBIJXSGGWSAYRZ-UHFFFAOYSA-N 0.000 description 4
FKDMFDMYQZIZMI-UHFFFAOYSA-N 8-fluoro-2,3-dihydrochromen-4-one Chemical compound O=C1CCOC2=C1C=CC=C2F FKDMFDMYQZIZMI-UHFFFAOYSA-N 0.000 description 4
HXACNHXAKSMYNU-UHFFFAOYSA-N 8-fluoro-3,4-dihydro-2h-chromen-4-amine Chemical compound C1=CC=C2C(N)CCOC2=C1F HXACNHXAKSMYNU-UHFFFAOYSA-N 0.000 description 4
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 4
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
108010010803 Gelatin Proteins 0.000 description 4
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
108010002350 Interleukin-2 Proteins 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
206010025323 Lymphomas Diseases 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 4
206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 4
230000029936 alkylation Effects 0.000 description 4
238000005804 alkylation reaction Methods 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 4
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
150000003857 carboxamides Chemical group 0.000 description 4
208000035475 disorder Diseases 0.000 description 4
238000009472 formulation Methods 0.000 description 4
229920000159 gelatin Polymers 0.000 description 4
239000008273 gelatin Substances 0.000 description 4
235000019322 gelatine Nutrition 0.000 description 4
235000011852 gelatine desserts Nutrition 0.000 description 4
150000004820 halides Chemical class 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
125000004356 hydroxy functional group Chemical group O* 0.000 description 4
239000007924 injection Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
230000004048 modification Effects 0.000 description 4
238000012986 modification Methods 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
102000005962 receptors Human genes 0.000 description 4
108020003175 receptors Proteins 0.000 description 4
239000007858 starting material Substances 0.000 description 4
239000011593 sulfur Substances 0.000 description 4
238000012360 testing method Methods 0.000 description 4
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical group C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 4
210000001519 tissue Anatomy 0.000 description 4
238000002054 transplantation Methods 0.000 description 4
CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 4
DYKTWSCZBLROFI-UHFFFAOYSA-N 2-amino-6-chloro-9-(4-hydroxycyclohexyl)-7h-purin-8-one Chemical compound C12=NC(N)=NC(Cl)=C2NC(=O)N1C1CCC(O)CC1 DYKTWSCZBLROFI-UHFFFAOYSA-N 0.000 description 3
OMWDTYVGVCRRLN-UHFFFAOYSA-N 2-amino-9-(oxan-4-yl)-6-pyridin-4-yl-7h-purin-8-one Chemical compound C=12NC(=O)N(C3CCOCC3)C2=NC(N)=NC=1C1=CC=NC=C1 OMWDTYVGVCRRLN-UHFFFAOYSA-N 0.000 description 3
VFMAPIFSXMBTQP-UHFFFAOYSA-N 2-bromo-4-chloro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1Br VFMAPIFSXMBTQP-UHFFFAOYSA-N 0.000 description 3
VGYVBEJDXIPSDL-UHFFFAOYSA-N 2-bromo-4-fluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1Br VGYVBEJDXIPSDL-UHFFFAOYSA-N 0.000 description 3
RNDBDEZITHKFEU-UHFFFAOYSA-N 3-bromo-4-nitrobenzonitrile Chemical compound [O-][N+](=O)C1=CC=C(C#N)C=C1Br RNDBDEZITHKFEU-UHFFFAOYSA-N 0.000 description 3
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
238000006443 Buchwald-Hartwig cross coupling reaction Methods 0.000 description 3
WSLGPUSLBNYPAE-JOCQHMNTSA-N C1C[C@@H](OC)CC[C@@H]1N1C(=O)NC2=C(Cl)N=C(N3C4=CC(=CC=C4N=C3)C#N)N=C21 Chemical compound C1C[C@@H](OC)CC[C@@H]1N1C(=O)NC2=C(Cl)N=C(N3C4=CC(=CC=C4N=C3)C#N)N=C21 WSLGPUSLBNYPAE-JOCQHMNTSA-N 0.000 description 3
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 3
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 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
206010061218 Inflammation Diseases 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
NUIFRKLGCDPATC-ZKCHVHJHSA-N NC(N=C1N2[C@H](CC3)CC[C@@H]3C3=NC=CN3C(O)=O)=NC(Cl)=C1NC2=O Chemical compound NC(N=C1N2[C@H](CC3)CC[C@@H]3C3=NC=CN3C(O)=O)=NC(Cl)=C1NC2=O NUIFRKLGCDPATC-ZKCHVHJHSA-N 0.000 description 3
239000004793 Polystyrene Substances 0.000 description 3
108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 3
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 3
210000001744 T-lymphocyte Anatomy 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
239000002253 acid Substances 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
230000001154 acute effect Effects 0.000 description 3
150000001351 alkyl iodides Chemical class 0.000 description 3
229910021529 ammonia Inorganic materials 0.000 description 3
150000001543 aryl boronic acids Chemical class 0.000 description 3
208000006673 asthma Diseases 0.000 description 3
125000004429 atom Chemical group 0.000 description 3
239000000969 carrier Substances 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
238000011097 chromatography purification Methods 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
239000000284 extract Substances 0.000 description 3
238000000605 extraction Methods 0.000 description 3
239000012634 fragment Substances 0.000 description 3
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
230000004054 inflammatory process Effects 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000007788 liquid Substances 0.000 description 3
238000011068 loading method Methods 0.000 description 3
238000007069 methylation reaction Methods 0.000 description 3
BEXWAXYTSUVJOB-SNVBAGLBSA-N n-[(4r)-8-fluoro-3,4-dihydro-2h-chromen-4-yl]-2-methoxyacetamide Chemical compound C1=CC=C2[C@H](NC(=O)COC)CCOC2=C1F BEXWAXYTSUVJOB-SNVBAGLBSA-N 0.000 description 3
125000006501 nitrophenyl group Chemical group 0.000 description 3
239000003921 oil Substances 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
AHVQYHFYQWKUKB-UHFFFAOYSA-N oxan-4-amine Chemical compound NC1CCOCC1 AHVQYHFYQWKUKB-UHFFFAOYSA-N 0.000 description 3
238000004806 packaging method and process Methods 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
229920002223 polystyrene Polymers 0.000 description 3
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
239000001267 polyvinylpyrrolidone Substances 0.000 description 3
229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
235000015320 potassium carbonate Nutrition 0.000 description 3
QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 3
OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 3
YPOXGDJGKBXRFP-UHFFFAOYSA-M pyrimidine-4-carboxylate Chemical compound [O-]C(=O)C1=CC=NC=N1 YPOXGDJGKBXRFP-UHFFFAOYSA-M 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
210000002966 serum Anatomy 0.000 description 3
238000000935 solvent evaporation Methods 0.000 description 3
239000000600 sorbitol Substances 0.000 description 3
239000003381 stabilizer Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 3
CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
HXACNHXAKSMYNU-QMMMGPOBSA-N (4s)-8-fluoro-3,4-dihydro-2h-chromen-4-amine Chemical compound C1=CC=C2[C@@H](N)CCOC2=C1F HXACNHXAKSMYNU-QMMMGPOBSA-N 0.000 description 2
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 2
NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 2
UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical group C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 2
KDMMRYSLGGCOHT-UHFFFAOYSA-N 2,4-dichloro-5-nitro-6-phenylpyrimidine Chemical compound [O-][N+](=O)C1=C(Cl)N=C(Cl)N=C1C1=CC=CC=C1 KDMMRYSLGGCOHT-UHFFFAOYSA-N 0.000 description 2
KVVCDQYSKUTBKQ-UHFFFAOYSA-N 2-(2-amino-5-chloroanilino)-6-chloro-9-(oxan-4-yl)-7h-purin-8-one Chemical compound NC1=CC=C(Cl)C=C1NC1=NC(Cl)=C(NC(=O)N2C3CCOCC3)C2=N1 KVVCDQYSKUTBKQ-UHFFFAOYSA-N 0.000 description 2
ZEHTZXMRRLJMTC-UHFFFAOYSA-N 2-(2-amino-5-chloroanilino)-9-(oxan-4-yl)-6-pyridin-4-yl-7h-purin-8-one Chemical compound NC1=CC=C(Cl)C=C1NC1=NC(C=2C=CN=CC=2)=C(NC(=O)N2C3CCOCC3)C2=N1 ZEHTZXMRRLJMTC-UHFFFAOYSA-N 0.000 description 2
COXFBLUGJPLIEU-UHFFFAOYSA-N 2-(5-chloro-2-nitroanilino)-9-(oxan-4-yl)-6-pyridin-4-yl-7h-purin-8-one Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1NC1=NC(C=2C=CN=CC=2)=C(NC(=O)N2C3CCOCC3)C2=N1 COXFBLUGJPLIEU-UHFFFAOYSA-N 0.000 description 2
FAPKTYYVUSMMIC-UHFFFAOYSA-N 2-(benzimidazol-1-yl)-5-nitro-n-(oxan-4-yl)-6-phenylpyrimidin-4-amine Chemical compound N1=C(N2C3=CC=CC=C3N=C2)N=C(C=2C=CC=CC=2)C([N+](=O)[O-])=C1NC1CCOCC1 FAPKTYYVUSMMIC-UHFFFAOYSA-N 0.000 description 2
HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical class O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 2
ZYBBWVMFTRWSKM-UHFFFAOYSA-N 2-[2-amino-5-(trifluoromethoxy)anilino]-9-(oxan-4-yl)-6-pyridin-4-yl-7h-purin-8-one Chemical compound NC1=CC=C(OC(F)(F)F)C=C1NC1=NC(C=2C=CN=CC=2)=C(NC(=O)N2C3CCOCC3)C2=N1 ZYBBWVMFTRWSKM-UHFFFAOYSA-N 0.000 description 2
BACXFRHGEVIZPV-UHFFFAOYSA-N 2-amino-6-chloro-7,9-dihydropurin-8-one Chemical compound NC1=NC(Cl)=C2NC(=O)NC2=N1 BACXFRHGEVIZPV-UHFFFAOYSA-N 0.000 description 2
MVAWATQAHDUZQJ-UHFFFAOYSA-N 2-amino-6-chloro-9-(4-methoxycyclohexyl)-7h-purin-8-one Chemical compound C1CC(OC)CCC1N1C(=O)NC2=C(Cl)N=C(N)N=C21 MVAWATQAHDUZQJ-UHFFFAOYSA-N 0.000 description 2
BJWWKRPYBNTTBC-MRVPVSSYSA-N 2-amino-6-chloro-9-[(4r)-8-fluoro-3,4-dihydro-2h-chromen-4-yl]-7h-purin-8-one Chemical compound C1COC2=C(F)C=CC=C2[C@@H]1N1C(=O)NC2=C(Cl)N=C(N)N=C21 BJWWKRPYBNTTBC-MRVPVSSYSA-N 0.000 description 2
JFYFFSJMUQSMPC-UHFFFAOYSA-N 2-benzylsulfanyl-6-(2-chlorophenyl)-5-nitro-n-(oxan-4-yl)pyrimidin-4-amine Chemical compound N1=C(SCC=2C=CC=CC=2)N=C(C=2C(=CC=CC=2)Cl)C([N+](=O)[O-])=C1NC1CCOCC1 JFYFFSJMUQSMPC-UHFFFAOYSA-N 0.000 description 2
HCYSMGYMAYCENH-UHFFFAOYSA-N 2-benzylsulfanyl-6-chloro-5-nitro-n-(oxan-4-yl)pyrimidin-4-amine Chemical compound N1=C(NC2CCOCC2)C([N+](=O)[O-])=C(Cl)N=C1SCC1=CC=CC=C1 HCYSMGYMAYCENH-UHFFFAOYSA-N 0.000 description 2
LMEWOXRLKHANRA-UHFFFAOYSA-N 2-benzylsulfonyl-6-(2-chlorophenyl)-5-nitro-n-(oxan-4-yl)pyrimidin-4-amine Chemical compound N1=C(S(=O)(=O)CC=2C=CC=CC=2)N=C(C=2C(=CC=CC=2)Cl)C([N+](=O)[O-])=C1NC1CCOCC1 LMEWOXRLKHANRA-UHFFFAOYSA-N 0.000 description 2
LCPGLDQHVPTGOR-UHFFFAOYSA-N 2-chloro-5-nitro-n-(oxan-4-yl)-6-phenylpyrimidin-4-amine Chemical compound N1=C(Cl)N=C(C=2C=CC=CC=2)C([N+](=O)[O-])=C1NC1CCOCC1 LCPGLDQHVPTGOR-UHFFFAOYSA-N 0.000 description 2
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
QUHVRXKSQHIZNV-UHFFFAOYSA-N 3,3-difluoroazetidine Chemical compound FC1(F)CNC1 QUHVRXKSQHIZNV-UHFFFAOYSA-N 0.000 description 2
CDBAEFXTCRKJPZ-UHFFFAOYSA-N 3,3-difluoroazetidine;hydron;chloride Chemical compound Cl.FC1(F)CNC1 CDBAEFXTCRKJPZ-UHFFFAOYSA-N 0.000 description 2
HTFQCXHHEIUZPM-UHFFFAOYSA-N 3-(2-fluorophenoxy)propanoic acid Chemical compound OC(=O)CCOC1=CC=CC=C1F HTFQCXHHEIUZPM-UHFFFAOYSA-N 0.000 description 2
BXQOQVXIENSALP-UHFFFAOYSA-N 3-(6-chloro-8-oxo-7,9-dihydropurin-2-yl)benzimidazole-5-carbonitrile Chemical compound C1=NC2=CC=C(C#N)C=C2N1C(N=C1Cl)=NC2=C1NC(=O)N2 BXQOQVXIENSALP-UHFFFAOYSA-N 0.000 description 2
NXKQLUJKWVTJIM-UHFFFAOYSA-N 3-[(6-chloro-8-oxo-7,9-dihydropurin-2-yl)amino]-4-nitrobenzonitrile Chemical compound [O-][N+](=O)C1=CC=C(C#N)C=C1NC1=NC(Cl)=C(NC(=O)N2)C2=N1 NXKQLUJKWVTJIM-UHFFFAOYSA-N 0.000 description 2
OCJJQVCBZZVWEY-UHFFFAOYSA-N 3-[6-chloro-9-(4-hydroxycyclohexyl)-7-methyl-8-oxopurin-2-yl]benzimidazole-5-carbonitrile Chemical compound O=C1N(C)C2=C(Cl)N=C(N3C4=CC(=CC=C4N=C3)C#N)N=C2N1C1CCC(O)CC1 OCJJQVCBZZVWEY-UHFFFAOYSA-N 0.000 description 2
XCWFLSBLGYEDKK-UHFFFAOYSA-N 3-[[6-chloro-9-(oxan-4-yl)-8-oxo-7h-purin-2-yl]amino]-4-nitrobenzonitrile Chemical compound [O-][N+](=O)C1=CC=C(C#N)C=C1NC1=NC(Cl)=C(NC(=O)N2C3CCOCC3)C2=N1 XCWFLSBLGYEDKK-UHFFFAOYSA-N 0.000 description 2
GRFNBEZIAWKNCO-UHFFFAOYSA-N 3-pyridinol Chemical compound OC1=CC=CN=C1 GRFNBEZIAWKNCO-UHFFFAOYSA-N 0.000 description 2
UBOOKRVGOBKDMM-UHFFFAOYSA-N 3h-imidazo[4,5-c]pyridine Chemical compound C1=NC=C2NC=NC2=C1 UBOOKRVGOBKDMM-UHFFFAOYSA-N 0.000 description 2
HOZUXBLMYUPGPZ-UHFFFAOYSA-N 4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenol Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=C(O)C=C1 HOZUXBLMYUPGPZ-UHFFFAOYSA-N 0.000 description 2
BRPZONGSCLMVRY-UHFFFAOYSA-N 4-[2-benzylsulfanyl-5-nitro-6-(oxan-4-ylamino)pyrimidin-4-yl]benzonitrile Chemical compound N1=C(SCC=2C=CC=CC=2)N=C(C=2C=CC(=CC=2)C#N)C([N+](=O)[O-])=C1NC1CCOCC1 BRPZONGSCLMVRY-UHFFFAOYSA-N 0.000 description 2
XCDDFPALCKEJME-UHFFFAOYSA-N 4-amino-3-[(6-chloro-8-oxo-7,9-dihydropurin-2-yl)amino]benzonitrile Chemical compound NC1=CC=C(C#N)C=C1NC1=NC(Cl)=C(NC(=O)N2)C2=N1 XCDDFPALCKEJME-UHFFFAOYSA-N 0.000 description 2
VXCUSPQAKBNJCT-UHFFFAOYSA-N 4-amino-3-[[6-chloro-9-(oxan-4-yl)-8-oxo-7h-purin-2-yl]amino]benzonitrile Chemical compound NC1=CC=C(C#N)C=C1NC1=NC(Cl)=C(NC(=O)N2C3CCOCC3)C2=N1 VXCUSPQAKBNJCT-UHFFFAOYSA-N 0.000 description 2
RIRHXBALKPGCJE-UHFFFAOYSA-N 6-chloro-2-(5-chloro-2-nitroanilino)-9-(oxan-4-yl)-7h-purin-8-one Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1NC1=NC(Cl)=C(NC(=O)N2C3CCOCC3)C2=N1 RIRHXBALKPGCJE-UHFFFAOYSA-N 0.000 description 2
ZVPBYCYSTLWCGC-UHFFFAOYSA-N 6-chloro-2-(5-fluoro-2-nitroanilino)-9-(oxan-4-yl)-7h-purin-8-one Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1NC1=NC(Cl)=C(NC(=O)N2C3CCOCC3)C2=N1 ZVPBYCYSTLWCGC-UHFFFAOYSA-N 0.000 description 2
KDNBUJTVZJYLHI-UHFFFAOYSA-N 6-chloro-2-(6-fluorobenzimidazol-1-yl)-9-(oxan-4-yl)-7h-purin-8-one Chemical compound C12=CC(F)=CC=C2N=CN1C(N=C12)=NC(Cl)=C1NC(=O)N2C1CCOCC1 KDNBUJTVZJYLHI-UHFFFAOYSA-N 0.000 description 2
QPHQATAAWICPEZ-UHFFFAOYSA-N 6-chloro-4-n-(4-methoxycyclohexyl)pyrimidine-2,4,5-triamine Chemical compound C1CC(OC)CCC1NC1=NC(N)=NC(Cl)=C1N QPHQATAAWICPEZ-UHFFFAOYSA-N 0.000 description 2
AUSKZVKRDHNJGZ-MRVPVSSYSA-N 6-chloro-4-n-[(4r)-8-fluoro-3,4-dihydro-2h-chromen-4-yl]pyrimidine-2,4,5-triamine Chemical compound NC1=NC(Cl)=C(N)C(N[C@H]2C3=CC=CC(F)=C3OCC2)=N1 AUSKZVKRDHNJGZ-MRVPVSSYSA-N 0.000 description 2
POUWVUXRFUTDBL-UHFFFAOYSA-N 6-chloro-8-methyl-9-(oxan-4-yl)purin-2-amine Chemical compound CC1=NC2=C(Cl)N=C(N)N=C2N1C1CCOCC1 POUWVUXRFUTDBL-UHFFFAOYSA-N 0.000 description 2
SOMJHNVYNAJBGG-UHFFFAOYSA-N 6-chloropyrimidine-2,4,5-triamine;hydrochloride Chemical compound Cl.NC1=NC(N)=C(N)C(Cl)=N1 SOMJHNVYNAJBGG-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
YPDSIEMYVQERLJ-UHFFFAOYSA-N 8-Hydroxypurine Chemical compound C1=NC=C2NC(O)=NC2=N1 YPDSIEMYVQERLJ-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
KPDRVLMDRATSLX-UHFFFAOYSA-N 8-methyl-9-(oxan-4-yl)-6-pyridin-4-ylpurin-2-amine Chemical compound CC1=NC2=C(C=3C=CN=CC=3)N=C(N)N=C2N1C1CCOCC1 KPDRVLMDRATSLX-UHFFFAOYSA-N 0.000 description 2
208000026872 Addison Disease Diseases 0.000 description 2
206010002198 Anaphylactic reaction Diseases 0.000 description 2
208000023328 Basedow disease Diseases 0.000 description 2
JWSNTMMGKSDPHH-XYPYZODXSA-N C1C[C@@H](O)CC[C@@H]1N1C(=O)NC2=C(Cl)N=C(N3C4=CC(F)=CC=C4N=C3)N=C21 Chemical compound C1C[C@@H](O)CC[C@@H]1N1C(=O)NC2=C(Cl)N=C(N3C4=CC(F)=CC=C4N=C3)N=C21 JWSNTMMGKSDPHH-XYPYZODXSA-N 0.000 description 2
GAUKCWIITXNWPT-MGCOHNPYSA-N C1C[C@@H](O)CC[C@@H]1N1C(=O)NC2=C(Cl)N=C(NC=3C(=CC=C(F)C=3)[N+]([O-])=O)N=C21 Chemical compound C1C[C@@H](O)CC[C@@H]1N1C(=O)NC2=C(Cl)N=C(NC=3C(=CC=C(F)C=3)[N+]([O-])=O)N=C21 GAUKCWIITXNWPT-MGCOHNPYSA-N 0.000 description 2
CDQXMDLULZIOII-HAQNSBGRSA-N C1C[C@@H](OC)CC[C@@H]1N1C(=O)NC2=C(Cl)N=C(NC=3C(=CC=C(C=3)C#N)[N+]([O-])=O)N=C21 Chemical compound C1C[C@@H](OC)CC[C@@H]1N1C(=O)NC2=C(Cl)N=C(NC=3C(=CC=C(C=3)C#N)[N+]([O-])=O)N=C21 CDQXMDLULZIOII-HAQNSBGRSA-N 0.000 description 2
206010008909 Chronic Hepatitis Diseases 0.000 description 2
ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 2
238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 2
208000015023 Graves' disease Diseases 0.000 description 2
208000030836 Hashimoto thyroiditis Diseases 0.000 description 2
206010019755 Hepatitis chronic active Diseases 0.000 description 2
101000934996 Homo sapiens Tyrosine-protein kinase JAK3 Proteins 0.000 description 2
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 2
208000022559 Inflammatory bowel disease Diseases 0.000 description 2
101150009057 JAK2 gene Proteins 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
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
238000006751 Mitsunobu reaction Methods 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
241000699666 Mus <mouse, genus> Species 0.000 description 2
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
229910004878 Na2S2O4 Inorganic materials 0.000 description 2
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 2
108010084311 Novozyme 435 Proteins 0.000 description 2
101100272976 Panax ginseng CYP716A53v2 gene Proteins 0.000 description 2
208000031845 Pernicious anaemia Diseases 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
201000004681 Psoriasis Diseases 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
229940124639 Selective inhibitor Drugs 0.000 description 2
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
102100028651 Tenascin-N Human genes 0.000 description 2
101710087911 Tenascin-N Proteins 0.000 description 2
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 description 2
208000024780 Urticaria Diseases 0.000 description 2
LQWJDVVMLCBJAN-UHFFFAOYSA-N [4-(2-amino-6-chloro-8-oxo-7h-purin-9-yl)cyclohexyl] methyl carbonate Chemical compound C1CC(OC(=O)OC)CCC1N1C(=O)NC2=C(Cl)N=C(N)N=C21 LQWJDVVMLCBJAN-UHFFFAOYSA-N 0.000 description 2
230000001594 aberrant effect Effects 0.000 description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
230000004913 activation Effects 0.000 description 2
239000000443 aerosol Substances 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
235000019270 ammonium chloride Nutrition 0.000 description 2
230000036783 anaphylactic response Effects 0.000 description 2
208000003455 anaphylaxis Diseases 0.000 description 2
238000013459 approach Methods 0.000 description 2
150000001499 aryl bromides Chemical class 0.000 description 2
238000003556 assay Methods 0.000 description 2
230000001363 autoimmune Effects 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
238000010322 bone marrow transplantation Methods 0.000 description 2
239000000872 buffer Substances 0.000 description 2
239000001569 carbon dioxide Substances 0.000 description 2
229910002092 carbon dioxide Inorganic materials 0.000 description 2
239000013592 cell lysate Substances 0.000 description 2
VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical compound C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 2
239000002299 complementary DNA Substances 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
238000010511 deprotection reaction Methods 0.000 description 2
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
ZHXTWWCDMUWMDI-UHFFFAOYSA-N dihydroxyboron Chemical compound O[B]O ZHXTWWCDMUWMDI-UHFFFAOYSA-N 0.000 description 2
208000037765 diseases and disorders Diseases 0.000 description 2
239000008298 dragée Substances 0.000 description 2
239000003814 drug Substances 0.000 description 2
238000005516 engineering process Methods 0.000 description 2
239000010685 fatty oil Substances 0.000 description 2
239000000945 filler Substances 0.000 description 2
229940093915 gynecological organic acid Drugs 0.000 description 2
238000002868 homogeneous time resolved fluorescence Methods 0.000 description 2
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
210000000987 immune system Anatomy 0.000 description 2
238000011534 incubation Methods 0.000 description 2
PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
230000005764 inhibitory process 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
239000000543 intermediate Substances 0.000 description 2
239000011630 iodine Substances 0.000 description 2
238000000021 kinase assay Methods 0.000 description 2
230000000670 limiting effect Effects 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
230000011987 methylation Effects 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
238000010172 mouse model Methods 0.000 description 2
201000006417 multiple sclerosis Diseases 0.000 description 2
206010028417 myasthenia gravis Diseases 0.000 description 2
201000005962 mycosis fungoides Diseases 0.000 description 2
HAZJXELXJAWKQA-UHFFFAOYSA-N n-(5-chloro-2-nitrophenyl)-8-methyl-9-(oxan-4-yl)-6-pyridin-4-ylpurin-2-amine Chemical compound N1=C2N(C3CCOCC3)C(C)=NC2=C(C=2C=CN=CC=2)N=C1NC1=CC(Cl)=CC=C1[N+]([O-])=O HAZJXELXJAWKQA-UHFFFAOYSA-N 0.000 description 2
239000006199 nebulizer Substances 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
201000010065 polycystic ovary syndrome Diseases 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
235000011181 potassium carbonates Nutrition 0.000 description 2
239000000843 powder Substances 0.000 description 2
230000008569 process Effects 0.000 description 2
238000012545 processing Methods 0.000 description 2
125000004542 purin-6-yl group Chemical group N1=CN=C2N=CNC2=C1* 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 2
CSNFMBGHUOSBFU-UHFFFAOYSA-N pyrimidine-2,4,5-triamine Chemical compound NC1=NC=C(N)C(N)=N1 CSNFMBGHUOSBFU-UHFFFAOYSA-N 0.000 description 2
YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical compound NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 description 2
XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 2
230000004044 response Effects 0.000 description 2
206010039073 rheumatoid arthritis Diseases 0.000 description 2
239000012047 saturated solution Substances 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 2
239000008107 starch Substances 0.000 description 2
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 2
150000003536 tetrazoles Chemical class 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
229930192474 thiophene Natural products 0.000 description 2
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
BSVHTRRLCAVQCZ-JDEXMCKMSA-N (2s)-1-[(2s)-1-[(2s)-1-[(2s)-1-[(2s)-1-[(2s)-1-[(2s)-2-[[(2s)-1-[(2s)-2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-carboxypropanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]pyrro Chemical compound C([C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(O)=O)C1=CC=C(O)C=C1 BSVHTRRLCAVQCZ-JDEXMCKMSA-N 0.000 description 1
LENYOXXELREKGZ-WCCKRBBISA-N (3s)-3-fluoropyrrolidin-1-ium;chloride Chemical compound Cl.F[C@H]1CCNC1 LENYOXXELREKGZ-WCCKRBBISA-N 0.000 description 1
WVQYSVLMDHXHOV-MRVPVSSYSA-N (4r)-6-fluoro-3,4-dihydro-2h-chromen-4-amine Chemical compound C1=C(F)C=C2[C@H](N)CCOC2=C1 WVQYSVLMDHXHOV-MRVPVSSYSA-N 0.000 description 1
HXACNHXAKSMYNU-MRVPVSSYSA-N (4r)-8-fluoro-3,4-dihydro-2h-chromen-4-amine Chemical compound C1=CC=C2[C@H](N)CCOC2=C1F HXACNHXAKSMYNU-MRVPVSSYSA-N 0.000 description 1
CDKWCMPLLLFKBM-DDWIOCJRSA-N (4r)-8-fluoro-3,4-dihydro-2h-chromen-4-amine;hydrochloride Chemical compound Cl.C1=CC=C2[C@H](N)CCOC2=C1F CDKWCMPLLLFKBM-DDWIOCJRSA-N 0.000 description 1
KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
CXBDYQVECUFKRK-UHFFFAOYSA-N 1-methoxybutane Chemical compound CCCCOC CXBDYQVECUFKRK-UHFFFAOYSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
QMDUEBURHKSKDG-UHFFFAOYSA-N 1-pyridin-3-ylethanol Chemical compound CC(O)C1=CC=CN=C1 QMDUEBURHKSKDG-UHFFFAOYSA-N 0.000 description 1
VUQYBVYYRREKMC-UHFFFAOYSA-N 2,3-dihydroinden-1-one Chemical compound C1=CC=C2C(=O)CCC2=C1.C1=CC=C2C(=O)CCC2=C1 VUQYBVYYRREKMC-UHFFFAOYSA-N 0.000 description 1
RVZMPNMUBCAPQO-UHFFFAOYSA-N 2,4-dimethoxyquinazoline Chemical class C1=CC=CC2=NC(OC)=NC(OC)=C21 RVZMPNMUBCAPQO-UHFFFAOYSA-N 0.000 description 1
VINAKIWCTBTQDJ-UHFFFAOYSA-N 2-(2-amino-5-fluoroanilino)-6-(2-chlorophenyl)-9-(oxan-4-yl)-7h-purin-8-one Chemical compound NC1=CC=C(F)C=C1NC1=NC(C=2C(=CC=CC=2)Cl)=C(NC(=O)N2C3CCOCC3)C2=N1 VINAKIWCTBTQDJ-UHFFFAOYSA-N 0.000 description 1
KHIOKOBYCPLYBJ-UHFFFAOYSA-N 2-(2-amino-5-fluoroanilino)-6-chloro-9-(oxan-4-yl)-7h-purin-8-one Chemical compound NC1=CC=C(F)C=C1NC1=NC(Cl)=C(NC(=O)N2C3CCOCC3)C2=N1 KHIOKOBYCPLYBJ-UHFFFAOYSA-N 0.000 description 1
DWNSEFDMOYDZGO-CQSZACIVSA-N 2-(2-amino-5-fluoroanilino)-6-chloro-9-[(4r)-8-fluoro-3,4-dihydro-2h-chromen-4-yl]-7h-purin-8-one Chemical compound NC1=CC=C(F)C=C1NC1=NC(Cl)=C(NC(=O)N2[C@H]3C4=CC=CC(F)=C4OCC3)C2=N1 DWNSEFDMOYDZGO-CQSZACIVSA-N 0.000 description 1
HMJIDQAHBRTOFU-UHFFFAOYSA-N 2-(6-chlorobenzimidazol-1-yl)-6-(3,3-difluoroazetidin-1-yl)-9-(oxan-4-yl)-7h-purin-8-one Chemical compound C1C(F)(F)CN1C1=NC(N2C3=CC(Cl)=CC=C3N=C2)=NC2=C1NC(=O)N2C1CCOCC1 HMJIDQAHBRTOFU-UHFFFAOYSA-N 0.000 description 1
CRCMPBQKDVDVHP-UHFFFAOYSA-N 2-(6-chlorobenzimidazol-1-yl)-8-methyl-9-(oxan-4-yl)-6-pyridin-4-ylpurine Chemical compound CC1=NC2=C(C=3C=CN=CC=3)N=C(N3C4=CC(Cl)=CC=C4N=C3)N=C2N1C1CCOCC1 CRCMPBQKDVDVHP-UHFFFAOYSA-N 0.000 description 1
FAZHDROMKCMCIK-UHFFFAOYSA-N 2-(6-fluorobenzimidazol-1-yl)-9-(oxan-4-yl)-8-oxo-7h-purine-6-carboxylic acid Chemical compound O=C1NC=2C(C(=O)O)=NC(N3C4=CC(F)=CC=C4N=C3)=NC=2N1C1CCOCC1 FAZHDROMKCMCIK-UHFFFAOYSA-N 0.000 description 1
KDIZLOZBCRTEOJ-LJQANCHMSA-N 2-(benzimidazol-1-yl)-4-n-[(4r)-6-fluoro-3,4-dihydro-2h-chromen-4-yl]-6-phenylpyrimidine-4,5-diamine Chemical compound NC1=C(N[C@H]2C3=CC(F)=CC=C3OCC2)N=C(N2C3=CC=CC=C3N=C2)N=C1C1=CC=CC=C1 KDIZLOZBCRTEOJ-LJQANCHMSA-N 0.000 description 1
IEGOABAJYMWUSE-UHFFFAOYSA-N 2-(benzimidazol-1-yl)-9-(oxan-4-yl)-6-phenyl-7h-purin-8-one Chemical compound O=C1NC2=C(C=3C=CC=CC=3)N=C(N3C4=CC=CC=C4N=C3)N=C2N1C1CCOCC1 IEGOABAJYMWUSE-UHFFFAOYSA-N 0.000 description 1
IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
QTXLQPDSLBHWPF-UHFFFAOYSA-N 2-[2-(2,5-dimethylpyrrol-1-yl)-5-(trifluoromethoxy)anilino]-9-(oxan-4-yl)-6-pyridin-4-yl-7h-purin-8-one Chemical compound CC1=CC=C(C)N1C1=CC=C(OC(F)(F)F)C=C1NC1=NC(C=2C=CN=CC=2)=C(NC(=O)N2C3CCOCC3)C2=N1 QTXLQPDSLBHWPF-UHFFFAOYSA-N 0.000 description 1
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 1
GGHQYUNKXPSLJV-UHFFFAOYSA-N 2-amino-6-(2-chlorophenyl)-9-(oxan-4-yl)-7h-purin-8-one Chemical compound C=12NC(=O)N(C3CCOCC3)C2=NC(N)=NC=1C1=CC=CC=C1Cl GGHQYUNKXPSLJV-UHFFFAOYSA-N 0.000 description 1
FONJIJWCXJZLND-UHFFFAOYSA-N 2-benzylsulfanyl-4,6-dichloro-5-nitropyrimidine Chemical compound N1=C(Cl)C([N+](=O)[O-])=C(Cl)N=C1SCC1=CC=CC=C1 FONJIJWCXJZLND-UHFFFAOYSA-N 0.000 description 1
CBIAKDAYHRWZCU-UHFFFAOYSA-N 2-bromo-4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenol Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=C(O)C(Br)=C1 CBIAKDAYHRWZCU-UHFFFAOYSA-N 0.000 description 1
KKQPWVOGOSKRPT-CQSZACIVSA-N 2-chloro-n-[(4r)-6-fluoro-3,4-dihydro-2h-chromen-4-yl]-5-nitro-6-phenylpyrimidin-4-amine Chemical compound [O-][N+](=O)C1=C(N[C@H]2C3=CC(F)=CC=C3OCC2)N=C(Cl)N=C1C1=CC=CC=C1 KKQPWVOGOSKRPT-CQSZACIVSA-N 0.000 description 1
HZLCGUXUOFWCCN-UHFFFAOYSA-N 2-hydroxynonadecane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)C(O)(C(O)=O)CC(O)=O HZLCGUXUOFWCCN-UHFFFAOYSA-N 0.000 description 1
125000006088 2-oxoazepinyl group Chemical group 0.000 description 1
125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical group OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
SJSBKIXOCNOEFF-UHFFFAOYSA-N 2h-thiopyran 1,1-dioxide Chemical compound O=S1(=O)CC=CC=C1 SJSBKIXOCNOEFF-UHFFFAOYSA-N 0.000 description 1
FXNWFHZWTZLZTJ-UHFFFAOYSA-N 3-[6-(3,3-difluoroazetidin-1-yl)-8-oxo-7,9-dihydropurin-2-yl]benzimidazole-5-carbonitrile Chemical compound C1C(F)(F)CN1C1=NC(N2C3=CC(=CC=C3N=C2)C#N)=NC2=C1NC(=O)N2 FXNWFHZWTZLZTJ-UHFFFAOYSA-N 0.000 description 1
RMDMOYMMOIDUKC-UHFFFAOYSA-N 3-[6-(3,3-difluoroazetidin-1-yl)-8-oxo-9-(1-pyridin-3-ylethyl)-7h-purin-2-yl]benzimidazole-5-carbonitrile Chemical compound C12=NC(N3C4=CC(=CC=C4N=C3)C#N)=NC(N3CC(F)(F)C3)=C2NC(=O)N1C(C)C1=CC=CN=C1 RMDMOYMMOIDUKC-UHFFFAOYSA-N 0.000 description 1
LWGSYYASBQTCAE-UHFFFAOYSA-N 3-[6-(3,3-difluoroazetidin-1-yl)-8-oxo-9-(oxolan-3-ylmethyl)-7h-purin-2-yl]benzimidazole-5-carbonitrile Chemical compound C1C(F)(F)CN1C1=NC(N2C3=CC(=CC=C3N=C2)C#N)=NC2=C1NC(=O)N2CC1COCC1 LWGSYYASBQTCAE-UHFFFAOYSA-N 0.000 description 1
ONNXZQOHEYQASN-UHFFFAOYSA-N 3-[6-(3,3-difluoroazetidin-1-yl)-9-(4-hydroxycyclohexyl)-8-oxo-7h-purin-2-yl]benzimidazole-5-carbonitrile Chemical compound C1CC(O)CCC1N1C(=O)NC2=C(N3CC(F)(F)C3)N=C(N3C4=CC(=CC=C4N=C3)C#N)N=C21 ONNXZQOHEYQASN-UHFFFAOYSA-N 0.000 description 1
DWMMKUNSPINXMH-UHFFFAOYSA-N 3-[6-chloro-8-oxo-9-(1-pyridin-3-ylethyl)-7h-purin-2-yl]benzimidazole-5-carbonitrile Chemical compound C12=NC(N3C4=CC(=CC=C4N=C3)C#N)=NC(Cl)=C2NC(=O)N1C(C)C1=CC=CN=C1 DWMMKUNSPINXMH-UHFFFAOYSA-N 0.000 description 1
QEGZCZYZKZUVIW-UHFFFAOYSA-N 3-[6-chloro-9-(oxan-4-yl)-8-oxo-7h-purin-2-yl]benzimidazole-5-carbonitrile Chemical compound O=C1NC=2C(Cl)=NC(N3C4=CC(=CC=C4N=C3)C#N)=NC=2N1C1CCOCC1 QEGZCZYZKZUVIW-UHFFFAOYSA-N 0.000 description 1
DHXNZYCXMFBMHE-UHFFFAOYSA-N 3-bromopropanoic acid Chemical compound OC(=O)CCBr DHXNZYCXMFBMHE-UHFFFAOYSA-N 0.000 description 1
NICYTXJGZRYCEQ-UHFFFAOYSA-N 3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2N=CNC2=C1 NICYTXJGZRYCEQ-UHFFFAOYSA-N 0.000 description 1
PPAULTVPKLVLII-UHFFFAOYSA-N 4,5-diaminopyrimidine Chemical compound NC1=CN=CN=C1N PPAULTVPKLVLII-UHFFFAOYSA-N 0.000 description 1
NLTIETZTDSJANS-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=NC=C1 NLTIETZTDSJANS-UHFFFAOYSA-N 0.000 description 1
WBEMFKMQDJWCNP-UHFFFAOYSA-N 4-[2,5-diamino-6-(oxan-4-ylamino)pyrimidin-4-yl]benzonitrile Chemical compound NC=1C(C=2C=CC(=CC=2)C#N)=NC(N)=NC=1NC1CCOCC1 WBEMFKMQDJWCNP-UHFFFAOYSA-N 0.000 description 1
BEZRAIFOHWITHN-UHFFFAOYSA-N 4-[2-(5-fluoro-2-nitroanilino)-9-(oxan-4-yl)-8-oxo-7h-purin-6-yl]benzonitrile Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1NC1=NC(C=2C=CC(=CC=2)C#N)=C(NC(=O)N2C3CCOCC3)C2=N1 BEZRAIFOHWITHN-UHFFFAOYSA-N 0.000 description 1
VRILBCMSATZYHI-UHFFFAOYSA-N 4-[2-amino-5-nitro-6-(oxan-4-ylamino)pyrimidin-4-yl]benzonitrile Chemical compound [O-][N+](=O)C=1C(C=2C=CC(=CC=2)C#N)=NC(N)=NC=1NC1CCOCC1 VRILBCMSATZYHI-UHFFFAOYSA-N 0.000 description 1
QLOVKSOHEHUBOQ-UHFFFAOYSA-N 4-[2-amino-9-(oxan-4-yl)-8-oxo-7h-purin-6-yl]benzonitrile Chemical compound C=12NC(=O)N(C3CCOCC3)C2=NC(N)=NC=1C1=CC=C(C#N)C=C1 QLOVKSOHEHUBOQ-UHFFFAOYSA-N 0.000 description 1
CUGFPIMZGLVAMJ-UHFFFAOYSA-N 4-[2-benzylsulfonyl-5-nitro-6-(oxan-4-ylamino)pyrimidin-4-yl]benzonitrile Chemical compound N1=C(S(=O)(=O)CC=2C=CC=CC=2)N=C(C=2C=CC(=CC=2)C#N)C([N+](=O)[O-])=C1NC1CCOCC1 CUGFPIMZGLVAMJ-UHFFFAOYSA-N 0.000 description 1
IMLXLGZJLAOKJN-UHFFFAOYSA-N 4-aminocyclohexan-1-ol Chemical compound NC1CCC(O)CC1 IMLXLGZJLAOKJN-UHFFFAOYSA-N 0.000 description 1
DOMKNBFBVOTZQA-UHFFFAOYSA-N 4-chloro-1-n-[8-methyl-9-(oxan-4-yl)-6-pyridin-4-ylpurin-2-yl]benzene-1,2-diamine Chemical compound N1=C2N(C3CCOCC3)C(C)=NC2=C(C=2C=CN=CC=2)N=C1NC1=CC=C(Cl)C=C1N DOMKNBFBVOTZQA-UHFFFAOYSA-N 0.000 description 1
SDMXLAZIFYYECU-UHFFFAOYSA-N 4-methoxycyclohexan-1-amine Chemical compound COC1CCC(N)CC1 SDMXLAZIFYYECU-UHFFFAOYSA-N 0.000 description 1
125000006618 5- to 10-membered aromatic heterocyclic group Chemical group 0.000 description 1
CWNUZKROBZOONP-UHFFFAOYSA-N 6-(2-chlorophenyl)-2-(5-fluoro-2-nitroanilino)-9-(oxan-4-yl)-7h-purin-8-one Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1NC1=NC(C=2C(=CC=CC=2)Cl)=C(NC(=O)N2C3CCOCC3)C2=N1 CWNUZKROBZOONP-UHFFFAOYSA-N 0.000 description 1
CZQIZAWWHSRXRJ-UHFFFAOYSA-N 6-(2-chlorophenyl)-5-nitro-4-n-(oxan-4-yl)pyrimidine-2,4-diamine Chemical compound [O-][N+](=O)C=1C(C=2C(=CC=CC=2)Cl)=NC(N)=NC=1NC1CCOCC1 CZQIZAWWHSRXRJ-UHFFFAOYSA-N 0.000 description 1
PLFDNFHPGQPJFU-UHFFFAOYSA-N 6-chloro-2-(6-fluorobenzimidazol-1-yl)-9-(4-hydroxycyclohexyl)-7-methylpurin-8-one Chemical compound O=C1N(C)C2=C(Cl)N=C(N3C4=CC(F)=CC=C4N=C3)N=C2N1C1CCC(O)CC1 PLFDNFHPGQPJFU-UHFFFAOYSA-N 0.000 description 1
MVILGOJJYHZDQI-CQSZACIVSA-N 6-chloro-2-(6-fluorobenzimidazol-1-yl)-9-[(4r)-8-fluoro-3,4-dihydro-2h-chromen-4-yl]-7h-purin-8-one Chemical compound C1COC2=C(F)C=CC=C2[C@@H]1N(C1=N2)C(=O)NC1=C(Cl)N=C2N1C=NC2=CC=C(F)C=C21 MVILGOJJYHZDQI-CQSZACIVSA-N 0.000 description 1
BLOJJKRFEQXTFS-CYBMUJFWSA-N 6-chloro-9-[(4r)-8-fluoro-3,4-dihydro-2h-chromen-4-yl]-2-(5-fluoro-2-nitroanilino)-7h-purin-8-one Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1NC1=NC(Cl)=C(NC(=O)N2[C@H]3C4=CC=CC(F)=C4OCC3)C2=N1 BLOJJKRFEQXTFS-CYBMUJFWSA-N 0.000 description 1
ZZERPPZUMBLBLA-UHFFFAOYSA-N 9-(oxan-4-yl)-6-pyridin-4-yl-2-[6-(trifluoromethoxy)benzimidazol-1-yl]-7h-purin-8-one Chemical compound C12=CC(OC(F)(F)F)=CC=C2N=CN1C(N=C1N(C2CCOCC2)C(=O)NC1=1)=NC=1C1=CC=NC=C1 ZZERPPZUMBLBLA-UHFFFAOYSA-N 0.000 description 1
208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
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 1
208000028185 Angioedema Diseases 0.000 description 1
206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
238000011725 BALB/c mouse Methods 0.000 description 1
206010048396 Bone marrow transplant rejection Diseases 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
DYKTWSCZBLROFI-IZLXSQMJSA-N C12=NC(N)=NC(Cl)=C2NC(=O)N1[C@H]1CC[C@H](O)CC1 Chemical compound C12=NC(N)=NC(Cl)=C2NC(=O)N1[C@H]1CC[C@H](O)CC1 DYKTWSCZBLROFI-IZLXSQMJSA-N 0.000 description 1
KVWJPTMNFUDCBC-XYPYZODXSA-N C1C[C@@H](OC)CC[C@@H]1N1C(=O)NC2=C(Cl)N=C(NC=3C(=CC=C(Cl)C=3)N)N=C21 Chemical compound C1C[C@@H](OC)CC[C@@H]1N1C(=O)NC2=C(Cl)N=C(NC=3C(=CC=C(Cl)C=3)N)N=C21 KVWJPTMNFUDCBC-XYPYZODXSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
238000003734 CellTiter-Glo Luminescent Cell Viability Assay Methods 0.000 description 1
MADDWNUAYOHWRC-UHFFFAOYSA-M ClC1=CC=CC=C1[Zn]I Chemical compound ClC1=CC=CC=C1[Zn]I MADDWNUAYOHWRC-UHFFFAOYSA-M 0.000 description 1
208000015943 Coeliac disease Diseases 0.000 description 1
206010009900 Colitis ulcerative Diseases 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
208000011231 Crohn disease Diseases 0.000 description 1
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
229920000858 Cyclodextrin Polymers 0.000 description 1
PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
108010036949 Cyclosporine Proteins 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
201000004624 Dermatitis Diseases 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
239000004338 Dichlorodifluoromethane Substances 0.000 description 1
BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
241000792859 Enema Species 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
229910052693 Europium Inorganic materials 0.000 description 1
206010073306 Exposure to radiation Diseases 0.000 description 1
102000020897 Formins Human genes 0.000 description 1
108091022623 Formins Proteins 0.000 description 1
208000018522 Gastrointestinal disease Diseases 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
229910004373 HOAc Inorganic materials 0.000 description 1
206010066476 Haematological malignancy Diseases 0.000 description 1
208000002250 Hematologic Neoplasms Diseases 0.000 description 1
241000238631 Hexapoda Species 0.000 description 1
241000282412 Homo Species 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
102000009438 IgE Receptors Human genes 0.000 description 1
108010073816 IgE Receptors Proteins 0.000 description 1
102000004877 Insulin Human genes 0.000 description 1
108090001061 Insulin Proteins 0.000 description 1
108010002386 Interleukin-3 Proteins 0.000 description 1
108010024121 Janus Kinases Proteins 0.000 description 1
102000015617 Janus Kinases Human genes 0.000 description 1
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
235000019759 Maize starch Nutrition 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
QRMHDGWGLNLHMN-UHFFFAOYSA-N Methyl methoxyacetate Chemical compound COCC(=O)OC QRMHDGWGLNLHMN-UHFFFAOYSA-N 0.000 description 1
101100280403 Mus musculus F7 gene Proteins 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
PCANEWAPOOCLCD-MGCOHNPYSA-N NC1=CC=C(F)C=C1NC1=NC(Cl)=C(NC(=O)N2[C@@H]3CC[C@@H](O)CC3)C2=N1 Chemical compound NC1=CC=C(F)C=C1NC1=NC(Cl)=C(NC(=O)N2[C@@H]3CC[C@@H](O)CC3)C2=N1 PCANEWAPOOCLCD-MGCOHNPYSA-N 0.000 description 1
229910017912 NH2OH Inorganic materials 0.000 description 1
229910017974 NH40H Inorganic materials 0.000 description 1
229910020700 Na3VO4 Inorganic materials 0.000 description 1
101000800755 Naja oxiana Alpha-elapitoxin-Nno2a Proteins 0.000 description 1
206010029155 Nephropathy toxic Diseases 0.000 description 1
GTPRSFOZMZHJGX-DBTMUERSSA-N O([C@H]1CC[C@@H](CC1)N1C2=NC(=NC(Cl)=C2N(C1=O)C)N1C2=CC(F)=CC=C2N=C1)C1CCCCO1 Chemical compound O([C@H]1CC[C@@H](CC1)N1C2=NC(=NC(Cl)=C2N(C1=O)C)N1C2=CC(F)=CC=C2N=C1)C1CCCCO1 GTPRSFOZMZHJGX-DBTMUERSSA-N 0.000 description 1
PLFDNFHPGQPJFU-HAQNSBGRSA-N O=C1N(C)C2=C(Cl)N=C(N3C4=CC(F)=CC=C4N=C3)N=C2N1[C@H]1CC[C@H](O)CC1 Chemical compound O=C1N(C)C2=C(Cl)N=C(N3C4=CC(F)=CC=C4N=C3)N=C2N1[C@H]1CC[C@H](O)CC1 PLFDNFHPGQPJFU-HAQNSBGRSA-N 0.000 description 1
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
108010077495 Peptide oostatic hormone Proteins 0.000 description 1
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
108091000080 Phosphotransferase Proteins 0.000 description 1
208000010067 Pituitary ACTH Hypersecretion Diseases 0.000 description 1
208000020627 Pituitary-dependent Cushing syndrome Diseases 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
239000012980 RPMI-1640 medium Substances 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
206010039085 Rhinitis allergic Diseases 0.000 description 1
206010039710 Scleroderma Diseases 0.000 description 1
208000000453 Skin Neoplasms Diseases 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 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
DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
201000006704 Ulcerative Colitis Diseases 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
BBKCOQYMKGEAAJ-UHFFFAOYSA-M [Br-].[Zn+]C1CCC1 Chemical compound [Br-].[Zn+]C1CCC1 BBKCOQYMKGEAAJ-UHFFFAOYSA-M 0.000 description 1
QTBSBXVTEAMEQO-GUEYOVJQSA-N acetic acid-d4 Chemical compound [2H]OC(=O)C([2H])([2H])[2H] QTBSBXVTEAMEQO-GUEYOVJQSA-N 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
239000012190 activator Substances 0.000 description 1
239000013543 active substance Substances 0.000 description 1
125000004442 acylamino group Chemical group 0.000 description 1
210000004100 adrenal gland Anatomy 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
229940040563 agaric acid Drugs 0.000 description 1
230000016571 aggressive behavior Effects 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
125000001931 aliphatic group Chemical group 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
125000004457 alkyl amino carbonyl group Chemical group 0.000 description 1
125000003282 alkyl amino group Chemical group 0.000 description 1
125000004414 alkyl thio group Chemical group 0.000 description 1
125000000304 alkynyl group Chemical group 0.000 description 1
201000009961 allergic asthma Diseases 0.000 description 1
230000000172 allergic effect Effects 0.000 description 1
230000009285 allergic inflammation Effects 0.000 description 1
201000010105 allergic rhinitis Diseases 0.000 description 1
201000010435 allergic urticaria Diseases 0.000 description 1
230000000735 allogeneic effect Effects 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 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
150000001408 amides Chemical class 0.000 description 1
239000012296 anti-solvent Substances 0.000 description 1
125000003710 aryl alkyl group Chemical group 0.000 description 1
208000010216 atopic IgE responsiveness Diseases 0.000 description 1
208000010668 atopic eczema Diseases 0.000 description 1
229960002170 azathioprine Drugs 0.000 description 1
LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
125000002785 azepinyl group Chemical group 0.000 description 1
GMWFCJXSQQHBPI-UHFFFAOYSA-N azetidin-3-ol Chemical compound OC1CNC1 GMWFCJXSQQHBPI-UHFFFAOYSA-N 0.000 description 1
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
210000003719 b-lymphocyte Anatomy 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical group CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
150000001556 benzimidazoles Chemical group 0.000 description 1
125000005605 benzo group Chemical group 0.000 description 1
BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
239000011942 biocatalyst Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000001185 bone marrow Anatomy 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
229960004424 carbon dioxide Drugs 0.000 description 1
125000005518 carboxamido group Chemical group 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
238000012754 cardiac puncture Methods 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
230000020411 cell activation Effects 0.000 description 1
238000000423 cell based assay Methods 0.000 description 1
238000001516 cell proliferation assay Methods 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
230000036755 cellular response Effects 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
239000007810 chemical reaction solvent Substances 0.000 description 1
208000011654 childhood malignant neoplasm Diseases 0.000 description 1
238000004296 chiral HPLC Methods 0.000 description 1
239000012069 chiral reagent Substances 0.000 description 1
VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
229960002023 chloroprocaine Drugs 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
229960001231 choline Drugs 0.000 description 1
208000037976 chronic inflammation Diseases 0.000 description 1
230000006020 chronic inflammation Effects 0.000 description 1
229960001265 ciclosporin Drugs 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 1
238000004132 cross linking Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
KTHXBEHDVMTNOH-UHFFFAOYSA-N cyclobutanol Chemical compound OC1CCC1 KTHXBEHDVMTNOH-UHFFFAOYSA-N 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
229940097362 cyclodextrins Drugs 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
KFGVRWGDTLZAAO-UHFFFAOYSA-N cyclopenta-1,3-diene dicyclohexyl(cyclopenta-1,3-dien-1-yl)phosphane iron(2+) Chemical compound [Fe++].c1cc[cH-]c1.C1CCC(CC1)P(C1CCCCC1)c1ccc[cH-]1 KFGVRWGDTLZAAO-UHFFFAOYSA-N 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical compound NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 description 1
229930182912 cyclosporin Natural products 0.000 description 1
102000003675 cytokine receptors Human genes 0.000 description 1
108010057085 cytokine receptors Proteins 0.000 description 1
230000006378 damage Effects 0.000 description 1
230000017858 demethylation Effects 0.000 description 1
238000010520 demethylation reaction Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
125000004663 dialkyl amino group Chemical group 0.000 description 1
125000003963 dichloro group Chemical group Cl* 0.000 description 1
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
229940042935 dichlorodifluoromethane Drugs 0.000 description 1
235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
229940043237 diethanolamine Drugs 0.000 description 1
BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000012636 effector Substances 0.000 description 1
239000007920 enema Substances 0.000 description 1
229940079360 enema for constipation Drugs 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
238000009505 enteric coating Methods 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
CXMOEGSGXAUCNZ-UHFFFAOYSA-N ethyl 2,6-dichloro-5-nitropyrimidine-4-carboxylate Chemical compound CCOC(=O)C1=NC(Cl)=NC(Cl)=C1[N+]([O-])=O CXMOEGSGXAUCNZ-UHFFFAOYSA-N 0.000 description 1
ZECBXBKMYYMMPM-UHFFFAOYSA-N ethyl 2-(6-fluorobenzimidazol-1-yl)-5-nitro-6-(oxan-4-ylamino)pyrimidine-4-carboxylate Chemical compound [O-][N+](=O)C=1C(C(=O)OCC)=NC(N2C3=CC(F)=CC=C3N=C2)=NC=1NC1CCOCC1 ZECBXBKMYYMMPM-UHFFFAOYSA-N 0.000 description 1
JZVJLRKZOLIOHW-UHFFFAOYSA-N ethyl 2-(6-fluorobenzimidazol-1-yl)-9-(oxan-4-yl)-8-oxo-7h-purine-6-carboxylate Chemical compound O=C1NC=2C(C(=O)OCC)=NC(N3C4=CC(F)=CC=C4N=C3)=NC=2N1C1CCOCC1 JZVJLRKZOLIOHW-UHFFFAOYSA-N 0.000 description 1
VMXQFHLEMHCQLQ-UHFFFAOYSA-N ethyl 2-[5-fluoro-2-[(2-methylpropan-2-yl)oxycarbonyl]anilino]-5-nitro-6-(oxan-4-ylamino)pyrimidine-4-carboxylate Chemical compound N=1C(NC2CCOCC2)=C([N+]([O-])=O)C(C(=O)OCC)=NC=1NC1=CC(F)=CC=C1C(=O)OC(C)(C)C VMXQFHLEMHCQLQ-UHFFFAOYSA-N 0.000 description 1
UXUGFQNKBNDKOW-UHFFFAOYSA-N ethyl 5-amino-2-(6-fluorobenzimidazol-1-yl)-6-(oxan-4-ylamino)pyrimidine-4-carboxylate Chemical compound NC=1C(C(=O)OCC)=NC(N2C3=CC(F)=CC=C3N=C2)=NC=1NC1CCOCC1 UXUGFQNKBNDKOW-UHFFFAOYSA-N 0.000 description 1
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
229940012017 ethylenediamine Drugs 0.000 description 1
OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
239000012091 fetal bovine serum Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
239000011888 foil Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
230000037406 food intake Effects 0.000 description 1
238000004817 gas chromatography Methods 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
238000003304 gavage Methods 0.000 description 1
239000000499 gel Substances 0.000 description 1
125000005456 glyceride group Chemical group 0.000 description 1
239000008187 granular material Substances 0.000 description 1
238000000227 grinding Methods 0.000 description 1
230000003394 haemopoietic effect Effects 0.000 description 1
125000001188 haloalkyl group Chemical group 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
230000002489 hematologic effect Effects 0.000 description 1
125000004446 heteroarylalkyl group Chemical group 0.000 description 1
125000005553 heteroaryloxy group Chemical group 0.000 description 1
BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
239000005457 ice water Substances 0.000 description 1
125000002632 imidazolidinyl group Chemical group 0.000 description 1
125000002636 imidazolinyl group Chemical group 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
230000008629 immune suppression Effects 0.000 description 1
230000001861 immunosuppressant effect Effects 0.000 description 1
229940125721 immunosuppressive agent Drugs 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
230000006698 induction Effects 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
108040006849 interleukin-2 receptor activity proteins Proteins 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
230000004068 intracellular signaling Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
XJTQJERLRPWUGL-UHFFFAOYSA-N iodomethylbenzene Chemical compound ICC1=CC=CC=C1 XJTQJERLRPWUGL-UHFFFAOYSA-N 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
210000004153 islets of langerhan Anatomy 0.000 description 1
238000002955 isolation Methods 0.000 description 1
FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
125000003965 isoxazolidinyl group Chemical group 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
230000002045 lasting effect Effects 0.000 description 1
239000002502 liposome Substances 0.000 description 1
229940057995 liquid paraffin Drugs 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
206010025135 lupus erythematosus Diseases 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
230000036210 malignancy Effects 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
229960003194 meglumine Drugs 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
238000003032 molecular docking Methods 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
210000000066 myeloid cell Anatomy 0.000 description 1
OFOMMTJRFCSXNT-UHFFFAOYSA-N n-(8-fluoro-2,3-dihydrochromen-4-ylidene)hydroxylamine Chemical compound C1=CC=C2C(=NO)CCOC2=C1F OFOMMTJRFCSXNT-UHFFFAOYSA-N 0.000 description 1
125000004998 naphthylethyl group Chemical group C1(=CC=CC2=CC=CC=C12)CC* 0.000 description 1
210000000822 natural killer cell Anatomy 0.000 description 1
230000007694 nephrotoxicity Effects 0.000 description 1
231100000417 nephrotoxicity Toxicity 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Substances [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
229910000069 nitrogen hydride Inorganic materials 0.000 description 1
125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
238000010915 one-step procedure Methods 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
125000001715 oxadiazolyl group Chemical group 0.000 description 1
KWZSCXIYGVEHOB-UHFFFAOYSA-N oxan-4-amine;hydrochloride Chemical compound [Cl-].[NH3+]C1CCOCC1 KWZSCXIYGVEHOB-UHFFFAOYSA-N 0.000 description 1
125000000160 oxazolidinyl group Chemical group 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
PCPUMGYALMOCHF-UHFFFAOYSA-N oxolan-3-ylmethanol Chemical compound OCC1CCOC1 PCPUMGYALMOCHF-UHFFFAOYSA-N 0.000 description 1
LVSJDHGRKAEGLX-UHFFFAOYSA-N oxolane;2,2,2-trifluoroacetic acid Chemical compound C1CCOC1.OC(=O)C(F)(F)F LVSJDHGRKAEGLX-UHFFFAOYSA-N 0.000 description 1
BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
230000037361 pathway Effects 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
102000020233 phosphotransferase Human genes 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
239000006187 pill Substances 0.000 description 1
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
239000013612 plasmid Substances 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
239000004014 plasticizer Substances 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
210000001586 pre-b-lymphocyte Anatomy 0.000 description 1
239000002243 precursor Substances 0.000 description 1
208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
238000011809 primate model Methods 0.000 description 1
210000001948 pro-b lymphocyte Anatomy 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
239000003380 propellant Substances 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
CIEQXUBLKKQRIS-UHFFFAOYSA-N purine-6-carboxylic acid Chemical compound OC(=O)C1=NC=NC2=C1N=CN2 CIEQXUBLKKQRIS-UHFFFAOYSA-N 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003072 pyrazolidinyl group Chemical group 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
125000006513 pyridinyl methyl group Chemical group 0.000 description 1
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
230000004043 responsiveness Effects 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
229940100486 rice starch Drugs 0.000 description 1
HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 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
230000003248 secreting effect Effects 0.000 description 1
230000028327 secretion Effects 0.000 description 1
239000012679 serum free medium Substances 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
230000035939 shock Effects 0.000 description 1
230000019491 signal transduction Effects 0.000 description 1
230000011664 signaling Effects 0.000 description 1
201000000849 skin cancer Diseases 0.000 description 1
239000002002 slurry Substances 0.000 description 1
235000015424 sodium Nutrition 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
239000012439 solid excipient Substances 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
239000007921 spray Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000000758 substrate Substances 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
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000002511 suppository base Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
201000000596 systemic lupus erythematosus Diseases 0.000 description 1
239000003826 tablet Substances 0.000 description 1
229960001967 tacrolimus Drugs 0.000 description 1
QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
230000008685 targeting Effects 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
238000003419 tautomerization reaction Methods 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
IBKSOWUYKOORFF-UHFFFAOYSA-N tert-butyl n-(2-amino-4-fluorophenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(F)C=C1N IBKSOWUYKOORFF-UHFFFAOYSA-N 0.000 description 1
QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
238000005708 tetrahydropyranylation reaction Methods 0.000 description 1
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000006090 thiamorpholinyl sulfone group Chemical group 0.000 description 1
125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1
238000001890 transfection Methods 0.000 description 1
230000009466 transformation Effects 0.000 description 1
230000017105 transposition Effects 0.000 description 1
150000003626 triacylglycerols Chemical class 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
229940029284 trichlorofluoromethane Drugs 0.000 description 1
229940086542 triethylamine Drugs 0.000 description 1
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
235000019798 tripotassium phosphate Nutrition 0.000 description 1
IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
229940100445 wheat starch Drugs 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1
HEOMKTNNZDZMJZ-UHFFFAOYSA-M zinc;benzonitrile;bromide Chemical compound Br[Zn+].N#CC1=CC=[C-]C=C1 HEOMKTNNZDZMJZ-UHFFFAOYSA-M 0.000 description 1
HEHCQTGEYNYOSF-UHFFFAOYSA-M zinc;butanenitrile;bromide Chemical compound Br[Zn+].[CH2-]CCC#N HEHCQTGEYNYOSF-UHFFFAOYSA-M 0.000 description 1
WRSWIWOVJBYZAW-UHFFFAOYSA-M zinc;methanidylbenzene;bromide Chemical compound Br[Zn+].[CH2-]C1=CC=CC=C1 WRSWIWOVJBYZAW-UHFFFAOYSA-M 0.000 description 1