JP2009510152A - Ａ２ｂアデノシン受容体アンタゴニストとしての、イミダゾピリジン誘導体 - Google Patents

Info

Publication number

JP2009510152A

JP2009510152A JP2008533934A JP2008533934A JP2009510152A JP 2009510152 A JP2009510152 A JP 2009510152A JP 2008533934 A JP2008533934 A JP 2008533934A JP 2008533934 A JP2008533934 A JP 2008533934A JP 2009510152 A JP2009510152 A JP 2009510152A

Authority

JP

Japan

Prior art keywords

pyridin

imidazo

pyridine

fluoropyridin

mmol

Prior art date

2005-10-06

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Pending

Links

• Espacenet
• Global Dossier
• Discuss

• 125000004857 imidazopyridinyl group Chemical class N1C(=NC2=C1C=CC=N2)* 0.000 title abstract 2
• 101150078577 Adora2b gene Proteins 0.000 title description 2
• 229940121359 adenosine receptor antagonist Drugs 0.000 title 1
• 239000000296 purinergic P1 receptor antagonist Substances 0.000 title 1
• 102000009346 Adenosine receptors Human genes 0.000 claims abstract description 13
• 108050000203 Adenosine receptors Proteins 0.000 claims abstract description 13
• 150000001875 compounds Chemical class 0.000 claims description 133
• -1 piperidinylmethyl Chemical group 0.000 claims description 105
• 238000000034 method Methods 0.000 claims description 73
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 41
• 125000000217 alkyl group Chemical group 0.000 claims description 29
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 22
• 125000001424 substituent group Chemical group 0.000 claims description 22
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
• 125000005843 halogen group Chemical group 0.000 claims description 21
• 238000011282 treatment Methods 0.000 claims description 20
• 125000003545 alkoxy group Chemical group 0.000 claims description 18
• 125000003118 aryl group Chemical group 0.000 claims description 16
• 201000010099 disease Diseases 0.000 claims description 15
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
• 125000001072 heteroaryl group Chemical group 0.000 claims description 13
• 239000005557 antagonist Substances 0.000 claims description 12
• 125000000623 heterocyclic group Chemical group 0.000 claims description 12
• 150000003839 salts Chemical class 0.000 claims description 12
• 125000003282 alkyl amino group Chemical group 0.000 claims description 11
• 125000004414 alkyl thio group Chemical group 0.000 claims description 11
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 10
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 10
• 230000001668 ameliorated effect Effects 0.000 claims description 8
• 230000008485 antagonism Effects 0.000 claims description 8
• 229940043355 kinase inhibitor Drugs 0.000 claims description 8
• 238000004519 manufacturing process Methods 0.000 claims description 8
• 239000003757 phosphotransferase inhibitor Substances 0.000 claims description 8
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
• WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 6
• 208000006673 asthma Diseases 0.000 claims description 6
• 125000002887 hydroxy group Chemical group [H]O* 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
• 125000004076 pyridyl group Chemical group 0.000 claims description 6
• 201000001320 Atherosclerosis Diseases 0.000 claims description 5
• 239000005711 Benzoic acid Substances 0.000 claims description 5
• 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 5
• 206010020772 Hypertension Diseases 0.000 claims description 5
• 206010061218 Inflammation Diseases 0.000 claims description 5
• 206010063837 Reperfusion injury Diseases 0.000 claims description 5
• 208000017442 Retinal disease Diseases 0.000 claims description 5
• 206010038923 Retinopathy Diseases 0.000 claims description 5
• 229960005305 adenosine Drugs 0.000 claims description 5
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
• 206010012601 diabetes mellitus Diseases 0.000 claims description 5
• 208000035475 disorder Diseases 0.000 claims description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
• 230000004054 inflammatory process Effects 0.000 claims description 5
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
• ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 claims description 4
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
• 208000026935 allergic disease Diseases 0.000 claims description 4
• 235000010233 benzoic acid Nutrition 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 4
• 208000031225 myocardial ischemia Diseases 0.000 claims description 4
• 125000004193 piperazinyl group Chemical group 0.000 claims description 4
• 102000005962 receptors Human genes 0.000 claims description 4
• 108020003175 receptors Proteins 0.000 claims description 4
• CMGXDPCRFRFEQJ-UHFFFAOYSA-N 2-(2,3-dihydro-1,4-benzodioxin-6-yl)-6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(C=1C=C3OCCOC3=CC=1)=N2 CMGXDPCRFRFEQJ-UHFFFAOYSA-N 0.000 claims description 3
• LOUMZSUMBGYUSB-UHFFFAOYSA-N 2-(2,4-dichloro-5-fluorophenyl)-6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound C1=C(Cl)C(F)=CC(C=2NC3=NC(=C(C=4C(=CN=CC=4)F)C=C3N=2)C=2C=NC=CC=2)=C1Cl LOUMZSUMBGYUSB-UHFFFAOYSA-N 0.000 claims description 3
• WELTYXZXXJRVNV-UHFFFAOYSA-N 2-(4-tert-butylphenyl)-6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=NC2=CC(C=3C(=CN=CC=3)F)=C(C=3C=NC=CC=3)N=C2N1 WELTYXZXXJRVNV-UHFFFAOYSA-N 0.000 claims description 3
• LGHGHJRAFKVZEZ-UHFFFAOYSA-N 4-[6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridin-2-yl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=NC2=CC(C=3C(=CN=CC=3)F)=C(C=3C=NC=CC=3)N=C2N1 LGHGHJRAFKVZEZ-UHFFFAOYSA-N 0.000 claims description 3
• CUEWSJXBADPEGT-UHFFFAOYSA-N 4-[6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridin-2-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=NC2=CC(C=3C(=CN=CC=3)F)=C(C=3C=NC=CC=3)N=C2N1 CUEWSJXBADPEGT-UHFFFAOYSA-N 0.000 claims description 3
• KBPBAPCTVKVIKQ-UHFFFAOYSA-N 5-(1,3-oxazol-5-yl)-6-pyridin-4-yl-1,3-dihydroimidazo[4,5-b]pyridin-2-one Chemical compound C=1N=COC=1C=1N=C2NC(=O)NC2=CC=1C1=CC=NC=C1 KBPBAPCTVKVIKQ-UHFFFAOYSA-N 0.000 claims description 3
• JVJZXCPOFNLDOW-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-2-[3-fluoro-4-(trifluoromethyl)phenyl]-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(C=1C=C(F)C(=CC=1)C(F)(F)F)=N2 JVJZXCPOFNLDOW-UHFFFAOYSA-N 0.000 claims description 3
• 206010006482 Bronchospasm Diseases 0.000 claims description 3
• 108010008212 Integrin alpha4beta1 Proteins 0.000 claims description 3
• 229940121948 Muscarinic receptor antagonist Drugs 0.000 claims description 3
• 150000001204 N-oxides Chemical class 0.000 claims description 3
• 108010040718 Neurokinin-1 Receptors Proteins 0.000 claims description 3
• 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 claims description 3
• 102100037346 Substance-P receptor Human genes 0.000 claims description 3
• 102000000551 Syk Kinase Human genes 0.000 claims description 3
• 108010016672 Syk Kinase Proteins 0.000 claims description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
• 229940124748 beta 2 agonist Drugs 0.000 claims description 3
• 230000007885 bronchoconstriction Effects 0.000 claims description 3
• 239000003814 drug Substances 0.000 claims description 3
• 239000003149 muscarinic antagonist Substances 0.000 claims description 3
• 125000002971 oxazolyl group Chemical group 0.000 claims description 3
• 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims description 3
• 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims description 3
• 229940044601 receptor agonist Drugs 0.000 claims description 3
• 239000000018 receptor agonist Substances 0.000 claims description 3
• HAODEOLEIIJMMV-UHFFFAOYSA-N (3,5-difluorophenyl)-[6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridin-2-yl]methanone Chemical compound FC1=CC(F)=CC(C(=O)C=2NC3=NC(=C(C=4C(=CN=CC=4)F)C=C3N=2)C=2C=NC=CC=2)=C1 HAODEOLEIIJMMV-UHFFFAOYSA-N 0.000 claims description 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
• UIIMBCQUZAGZOW-UHFFFAOYSA-N 2-cyclohexyl-6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1H-imidazo[4,5-b]pyridine 6-(3-fluoropyridin-4-yl)-2-methyl-5-pyridin-3-yl-1H-imidazo[4,5-b]pyridine Chemical compound FC=1C=NC=CC1C=1C=C2C(=NC1C=1C=NC=CC1)NC(=N2)C.C2(CCCCC2)C2=NC=1C(=NC(=C(C1)C1=C(C=NC=C1)F)C=1C=NC=CC1)N2 UIIMBCQUZAGZOW-UHFFFAOYSA-N 0.000 claims description 2
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• DANLZOIRUUHIIX-UHFFFAOYSA-N 4-[1-[2-chloro-6-(trifluoromethyl)benzoyl]indazol-3-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C(C1=CC=CC=C11)=NN1C(=O)C1=C(Cl)C=CC=C1C(F)(F)F DANLZOIRUUHIIX-UHFFFAOYSA-N 0.000 claims description 2
• CREHNQNSIKXYDP-UHFFFAOYSA-N 4-[2-[6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridin-2-yl]ethyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1CCC1=NC2=CC(C=3C(=CN=CC=3)F)=C(C=3C=NC=CC=3)N=C2N1 CREHNQNSIKXYDP-UHFFFAOYSA-N 0.000 claims description 2
• 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 2
• DOKIWYXXGULGJJ-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-2-(1H-1,2,4-triazol-5-yl)-1H-imidazo[4,5-b]pyridine Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(C=1NC=NN=1)=N2 DOKIWYXXGULGJJ-UHFFFAOYSA-N 0.000 claims description 2
• STRHNGYZIUTJMX-UHFFFAOYSA-N C1(CC1)C1=NC=2C(=NC(=C(C2)C2=C(C=NC=C2)F)C=2C=NC=CC2)N1.FC=1C=NC=CC1C=1C=C2C(=NC1C=1C=NC=CC1)NC(N2)=O Chemical compound C1(CC1)C1=NC=2C(=NC(=C(C2)C2=C(C=NC=C2)F)C=2C=NC=CC2)N1.FC=1C=NC=CC1C=1C=C2C(=NC1C=1C=NC=CC1)NC(N2)=O STRHNGYZIUTJMX-UHFFFAOYSA-N 0.000 claims description 2
• JVKAVADTDJHXOH-UHFFFAOYSA-N ClC=1C=NC=CC1C=1C=C2C(=NC1C1=CC=NC=C1)NC(=N2)C2=CC=C(C=C2)F.ClC=2C=NC=CC2C=2C=C1C(=NC2C2=CC=NC=C2)NC(N1)=O Chemical compound ClC=1C=NC=CC1C=1C=C2C(=NC1C1=CC=NC=C1)NC(=N2)C2=CC=C(C=C2)F.ClC=2C=NC=CC2C=2C=C1C(=NC2C2=CC=NC=C2)NC(N1)=O JVKAVADTDJHXOH-UHFFFAOYSA-N 0.000 claims description 2
• CVNUXUZZJHKKJZ-UHFFFAOYSA-N FC=1C=NC=CC1C=1C=C2C(=NC1C=1C=NC=CC1)NC(=N2)C2=CC=C(C=C2)OC.FC2=CC=C(C=C2)C2=NC=1C(=NC(=C(C1)C1=C(C=NC=C1)F)C=1C=NC=CC1)N2 Chemical compound FC=1C=NC=CC1C=1C=C2C(=NC1C=1C=NC=CC1)NC(=N2)C2=CC=C(C=C2)OC.FC2=CC=C(C=C2)C2=NC=1C(=NC(=C(C1)C1=C(C=NC=C1)F)C=1C=NC=CC1)N2 CVNUXUZZJHKKJZ-UHFFFAOYSA-N 0.000 claims description 2
• HNBMFBBYJKQYDH-UHFFFAOYSA-N FC=1C=NC=CC1C=1C=C2C(=NC1C=1OC=CN1)NC=N2.FC=2C=NC=CC2C=2C=C1C(=NC2C=2OC=CN2)NC(N1)=O Chemical compound FC=1C=NC=CC1C=1C=C2C(=NC1C=1OC=CN1)NC=N2.FC=2C=NC=CC2C=2C=C1C(=NC2C=2OC=CN2)NC(N1)=O HNBMFBBYJKQYDH-UHFFFAOYSA-N 0.000 claims description 2
• 241001465754 Metazoa Species 0.000 claims description 2
• 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
• WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 claims description 2
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
• 230000005784 autoimmunity Effects 0.000 claims 2
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 2
• 230000004663 cell proliferation Effects 0.000 claims 2
• 210000001035 gastrointestinal tract Anatomy 0.000 claims 2
• NDZYPHLNJZSQJY-QNWVGRARSA-N 1-(5-acetyl-4-methyl-1,3-thiazol-2-yl)-3-[(1r,2s)-2-[[(3s)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]cyclohexyl]urea Chemical compound CC1=C(C(=O)C)SC(NC(=O)N[C@H]2[C@@H](CCCC2)CN2C[C@H](CC=3C=CC(F)=CC=3)CCC2)=N1 NDZYPHLNJZSQJY-QNWVGRARSA-N 0.000 claims 1
• 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 claims 1
• QNRWWMIRCJNAGS-UHFFFAOYSA-N 4-[[6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridin-2-yl]amino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC1=NC2=CC(C=3C(=CN=CC=3)F)=C(C=3C=NC=CC=3)N=C2N1 QNRWWMIRCJNAGS-UHFFFAOYSA-N 0.000 claims 1
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
• 229940124003 CRTH2 antagonist Drugs 0.000 claims 1
• SJFCINHHOUMMBA-UHFFFAOYSA-N ClC=1C=NC=CC1C1=NC=2C(=NC(=C(C2)C2=C(C=NC=C2)F)C=2C=NC=CC2)N1.FC=1C=NC=CC1C=1C=C2C(=NC1C=1C=NC=CC1)NC(=N2)C2=NC=CC=C2 Chemical compound ClC=1C=NC=CC1C1=NC=2C(=NC(=C(C2)C2=C(C=NC=C2)F)C=2C=NC=CC2)N1.FC=1C=NC=CC1C=1C=C2C(=NC1C=1C=NC=CC1)NC(=N2)C2=NC=CC=C2 SJFCINHHOUMMBA-UHFFFAOYSA-N 0.000 claims 1
• 239000013066 combination product Substances 0.000 claims 1
• 229940127555 combination product Drugs 0.000 claims 1
• 229940121647 egfr inhibitor Drugs 0.000 claims 1
• 239000003199 leukotriene receptor blocking agent Substances 0.000 claims 1
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
• 230000001575 pathological effect Effects 0.000 claims 1
• 239000000126 substance Substances 0.000 abstract description 2
• 239000000543 intermediate Substances 0.000 description 107
• 239000000203 mixture Substances 0.000 description 96
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 91
• YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 80
• 238000005160 1H NMR spectroscopy Methods 0.000 description 75
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 58
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 57
• 239000000243 solution Substances 0.000 description 57
• 239000007787 solid Substances 0.000 description 47
• 239000002904 solvent Substances 0.000 description 43
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
• PKIONYPNYKRWAC-UHFFFAOYSA-N 5-(3-fluoropyridin-4-yl)-6-pyridin-3-ylpyridine-2,3-diamine Chemical compound C=1C=CN=CC=1C=1N=C(N)C(N)=CC=1C1=CC=NC=C1F PKIONYPNYKRWAC-UHFFFAOYSA-N 0.000 description 32
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 28
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 28
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 25
• 238000003818 flash chromatography Methods 0.000 description 25
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
• 229910052757 nitrogen Inorganic materials 0.000 description 18
• 239000012044 organic layer Substances 0.000 description 17
• 239000000741 silica gel Substances 0.000 description 17
• 229910002027 silica gel Inorganic materials 0.000 description 17
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
• QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
• 229910052786 argon Inorganic materials 0.000 description 14
• 239000000460 chlorine Substances 0.000 description 14
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
• 238000002360 preparation method Methods 0.000 description 14
• 239000000725 suspension Substances 0.000 description 13
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
• 239000002253 acid Substances 0.000 description 12
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 10
• 229960000583 acetic acid Drugs 0.000 description 10
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• 235000011054 acetic acid Nutrition 0.000 description 9
• 239000002585 base Substances 0.000 description 9
• 238000006243 chemical reaction Methods 0.000 description 9
• 150000005232 imidazopyridines Chemical class 0.000 description 9
• 238000000746 purification Methods 0.000 description 9
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
• 239000004480 active ingredient Substances 0.000 description 8
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.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 8
• 239000000843 powder Substances 0.000 description 8
• CAAMSDWKXXPUJR-UHFFFAOYSA-N 3,5-dihydro-4H-imidazol-4-one Chemical compound O=C1CNC=N1 CAAMSDWKXXPUJR-UHFFFAOYSA-N 0.000 description 7
• 238000005481 NMR spectroscopy Methods 0.000 description 7
• 239000007864 aqueous solution Substances 0.000 description 7
• 239000012267 brine Substances 0.000 description 7
• 239000003921 oil Substances 0.000 description 7
• 239000011541 reaction mixture Substances 0.000 description 7
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
• 235000017557 sodium bicarbonate Nutrition 0.000 description 7
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
• 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 6
• FQFSWKVTOZFBOZ-UHFFFAOYSA-N 6-chloro-5-iodo-3-nitropyridin-2-amine Chemical compound NC1=NC(Cl)=C(I)C=C1[N+]([O-])=O FQFSWKVTOZFBOZ-UHFFFAOYSA-N 0.000 description 6
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• 229910021529 ammonia Inorganic materials 0.000 description 6
• 125000000753 cycloalkyl group Chemical group 0.000 description 6
• 238000009472 formulation Methods 0.000 description 6
• QJPQVXSHYBGQGM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 6
• 239000003826 tablet Substances 0.000 description 6
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 6
• SHCWQWRTKPNTEM-UHFFFAOYSA-N 2,6-dichloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Cl)N=C1Cl SHCWQWRTKPNTEM-UHFFFAOYSA-N 0.000 description 5
• OGFQRMVUODKPBV-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-2-methyl-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound C=1C=CN=CC=1C=1N=C2NC(C)=NC2=CC=1C1=CC=NC=C1F OGFQRMVUODKPBV-UHFFFAOYSA-N 0.000 description 5
• FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 5
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 5
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
• 125000004429 atom Chemical group 0.000 description 5
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 5
• 239000003054 catalyst Substances 0.000 description 5
• 239000003153 chemical reaction reagent Substances 0.000 description 5
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 5
• 239000000706 filtrate Substances 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 239000003880 polar aprotic solvent Substances 0.000 description 5
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 5
• 239000012312 sodium hydride Substances 0.000 description 5
• 229910000104 sodium hydride Inorganic materials 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
• 239000008096 xylene Substances 0.000 description 5
• MBQKVCQJYQZTAF-UHFFFAOYSA-N 2-[6-[(4-methoxyphenyl)methyl]-5-nitropyridin-2-yl]-1,3-oxazole Chemical compound COC1=CC=C(CC2=NC(=CC=C2[N+](=O)[O-])C=2OC=CN=2)C=C1 MBQKVCQJYQZTAF-UHFFFAOYSA-N 0.000 description 4
• KEWFVNBINRNTNV-UHFFFAOYSA-N 6-(1,3-oxazol-2-yl)-5-pyridin-4-ylpyridine-2,3-diamine Chemical compound N=1C=COC=1C=1N=C(N)C(N)=CC=1C1=CC=NC=C1 KEWFVNBINRNTNV-UHFFFAOYSA-N 0.000 description 4
• DRKNTNKZDWPWGD-UHFFFAOYSA-N 6-(1,3-oxazol-5-yl)-5-pyridin-4-ylpyridine-2,3-diamine Chemical compound C=1N=COC=1C=1N=C(N)C(N)=CC=1C1=CC=NC=C1 DRKNTNKZDWPWGD-UHFFFAOYSA-N 0.000 description 4
• WERABQRUGJIMKQ-UHFFFAOYSA-N 6-chloro-3-nitropyridin-2-amine Chemical compound NC1=NC(Cl)=CC=C1[N+]([O-])=O WERABQRUGJIMKQ-UHFFFAOYSA-N 0.000 description 4
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
• 150000001450 anions Chemical class 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 125000004432 carbon atom Chemical group C* 0.000 description 4
• 230000008878 coupling Effects 0.000 description 4
• 238000010168 coupling process Methods 0.000 description 4
• 238000005859 coupling reaction Methods 0.000 description 4
• 238000010438 heat treatment Methods 0.000 description 4
• 229910052739 hydrogen Inorganic materials 0.000 description 4
• 239000001257 hydrogen Substances 0.000 description 4
• 238000005984 hydrogenation reaction Methods 0.000 description 4
• 150000002576 ketones Chemical class 0.000 description 4
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
• 239000003960 organic solvent Substances 0.000 description 4
• 239000000546 pharmaceutical excipient Substances 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• 239000002244 precipitate Substances 0.000 description 4
• KKOFZNIMGWDVQS-UHFFFAOYSA-N tributyl-(3-fluoropyridin-4-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=NC=C1F KKOFZNIMGWDVQS-UHFFFAOYSA-N 0.000 description 4
• GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 4
• QRKNVSIQSMRYLM-UHFFFAOYSA-N 3-nitro-6-[2-tri(propan-2-yl)silyl-1,3-oxazol-5-yl]pyridin-2-amine Chemical compound O1C([Si](C(C)C)(C(C)C)C(C)C)=NC=C1C1=CC=C([N+]([O-])=O)C(N)=N1 QRKNVSIQSMRYLM-UHFFFAOYSA-N 0.000 description 3
• GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 3
• VHEUHISJNADBAE-UHFFFAOYSA-N 5-(3-fluoropyridin-4-yl)-6-pyridin-4-yl-1,3-dihydroimidazo[4,5-b]pyridin-2-one Chemical compound FC1=CN=CC=C1C(C(=C1)C=2C=CN=CC=2)=NC2=C1NC(=O)N2 VHEUHISJNADBAE-UHFFFAOYSA-N 0.000 description 3
• GTSWWZQRFNEHQE-UHFFFAOYSA-N 5-bromo-3-nitro-6-pyridin-3-ylpyridin-2-amine Chemical compound C1=C([N+]([O-])=O)C(N)=NC(C=2C=NC=CC=2)=C1Br GTSWWZQRFNEHQE-UHFFFAOYSA-N 0.000 description 3
• JTOPDADHARSMBZ-UHFFFAOYSA-N 6-(3,5-difluoropyridin-4-yl)-5-pyridin-3-yl-1,3-dihydroimidazo[4,5-b]pyridin-2-one Chemical compound FC1=CN=CC(F)=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(=O)N2 JTOPDADHARSMBZ-UHFFFAOYSA-N 0.000 description 3
• QEFGTGPZSGHXNT-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-2-(2-methylpyrazol-3-yl)-5-pyridin-3-yl-1H-imidazo[4,5-b]pyridine Chemical compound CN1N=CC=C1C1=NC2=CC(C=3C(=CN=CC=3)F)=C(C=3C=NC=CC=3)N=C2N1 QEFGTGPZSGHXNT-UHFFFAOYSA-N 0.000 description 3
• GTAJJJFAEJTSKM-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-2-methylsulfanyl-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound C=1C=CN=CC=1C=1N=C2NC(SC)=NC2=CC=1C1=CC=NC=C1F GTAJJJFAEJTSKM-UHFFFAOYSA-N 0.000 description 3
• JEBZHYRMRJAPRX-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-2-[[3-(trifluoromethyl)phenyl]methyl]-1h-imidazo[4,5-b]pyridine Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(CC=1C=C(C=CC=1)C(F)(F)F)=N2 JEBZHYRMRJAPRX-UHFFFAOYSA-N 0.000 description 3
• NGTFCCQJTBXYKU-UHFFFAOYSA-N 6-chloro-5-(3-chloropyridin-4-yl)-3-nitropyridin-2-amine Chemical compound C1=C([N+]([O-])=O)C(N)=NC(Cl)=C1C1=CC=NC=C1Cl NGTFCCQJTBXYKU-UHFFFAOYSA-N 0.000 description 3
• PDGKYOUTZYEIKA-UHFFFAOYSA-N 6-pyridin-3-yl-5-pyridin-4-ylpyridine-2,3-diamine Chemical compound C=1C=CN=CC=1C=1N=C(N)C(N)=CC=1C1=CC=NC=C1 PDGKYOUTZYEIKA-UHFFFAOYSA-N 0.000 description 3
• 208000023275 Autoimmune disease Diseases 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 3
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 3
• 206010014561 Emphysema Diseases 0.000 description 3
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
• 208000018522 Gastrointestinal disease Diseases 0.000 description 3
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 239000008346 aqueous phase Substances 0.000 description 3
• 239000012298 atmosphere Substances 0.000 description 3
• 230000015572 biosynthetic process Effects 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
• 229910000024 caesium carbonate Inorganic materials 0.000 description 3
• 238000006555 catalytic reaction Methods 0.000 description 3
• 229910052801 chlorine Inorganic materials 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 238000001816 cooling Methods 0.000 description 3
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 3
• 239000012065 filter cake Substances 0.000 description 3
• 239000011737 fluorine Substances 0.000 description 3
• 229910052731 fluorine Inorganic materials 0.000 description 3
• 125000005842 heteroatom Chemical group 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 210000004072 lung Anatomy 0.000 description 3
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
• IIBBZZOMKXQSGL-UHFFFAOYSA-N n-[2-amino-5-(3-fluoropyridin-4-yl)-6-pyridin-3-ylpyridin-3-yl]-3-fluoro-4-methylbenzamide Chemical compound C1=C(F)C(C)=CC=C1C(=O)NC1=CC(C=2C(=CN=CC=2)F)=C(C=2C=NC=CC=2)N=C1N IIBBZZOMKXQSGL-UHFFFAOYSA-N 0.000 description 3
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
• 125000004433 nitrogen atom Chemical group N* 0.000 description 3
• 229910052763 palladium Inorganic materials 0.000 description 3
• 230000002265 prevention Effects 0.000 description 3
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• 208000005069 pulmonary fibrosis Diseases 0.000 description 3
• 150000003335 secondary amines Chemical class 0.000 description 3
• 238000010561 standard procedure Methods 0.000 description 3
• 229910052717 sulfur Inorganic materials 0.000 description 3
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
• TWSMTGCRUGWDPG-UHFFFAOYSA-N tri(propan-2-yl)-(5-tributylstannyl-1,3-oxazol-2-yl)silane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CN=C([Si](C(C)C)(C(C)C)C(C)C)O1 TWSMTGCRUGWDPG-UHFFFAOYSA-N 0.000 description 3
• DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical class CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 3
• SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
• BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
• PBDIANQBYUQMPW-UHFFFAOYSA-N 1,3-oxazol-2-yl-tri(propan-2-yl)silane Chemical compound CC(C)[Si](C(C)C)(C(C)C)C1=NC=CO1 PBDIANQBYUQMPW-UHFFFAOYSA-N 0.000 description 2
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
• CNOMOQJYMHEVNH-UHFFFAOYSA-N 1-[6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridin-2-yl]pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1C1=NC2=CC(C=3C(=CN=CC=3)F)=C(C=3C=NC=CC=3)N=C2N1 CNOMOQJYMHEVNH-UHFFFAOYSA-N 0.000 description 2
• UQDQYSLQDYYJQJ-UHFFFAOYSA-N 2-(3-chloropyridin-4-yl)-6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(C=1C(=CN=CC=1)Cl)=N2 UQDQYSLQDYYJQJ-UHFFFAOYSA-N 0.000 description 2
• MFFAUUIPGAGUIS-UHFFFAOYSA-N 2-(3-fluoro-4-methylphenyl)-6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound C1=C(F)C(C)=CC=C1C1=NC2=CC(C=3C(=CN=CC=3)F)=C(C=3C=NC=CC=3)N=C2N1 MFFAUUIPGAGUIS-UHFFFAOYSA-N 0.000 description 2
• KUWIWMQUBPJPGE-UHFFFAOYSA-N 2-(3-fluorophenyl)-6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1H-imidazo[4,5-b]pyridine 6-(3-fluoropyridin-4-yl)-2,5-dipyridin-3-yl-1H-imidazo[4,5-b]pyridine Chemical compound FC=1C=NC=CC1C=1C=C2C(=NC1C=1C=NC=CC1)NC(=N2)C=2C=NC=CC2.FC=2C=C(C=CC2)C2=NC=1C(=NC(=C(C1)C1=C(C=NC=C1)F)C=1C=NC=CC1)N2 KUWIWMQUBPJPGE-UHFFFAOYSA-N 0.000 description 2
• JMNOPWJKGOGKSU-UHFFFAOYSA-N 2-[2-(4-chlorophenyl)propan-2-yl]-6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound C=1C=C(Cl)C=CC=1C(C)(C)C(NC1=NC=2C=3C=NC=CC=3)=NC1=CC=2C1=CC=NC=C1F JMNOPWJKGOGKSU-UHFFFAOYSA-N 0.000 description 2
• VITIPDJPNDEVKC-UHFFFAOYSA-N 2-[4-(3-fluoropyridin-4-yl)-6-[(4-methoxyphenyl)methyl]-5-nitropyridin-2-yl]-1,3-oxazole Chemical compound COC1=CC=C(CC2=NC(=CC(=C2[N+](=O)[O-])C2=C(C=NC=C2)F)C=2OC=CN=2)C=C1 VITIPDJPNDEVKC-UHFFFAOYSA-N 0.000 description 2
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
• JAUPUQRPBNDMDT-UHFFFAOYSA-N 2-chloropyridine-3-carbonitrile Chemical compound ClC1=NC=CC=C1C#N JAUPUQRPBNDMDT-UHFFFAOYSA-N 0.000 description 2
• IERSHQMSCGIMDP-UHFFFAOYSA-N 2-cyclohexyl-6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(C1CCCCC1)=N2 IERSHQMSCGIMDP-UHFFFAOYSA-N 0.000 description 2
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
• FWGNKHXOVCSOLW-UHFFFAOYSA-N 3-[6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridin-2-yl]benzonitrile Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(C=1C=C(C=CC=1)C#N)=N2 FWGNKHXOVCSOLW-UHFFFAOYSA-N 0.000 description 2
• VUWRRLUCWJCPMF-UHFFFAOYSA-N 3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=NC=C1Cl VUWRRLUCWJCPMF-UHFFFAOYSA-N 0.000 description 2
• DPWCZSXNEGNALT-UHFFFAOYSA-N 3-fluoro-4-methylbenzoyl chloride Chemical compound CC1=CC=C(C(Cl)=O)C=C1F DPWCZSXNEGNALT-UHFFFAOYSA-N 0.000 description 2
• JOICQOFBBBNORI-UHFFFAOYSA-N 3-nitro-6-pyridin-3-ylpyridin-2-amine Chemical compound C1=C([N+]([O-])=O)C(N)=NC(C=2C=NC=CC=2)=C1 JOICQOFBBBNORI-UHFFFAOYSA-N 0.000 description 2
• NJGZLFGSYMUZSO-UHFFFAOYSA-N 3-nitro-6-pyridin-4-ylpyridin-2-amine Chemical compound C1=C([N+]([O-])=O)C(N)=NC(C=2C=CN=CC=2)=C1 NJGZLFGSYMUZSO-UHFFFAOYSA-N 0.000 description 2
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
• CZKLEJHVLCMVQR-UHFFFAOYSA-N 4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1 CZKLEJHVLCMVQR-UHFFFAOYSA-N 0.000 description 2
• KMTNDFDXRGTICM-UHFFFAOYSA-N 5,6-dipyridin-4-ylpyridine-2,3-diamine Chemical compound C=1C=NC=CC=1C=1N=C(N)C(N)=CC=1C1=CC=NC=C1 KMTNDFDXRGTICM-UHFFFAOYSA-N 0.000 description 2
• OQDDFWYRYQUDKX-UHFFFAOYSA-N 5-(3,5-difluoropyridin-4-yl)-6-pyridin-3-ylpyridine-2,3-diamine Chemical compound N1=C(N)C(N)=CC(C=2C(=CN=CC=2F)F)=C1C1=CC=CN=C1 OQDDFWYRYQUDKX-UHFFFAOYSA-N 0.000 description 2
• RTCDVNXVIOODPN-UHFFFAOYSA-N 5-(3-chloropyridin-4-yl)-6-pyridin-3-ylpyridine-2,3-diamine Chemical compound C=1C=CN=CC=1C=1N=C(N)C(N)=CC=1C1=CC=NC=C1Cl RTCDVNXVIOODPN-UHFFFAOYSA-N 0.000 description 2
• DYIPPQWXLGIVRC-UHFFFAOYSA-N 5-(3-fluoropyridin-4-yl)-6-(1,3-oxazol-2-yl)pyridine-2,3-diamine Chemical compound N=1C=COC=1C=1N=C(N)C(N)=CC=1C1=CC=NC=C1F DYIPPQWXLGIVRC-UHFFFAOYSA-N 0.000 description 2
• WMVFCWBYEALFGT-UHFFFAOYSA-N 5-(3-fluoropyridin-4-yl)-6-(1,3-oxazol-5-yl)pyridine-2,3-diamine Chemical compound C=1N=COC=1C=1N=C(N)C(N)=CC=1C1=CC=NC=C1F WMVFCWBYEALFGT-UHFFFAOYSA-N 0.000 description 2
• YLDZZXKJGXMJHQ-UHFFFAOYSA-N 5-bromo-3-nitro-6-[2-tri(propan-2-yl)silyl-1,3-oxazol-5-yl]pyridin-2-amine Chemical compound O1C([Si](C(C)C)(C(C)C)C(C)C)=NC=C1C1=NC(N)=C([N+]([O-])=O)C=C1Br YLDZZXKJGXMJHQ-UHFFFAOYSA-N 0.000 description 2
• JDDVEBLZYLTZDF-UHFFFAOYSA-N 5-bromo-3-nitro-6-pyridin-4-ylpyridin-2-amine Chemical compound C1=C([N+]([O-])=O)C(N)=NC(C=2C=CN=CC=2)=C1Br JDDVEBLZYLTZDF-UHFFFAOYSA-N 0.000 description 2
• MLCVDABCSJGNKW-UHFFFAOYSA-N 5-bromo-6-(3-chloropyridin-4-yl)-3-nitropyridin-2-amine Chemical compound C1=C([N+]([O-])=O)C(N)=NC(C=2C(=CN=CC=2)Cl)=C1Br MLCVDABCSJGNKW-UHFFFAOYSA-N 0.000 description 2
• AUHKQACTCSTFNA-UHFFFAOYSA-N 6-(3-chloropyridin-4-yl)-2-(4-fluorophenyl)-5-pyridin-4-yl-1h-imidazo[4,5-b]pyridine Chemical compound C1=CC(F)=CC=C1C1=NC2=CC(C=3C(=CN=CC=3)Cl)=C(C=3C=CN=CC=3)N=C2N1 AUHKQACTCSTFNA-UHFFFAOYSA-N 0.000 description 2
• JEWJMFUPZRVWIT-UHFFFAOYSA-N 6-(3-chloropyridin-4-yl)-5-(3-fluoropyridin-4-yl)pyridine-2,3-diamine Chemical compound C=1C=NC=C(Cl)C=1C=1N=C(N)C(N)=CC=1C1=CC=NC=C1F JEWJMFUPZRVWIT-UHFFFAOYSA-N 0.000 description 2
• MMAZBBTVGGVGIM-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-2-(4-methoxyphenyl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound C1=CC(OC)=CC=C1C1=NC2=CC(C=3C(=CN=CC=3)F)=C(C=3C=NC=CC=3)N=C2N1 MMAZBBTVGGVGIM-UHFFFAOYSA-N 0.000 description 2
• YJJBVCAWJOZRLC-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-2-[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]-5-pyridin-3-yl-1H-imidazo[4,5-b]pyridine Chemical compound CN1N=C(C(F)(F)F)C=C1C1=NC2=CC(C=3C(=CN=CC=3)F)=C(C=3C=NC=CC=3)N=C2N1 YJJBVCAWJOZRLC-UHFFFAOYSA-N 0.000 description 2
• PFFDJFBNBGBJBF-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-2-piperidin-1-yl-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(N1CCCCC1)=N2 PFFDJFBNBGBJBF-UHFFFAOYSA-N 0.000 description 2
• OVVBXVJFGCFEFK-UHFFFAOYSA-N 6-chloro-2-methoxy-3-nitropyridine Chemical compound COC1=NC(Cl)=CC=C1[N+]([O-])=O OVVBXVJFGCFEFK-UHFFFAOYSA-N 0.000 description 2
• HRVAXMNSTZAUIX-UHFFFAOYSA-N 6-chloro-3-nitro-5-pyridin-4-ylpyridin-2-amine Chemical compound C1=C([N+]([O-])=O)C(N)=NC(Cl)=C1C1=CC=NC=C1 HRVAXMNSTZAUIX-UHFFFAOYSA-N 0.000 description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 102100024167 C-C chemokine receptor type 3 Human genes 0.000 description 2
• 101710149862 C-C chemokine receptor type 3 Proteins 0.000 description 2
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
• 108060006698 EGF receptor Proteins 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
• 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 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
• YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 150000001350 alkyl halides Chemical class 0.000 description 2
• 150000001543 aryl boronic acids Chemical class 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
• 150000001642 boronic acid derivatives Chemical class 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 125000002837 carbocyclic group Chemical group 0.000 description 2
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
• 210000004027 cell Anatomy 0.000 description 2
• 239000003795 chemical substances by application Substances 0.000 description 2
• 230000002860 competitive effect Effects 0.000 description 2
• 238000006880 cross-coupling reaction Methods 0.000 description 2
• 239000010779 crude oil Substances 0.000 description 2
• RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 2
• 150000004985 diamines Chemical class 0.000 description 2
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
• KACZQOKEFKFNDB-UHFFFAOYSA-N ethyl 1h-pyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NNC=1 KACZQOKEFKFNDB-UHFFFAOYSA-N 0.000 description 2
• QZLDTUQTWFVMQT-UHFFFAOYSA-N ethyl 4-[[6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridin-2-yl]amino]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1NC1=NC2=CC(C=3C(=CN=CC=3)F)=C(C=3C=NC=CC=3)N=C2N1 QZLDTUQTWFVMQT-UHFFFAOYSA-N 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 235000013355 food flavoring agent Nutrition 0.000 description 2
• 235000019253 formic acid Nutrition 0.000 description 2
• 125000002541 furyl group Chemical group 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 230000026030 halogenation Effects 0.000 description 2
• 238000005658 halogenation reaction Methods 0.000 description 2
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
• 230000002757 inflammatory effect Effects 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• 229910052742 iron Inorganic materials 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
• 239000012528 membrane Substances 0.000 description 2
• LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 2
• OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 2
• ZQYYXKXTXVOABI-UHFFFAOYSA-N methyl 4-[6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridin-2-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=NC2=CC(C=3C(=CN=CC=3)F)=C(C=3C=NC=CC=3)N=C2N1 ZQYYXKXTXVOABI-UHFFFAOYSA-N 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 125000002950 monocyclic group Chemical group 0.000 description 2
• 125000002757 morpholinyl group Chemical group 0.000 description 2
• IBLFTIBUHMOLGB-UHFFFAOYSA-N n-(4-chlorophenyl)-6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridin-2-amine Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(NC=1C=CC(Cl)=CC=1)=N2 IBLFTIBUHMOLGB-UHFFFAOYSA-N 0.000 description 2
• PJOCPQDBUXNSMR-UHFFFAOYSA-N n-[2-amino-5-(3-fluoropyridin-4-yl)-6-pyridin-3-ylpyridin-3-yl]-1h-1,2,4-triazole-5-carboxamide Chemical compound C=1C=NC=C(F)C=1C=1C=C(NC(=O)C=2NN=CN=2)C(N)=NC=1C1=CC=CN=C1 PJOCPQDBUXNSMR-UHFFFAOYSA-N 0.000 description 2
• YQYCMVYDBYCKHT-UHFFFAOYSA-N n-[2-amino-5-(3-fluoropyridin-4-yl)-6-pyridin-3-ylpyridin-3-yl]-3-methylimidazole-4-carboxamide Chemical compound CN1C=NC=C1C(=O)NC1=CC(C=2C(=CN=CC=2)F)=C(C=2C=NC=CC=2)N=C1N YQYCMVYDBYCKHT-UHFFFAOYSA-N 0.000 description 2
• BPHJYRHGVLFLBZ-UHFFFAOYSA-N n-[2-amino-5-(3-fluoropyridin-4-yl)-6-pyridin-3-ylpyridin-3-yl]-4-methoxybenzamide Chemical compound C1=CC(OC)=CC=C1C(=O)NC1=CC(C=2C(=CN=CC=2)F)=C(C=2C=NC=CC=2)N=C1N BPHJYRHGVLFLBZ-UHFFFAOYSA-N 0.000 description 2
• KJOSBIGXFYDLES-UHFFFAOYSA-N n-[2-amino-5-(3-fluoropyridin-4-yl)-6-pyridin-3-ylpyridin-3-yl]cyclopropanecarboxamide Chemical compound C=1C=NC=C(F)C=1C=1C=C(NC(=O)C2CC2)C(N)=NC=1C1=CC=CN=C1 KJOSBIGXFYDLES-UHFFFAOYSA-N 0.000 description 2
• ZGPGSZYDPXMZPY-UHFFFAOYSA-N n-[2-amino-5-(3-fluoropyridin-4-yl)-6-pyridin-3-ylpyridin-3-yl]pyrazine-2-carboxamide Chemical compound C=1C=NC=C(F)C=1C=1C=C(NC(=O)C=2N=CC=NC=2)C(N)=NC=1C1=CC=CN=C1 ZGPGSZYDPXMZPY-UHFFFAOYSA-N 0.000 description 2
• XQPQZOASAKBLDA-UHFFFAOYSA-N n-[2-amino-5-(3-fluoropyridin-4-yl)-6-pyridin-3-ylpyridin-3-yl]pyrimidine-5-carboxamide Chemical compound C=1C=NC=C(F)C=1C=1C=C(NC(=O)C=2C=NC=NC=2)C(N)=NC=1C1=CC=CN=C1 XQPQZOASAKBLDA-UHFFFAOYSA-N 0.000 description 2
• 229910017604 nitric acid Inorganic materials 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
• 239000007800 oxidant agent Substances 0.000 description 2
• 229910052760 oxygen Inorganic materials 0.000 description 2
• 239000012071 phase Substances 0.000 description 2
• 125000005936 piperidyl group Chemical group 0.000 description 2
• 229910000027 potassium carbonate Inorganic materials 0.000 description 2
• 125000003226 pyrazolyl group Chemical group 0.000 description 2
• 125000002098 pyridazinyl group Chemical group 0.000 description 2
• 125000000168 pyrrolyl group Chemical group 0.000 description 2
• 238000003653 radioligand binding assay Methods 0.000 description 2
• 230000008707 rearrangement Effects 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 239000011347 resin Substances 0.000 description 2
• 229920005989 resin Polymers 0.000 description 2
• 208000023504 respiratory system disease Diseases 0.000 description 2
• 238000007363 ring formation reaction Methods 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 239000007921 spray Substances 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 125000001544 thienyl group Chemical group 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• YOWGRWHKDCHINP-UHFFFAOYSA-N tributyl(1,3-oxazol-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=NC=CO1 YOWGRWHKDCHINP-UHFFFAOYSA-N 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• 239000003643 water by type Substances 0.000 description 2
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-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
• 125000005918 1,2-dimethylbutyl group Chemical group 0.000 description 1
• HBKPDEWGANZHJO-UHFFFAOYSA-N 1-(4-methoxyphenyl)-n-[(4-methoxyphenyl)methyl]methanamine Chemical compound C1=CC(OC)=CC=C1CNCC1=CC=C(OC)C=C1 HBKPDEWGANZHJO-UHFFFAOYSA-N 0.000 description 1
• IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 1
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
• 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
• LJVQHXICFCZRJN-UHFFFAOYSA-N 1h-1,2,4-triazole-5-carboxylic acid Chemical compound OC(=O)C1=NC=NN1 LJVQHXICFCZRJN-UHFFFAOYSA-N 0.000 description 1
• UUVNGFJBAZPFSQ-UHFFFAOYSA-N 2,3-dichloro-5-fluorobenzoyl chloride Chemical compound FC1=CC(Cl)=C(Cl)C(C(Cl)=O)=C1 UUVNGFJBAZPFSQ-UHFFFAOYSA-N 0.000 description 1
• QECXDXFCJKMZLA-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-6-carbonyl chloride Chemical compound O1CCOC2=CC(C(=O)Cl)=CC=C21 QECXDXFCJKMZLA-UHFFFAOYSA-N 0.000 description 1
• DNBIDYXUQOSGDT-UHFFFAOYSA-N 2-(2-chlorophenyl)propanoic acid Chemical compound OC(=O)C(C)C1=CC=CC=C1Cl DNBIDYXUQOSGDT-UHFFFAOYSA-N 0.000 description 1
• LQIUQSPMXZDVKL-UHFFFAOYSA-N 2-(3-fluorophenyl)-6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound FC1=CC=CC(C=2NC3=NC(=C(C=4C(=CN=CC=4)F)C=C3N=2)C=2C=NC=CC=2)=C1 LQIUQSPMXZDVKL-UHFFFAOYSA-N 0.000 description 1
• ULGMSDJMITWSEY-UHFFFAOYSA-N 2-(4-fluorophenyl)-5-pyridin-3-yl-6-pyridin-4-yl-1h-imidazo[4,5-b]pyridine Chemical compound C1=CC(F)=CC=C1C1=NC2=CC(C=3C=CN=CC=3)=C(C=3C=NC=CC=3)N=C2N1 ULGMSDJMITWSEY-UHFFFAOYSA-N 0.000 description 1
• KAZUSWOHYPVEKM-UHFFFAOYSA-N 2-(4-fluorophenyl)-6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound C1=CC(F)=CC=C1C1=NC2=CC(C=3C(=CN=CC=3)F)=C(C=3C=NC=CC=3)N=C2N1 KAZUSWOHYPVEKM-UHFFFAOYSA-N 0.000 description 1
• SIOJFYRPBYGHOO-UHFFFAOYSA-N 2-(4-fluorophenyl)acetyl chloride Chemical compound FC1=CC=C(CC(Cl)=O)C=C1 SIOJFYRPBYGHOO-UHFFFAOYSA-N 0.000 description 1
• AZWKGGUSNXWIBG-UHFFFAOYSA-N 2-(6-methoxy-5-nitropyridin-2-yl)-1,3-oxazole Chemical compound C1=C([N+]([O-])=O)C(OC)=NC(C=2OC=CN=2)=C1 AZWKGGUSNXWIBG-UHFFFAOYSA-N 0.000 description 1
• PCSZTOZNVAACFY-UHFFFAOYSA-N 2-(6-pyridin-4-yl-1h-imidazo[4,5-b]pyridin-5-yl)-1,3-oxazole Chemical compound C1=COC(C=2C(=CC=3N=CNC=3N=2)C=2C=CN=CC=2)=N1 PCSZTOZNVAACFY-UHFFFAOYSA-N 0.000 description 1
• NEKLJQZEHUUVND-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound C1=CC(F)=CC=C1CC1=NC2=CC(C=3C(=CN=CC=3)F)=C(C=3C=NC=CC=3)N=C2N1 NEKLJQZEHUUVND-UHFFFAOYSA-N 0.000 description 1
• CEEBIXJLOBIHFK-UHFFFAOYSA-N 2-[1-(4-chlorophenyl)ethyl]-6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound C=1C=C(Cl)C=CC=1C(C)C(NC1=NC=2C=3C=NC=CC=3)=NC1=CC=2C1=CC=NC=C1F CEEBIXJLOBIHFK-UHFFFAOYSA-N 0.000 description 1
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
• FEVJJJQOPGZSIG-UHFFFAOYSA-N 2-[3-(trifluoromethyl)phenyl]acetyl chloride Chemical compound FC(F)(F)C1=CC=CC(CC(Cl)=O)=C1 FEVJJJQOPGZSIG-UHFFFAOYSA-N 0.000 description 1
• OPJFOSDWIWFYRW-UHFFFAOYSA-N 2-[6-(3-fluoropyridin-4-yl)-1h-imidazo[4,5-b]pyridin-5-yl]-1,3-oxazole Chemical compound FC1=CN=CC=C1C(C(=N1)C=2OC=CN=2)=CC2=C1NC=N2 OPJFOSDWIWFYRW-UHFFFAOYSA-N 0.000 description 1
• FNRMMDCDHWCQTH-UHFFFAOYSA-N 2-chloropyridine;3-chloropyridine;4-chloropyridine Chemical compound ClC1=CC=NC=C1.ClC1=CC=CN=C1.ClC1=CC=CC=N1 FNRMMDCDHWCQTH-UHFFFAOYSA-N 0.000 description 1
• MGGZXHWABWHQAR-UHFFFAOYSA-N 2-cyclopropyl-2-oxoacetyl chloride Chemical compound ClC(=O)C(=O)C1CC1 MGGZXHWABWHQAR-UHFFFAOYSA-N 0.000 description 1
• NBPQLPVAUZISNW-UHFFFAOYSA-N 2-cyclopropyl-6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(C1CC1)=N2 NBPQLPVAUZISNW-UHFFFAOYSA-N 0.000 description 1
• 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
• XXUNIGZDNWWYED-UHFFFAOYSA-N 2-methylbenzamide Chemical compound CC1=CC=CC=C1C(N)=O XXUNIGZDNWWYED-UHFFFAOYSA-N 0.000 description 1
• 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
• 125000005916 2-methylpentyl group Chemical group 0.000 description 1
• OYZWEOORLJBPMA-UHFFFAOYSA-N 3,5-difluorobenzoyl chloride Chemical compound FC1=CC(F)=CC(C(Cl)=O)=C1 OYZWEOORLJBPMA-UHFFFAOYSA-N 0.000 description 1
• BVRFVGOIELRZBU-UHFFFAOYSA-N 3-[4-[(2-methylpropan-2-yl)oxycarbonyl]phenyl]propanoic acid Chemical compound CC(C)(C)OC(=O)C1=CC=C(CCC(O)=O)C=C1 BVRFVGOIELRZBU-UHFFFAOYSA-N 0.000 description 1
• SIBXJJSFYUSKKF-UHFFFAOYSA-N 3-[6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridin-2-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC(C=2NC3=NC(=C(C=4C(=CN=CC=4)F)C=C3N=2)C=2C=NC=CC=2)=C1 SIBXJJSFYUSKKF-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• PPLLAHQNNDKXJU-UHFFFAOYSA-N 3-chloropyridine-4-carboxamide Chemical compound NC(=O)C1=CC=NC=C1Cl PPLLAHQNNDKXJU-UHFFFAOYSA-N 0.000 description 1
• DYUMBFTYRJMAFK-UHFFFAOYSA-N 3-cyano-2-pyridone Chemical compound OC1=NC=CC=C1C#N DYUMBFTYRJMAFK-UHFFFAOYSA-N 0.000 description 1
• RPESZQVUWMFBEO-UHFFFAOYSA-N 3-cyanobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(C#N)=C1 RPESZQVUWMFBEO-UHFFFAOYSA-N 0.000 description 1
• MLFGHAHGSVFKMI-UHFFFAOYSA-N 3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=NC=C1F MLFGHAHGSVFKMI-UHFFFAOYSA-N 0.000 description 1
• SYVNVEGIRVXRQH-UHFFFAOYSA-N 3-fluorobenzoyl chloride Chemical compound FC1=CC=CC(C(Cl)=O)=C1 SYVNVEGIRVXRQH-UHFFFAOYSA-N 0.000 description 1
• CELKOWQJPVJKIL-UHFFFAOYSA-N 3-fluoropyridine Chemical compound FC1=CC=CN=C1 CELKOWQJPVJKIL-UHFFFAOYSA-N 0.000 description 1
• VMSZFBSYWXMXRF-UHFFFAOYSA-N 3-isothiocyanatopyridine Chemical compound S=C=NC1=CC=CN=C1 VMSZFBSYWXMXRF-UHFFFAOYSA-N 0.000 description 1
• 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000005917 3-methylpentyl group Chemical group 0.000 description 1
• YEORVBKKTIHVKX-UHFFFAOYSA-N 3-nitro-6-(1,3-oxazol-2-yl)pyridin-2-amine Chemical compound C1=C([N+]([O-])=O)C(N)=NC(C=2OC=CN=2)=C1 YEORVBKKTIHVKX-UHFFFAOYSA-N 0.000 description 1
• OKLOACZNEVKTCV-UHFFFAOYSA-N 3-nitro-6-(1,3-oxazol-5-yl)-5-pyridin-4-ylpyridin-2-amine Chemical compound C=1C=NC=CC=1C=1C=C([N+]([O-])=O)C(N)=NC=1C1=CN=CO1 OKLOACZNEVKTCV-UHFFFAOYSA-N 0.000 description 1
• BPYHGTCRXDWOIQ-UHFFFAOYSA-N 3-nitropyridin-2-amine Chemical compound NC1=NC=CC=C1[N+]([O-])=O BPYHGTCRXDWOIQ-UHFFFAOYSA-N 0.000 description 1
• MFEILWXBDBCWKF-UHFFFAOYSA-N 3-phenylpropanoyl chloride Chemical compound ClC(=O)CCC1=CC=CC=C1 MFEILWXBDBCWKF-UHFFFAOYSA-N 0.000 description 1
• UGJDXRVQCYBXAJ-UHFFFAOYSA-N 4-(dimethylamino)benzoyl chloride Chemical compound CN(C)C1=CC=C(C(Cl)=O)C=C1 UGJDXRVQCYBXAJ-UHFFFAOYSA-N 0.000 description 1
• IBSMTARMKOSAMM-UHFFFAOYSA-N 4-[6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridin-2-yl]morpholine Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(N1CCOCC1)=N2 IBSMTARMKOSAMM-UHFFFAOYSA-N 0.000 description 1
• OYEQKMASMPBQMP-UHFFFAOYSA-N 4-carbonochloridoylbenzoic acid Chemical compound OC(=O)C1=CC=C(C(Cl)=O)C=C1 OYEQKMASMPBQMP-UHFFFAOYSA-N 0.000 description 1
• UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 1
• RBEFRYQKJYMLCC-UHFFFAOYSA-N 4-isothiocyanatobenzoic acid Chemical compound OC(=O)C1=CC=C(N=C=S)C=C1 RBEFRYQKJYMLCC-UHFFFAOYSA-N 0.000 description 1
• WNLMYNASWOULQY-UHFFFAOYSA-N 4-tert-butylbenzoyl chloride Chemical compound CC(C)(C)C1=CC=C(C(Cl)=O)C=C1 WNLMYNASWOULQY-UHFFFAOYSA-N 0.000 description 1
• 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 1
• VENIDIZFNHVWLJ-UHFFFAOYSA-N 5,6-bis(3-chloropyridin-4-yl)-1,3-dihydroimidazo[4,5-b]pyridin-2-one Chemical compound ClC1=CN=CC=C1C(C(=N1)C=2C(=CN=CC=2)Cl)=CC2=C1NC(=O)N2 VENIDIZFNHVWLJ-UHFFFAOYSA-N 0.000 description 1
• GQCUXDBFVWFDHY-UHFFFAOYSA-N 5,6-dipyridin-4-yl-1,3-dihydroimidazo[4,5-b]pyridin-2-one Chemical compound C=1C=NC=CC=1C=1N=C2NC(=O)NC2=CC=1C1=CC=NC=C1 GQCUXDBFVWFDHY-UHFFFAOYSA-N 0.000 description 1
• SLTIUZBNBDSTRB-UHFFFAOYSA-N 5-(3-chloropyridin-4-yl)-2-(4-fluorophenyl)-6-pyridin-4-yl-1h-imidazo[4,5-b]pyridine Chemical compound C1=CC(F)=CC=C1C1=NC2=CC(C=3C=CN=CC=3)=C(C=3C(=CN=CC=3)Cl)N=C2N1 SLTIUZBNBDSTRB-UHFFFAOYSA-N 0.000 description 1
• NVIMJSZNQGYNMM-UHFFFAOYSA-N 5-(3-chloropyridin-4-yl)-6-pyridin-4-yl-1,3-dihydroimidazo[4,5-b]pyridin-2-one Chemical compound ClC1=CN=CC=C1C(C(=C1)C=2C=CN=CC=2)=NC2=C1NC(=O)N2 NVIMJSZNQGYNMM-UHFFFAOYSA-N 0.000 description 1
• UHTCSZCOFYWPBM-UHFFFAOYSA-N 5-(3-fluoropyridin-4-yl)-3-nitro-6-(1,3-oxazol-2-yl)pyridin-2-amine Chemical compound C=1C=NC=C(F)C=1C=1C=C([N+]([O-])=O)C(N)=NC=1C1=NC=CO1 UHTCSZCOFYWPBM-UHFFFAOYSA-N 0.000 description 1
• JTIDLXJFJVVPKS-UHFFFAOYSA-N 5-(3-fluoropyridin-4-yl)-3-nitro-6-(1,3-oxazol-5-yl)pyridin-2-amine Chemical compound C=1C=NC=C(F)C=1C=1C=C([N+]([O-])=O)C(N)=NC=1C1=CN=CO1 JTIDLXJFJVVPKS-UHFFFAOYSA-N 0.000 description 1
• KTUQRRZIWJDXCS-UHFFFAOYSA-N 5-(6-pyridin-4-yl-1h-imidazo[4,5-b]pyridin-5-yl)-1,3-oxazole Chemical compound C=1N=COC=1C=1N=C2NC=NC2=CC=1C1=CC=NC=C1 KTUQRRZIWJDXCS-UHFFFAOYSA-N 0.000 description 1
• VAPFKAQLLVGEKA-UHFFFAOYSA-N 5-[6-(3-fluoropyridin-4-yl)-1h-imidazo[4,5-b]pyridin-5-yl]-1,3-oxazole Chemical compound FC1=CN=CC=C1C(C(=N1)C=2OC=NC=2)=CC2=C1NC=N2 VAPFKAQLLVGEKA-UHFFFAOYSA-N 0.000 description 1
• MNLKRTCTWKXNST-UHFFFAOYSA-N 5-bromo-3-nitro-6-(1,3-oxazol-2-yl)pyridin-2-amine Chemical compound C1=C([N+]([O-])=O)C(N)=NC(C=2OC=CN=2)=C1Br MNLKRTCTWKXNST-UHFFFAOYSA-N 0.000 description 1
• KUJGPWCHTNKMII-UHFFFAOYSA-N 5-pyridin-4-ylpyridin-2-amine Chemical compound C1=NC(N)=CC=C1C1=CC=NC=C1 KUJGPWCHTNKMII-UHFFFAOYSA-N 0.000 description 1
• GCETZIHCDDRCER-UHFFFAOYSA-N 6-(3,5-difluoropyridin-4-yl)-2-(4-fluorophenyl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound C1=CC(F)=CC=C1C1=NC2=CC(C=3C(=CN=CC=3F)F)=C(C=3C=NC=CC=3)N=C2N1 GCETZIHCDDRCER-UHFFFAOYSA-N 0.000 description 1
• HHWZIYKSFXPFSB-UHFFFAOYSA-N 6-(3-chloropyridin-4-yl)-5-pyridin-3-yl-1,3-dihydroimidazo[4,5-b]pyridin-2-one Chemical compound ClC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(=O)N2 HHWZIYKSFXPFSB-UHFFFAOYSA-N 0.000 description 1
• HEQZBTGQAYDCKB-UHFFFAOYSA-N 6-(3-chloropyridin-4-yl)-5-pyridin-4-yl-1,3-dihydroimidazo[4,5-b]pyridin-2-one Chemical compound ClC1=CN=CC=C1C(C(=N1)C=2C=CN=CC=2)=CC2=C1NC(=O)N2 HEQZBTGQAYDCKB-UHFFFAOYSA-N 0.000 description 1
• ITIYCIWYRCMLIT-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-2,5-dipyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(C=1C=NC=CC=1)=N2 ITIYCIWYRCMLIT-UHFFFAOYSA-N 0.000 description 1
• JSSLEBFKIMPAHU-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-2-(2-phenylethyl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(CCC=1C=CC=CC=1)=N2 JSSLEBFKIMPAHU-UHFFFAOYSA-N 0.000 description 1
• IRXYSYPIUJXRSJ-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-2-(4-methylpiperazin-1-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound C1CN(C)CCN1C1=NC2=CC(C=3C(=CN=CC=3)F)=C(C=3C=NC=CC=3)N=C2N1 IRXYSYPIUJXRSJ-UHFFFAOYSA-N 0.000 description 1
• ISJJZCLSLSJRAJ-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-2-methylsulfonyl-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound C=1C=CN=CC=1C=1N=C2NC(S(=O)(=O)C)=NC2=CC=1C1=CC=NC=C1F ISJJZCLSLSJRAJ-UHFFFAOYSA-N 0.000 description 1
• ORELQBRROALSIR-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-2-pyrazin-2-yl-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(C=1N=CC=NC=1)=N2 ORELQBRROALSIR-UHFFFAOYSA-N 0.000 description 1
• RHDJTDBXIPAPPM-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-2-pyridin-2-yl-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridine Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(C=1N=CC=CC=1)=N2 RHDJTDBXIPAPPM-UHFFFAOYSA-N 0.000 description 1
• QAKYRFJMYLPPNY-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1,3-dihydroimidazo[4,5-b]pyridin-2-one Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(=O)N2 QAKYRFJMYLPPNY-UHFFFAOYSA-N 0.000 description 1
• ZFCVNBIWAOPRSA-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1,3-dihydroimidazo[4,5-b]pyridine-2-thione Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(=S)N2 ZFCVNBIWAOPRSA-UHFFFAOYSA-N 0.000 description 1
• GMWHHARQHQFMQF-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridin-2-amine Chemical compound C=1C=CN=CC=1C=1N=C2NC(N)=NC2=CC=1C1=CC=NC=C1F GMWHHARQHQFMQF-UHFFFAOYSA-N 0.000 description 1
• HLKCDGMRIKFNNR-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-2-(2-pyridin-3-ylethyl)-1h-imidazo[4,5-b]pyridine Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(CCC=1C=NC=CC=1)=N2 HLKCDGMRIKFNNR-UHFFFAOYSA-N 0.000 description 1
• CSPSBRHWRRLXMI-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-2-[4-(trifluoromethyl)phenyl]-1h-imidazo[4,5-b]pyridine Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(C=1C=CC(=CC=1)C(F)(F)F)=N2 CSPSBRHWRRLXMI-UHFFFAOYSA-N 0.000 description 1
• QCAGPDXBMNNMBH-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-2-pyridin-4-yl-1h-imidazo[4,5-b]pyridine Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(C=1C=CN=CC=1)=N2 QCAGPDXBMNNMBH-UHFFFAOYSA-N 0.000 description 1
• SKYQVBYKSDFUTD-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-2-pyrimidin-5-yl-1h-imidazo[4,5-b]pyridine Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(C=1C=NC=NC=1)=N2 SKYQVBYKSDFUTD-UHFFFAOYSA-N 0.000 description 1
• JNJZPKODYHXOKE-UHFFFAOYSA-N 6-(3-fluoropyridin-4-yl)-n,5-dipyridin-3-yl-1h-imidazo[4,5-b]pyridin-2-amine Chemical compound FC1=CN=CC=C1C(C(=N1)C=2C=NC=CC=2)=CC2=C1NC(NC=1C=NC=CC=1)=N2 JNJZPKODYHXOKE-UHFFFAOYSA-N 0.000 description 1
• 208000026872 Addison Disease Diseases 0.000 description 1
• 102000055025 Adenosine deaminases Human genes 0.000 description 1
• 208000023328 Basedow disease Diseases 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• LNSAGAODAALRNC-UHFFFAOYSA-N CC1=NC2=CC(c3ccncc3F)=C(c3cnccc3)[N-]C2N1 Chemical compound CC1=NC2=CC(c3ccncc3F)=C(c3cnccc3)[N-]C2N1 LNSAGAODAALRNC-UHFFFAOYSA-N 0.000 description 1
• 0 C[C@]1N*C[C@@](CCCN(CC2CCNCC2)N)[C@@]1Cl Chemical compound C[C@]1N*C[C@@](CCCN(CC2CCNCC2)N)[C@@]1Cl 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 208000011231 Crohn disease Diseases 0.000 description 1
• 238000006969 Curtius rearrangement reaction Methods 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 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
• DUXGMEWEIRRRTL-UHFFFAOYSA-N FC=1C=C(C=CC1C)C1=NC=2C(=NC(=C(C2)C2=C(C=NC=C2)F)C=2C=NC=CC2)N1.FC=1C=NC=CC1C=1C=C2C(=NC1C1=CN=CO1)NC=N2 Chemical compound FC=1C=C(C=CC1C)C1=NC=2C(=NC(=C(C2)C2=C(C=NC=C2)F)C=2C=NC=CC2)N1.FC=1C=NC=CC1C=1C=C2C(=NC1C1=CN=CO1)NC=N2 DUXGMEWEIRRRTL-UHFFFAOYSA-N 0.000 description 1
• FUNCKMRRMDSPIY-UHFFFAOYSA-N FC=1C=NC=C(C1C=1C=C2C(=NC1C=1C=NC=CC1)NC(=N2)C2=CC=C(C(=O)O)C=C2)F.FC=2C=NC=C(C2C=2C=C1C(=NC2C=2C=NC=CC2)NC(=N1)C1=CC=C(C=C1)F)F Chemical compound FC=1C=NC=C(C1C=1C=C2C(=NC1C=1C=NC=CC1)NC(=N2)C2=CC=C(C(=O)O)C=C2)F.FC=2C=NC=C(C2C=2C=C1C(=NC2C=2C=NC=CC2)NC(=N1)C1=CC=C(C=C1)F)F FUNCKMRRMDSPIY-UHFFFAOYSA-N 0.000 description 1
• NSNCSEKOOAQWAU-UHFFFAOYSA-N FC=1C=NC=CC1C=1C=C2C(=NC1C=1C=NC=CC1)NC(=N2)C2=NC=CC=C2.FC=2C=NC=CC2C=2C=C1C(=NC2C=2C=NC=CC2)NC(=N1)C=1C=NC=NC1 Chemical compound FC=1C=NC=CC1C=1C=C2C(=NC1C=1C=NC=CC1)NC(=N2)C2=NC=CC=C2.FC=2C=NC=CC2C=2C=C1C(=NC2C=2C=NC=CC2)NC(=N1)C=1C=NC=NC1 NSNCSEKOOAQWAU-UHFFFAOYSA-N 0.000 description 1
• DBOQWETUJAPBEM-UHFFFAOYSA-N FC=1C=NC=CC1C=1C=C2C(=NC1C=1C=NC=CC1)NC(=N2)C=2C=C(C#N)C=CC2.FC=2C=NC=CC2C=2C=C1C(=NC2C=2C=NC=CC2)NC(=N1)C1=NC=CN=C1 Chemical compound FC=1C=NC=CC1C=1C=C2C(=NC1C=1C=NC=CC1)NC(=N2)C=2C=C(C#N)C=CC2.FC=2C=NC=CC2C=2C=C1C(=NC2C=2C=NC=CC2)NC(=N1)C1=NC=CN=C1 DBOQWETUJAPBEM-UHFFFAOYSA-N 0.000 description 1
• LKKALPDUDOVQOK-UHFFFAOYSA-N FC=1C=NC=CC1C=1C=C2C(=NC1C=1C=NC=CC1)NC(=N2)N.FC=2C=NC=CC2C=2C=C1C(=NC2C=2C=NC=CC2)NC(=N1)N1CCN(CC1)C Chemical compound FC=1C=NC=CC1C=1C=C2C(=NC1C=1C=NC=CC1)NC(=N2)N.FC=2C=NC=CC2C=2C=C1C(=NC2C=2C=NC=CC2)NC(=N1)N1CCN(CC1)C LKKALPDUDOVQOK-UHFFFAOYSA-N 0.000 description 1
• CDYVNSLDLSBKKS-UHFFFAOYSA-N FC=1C=NC=CC1C=1C=C2C(=NC1C=1C=NC=CC1)NC(=N2)N2CCCCC2.FC=2C=NC=CC2C=2C=C1C(=NC2C=2C=NC=CC2)NC(=N1)N1CCOCC1 Chemical compound FC=1C=NC=CC1C=1C=C2C(=NC1C=1C=NC=CC1)NC(=N2)N2CCCCC2.FC=2C=NC=CC2C=2C=C1C(=NC2C=2C=NC=CC2)NC(=N1)N1CCOCC1 CDYVNSLDLSBKKS-UHFFFAOYSA-N 0.000 description 1
• KJVBGNNUBFYDGN-UHFFFAOYSA-N FC=1C=NC=CC1C=1C=C2C(=NC1C=1C=NC=CC1)NC(=N2)N2N=CC(=C2)C(=O)O.FC=2C=NC=CC2C=2C=C1C(=NC2C=2C=NC=CC2)NC(=N1)SC Chemical compound FC=1C=NC=CC1C=1C=C2C(=NC1C=1C=NC=CC1)NC(=N2)N2N=CC(=C2)C(=O)O.FC=2C=NC=CC2C=2C=C1C(=NC2C=2C=NC=CC2)NC(=N1)SC KJVBGNNUBFYDGN-UHFFFAOYSA-N 0.000 description 1
• PKVOSLIELFMLOL-UHFFFAOYSA-N FC=1C=NC=CC1C=1C=C2C(=NC1C=1C=NC=CC1)NC(=N2)NC=2C=NC=CC2.FC=2C=NC=CC2C=2C=C1C(=NC2C=2C=NC=CC2)NC(=N1)CCC1=CC=C(C(=O)O)C=C1 Chemical compound FC=1C=NC=CC1C=1C=C2C(=NC1C=1C=NC=CC1)NC(=N2)NC=2C=NC=CC2.FC=2C=NC=CC2C=2C=C1C(=NC2C=2C=NC=CC2)NC(=N1)CCC1=CC=C(C(=O)O)C=C1 PKVOSLIELFMLOL-UHFFFAOYSA-N 0.000 description 1
• FLKLRVVXWCEUFS-UHFFFAOYSA-N Fc(cc1)ccc1C1=NC2=CC(c3ccncc3)=C(c3cnccc3)[N-]C2N1 Chemical compound Fc(cc1)ccc1C1=NC2=CC(c3ccncc3)=C(c3cnccc3)[N-]C2N1 FLKLRVVXWCEUFS-UHFFFAOYSA-N 0.000 description 1
• 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
• 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
• 208000024869 Goodpasture syndrome Diseases 0.000 description 1
• 208000015023 Graves' disease Diseases 0.000 description 1
• 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
• 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
• 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
• 239000002841 Lewis acid Substances 0.000 description 1
• QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
• JADDQZYHOWSFJD-FLNNQWSLSA-N N-ethyl-5'-carboxamidoadenosine Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 JADDQZYHOWSFJD-FLNNQWSLSA-N 0.000 description 1
• FLIFYUQSXDRNHF-UHFFFAOYSA-N NC(C([N+]([O-])=O)=C1)[N-]C(c2ccncc2)=C1c1ccncc1Cl Chemical compound NC(C([N+]([O-])=O)=C1)[N-]C(c2ccncc2)=C1c1ccncc1Cl FLIFYUQSXDRNHF-UHFFFAOYSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• 208000026344 Nasal disease Diseases 0.000 description 1
• MASIDXFLOOYIMR-UHFFFAOYSA-N Nc1cc(-c2ccncc2)c(-c(ccnc2)c2Cl)nc1N Chemical compound Nc1cc(-c2ccncc2)c(-c(ccnc2)c2Cl)nc1N MASIDXFLOOYIMR-UHFFFAOYSA-N 0.000 description 1
• TXRMXICXIJLQRL-UHFFFAOYSA-N Nc1cc(-c2ccncc2Cl)c(-c2ccncc2)nc1N Chemical compound Nc1cc(-c2ccncc2Cl)c(-c2ccncc2)nc1N TXRMXICXIJLQRL-UHFFFAOYSA-N 0.000 description 1
• 208000030880 Nose disease Diseases 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-L Oxalate Chemical compound [O-]C(=O)C([O-])=O MUBZPKHOEPUJKR-UHFFFAOYSA-L 0.000 description 1
• 101150003085 Pdcl gene Proteins 0.000 description 1
• 201000011152 Pemphigus Diseases 0.000 description 1
• 208000031845 Pernicious anaemia Diseases 0.000 description 1
• 239000004793 Polystyrene Substances 0.000 description 1
• 206010036303 Post streptococcal glomerulonephritis Diseases 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 208000021386 Sjogren Syndrome Diseases 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-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
• 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
• GCTFWCDSFPMHHS-UHFFFAOYSA-M Tributyltin chloride Chemical compound CCCC[Sn](Cl)(CCCC)CCCC GCTFWCDSFPMHHS-UHFFFAOYSA-M 0.000 description 1
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• YTAHJIFKAKIKAV-XNMGPUDCSA-N [(1R)-3-morpholin-4-yl-1-phenylpropyl] N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]carbamate Chemical compound O=C1[C@H](N=C(C2=C(N1)C=CC=C2)C1=CC=CC=C1)NC(O[C@H](CCN1CCOCC1)C1=CC=CC=C1)=O YTAHJIFKAKIKAV-XNMGPUDCSA-N 0.000 description 1
• LDDAEZJMTNDCEX-UHFFFAOYSA-N [6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridin-2-yl]hydrazine Chemical compound C=1C=CN=CC=1C=1N=C2NC(NN)=NC2=CC=1C1=CC=NC=C1F LDDAEZJMTNDCEX-UHFFFAOYSA-N 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 201000005638 acute proliferative glomerulonephritis Diseases 0.000 description 1
• 150000001263 acyl chlorides Chemical class 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 150000004703 alkoxides Chemical class 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• 150000001356 alkyl thiols Chemical class 0.000 description 1
• 230000000172 allergic effect Effects 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 1
• 125000005427 anthranyl group Chemical group 0.000 description 1
• 239000000010 aprotic solvent Substances 0.000 description 1
• 239000011260 aqueous acid Substances 0.000 description 1
• 239000012736 aqueous medium Substances 0.000 description 1
• 239000003125 aqueous solvent Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 239000012300 argon atmosphere Substances 0.000 description 1
• 150000003975 aryl alkyl amines Chemical class 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 125000004104 aryloxy group Chemical group 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 208000010668 atopic eczema Diseases 0.000 description 1
• 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
• 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
• PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• 229960004365 benzoic acid Drugs 0.000 description 1
• 230000027455 binding Effects 0.000 description 1
• 230000008827 biological function Effects 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 229910052799 carbon Inorganic materials 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 239000012320 chlorinating reagent Substances 0.000 description 1
• 238000013375 chromatographic separation Methods 0.000 description 1
• 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 239000007822 coupling agent Substances 0.000 description 1
• 239000012043 crude product Substances 0.000 description 1
• DGJMPUGMZIKDRO-UHFFFAOYSA-N cyanoacetamide Chemical compound NC(=O)CC#N DGJMPUGMZIKDRO-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
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 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
• 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
• 239000012024 dehydrating agents‎ Substances 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
• XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 description 1
• 230000006806 disease prevention Effects 0.000 description 1
• 208000037765 diseases and disorders Diseases 0.000 description 1
• 238000011067 equilibration Methods 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000011888 foil Substances 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 230000009229 glucose formation Effects 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 230000002140 halogenating effect Effects 0.000 description 1
• 125000004970 halomethyl group Chemical group 0.000 description 1
• 230000002440 hepatic effect Effects 0.000 description 1
• 210000003630 histaminocyte Anatomy 0.000 description 1
• 150000002430 hydrocarbons Chemical group 0.000 description 1
• 229940071870 hydroiodic acid Drugs 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• MSYBLBLAMDYKKZ-UHFFFAOYSA-N hydron;pyridine-3-carbonyl chloride;chloride Chemical compound Cl.ClC(=O)C1=CC=CN=C1 MSYBLBLAMDYKKZ-UHFFFAOYSA-N 0.000 description 1
• 150000004679 hydroxides Chemical class 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 150000002466 imines Chemical class 0.000 description 1
• 238000010952 in-situ formation Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 208000000509 infertility Diseases 0.000 description 1
• 230000036512 infertility Effects 0.000 description 1
• 231100000535 infertility Toxicity 0.000 description 1
• 239000003112 inhibitor Substances 0.000 description 1
• 239000003999 initiator Substances 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 210000002011 intestinal secretion Anatomy 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 239000012948 isocyanate Substances 0.000 description 1
• 150000002513 isocyanates Chemical class 0.000 description 1
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 150000007517 lewis acids Chemical class 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
• UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• 235000019341 magnesium sulphate Nutrition 0.000 description 1
• BJEPYKJPYRNKOW-UWTATZPHSA-M malate ion Chemical compound [O-]C(=O)[C@H](O)CC(O)=O BJEPYKJPYRNKOW-UWTATZPHSA-M 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 229940099690 malic acid Drugs 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 102000006240 membrane receptors Human genes 0.000 description 1
• 108020004084 membrane receptors Proteins 0.000 description 1
• 229910000474 mercury oxide Inorganic materials 0.000 description 1
• UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• VQSFKPRSTZBSQI-UHFFFAOYSA-N methyl 4-[6-(3,5-difluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridin-2-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=NC2=CC(C=3C(=CN=CC=3F)F)=C(C=3C=NC=CC=3)N=C2N1 VQSFKPRSTZBSQI-UHFFFAOYSA-N 0.000 description 1
• 229940095102 methyl benzoate Drugs 0.000 description 1
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 239000002808 molecular sieve Substances 0.000 description 1
• 230000004899 motility Effects 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 206010028417 myasthenia gravis Diseases 0.000 description 1
• 230000002107 myocardial effect Effects 0.000 description 1
• UHAAFJWANJYDIS-UHFFFAOYSA-N n,n'-diethylmethanediimine Chemical compound CCN=C=NCC UHAAFJWANJYDIS-UHFFFAOYSA-N 0.000 description 1
• CVKYNSKSNYSKPL-UHFFFAOYSA-N n-(4-fluorophenyl)-6-(3-fluoropyridin-4-yl)-5-pyridin-3-yl-1h-imidazo[4,5-b]pyridin-2-amine Chemical compound C1=CC(F)=CC=C1NC1=NC2=CC(C=3C(=CN=CC=3)F)=C(C=3C=NC=CC=3)N=C2N1 CVKYNSKSNYSKPL-UHFFFAOYSA-N 0.000 description 1
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 230000003472 neutralizing effect Effects 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 229960003512 nicotinic acid Drugs 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 150000002825 nitriles Chemical class 0.000 description 1
• 230000009871 nonspecific binding Effects 0.000 description 1
• 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
• 239000012038 nucleophile Substances 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 125000002524 organometallic group Chemical group 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 229940116315 oxalic acid Drugs 0.000 description 1
• 238000004806 packaging method and process Methods 0.000 description 1
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
• 238000010651 palladium-catalyzed cross coupling reaction Methods 0.000 description 1
• 201000001976 pemphigus vulgaris Diseases 0.000 description 1
• GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 description 1
• 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 125000005561 phenanthryl group Chemical group 0.000 description 1
• QKFJKGMPGYROCL-UHFFFAOYSA-N phenyl isothiocyanate Chemical compound S=C=NC1=CC=CC=C1 QKFJKGMPGYROCL-UHFFFAOYSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 229940085991 phosphate ion Drugs 0.000 description 1
• RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
• FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
• 230000001766 physiological effect Effects 0.000 description 1
• 239000003495 polar organic solvent Substances 0.000 description 1
• 125000003367 polycyclic group Chemical group 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 229920002223 polystyrene Polymers 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 238000009516 primary packaging Methods 0.000 description 1
• 239000000047 product Substances 0.000 description 1
• 230000002062 proliferating effect Effects 0.000 description 1
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
• 125000002755 pyrazolinyl group Chemical group 0.000 description 1
• ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
• PSAYJRPASWETSH-UHFFFAOYSA-N pyridine-2-carbonyl chloride Chemical compound ClC(=O)C1=CC=CC=N1 PSAYJRPASWETSH-UHFFFAOYSA-N 0.000 description 1
• RVQZKNOMKUSGCI-UHFFFAOYSA-N pyridine-4-carbonyl chloride Chemical compound ClC(=O)C1=CC=NC=C1 RVQZKNOMKUSGCI-UHFFFAOYSA-N 0.000 description 1
• 125000006513 pyridinyl methyl group Chemical group 0.000 description 1
• 125000001422 pyrrolinyl group Chemical group 0.000 description 1
• 150000003856 quaternary ammonium compounds Chemical class 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
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 230000026267 regulation of growth Effects 0.000 description 1
• 238000010405 reoxidation reaction Methods 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 239000012047 saturated solution Substances 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 150000005619 secondary aliphatic amines Chemical class 0.000 description 1
• YPNVIBVEFVRZPJ-UHFFFAOYSA-L silver sulfate Chemical compound [Ag+].[Ag+].[O-]S([O-])(=O)=O YPNVIBVEFVRZPJ-UHFFFAOYSA-L 0.000 description 1
• 229910000367 silver sulfate Inorganic materials 0.000 description 1
• 210000002460 smooth muscle Anatomy 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
• 229910001948 sodium oxide Inorganic materials 0.000 description 1
• 239000011877 solvent mixture Substances 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000006190 sub-lingual tablet Substances 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 150000003457 sulfones Chemical class 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229960001367 tartaric acid Drugs 0.000 description 1
• 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• LHJCZOXMCGQVDQ-UHFFFAOYSA-N tri(propan-2-yl)silyl trifluoromethanesulfonate Chemical compound CC(C)[Si](C(C)C)(C(C)C)OS(=O)(=O)C(F)(F)F LHJCZOXMCGQVDQ-UHFFFAOYSA-N 0.000 description 1
• UXHMGTYELGTNSJ-UHFFFAOYSA-N triazole-1-carboxamide Chemical compound NC(=O)N1C=CN=N1 UXHMGTYELGTNSJ-UHFFFAOYSA-N 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• ITBMRVUPEVXILF-UHFFFAOYSA-N tributyl-(3,5-difluoropyridin-4-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=C(F)C=NC=C1F ITBMRVUPEVXILF-UHFFFAOYSA-N 0.000 description 1
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 1
• GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
• MBYLVOKEDDQJDY-UHFFFAOYSA-N tris(2-aminoethyl)amine Chemical compound NCCN(CCN)CCN MBYLVOKEDDQJDY-UHFFFAOYSA-N 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
• 230000006442 vascular tone Effects 0.000 description 1
• 230000009278 visceral effect Effects 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1
• 239000011592 zinc chloride Substances 0.000 description 1
• 235000005074 zinc chloride Nutrition 0.000 description 1