JP2005539000A

JP2005539000A - Ａｌｋ５阻害剤としての２−フェニルピリジン−４−イル誘導体

Ａｌｋ５阻害剤としての２−フェニルピリジン−４−イル誘導体 Download PDF

Info

Publication number: JP2005539000A
Authority: JP; Japan
Prior art keywords: mmol; pyridin; alkyl; compound; hydrogen
Prior art date: 2002-07-31
Legal status : Pending

Application number

JP2004525405A

Other languages

English (en)

Japanese (ja)

Other versions

JP2005539000A5 (https=

Inventor

ネリナ・ドディック

フランソワーズ・ジャンヌ・ジェリベール

Current Assignee

SmithKline Beecham Corp

Original Assignee

SmithKline Beecham Corp

Priority date

2002-07-31

Filing date

2003-07-29

Publication date

2005-12-22

2002-07-31 Priority claimed from GB0217751A external-priority patent/GB0217751D0/en

2003-06-24 Priority claimed from GB0314698A external-priority patent/GB0314698D0/en

2003-07-29 Application filed by SmithKline Beecham Corp filed Critical SmithKline Beecham Corp

2005-12-22 Publication of JP2005539000A publication Critical patent/JP2005539000A/ja

2006-09-14 Publication of JP2005539000A5 publication Critical patent/JP2005539000A5/ja

Status Pending legal-status Critical Current

Links

-1 2-Phenylpyridin-4-yl Chemical class 0.000 title claims description 49
239000003112 inhibitor Substances 0.000 title abstract description 5
238000011282 treatment Methods 0.000 claims abstract description 20
239000003814 drug Substances 0.000 claims abstract description 8
230000001404 mediated effect Effects 0.000 claims abstract description 6
230000002265 prevention Effects 0.000 claims abstract description 5
150000001875 compounds Chemical class 0.000 claims description 365
125000000217 alkyl group Chemical group 0.000 claims description 73
229910052739 hydrogen Inorganic materials 0.000 claims description 65
239000001257 hydrogen Substances 0.000 claims description 59
125000005843 halogen group Chemical group 0.000 claims description 41
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 40
125000003545 alkoxy group Chemical group 0.000 claims description 36
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 33
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 33
150000002431 hydrogen Chemical class 0.000 claims description 31
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
125000004093 cyano group Chemical group *C#N 0.000 claims description 27
229910052757 nitrogen Inorganic materials 0.000 claims description 22
229920006395 saturated elastomer Polymers 0.000 claims description 22
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 20
FXXJRBVEYNARBS-UHFFFAOYSA-N 4-[[4-[4-[5-(6-methylpyridin-2-yl)-2-propan-2-yl-1h-imidazol-4-yl]pyridin-2-yl]phenyl]methyl]morpholine Chemical compound N1C(C(C)C)=NC(C=2C=C(N=CC=2)C=2C=CC(CN3CCOCC3)=CC=2)=C1C1=CC=CC(C)=N1 FXXJRBVEYNARBS-UHFFFAOYSA-N 0.000 claims description 19
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 15
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
229910052717 sulfur Inorganic materials 0.000 claims description 12
125000001153 fluoro group Chemical group F* 0.000 claims description 11
150000003839 salts Chemical class 0.000 claims description 10
239000012453 solvate Substances 0.000 claims description 10
ZNEWDLYYLKDPRH-UHFFFAOYSA-N 4-[4-[5-(6-methylpyridin-2-yl)-2-propan-2-yl-1h-imidazol-4-yl]pyridin-2-yl]-n-(oxan-4-yl)benzamide Chemical compound N1C(C(C)C)=NC(C=2C=C(N=CC=2)C=2C=CC(=CC=2)C(=O)NC2CCOCC2)=C1C1=CC=CC(C)=N1 ZNEWDLYYLKDPRH-UHFFFAOYSA-N 0.000 claims description 9
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 9
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 9
125000001309 chloro group Chemical group Cl* 0.000 claims description 9
IVTGNDUCNRHJET-UHFFFAOYSA-N 4-[4-[2-tert-butyl-5-(6-methylpyridin-2-yl)-1h-imidazol-4-yl]pyridin-2-yl]-n-(oxan-4-yl)benzamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C(C)(C)C)C=2C=C(N=CC=2)C=2C=CC(=CC=2)C(=O)NC2CCOCC2)=N1 IVTGNDUCNRHJET-UHFFFAOYSA-N 0.000 claims description 8
GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 claims description 8
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 8
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 8
208000007107 Stomach Ulcer Diseases 0.000 claims description 8
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 8
125000001246 bromo group Chemical group Br* 0.000 claims description 8
201000005917 gastric ulcer Diseases 0.000 claims description 8
125000005842 heteroatom Chemical group 0.000 claims description 8
125000000623 heterocyclic group Chemical group 0.000 claims description 8
229910052760 oxygen Inorganic materials 0.000 claims description 8
150000003852 triazoles Chemical class 0.000 claims description 8
229910052799 carbon Inorganic materials 0.000 claims description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
208000017169 kidney disease Diseases 0.000 claims description 7
238000004519 manufacturing process Methods 0.000 claims description 7
125000003226 pyrazolyl group Chemical group 0.000 claims description 7
125000001424 substituent group Chemical group 0.000 claims description 7
241000711549 Hepacivirus C Species 0.000 claims description 6
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 6
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 6
125000004429 atom Chemical group 0.000 claims description 6
201000010099 disease Diseases 0.000 claims description 6
208000035475 disorder Diseases 0.000 claims description 6
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 6
125000004433 nitrogen atom Chemical group N* 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
125000004193 piperazinyl group Chemical group 0.000 claims description 6
125000003342 alkenyl group Chemical group 0.000 claims description 5
125000003118 aryl group Chemical group 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
201000001320 Atherosclerosis Diseases 0.000 claims description 4
206010016654 Fibrosis Diseases 0.000 claims description 4
241000124008 Mammalia Species 0.000 claims description 4
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 4
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
208000027418 Wounds and injury Diseases 0.000 claims description 4
208000020832 chronic kidney disease Diseases 0.000 claims description 4
230000004761 fibrosis Effects 0.000 claims description 4
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 4
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
201000002793 renal fibrosis Diseases 0.000 claims description 4
208000037803 restenosis Diseases 0.000 claims description 4
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 4
229930192474 thiophene Natural products 0.000 claims description 4
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 3
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 3
IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 claims description 3
VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 claims description 3
MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 claims description 3
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
208000024827 Alzheimer disease Diseases 0.000 claims description 3
208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 3
208000033222 Biliary cirrhosis primary Diseases 0.000 claims description 3
206010007559 Cardiac failure congestive Diseases 0.000 claims description 3
208000007342 Diabetic Nephropathies Diseases 0.000 claims description 3
201000009273 Endometriosis Diseases 0.000 claims description 3
206010019280 Heart failures Diseases 0.000 claims description 3
208000018565 Hemochromatosis Diseases 0.000 claims description 3
241000700721 Hepatitis B virus Species 0.000 claims description 3
208000002260 Keloid Diseases 0.000 claims description 3
206010027398 Mesenteric fibrosis Diseases 0.000 claims description 3
208000001132 Osteoporosis Diseases 0.000 claims description 3
WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 claims description 3
208000012654 Primary biliary cholangitis Diseases 0.000 claims description 3
206010052428 Wound Diseases 0.000 claims description 3
JTBSSXWFYSSVJP-UHFFFAOYSA-N [S].C1=CSC=N1 Chemical compound [S].C1=CSC=N1 JTBSSXWFYSSVJP-UHFFFAOYSA-N 0.000 claims description 3
230000001154 acute effect Effects 0.000 claims description 3
206010003246 arthritis Diseases 0.000 claims description 3
RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 3
208000019425 cirrhosis of liver Diseases 0.000 claims description 3
208000033679 diabetic kidney disease Diseases 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
208000030533 eye disease Diseases 0.000 claims description 3
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 3
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 3
210000001117 keloid Anatomy 0.000 claims description 3
230000009251 neurologic dysfunction Effects 0.000 claims description 3
208000015015 neurological dysfunction Diseases 0.000 claims description 3
208000005069 pulmonary fibrosis Diseases 0.000 claims description 3
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 3
XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 claims description 3
238000007920 subcutaneous administration Methods 0.000 claims description 3
230000029663 wound healing Effects 0.000 claims description 3
HEEWFRYQSLPADJ-UHFFFAOYSA-N 2-[2-tert-butyl-4-[2-[4-(pyrrolidin-1-ylmethyl)phenyl]pyridin-4-yl]-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C(C)(C)C)C=2C=C(N=CC=2)C=2C=CC(CN3CCCC3)=CC=2)=N1 HEEWFRYQSLPADJ-UHFFFAOYSA-N 0.000 claims description 2
206010019728 Hepatitis alcoholic Diseases 0.000 claims description 2
208000002353 alcoholic hepatitis Diseases 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
206010034665 Peritoneal fibrosis Diseases 0.000 claims 1
238000000034 method Methods 0.000 abstract description 32
102000004887 Transforming Growth Factor beta Human genes 0.000 abstract description 20
108090001012 Transforming Growth Factor beta Proteins 0.000 abstract description 20
ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 abstract description 17
108091000080 Phosphotransferase Proteins 0.000 abstract description 6
102000020233 phosphotransferase Human genes 0.000 abstract description 6
108010009583 Transforming Growth Factors Proteins 0.000 abstract description 5
102000009618 Transforming Growth Factors Human genes 0.000 abstract description 5
238000002360 preparation method Methods 0.000 abstract description 5
230000026731 phosphorylation Effects 0.000 abstract description 2
238000006366 phosphorylation reaction Methods 0.000 abstract description 2
230000019491 signal transduction Effects 0.000 abstract description 2
239000000543 intermediate Substances 0.000 description 197
239000000460 chlorine Substances 0.000 description 156
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 143
239000000243 solution Substances 0.000 description 133
239000000203 mixture Substances 0.000 description 116
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 92
238000006243 chemical reaction Methods 0.000 description 82
230000002829 reductive effect Effects 0.000 description 79
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 75
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 75
UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 74
239000007787 solid Substances 0.000 description 72
239000011734 sodium Substances 0.000 description 71
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 64
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 57
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 55
239000002904 solvent Substances 0.000 description 55
238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 52
239000012074 organic phase Substances 0.000 description 51
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 45
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
238000004587 chromatography analysis Methods 0.000 description 42
239000000741 silica gel Substances 0.000 description 42
229910002027 silica gel Inorganic materials 0.000 description 42
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 41
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 38
238000010992 reflux Methods 0.000 description 36
238000005481 NMR spectroscopy Methods 0.000 description 31
239000011347 resin Substances 0.000 description 31
229920005989 resin Polymers 0.000 description 31
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 30
239000011541 reaction mixture Substances 0.000 description 29
239000003921 oil Substances 0.000 description 28
235000019198 oils Nutrition 0.000 description 28
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 25
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
235000019439 ethyl acetate Nutrition 0.000 description 23
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 23
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 20
210000004027 cell Anatomy 0.000 description 20
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
239000000047 product Substances 0.000 description 18
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 17
239000007858 starting material Substances 0.000 description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 16
230000000694 effects Effects 0.000 description 15
238000000605 extraction Methods 0.000 description 14
229910000027 potassium carbonate Inorganic materials 0.000 description 14
108020003175 receptors Proteins 0.000 description 14
102000005962 receptors Human genes 0.000 description 14
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 13
229960000583 acetic acid Drugs 0.000 description 13
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
101800002279 Transforming growth factor beta-1 Proteins 0.000 description 12
235000011054 acetic acid Nutrition 0.000 description 12
239000006071 cream Substances 0.000 description 12
102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 11
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
235000019441 ethanol Nutrition 0.000 description 11
239000000706 filtrate Substances 0.000 description 11
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
239000012044 organic layer Substances 0.000 description 11
239000000843 powder Substances 0.000 description 11
CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 10
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 10
239000008346 aqueous phase Substances 0.000 description 10
YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 10
229910052796 boron Inorganic materials 0.000 description 10
239000003054 catalyst Substances 0.000 description 10
238000001816 cooling Methods 0.000 description 10
239000013078 crystal Substances 0.000 description 10
229910000029 sodium carbonate Inorganic materials 0.000 description 10
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 9
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
238000003556 assay Methods 0.000 description 9
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 9
229910052794 bromium Inorganic materials 0.000 description 9
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 9
239000012299 nitrogen atmosphere Substances 0.000 description 9
WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 9
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
LSZMVESSGLHDJE-UHFFFAOYSA-N 2-bromo-4-methylpyridine Chemical compound CC1=CC=NC(Br)=C1 LSZMVESSGLHDJE-UHFFFAOYSA-N 0.000 description 8
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
229910052763 palladium Inorganic materials 0.000 description 8
239000002244 precipitate Substances 0.000 description 8
108090000765 processed proteins & peptides Proteins 0.000 description 8
239000000725 suspension Substances 0.000 description 8
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 8
VXWBQOJISHAKKM-UHFFFAOYSA-N (4-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(C=O)C=C1 VXWBQOJISHAKKM-UHFFFAOYSA-N 0.000 description 7
238000002425 crystallisation Methods 0.000 description 7
230000008025 crystallization Effects 0.000 description 7
238000000746 purification Methods 0.000 description 7
239000012321 sodium triacetoxyborohydride Substances 0.000 description 7
238000001665 trituration Methods 0.000 description 7
239000003981 vehicle Substances 0.000 description 7
108060001084 Luciferase Proteins 0.000 description 6
239000005089 Luciferase Substances 0.000 description 6
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
229910052786 argon Inorganic materials 0.000 description 6
239000012300 argon atmosphere Substances 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
239000010779 crude oil Substances 0.000 description 6
239000012312 sodium hydride Substances 0.000 description 6
229910000104 sodium hydride Inorganic materials 0.000 description 6
VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 6
0 C*C(*1)=C(*)C=CC1=C(***1)C1=C(C=C*1)C=C1c1ccc(*C)cc1 Chemical compound C*C(*1)=C(*)C=CC1=C(***1)C1=C(C=C*1)C=C1c1ccc(*C)cc1 0.000 description 5
108010037362 Extracellular Matrix Proteins Proteins 0.000 description 5
102000010834 Extracellular Matrix Proteins Human genes 0.000 description 5
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 5
MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 5
239000006227 byproduct Substances 0.000 description 5
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
229910000024 caesium carbonate Inorganic materials 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
230000008878 coupling Effects 0.000 description 5
238000010168 coupling process Methods 0.000 description 5
238000005859 coupling reaction Methods 0.000 description 5
239000012043 crude product Substances 0.000 description 5
238000001914 filtration Methods 0.000 description 5
238000009472 formulation Methods 0.000 description 5
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 5
238000003756 stirring Methods 0.000 description 5
238000012360 testing method Methods 0.000 description 5
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 4
JUIKUQOUMZUFQT-UHFFFAOYSA-N 2-bromoacetamide Chemical compound NC(=O)CBr JUIKUQOUMZUFQT-UHFFFAOYSA-N 0.000 description 4
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
108090000331 Firefly luciferases Proteins 0.000 description 4
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
DIGAKNYLLTZJHM-UHFFFAOYSA-N OI(=O)(=O)=O.C1=CC=NC=C1 Chemical compound OI(=O)(=O)=O.C1=CC=NC=C1 DIGAKNYLLTZJHM-UHFFFAOYSA-N 0.000 description 4
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
150000001408 amides Chemical class 0.000 description 4
238000007796 conventional method Methods 0.000 description 4
210000002744 extracellular matrix Anatomy 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
239000003826 tablet Substances 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 4
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
COIQUVGFTILYGA-UHFFFAOYSA-N (4-hydroxyphenyl)boronic acid Chemical compound OB(O)C1=CC=C(O)C=C1 COIQUVGFTILYGA-UHFFFAOYSA-N 0.000 description 3
VDUKDQTYMWUSAC-UHFFFAOYSA-N (4-methylsulfonylphenyl)boronic acid Chemical compound CS(=O)(=O)C1=CC=C(B(O)O)C=C1 VDUKDQTYMWUSAC-UHFFFAOYSA-N 0.000 description 3
PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 3
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
BICZJRAGTCRORZ-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(O)C=C1 BICZJRAGTCRORZ-UHFFFAOYSA-N 0.000 description 3
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
244000166102 Eucalyptus leucoxylon Species 0.000 description 3
235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 3
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
241000700159 Rattus Species 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
238000006069 Suzuki reaction reaction Methods 0.000 description 3
239000003638 chemical reducing agent Substances 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
238000003776 cleavage reaction Methods 0.000 description 3
GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
238000010828 elution Methods 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
229910052736 halogen Inorganic materials 0.000 description 3
150000002367 halogens Chemical class 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
125000002883 imidazolyl group Chemical group 0.000 description 3
239000010410 layer Substances 0.000 description 3
239000003446 ligand Substances 0.000 description 3
238000003670 luciferase enzyme activity assay Methods 0.000 description 3
AHVQYHFYQWKUKB-UHFFFAOYSA-N oxan-4-amine Chemical compound NC1CCOCC1 AHVQYHFYQWKUKB-UHFFFAOYSA-N 0.000 description 3
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 3
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
229940075993 receptor modulator Drugs 0.000 description 3
230000007017 scission Effects 0.000 description 3
230000011664 signaling Effects 0.000 description 3
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
239000004317 sodium nitrate Substances 0.000 description 3
235000010344 sodium nitrate Nutrition 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
239000000600 sorbitol Substances 0.000 description 3
235000010356 sorbitol Nutrition 0.000 description 3
239000006188 syrup Substances 0.000 description 3
235000020357 syrup Nutrition 0.000 description 3
125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
DQWPFSLDHJDLRL-UHFFFAOYSA-N triethyl phosphate Chemical compound CCOP(=O)(OCC)OCC DQWPFSLDHJDLRL-UHFFFAOYSA-N 0.000 description 3
JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 3
QBLFZIBJXUQVRF-UHFFFAOYSA-N (4-bromophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Br)C=C1 QBLFZIBJXUQVRF-UHFFFAOYSA-N 0.000 description 2
CVBNDDGEVPNUNA-UHFFFAOYSA-N (4-ethylsulfonylphenyl)boronic acid Chemical compound CCS(=O)(=O)C1=CC=C(B(O)O)C=C1 CVBNDDGEVPNUNA-UHFFFAOYSA-N 0.000 description 2
RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical class NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 2
FSNGFFWICFYWQC-UHFFFAOYSA-N 1-(2-chloroethyl)pyrrolidine;hydron;chloride Chemical compound Cl.ClCCN1CCCC1 FSNGFFWICFYWQC-UHFFFAOYSA-N 0.000 description 2
FJJYHTVHBVXEEQ-UHFFFAOYSA-N 2,2-dimethylpropanal Chemical compound CC(C)(C)C=O FJJYHTVHBVXEEQ-UHFFFAOYSA-N 0.000 description 2
SJAHYONZGTUULM-UHFFFAOYSA-N 2-(4-ethylsulfonylphenyl)pyridine-4-carbaldehyde Chemical compound C1=CC(S(=O)(=O)CC)=CC=C1C1=CC(C=O)=CC=N1 SJAHYONZGTUULM-UHFFFAOYSA-N 0.000 description 2
SODXMQNNOKADLX-UHFFFAOYSA-N 2-[2-(4-morpholin-4-ylphenyl)pyridin-4-yl]-1-pyridin-2-ylethanone Chemical compound C=1C=CC=NC=1C(=O)CC(C=1)=CC=NC=1C(C=C1)=CC=C1N1CCOCC1 SODXMQNNOKADLX-UHFFFAOYSA-N 0.000 description 2
VHMOZRYEXQYKHZ-UHFFFAOYSA-N 2-bromo-4-(2-phenyl-5-pyridin-2-yl-1h-imidazol-4-yl)pyridine Chemical compound C1=NC(Br)=CC(C2=C(N=C(N2)C=2C=CC=CC=2)C=2N=CC=CC=2)=C1 VHMOZRYEXQYKHZ-UHFFFAOYSA-N 0.000 description 2
OOGALSDKTFQSKW-UHFFFAOYSA-N 2-bromo-n-methoxy-n-methylpyridine-4-carboxamide Chemical compound CON(C)C(=O)C1=CC=NC(Br)=C1 OOGALSDKTFQSKW-UHFFFAOYSA-N 0.000 description 2
CWORZGVWEFJASB-UHFFFAOYSA-N 2-chloro-4-[2-(6-methylpyridin-2-yl)ethynyl]pyridine Chemical compound CC1=CC=CC(C#CC=2C=C(Cl)N=CC=2)=N1 CWORZGVWEFJASB-UHFFFAOYSA-N 0.000 description 2
UCFSYHMCKWNKAH-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound CC1(C)OBOC1(C)C UCFSYHMCKWNKAH-UHFFFAOYSA-N 0.000 description 2
ZANPJXNYBVVNSD-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(N)C=C1 ZANPJXNYBVVNSD-UHFFFAOYSA-N 0.000 description 2
KNSAMIHAIQCBHB-UHFFFAOYSA-N 4-[4-[4-[3-(6-methylpyridin-2-yl)-1-tritylpyrazol-4-yl]pyridin-2-yl]phenyl]morpholine Chemical compound CC1=CC=CC(C=2C(=CN(N=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=2C=C(N=CC=2)C=2C=CC(=CC=2)N2CCOCC2)=N1 KNSAMIHAIQCBHB-UHFFFAOYSA-N 0.000 description 2
DCGMQOIPUNITNH-UHFFFAOYSA-N 4-[4-[5-(6-methylpyridin-2-yl)-2-propan-2-yl-1h-imidazol-4-yl]pyridin-2-yl]benzaldehyde Chemical compound N1C(C(C)C)=NC(C=2C=C(N=CC=2)C=2C=CC(C=O)=CC=2)=C1C1=CC=CC(C)=N1 DCGMQOIPUNITNH-UHFFFAOYSA-N 0.000 description 2
FKMRQZFVMZOWHD-UHFFFAOYSA-N 4-[[4-[4-[2-(6-methylpyridin-2-yl)ethynyl]pyridin-2-yl]phenyl]methyl]morpholine Chemical compound CC1=CC=CC(C#CC=2C=C(N=CC=2)C=2C=CC(CN3CCOCC3)=CC=2)=N1 FKMRQZFVMZOWHD-UHFFFAOYSA-N 0.000 description 2
UOHHVCYLYIQXFG-UHFFFAOYSA-N 5-[2-[4-(aminomethyl)phenyl]-5-pyridin-4-yl-1h-imidazol-4-yl]-2-chlorophenol Chemical compound C1=CC(CN)=CC=C1C1=NC(C=2C=C(O)C(Cl)=CC=2)=C(C=2C=CN=CC=2)N1 UOHHVCYLYIQXFG-UHFFFAOYSA-N 0.000 description 2
239000005541 ACE inhibitor Substances 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical class N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
239000005695 Ammonium acetate Chemical class 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
102000004127 Cytokines Human genes 0.000 description 2
108090000695 Cytokines Proteins 0.000 description 2
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 2
101000712674 Homo sapiens TGF-beta receptor type-1 Proteins 0.000 description 2
208000014919 IgG4-related retroperitoneal fibrosis Diseases 0.000 description 2
241000254158 Lampyridae Species 0.000 description 2
235000010643 Leucaena leucocephala Nutrition 0.000 description 2
240000007472 Leucaena leucocephala Species 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
235000019502 Orange oil Nutrition 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
102000012335 Plasminogen Activator Inhibitor 1 Human genes 0.000 description 2
108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 2
206010038979 Retroperitoneal fibrosis Diseases 0.000 description 2
102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
102100033456 TGF-beta receptor type-1 Human genes 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
208000025865 Ulcer Diseases 0.000 description 2
YSMRWZHDCKWGEE-UHFFFAOYSA-N [4-[4-[2-(6-methylpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]pyridin-2-yl]phenyl]-morpholin-4-ylmethanone Chemical compound CC1=CC=CC(C2=C(N3C=CC=CC3=N2)C=2C=C(N=CC=2)C=2C=CC(=CC=2)C(=O)N2CCOCC2)=N1 YSMRWZHDCKWGEE-UHFFFAOYSA-N 0.000 description 2
238000009825 accumulation Methods 0.000 description 2
SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
230000004913 activation Effects 0.000 description 2
230000032683 aging Effects 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
235000019257 ammonium acetate Nutrition 0.000 description 2
229940043376 ammonium acetate Drugs 0.000 description 2
239000002333 angiotensin II receptor antagonist Substances 0.000 description 2
229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
239000012131 assay buffer Substances 0.000 description 2
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-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
201000011510 cancer Diseases 0.000 description 2
239000002775 capsule Substances 0.000 description 2
235000011089 carbon dioxide Nutrition 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
238000010276 construction Methods 0.000 description 2
206010012601 diabetes mellitus Diseases 0.000 description 2
ASMQGLCHMVWBQR-UHFFFAOYSA-M diphenyl phosphate Chemical compound C=1C=CC=CC=1OP(=O)([O-])OC1=CC=CC=C1 ASMQGLCHMVWBQR-UHFFFAOYSA-M 0.000 description 2
231100000673 dose–response relationship Toxicity 0.000 description 2
239000008157 edible vegetable oil Substances 0.000 description 2
FQYYIPZPELSLDK-UHFFFAOYSA-N ethyl pyridine-2-carboxylate Chemical compound CCOC(=O)C1=CC=CC=N1 FQYYIPZPELSLDK-UHFFFAOYSA-N 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
238000011049 filling Methods 0.000 description 2
238000002875 fluorescence polarization Methods 0.000 description 2
125000002541 furyl group Chemical group 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
208000006454 hepatitis Diseases 0.000 description 2
231100000283 hepatitis Toxicity 0.000 description 2
208000027866 inflammatory disease Diseases 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
230000003834 intracellular effect Effects 0.000 description 2
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000007788 liquid Substances 0.000 description 2
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
239000012669 liquid formulation Substances 0.000 description 2
239000006210 lotion Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
239000011159 matrix material Substances 0.000 description 2
239000002480 mineral oil Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
238000006386 neutralization reaction Methods 0.000 description 2
QCYXGORGJYUYMT-UHFFFAOYSA-N nickel;triphenylphosphane Chemical compound [Ni].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QCYXGORGJYUYMT-UHFFFAOYSA-N 0.000 description 2
239000010502 orange oil Substances 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
229920000642 polymer Polymers 0.000 description 2
239000000651 prodrug Substances 0.000 description 2
229940002612 prodrug Drugs 0.000 description 2
150000003217 pyrazoles Chemical class 0.000 description 2
230000036573 scar formation Effects 0.000 description 2
235000004400 serine 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
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
230000000699 topical effect Effects 0.000 description 2
231100000419 toxicity Toxicity 0.000 description 2
230000001988 toxicity Effects 0.000 description 2
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 2
SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 2
CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 2
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
231100000397 ulcer Toxicity 0.000 description 2
239000008215 water for injection Substances 0.000 description 2
239000000080 wetting agent Substances 0.000 description 2
NLEAEGDBKRBJAP-UHFFFAOYSA-N (1-methylimidazol-4-yl)methanol Chemical compound CN1C=NC(CO)=C1 NLEAEGDBKRBJAP-UHFFFAOYSA-N 0.000 description 1
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
PQCXFUXRTRESBD-UHFFFAOYSA-N (4-methoxycarbonylphenyl)boronic acid Chemical compound COC(=O)C1=CC=C(B(O)O)C=C1 PQCXFUXRTRESBD-UHFFFAOYSA-N 0.000 description 1
VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 1
ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-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
DNXKRKIZBAPODA-UHFFFAOYSA-N 1,1,1-trifluoro-n-[4-[4-[2-(6-methylpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]pyridin-2-yl]phenyl]methanesulfonamide Chemical compound CC1=CC=CC(C2=C(N3C=CC=CC3=N2)C=2C=C(N=CC=2)C=2C=CC(NS(=O)(=O)C(F)(F)F)=CC=2)=N1 DNXKRKIZBAPODA-UHFFFAOYSA-N 0.000 description 1
ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
FBZVZUSVGKOWHG-UHFFFAOYSA-N 1,1-dimethoxy-n,n-dimethylethanamine Chemical compound COC(C)(OC)N(C)C FBZVZUSVGKOWHG-UHFFFAOYSA-N 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
LKEFQAPJECEKMP-UHFFFAOYSA-N 1-(2-bromopyridin-4-yl)-2-pyridin-2-ylethanone Chemical compound C1=NC(Br)=CC(C(=O)CC=2N=CC=CC=2)=C1 LKEFQAPJECEKMP-UHFFFAOYSA-N 0.000 description 1
CLEVZBPYLTYZHC-UHFFFAOYSA-N 1-(4-bromophenyl)-4-ethylpiperazine Chemical compound C1CN(CC)CCN1C1=CC=C(Br)C=C1 CLEVZBPYLTYZHC-UHFFFAOYSA-N 0.000 description 1
IPHDYJQRTVYZQP-UHFFFAOYSA-N 1-(6-methylpyridin-2-yl)-2-[2-(4-methylsulfonylphenyl)pyridin-4-yl]ethanone Chemical compound CC1=CC=CC(C(=O)CC=2C=C(N=CC=2)C=2C=CC(=CC=2)S(C)(=O)=O)=N1 IPHDYJQRTVYZQP-UHFFFAOYSA-N 0.000 description 1
WBUPCGAPZVHYFP-UHFFFAOYSA-N 1-(6-methylpyridin-2-yl)-2-[2-[4-(morpholin-4-ylmethyl)phenyl]pyridin-4-yl]ethanone Chemical compound CC1=CC=CC(C(=O)CC=2C=C(N=CC=2)C=2C=CC(CN3CCOCC3)=CC=2)=N1 WBUPCGAPZVHYFP-UHFFFAOYSA-N 0.000 description 1
UUSOYYGQBDGXLW-UHFFFAOYSA-N 1-(6-methylpyridin-2-yl)-2-[2-[4-(morpholine-4-carbonyl)phenyl]pyridin-4-yl]ethanone Chemical compound CC1=CC=CC(C(=O)CC=2C=C(N=CC=2)C=2C=CC(=CC=2)C(=O)N2CCOCC2)=N1 UUSOYYGQBDGXLW-UHFFFAOYSA-N 0.000 description 1
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
UQOHIHGLOBCJBW-UHFFFAOYSA-N 1-[2-(4-ethylsulfonylphenyl)pyridin-4-yl]-2-(6-methylpyridin-2-yl)ethanone Chemical compound C1=CC(S(=O)(=O)CC)=CC=C1C1=CC(C(=O)CC=2N=C(C)C=CC=2)=CC=N1 UQOHIHGLOBCJBW-UHFFFAOYSA-N 0.000 description 1
CWRJPBXIVVHQOC-UHFFFAOYSA-N 1-[2-(4-iodophenoxy)ethyl]pyrrolidine Chemical compound C1=CC(I)=CC=C1OCCN1CCCC1 CWRJPBXIVVHQOC-UHFFFAOYSA-N 0.000 description 1
GOBUEBRZJFNDIL-UHFFFAOYSA-N 1-[2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]ethyl]pyrrolidine Chemical compound O1C(C)(C)C(C)(C)OB1C(C=C1)=CC=C1OCCN1CCCC1 GOBUEBRZJFNDIL-UHFFFAOYSA-N 0.000 description 1
JQXLGLYYCVQNSB-UHFFFAOYSA-N 1-[2-[4-[(dimethylamino)methyl]phenyl]pyridin-4-yl]-2-(6-methylpyridin-2-yl)ethanone Chemical compound C1=CC(CN(C)C)=CC=C1C1=CC(C(=O)CC=2N=C(C)C=CC=2)=CC=N1 JQXLGLYYCVQNSB-UHFFFAOYSA-N 0.000 description 1
FRYUGGOICYEJHA-UHFFFAOYSA-N 1-[4-[4-[2-tert-butyl-5-(6-methylpyridin-2-yl)-1h-imidazol-4-yl]pyridin-2-yl]phenyl]-n,n-dimethylmethanamine Chemical compound C1=CC(CN(C)C)=CC=C1C1=CC(C2=C(NC(=N2)C(C)(C)C)C=2N=C(C)C=CC=2)=CC=N1 FRYUGGOICYEJHA-UHFFFAOYSA-N 0.000 description 1
OSJYTVPEVGWXNG-UHFFFAOYSA-N 1-ethyl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine Chemical compound C1CN(CC)CCN1C1=CC=C(B2OC(C)(C)C(C)(C)O2)C=C1 OSJYTVPEVGWXNG-UHFFFAOYSA-N 0.000 description 1
QUFYPJILXRCKSB-UHFFFAOYSA-N 1-ethyl-4-phenylpiperazine Chemical compound C1CN(CC)CCN1C1=CC=CC=C1 QUFYPJILXRCKSB-UHFFFAOYSA-N 0.000 description 1
WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 1
BCOZHCQIQWULQO-UHFFFAOYSA-N 1-morpholin-4-yl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]ethanone Chemical compound O1C(C)(C)C(C)(C)OB1C(C=C1)=CC=C1OCC(=O)N1CCOCC1 BCOZHCQIQWULQO-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
ZLGHROSJIVPXMQ-UHFFFAOYSA-N 2-(2-bromopyridin-4-yl)-1-(6-fluoropyridin-2-yl)ethanone Chemical compound FC1=CC=CC(C(=O)CC=2C=C(Br)N=CC=2)=N1 ZLGHROSJIVPXMQ-UHFFFAOYSA-N 0.000 description 1
ANVYOPGUUTWDND-UHFFFAOYSA-N 2-(2-bromopyridin-4-yl)-1-(6-methylpyridin-2-yl)ethanone Chemical compound CC1=CC=CC(C(=O)CC=2C=C(Br)N=CC=2)=N1 ANVYOPGUUTWDND-UHFFFAOYSA-N 0.000 description 1
RKVGSLYSLROWJI-UHFFFAOYSA-N 2-(2-bromopyridin-4-yl)-1-pyridin-2-ylethanone Chemical compound C1=NC(Br)=CC(CC(=O)C=2N=CC=CC=2)=C1 RKVGSLYSLROWJI-UHFFFAOYSA-N 0.000 description 1
RXURQJRTTMZJEN-UHFFFAOYSA-N 2-(2-bromopyridin-4-yl)-2-hydroxyimino-1-(6-methylpyridin-2-yl)ethanone Chemical compound CC1=CC=CC(C(=O)C(=NO)C=2C=C(Br)N=CC=2)=N1 RXURQJRTTMZJEN-UHFFFAOYSA-N 0.000 description 1
XIZICYZRYNWHSK-UHFFFAOYSA-N 2-(4-bromophenyl)-4-[3-(6-methylpyridin-2-yl)-1-tritylpyrazol-4-yl]pyridine Chemical compound CC1=CC=CC(C=2C(=CN(N=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=2C=C(N=CC=2)C=2C=CC(Br)=CC=2)=N1 XIZICYZRYNWHSK-UHFFFAOYSA-N 0.000 description 1
WWSOICDEJYWHAW-UHFFFAOYSA-N 2-(6-methylpyridin-2-yl)-1-[2-[4-(morpholin-4-ylmethyl)phenyl]pyridin-4-yl]ethanone Chemical compound CC1=CC=CC(CC(=O)C=2C=C(N=CC=2)C=2C=CC(CN3CCOCC3)=CC=2)=N1 WWSOICDEJYWHAW-UHFFFAOYSA-N 0.000 description 1
REJKYCQZRLYZDU-UHFFFAOYSA-N 2-(6-methylpyridin-2-yl)-1-[2-[4-(pyrrolidin-1-ylmethyl)phenyl]pyridin-4-yl]ethanone Chemical compound CC1=CC=CC(CC(=O)C=2C=C(N=CC=2)C=2C=CC(CN3CCCC3)=CC=2)=N1 REJKYCQZRLYZDU-UHFFFAOYSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
VXLQBJJTWLCASR-UHFFFAOYSA-N 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]acetamide Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(OCC(N)=O)C=C1 VXLQBJJTWLCASR-UHFFFAOYSA-N 0.000 description 1
SNVHBGDHYZMDEE-UHFFFAOYSA-N 2-[4-[2-(4-ethylsulfonylphenyl)pyridin-4-yl]-1h-pyrazol-5-yl]-6-methylpyridine Chemical compound C1=CC(S(=O)(=O)CC)=CC=C1C1=CC(C=2C(=NNC=2)C=2N=C(C)C=CC=2)=CC=N1 SNVHBGDHYZMDEE-UHFFFAOYSA-N 0.000 description 1
YSOAMSPADJLAHI-UHFFFAOYSA-N 2-[4-[4-[7-methyl-2-(6-methylpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]pyridin-2-yl]phenoxy]acetamide Chemical compound N1=C2C=C(C)C=CN2C(C=2C=C(N=CC=2)C=2C=CC(OCC(N)=O)=CC=2)=C1C1=CC=CC(C)=N1 YSOAMSPADJLAHI-UHFFFAOYSA-N 0.000 description 1
SAXOZKCDGRKDER-UHFFFAOYSA-N 2-[4-[4-[8-methyl-2-(6-methylpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]pyridin-2-yl]phenoxy]acetamide Chemical compound CC1=CC=CC(C2=C(N3C=CC=C(C)C3=N2)C=2C=C(N=CC=2)C=2C=CC(OCC(N)=O)=CC=2)=N1 SAXOZKCDGRKDER-UHFFFAOYSA-N 0.000 description 1
KZMKVPDVYKCZLG-UHFFFAOYSA-N 2-bromo-2-(2-bromopyridin-4-yl)-1-pyridin-2-ylethanone Chemical compound C=1C=NC(Br)=CC=1C(Br)C(=O)C1=CC=CC=N1 KZMKVPDVYKCZLG-UHFFFAOYSA-N 0.000 description 1
BWUAMQFOSCMITC-UHFFFAOYSA-N 2-bromo-4-[2-tert-butyl-5-(6-methylpyridin-2-yl)-1h-imidazol-4-yl]pyridine Chemical compound CC1=CC=CC(C2=C(NC(=N2)C(C)(C)C)C=2C=C(Br)N=CC=2)=N1 BWUAMQFOSCMITC-UHFFFAOYSA-N 0.000 description 1
BFFJBDMFOFAEFK-UHFFFAOYSA-N 2-bromo-4-[3-(6-methylpyridin-2-yl)-1-tritylpyrazol-4-yl]pyridine Chemical compound CC1=CC=CC(C=2C(=CN(N=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=2C=C(Br)N=CC=2)=N1 BFFJBDMFOFAEFK-UHFFFAOYSA-N 0.000 description 1
GKBTUXZBWAQUET-UHFFFAOYSA-N 2-bromo-4-[5-(6-methylpyridin-2-yl)-1h-pyrazol-4-yl]pyridine Chemical compound CC1=CC=CC(C=2C(=CNN=2)C=2C=C(Br)N=CC=2)=N1 GKBTUXZBWAQUET-UHFFFAOYSA-N 0.000 description 1
GEASTUPUWACIOE-UHFFFAOYSA-N 2-bromo-4-[5-methyl-3-(6-methylpyridin-2-yl)-1-tritylpyrazol-4-yl]pyridine Chemical compound CC1=C(C=2C=C(Br)N=CC=2)C(C=2N=C(C)C=CC=2)=NN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 GEASTUPUWACIOE-UHFFFAOYSA-N 0.000 description 1
TVWWPOMKPVJUQR-UHFFFAOYSA-N 2-bromo-4-[5-methyl-3-(6-methylpyridin-2-yl)-1h-pyrazol-4-yl]pyridine Chemical compound CC=1NN=C(C=2N=C(C)C=CC=2)C=1C1=CC=NC(Br)=C1 TVWWPOMKPVJUQR-UHFFFAOYSA-N 0.000 description 1
YMQRPXBBBOXHNZ-UHFFFAOYSA-N 2-chloro-1-morpholin-4-ylethanone Chemical compound ClCC(=O)N1CCOCC1 YMQRPXBBBOXHNZ-UHFFFAOYSA-N 0.000 description 1
KJKIPRQNFDUULB-UHFFFAOYSA-N 2-chloro-4-iodopyridine Chemical compound ClC1=CC(I)=CC=N1 KJKIPRQNFDUULB-UHFFFAOYSA-N 0.000 description 1
UFPOSTQMFOYHJI-UHFFFAOYSA-N 2-chloropyridine-4-carbaldehyde Chemical compound ClC1=CC(C=O)=CC=N1 UFPOSTQMFOYHJI-UHFFFAOYSA-N 0.000 description 1
LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 1
RUFOVPQUNXLVFW-UHFFFAOYSA-N 2-ethynyl-6-methylpyridine Chemical compound CC1=CC=CC(C#C)=N1 RUFOVPQUNXLVFW-UHFFFAOYSA-N 0.000 description 1
UDMNVTJFUISBFD-UHFFFAOYSA-N 2-fluoro-6-methylpyridine Chemical compound CC1=CC=CC(F)=N1 UDMNVTJFUISBFD-UHFFFAOYSA-N 0.000 description 1
LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 1
XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
DXSIVXWMQSJWQB-UHFFFAOYSA-N 2-methyl-6-[2-[2-(4-methylsulfonylphenyl)pyridin-4-yl]ethynyl]pyridine Chemical compound CC1=CC=CC(C#CC=2C=C(N=CC=2)C=2C=CC(=CC=2)S(C)(=O)=O)=N1 DXSIVXWMQSJWQB-UHFFFAOYSA-N 0.000 description 1
CMFHUVSDQOCGNU-UHFFFAOYSA-N 2-methyl-6-[4-[2-[4-(2-methylimidazol-1-yl)phenyl]pyridin-4-yl]-1h-pyrazol-5-yl]pyridine Chemical compound CC1=NC=CN1C1=CC=C(C=2N=CC=C(C=2)C=2C(=NNC=2)C=2N=C(C)C=CC=2)C=C1 CMFHUVSDQOCGNU-UHFFFAOYSA-N 0.000 description 1
WCJYXMQHCIEKAS-UHFFFAOYSA-N 2-methyl-6-[4-[2-[4-(pyrrolidin-1-ylmethyl)phenyl]pyridin-4-yl]-1h-pyrazol-5-yl]pyridine Chemical compound CC1=CC=CC(C=2C(=CNN=2)C=2C=C(N=CC=2)C=2C=CC(CN3CCCC3)=CC=2)=N1 WCJYXMQHCIEKAS-UHFFFAOYSA-N 0.000 description 1
BFLSKNVIEQFBIN-UHFFFAOYSA-N 2-methyl-6-[4-[2-[4-[(1-methylimidazol-4-yl)methoxy]phenyl]pyridin-4-yl]-1h-pyrazol-5-yl]pyridine Chemical compound CC1=CC=CC(C=2C(=CNN=2)C=2C=C(N=CC=2)C=2C=CC(OCC=3N=CN(C)C=3)=CC=2)=N1 BFLSKNVIEQFBIN-UHFFFAOYSA-N 0.000 description 1
ICGYBJNONRDZOP-UHFFFAOYSA-N 2-morpholin-4-ium-4-ylacetic acid;chloride Chemical compound Cl.OC(=O)CN1CCOCC1 ICGYBJNONRDZOP-UHFFFAOYSA-N 0.000 description 1
SFHCTSWZYNNONF-UHFFFAOYSA-N 2-pyridin-2-yl-3-[2-[4-(2-pyrrolidin-1-ylethoxy)phenyl]pyridin-4-yl]imidazo[1,2-a]pyridine Chemical compound C=1C=C(C=2N=CC=C(C=2)C=2N3C=CC=CC3=NC=2C=2N=CC=CC=2)C=CC=1OCCN1CCCC1 SFHCTSWZYNNONF-UHFFFAOYSA-N 0.000 description 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
GJVXSCSUXAGWDN-UHFFFAOYSA-N 3-(2-bromopyridin-4-yl)-2-pyridin-2-ylimidazo[1,2-a]pyridine Chemical compound C1=NC(Br)=CC(C=2N3C=CC=CC3=NC=2C=2N=CC=CC=2)=C1 GJVXSCSUXAGWDN-UHFFFAOYSA-N 0.000 description 1
UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
PQABMZRAKCAJQK-UHFFFAOYSA-N 3-[2-(4-methoxyphenyl)pyridin-4-yl]-2-pyridin-2-ylimidazo[1,2-a]pyridine Chemical compound C1=CC(OC)=CC=C1C1=CC(C=2N3C=CC=CC3=NC=2C=2N=CC=CC=2)=CC=N1 PQABMZRAKCAJQK-UHFFFAOYSA-N 0.000 description 1
QGEBVDXSHSKVRT-UHFFFAOYSA-N 3-[2-[4-(2-bromoethoxy)phenyl]pyridin-4-yl]-2-pyridin-2-ylimidazo[1,2-a]pyridine Chemical compound C1=CC(OCCBr)=CC=C1C1=CC(C=2N3C=CC=CC3=NC=2C=2N=CC=CC=2)=CC=N1 QGEBVDXSHSKVRT-UHFFFAOYSA-N 0.000 description 1
NPPIXSXSFGFFON-UHFFFAOYSA-N 3-[2-[4-(4-methylpiperazin-1-yl)phenyl]pyridin-4-yl]-2-pyridin-2-ylimidazo[1,2-a]pyridine Chemical compound C1CN(C)CCN1C1=CC=C(C=2N=CC=C(C=2)C=2N3C=CC=CC3=NC=2C=2N=CC=CC=2)C=C1 NPPIXSXSFGFFON-UHFFFAOYSA-N 0.000 description 1
XNEPQCOHCFFCBV-UHFFFAOYSA-N 3-[2-[4-[(1-methylimidazol-4-yl)methoxy]phenyl]pyridin-4-yl]-2-(6-methylpyridin-2-yl)imidazo[1,2-a]pyridine Chemical compound CC1=CC=CC(C2=C(N3C=CC=CC3=N2)C=2C=C(N=CC=2)C=2C=CC(OCC=3N=CN(C)C=3)=CC=2)=N1 XNEPQCOHCFFCBV-UHFFFAOYSA-N 0.000 description 1
UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
PKTSBFXIHLYGEY-UHFFFAOYSA-N 3-chloro-4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C(Cl)=C1 PKTSBFXIHLYGEY-UHFFFAOYSA-N 0.000 description 1
FAXDZWQIWUSWJH-UHFFFAOYSA-N 3-methoxypropan-1-amine Chemical compound COCCCN FAXDZWQIWUSWJH-UHFFFAOYSA-N 0.000 description 1
LZPWAYBEOJRFAX-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2$l^{2}-dioxaborolane Chemical compound CC1(C)O[B]OC1(C)C LZPWAYBEOJRFAX-UHFFFAOYSA-N 0.000 description 1
VHYYUYUCDQPTFE-UHFFFAOYSA-N 4-(2-tert-butyl-5-pyridin-2-yl-1h-imidazol-4-yl)-2-[4-[(1-methylimidazol-4-yl)methoxy]phenyl]pyridine Chemical compound CN1C=NC(COC=2C=CC(=CC=2)C=2N=CC=C(C=2)C2=C(NC(=N2)C(C)(C)C)C=2N=CC=CC=2)=C1 VHYYUYUCDQPTFE-UHFFFAOYSA-N 0.000 description 1
IYDKBQIEOBXLTP-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(C(O)=O)C=C1 IYDKBQIEOBXLTP-UHFFFAOYSA-N 0.000 description 1
UJTKZWNRUPTHSB-UHFFFAOYSA-N 4-(4-bromophenyl)morpholine Chemical compound C1=CC(Br)=CC=C1N1CCOCC1 UJTKZWNRUPTHSB-UHFFFAOYSA-N 0.000 description 1
UFWPWAYADRYSBA-UHFFFAOYSA-N 4-(chloromethyl)-1-methylimidazole;hydrochloride Chemical compound Cl.CN1C=NC(CCl)=C1 UFWPWAYADRYSBA-UHFFFAOYSA-N 0.000 description 1
BLBDTBCGPHPIJK-UHFFFAOYSA-N 4-Amino-2-chloropyridine Chemical compound NC1=CC=NC(Cl)=C1 BLBDTBCGPHPIJK-UHFFFAOYSA-N 0.000 description 1
UCPALIMHMYIZPZ-UHFFFAOYSA-N 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]morpholine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(N2CCOCC2)C=C1 UCPALIMHMYIZPZ-UHFFFAOYSA-N 0.000 description 1
IYFGFYLSWMJVLS-UHFFFAOYSA-N 4-[4-(4-methylpyridin-2-yl)phenyl]morpholine Chemical compound CC1=CC=NC(C=2C=CC(=CC=2)N2CCOCC2)=C1 IYFGFYLSWMJVLS-UHFFFAOYSA-N 0.000 description 1
MVKWEFIEDUOTEQ-UHFFFAOYSA-N 4-[4-[2-(6-methylpyridin-2-yl)-2-oxoethyl]pyridin-2-yl]-n-(oxan-4-yl)benzamide Chemical compound CC1=CC=CC(C(=O)CC=2C=C(N=CC=2)C=2C=CC(=CC=2)C(=O)NC2CCOCC2)=N1 MVKWEFIEDUOTEQ-UHFFFAOYSA-N 0.000 description 1
CIOMOYOUORHQKI-UHFFFAOYSA-N 4-[4-[2-(6-methylpyridin-2-yl)-2-oxoethyl]pyridin-2-yl]benzoic acid Chemical compound CC1=CC=CC(C(=O)CC=2C=C(N=CC=2)C=2C=CC(=CC=2)C(O)=O)=N1 CIOMOYOUORHQKI-UHFFFAOYSA-N 0.000 description 1
XICZBKYSRPYSOL-UHFFFAOYSA-N 4-[4-[2-(6-methylpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]pyridin-2-yl]aniline Chemical compound CC1=CC=CC(C2=C(N3C=CC=CC3=N2)C=2C=C(N=CC=2)C=2C=CC(N)=CC=2)=N1 XICZBKYSRPYSOL-UHFFFAOYSA-N 0.000 description 1
CRZLQMPIRZORCO-UHFFFAOYSA-N 4-[4-[2-(6-methylpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]pyridin-2-yl]benzaldehyde Chemical compound CC1=CC=CC(C2=C(N3C=CC=CC3=N2)C=2C=C(N=CC=2)C=2C=CC(C=O)=CC=2)=N1 CRZLQMPIRZORCO-UHFFFAOYSA-N 0.000 description 1
FFLXHMJABLAWTP-UHFFFAOYSA-N 4-[4-[2-tert-butyl-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl]pyridin-2-yl]phenol Chemical compound CC1=CC=CC(C2=C(N=C(N2)C(C)(C)C)C=2C=C(N=CC=2)C=2C=CC(O)=CC=2)=N1 FFLXHMJABLAWTP-UHFFFAOYSA-N 0.000 description 1
BCLUWYCKADHPLC-UHFFFAOYSA-N 4-[4-[2-tert-butyl-5-(6-methylpyridin-2-yl)-1h-imidazol-4-yl]pyridin-2-yl]benzaldehyde Chemical compound CC1=CC=CC(C2=C(N=C(N2)C(C)(C)C)C=2C=C(N=CC=2)C=2C=CC(C=O)=CC=2)=N1 BCLUWYCKADHPLC-UHFFFAOYSA-N 0.000 description 1
NQZCTTMAGFPKLZ-UHFFFAOYSA-N 4-[4-[3-(6-methylpyridin-2-yl)-1-tritylpyrazol-4-yl]pyridin-2-yl]aniline Chemical compound CC1=CC=CC(C=2C(=CN(N=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=2C=C(N=CC=2)C=2C=CC(N)=CC=2)=N1 NQZCTTMAGFPKLZ-UHFFFAOYSA-N 0.000 description 1
MJCKKHXIPPHTNX-UHFFFAOYSA-N 4-[4-[3-(6-methylpyridin-2-yl)-1-tritylpyrazol-4-yl]pyridin-2-yl]benzaldehyde Chemical compound CC1=CC=CC(C=2C(=CN(N=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=2C=C(N=CC=2)C=2C=CC(C=O)=CC=2)=N1 MJCKKHXIPPHTNX-UHFFFAOYSA-N 0.000 description 1
MMEZUGQUUAYCMA-UHFFFAOYSA-N 4-[4-[3-(6-methylpyridin-2-yl)-1-tritylpyrazol-4-yl]pyridin-2-yl]benzoic acid Chemical compound CC1=CC=CC(C=2C(=CN(N=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=2C=C(N=CC=2)C=2C=CC(=CC=2)C(O)=O)=N1 MMEZUGQUUAYCMA-UHFFFAOYSA-N 0.000 description 1
ZYANDFMHYAJFHN-UHFFFAOYSA-N 4-[4-[3-(6-methylpyridin-2-yl)-1-tritylpyrazol-4-yl]pyridin-2-yl]phenol Chemical compound CC1=CC=CC(C=2C(=CN(N=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=2C=C(N=CC=2)C=2C=CC(O)=CC=2)=N1 ZYANDFMHYAJFHN-UHFFFAOYSA-N 0.000 description 1
CCGRXCIJCYWWOY-UHFFFAOYSA-N 4-[4-[4-(2-pyridin-2-ylimidazo[1,2-a]pyridin-3-yl)pyridin-2-yl]phenyl]morpholine Chemical compound C1COCCN1C1=CC=C(C=2N=CC=C(C=2)C=2N3C=CC=CC3=NC=2C=2N=CC=CC=2)C=C1 CCGRXCIJCYWWOY-UHFFFAOYSA-N 0.000 description 1
RPQPZQIYRZCVAF-UHFFFAOYSA-N 4-[4-[4-(6-methylpyridin-2-yl)-1h-pyrazol-5-yl]pyridin-2-yl]-n-(oxan-4-yl)benzamide Chemical compound CC1=CC=CC(C=2C(=NNC=2)C=2C=C(N=CC=2)C=2C=CC(=CC=2)C(=O)NC2CCOCC2)=N1 RPQPZQIYRZCVAF-UHFFFAOYSA-N 0.000 description 1
BDWDPXVDMAZYPF-UHFFFAOYSA-N 4-[4-[4-[2-(6-methylpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]pyridin-2-yl]phenyl]morpholine Chemical compound CC1=CC=CC(C2=C(N3C=CC=CC3=N2)C=2C=C(N=CC=2)C=2C=CC(=CC=2)N2CCOCC2)=N1 BDWDPXVDMAZYPF-UHFFFAOYSA-N 0.000 description 1
OVUVYDQEZKASMR-UHFFFAOYSA-N 4-[4-[4-[5-(6-methylpyridin-2-yl)-1h-pyrazol-4-yl]pyridin-2-yl]phenyl]morpholine Chemical compound CC1=CC=CC(C=2C(=CNN=2)C=2C=C(N=CC=2)C=2C=CC(=CC=2)N2CCOCC2)=N1 OVUVYDQEZKASMR-UHFFFAOYSA-N 0.000 description 1
BICUUDDDRDOMIF-UHFFFAOYSA-N 4-[4-[4-[7-methyl-2-(6-methylpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]pyridin-2-yl]phenyl]morpholine Chemical compound N1=C2C=C(C)C=CN2C(C=2C=C(N=CC=2)C=2C=CC(=CC=2)N2CCOCC2)=C1C1=CC=CC(C)=N1 BICUUDDDRDOMIF-UHFFFAOYSA-N 0.000 description 1
MGMRJESXRVPMRC-UHFFFAOYSA-N 4-[4-[5-methyl-3-(6-methylpyridin-2-yl)-1-tritylpyrazol-4-yl]pyridin-2-yl]benzaldehyde Chemical compound CC1=C(C=2C=C(N=CC=2)C=2C=CC(C=O)=CC=2)C(C=2N=C(C)C=CC=2)=NN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 MGMRJESXRVPMRC-UHFFFAOYSA-N 0.000 description 1
NQQMVZUQPDMLHG-UHFFFAOYSA-N 4-[[4-[4-[2-(6-methylpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]pyridin-2-yl]phenyl]methyl]morpholine Chemical compound CC1=CC=CC(C2=C(N3C=CC=CC3=N2)C=2C=C(N=CC=2)C=2C=CC(CN3CCOCC3)=CC=2)=N1 NQQMVZUQPDMLHG-UHFFFAOYSA-N 0.000 description 1
SIAVMDKGVRXFAX-UHFFFAOYSA-N 4-carboxyphenylboronic acid Chemical compound OB(O)C1=CC=C(C(O)=O)C=C1 SIAVMDKGVRXFAX-UHFFFAOYSA-N 0.000 description 1
BBYDXOIZLAWGSL-UHFFFAOYSA-N 4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1 BBYDXOIZLAWGSL-UHFFFAOYSA-N 0.000 description 1
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
VSMDINRNYYEDRN-UHFFFAOYSA-N 4-iodophenol Chemical compound OC1=CC=C(I)C=C1 VSMDINRNYYEDRN-UHFFFAOYSA-N 0.000 description 1
FHQRDEDZJIFJAL-UHFFFAOYSA-N 4-phenylmorpholine Chemical compound C1COCCN1C1=CC=CC=C1 FHQRDEDZJIFJAL-UHFFFAOYSA-N 0.000 description 1
ZHEXKZSHMBMFEK-UHFFFAOYSA-N 5-(2-bromopyridin-4-yl)-4-(6-methylpyridin-2-yl)-1,3-thiazol-2-amine Chemical compound CC1=CC=CC(C2=C(SC(N)=N2)C=2C=C(Br)N=CC=2)=N1 ZHEXKZSHMBMFEK-UHFFFAOYSA-N 0.000 description 1
HGNHHZJYDDYVRK-UHFFFAOYSA-N 5-(2-bromopyridin-4-yl)-4-pyridin-2-yl-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2N=CC=CC=2)=C1C1=CC=NC(Br)=C1 HGNHHZJYDDYVRK-UHFFFAOYSA-N 0.000 description 1
ULVXJAZNDQLXAK-UHFFFAOYSA-N 5-[2-(4-morpholin-4-ylphenyl)pyridin-4-yl]-4-pyridin-2-yl-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2N=CC=CC=2)=C1C(C=1)=CC=NC=1C(C=C1)=CC=C1N1CCOCC1 ULVXJAZNDQLXAK-UHFFFAOYSA-N 0.000 description 1
MAQAGRJURDEYDQ-UHFFFAOYSA-N 6-methylpyridine Chemical compound CC1=C=CC=C[N]1 MAQAGRJURDEYDQ-UHFFFAOYSA-N 0.000 description 1
AHISYUZBWDSPQL-UHFFFAOYSA-N 6-methylpyridine-2-carbaldehyde Chemical compound CC1=CC=CC(C=O)=N1 AHISYUZBWDSPQL-UHFFFAOYSA-N 0.000 description 1
NBPMURLLBHYZII-UHFFFAOYSA-N 7-methyl-3-[2-[4-[(1-methylimidazol-4-yl)methoxy]phenyl]pyridin-4-yl]-2-(6-methylpyridin-2-yl)imidazo[1,2-a]pyridine Chemical compound N1=C2C=C(C)C=CN2C(C=2C=C(N=CC=2)C=2C=CC(OCC=3N=CN(C)C=3)=CC=2)=C1C1=CC=CC(C)=N1 NBPMURLLBHYZII-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
108010059616 Activins Proteins 0.000 description 1
102000005606 Activins Human genes 0.000 description 1
RYVZYACBVYKUHD-UHFFFAOYSA-N Alk5 Natural products CC#CC#CCCCCC=CC(=O)NCC(C)C RYVZYACBVYKUHD-UHFFFAOYSA-N 0.000 description 1
235000019489 Almond oil Nutrition 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 1
108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 1
101000856746 Bos taurus Cytochrome c oxidase subunit 7A1, mitochondrial Proteins 0.000 description 1
KGFLBIYHQWBWPI-UHFFFAOYSA-N C=1C=NC(Br)=CC=1C(=NO)C(=O)C1=CC=CC=N1 Chemical compound C=1C=NC(Br)=CC=1C(=NO)C(=O)C1=CC=CC=N1 KGFLBIYHQWBWPI-UHFFFAOYSA-N 0.000 description 1
WTFPPCPYLZHSQU-UHFFFAOYSA-N CCN(CC1)CCN1C(c1ccc(B2OC(C)(C)C(C)(C)O2)cc1)=O Chemical compound CCN(CC1)CCN1C(c1ccc(B2OC(C)(C)C(C)(C)O2)cc1)=O WTFPPCPYLZHSQU-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
NSDUFEVEPDYBPZ-UHFFFAOYSA-N Cc1cccc(-c2n[nH]cc2-c2cc(-c(cc3)ccc3C(O)=O)ncc2)n1 Chemical compound Cc1cccc(-c2n[nH]cc2-c2cc(-c(cc3)ccc3C(O)=O)ncc2)n1 NSDUFEVEPDYBPZ-UHFFFAOYSA-N 0.000 description 1
102000008186 Collagen Human genes 0.000 description 1
108010035532 Collagen Proteins 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
BZKFMUIJRXWWQK-UHFFFAOYSA-N Cyclopentenone Chemical compound O=C1CCC=C1 BZKFMUIJRXWWQK-UHFFFAOYSA-N 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
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
241000400611 Eucalyptus deanei Species 0.000 description 1
102000016359 Fibronectins Human genes 0.000 description 1
108010067306 Fibronectins Proteins 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
229920000663 Hydroxyethyl cellulose Polymers 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
102000002746 Inhibins Human genes 0.000 description 1
108010004250 Inhibins Proteins 0.000 description 1
206010023330 Keloid scar Diseases 0.000 description 1
206010023421 Kidney fibrosis Diseases 0.000 description 1
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 1
229910010082 LiAlH Inorganic materials 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
241000699660 Mus musculus Species 0.000 description 1
206010067482 No adverse event Diseases 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
229920001774 Perfluoroether Polymers 0.000 description 1
206010051246 Photodermatosis Diseases 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
239000004743 Polypropylene Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
239000004365 Protease Substances 0.000 description 1
241000242739 Renilla Species 0.000 description 1
108010052090 Renilla Luciferases Proteins 0.000 description 1
108700008625 Reporter Genes Proteins 0.000 description 1
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
206010039580 Scar Diseases 0.000 description 1
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
102000007374 Smad Proteins Human genes 0.000 description 1
108010007945 Smad Proteins Proteins 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
239000004902 Softening Agent Substances 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
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
239000004473 Threonine Substances 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
102000011117 Transforming Growth Factor beta2 Human genes 0.000 description 1
101800000304 Transforming growth factor beta-2 Proteins 0.000 description 1
ACZQZTDEUXGZGS-UHFFFAOYSA-N [4-[4-[5-(6-methylpyridin-2-yl)-1h-pyrazol-4-yl]pyridin-2-yl]phenyl]-morpholin-4-ylmethanone Chemical compound CC1=CC=CC(C=2C(=CNN=2)C=2C=C(N=CC=2)C=2C=CC(=CC=2)C(=O)N2CCOCC2)=N1 ACZQZTDEUXGZGS-UHFFFAOYSA-N 0.000 description 1
230000005856 abnormality Effects 0.000 description 1
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
239000002253 acid Substances 0.000 description 1
150000008043 acidic salts Chemical class 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000009471 action Effects 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
239000013543 active substance Substances 0.000 description 1
239000000488 activin Substances 0.000 description 1
239000000654 additive Substances 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
239000008168 almond oil Substances 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
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
229940063655 aluminum stearate Drugs 0.000 description 1
229950003476 aminothiazole Drugs 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
239000003443 antiviral agent Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
150000001543 aryl boronic acids Chemical class 0.000 description 1
238000011914 asymmetric synthesis Methods 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
125000002785 azepinyl group Chemical group 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
PXRIAVXPRVICRE-UHFFFAOYSA-N benzenesulfonic acid;4-methylbenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1.CC1=CC=C(S(O)(=O)=O)C=C1 PXRIAVXPRVICRE-UHFFFAOYSA-N 0.000 description 1
125000003310 benzodiazepinyl group Chemical group N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 1
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
ZDZHCHYQNPQSGG-UHFFFAOYSA-N binaphthyl group Chemical group C1(=CC=CC2=CC=CC=C12)C1=CC=CC2=CC=CC=C12 ZDZHCHYQNPQSGG-UHFFFAOYSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
230000004221 bone function Effects 0.000 description 1
229940112869 bone morphogenetic protein Drugs 0.000 description 1
239000000872 buffer Substances 0.000 description 1
239000006172 buffering agent Substances 0.000 description 1
229910052792 caesium Inorganic materials 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000001364 causal effect Effects 0.000 description 1
238000001311 chemical methods and process Methods 0.000 description 1
229960004106 citric acid Drugs 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
229920001436 collagen Polymers 0.000 description 1
239000003086 colorant Substances 0.000 description 1
230000009137 competitive binding Effects 0.000 description 1
239000012050 conventional carrier Substances 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
239000013058 crude material Substances 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
230000001086 cytosolic effect Effects 0.000 description 1
231100000433 cytotoxic Toxicity 0.000 description 1
230000001472 cytotoxic effect Effects 0.000 description 1
230000006378 damage Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 description 1
SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
125000004609 dihydroquinazolinyl group Chemical group N1(CN=CC2=CC=CC=C12)* 0.000 description 1
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
125000000532 dioxanyl group Chemical group 0.000 description 1
125000005879 dioxolanyl group Chemical group 0.000 description 1
FVWDBVACVTXVJN-UHFFFAOYSA-L dipotassium;propan-2-one;carbonate Chemical compound [K+].[K+].CC(C)=O.[O-]C([O-])=O FVWDBVACVTXVJN-UHFFFAOYSA-L 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
230000009977 dual effect Effects 0.000 description 1
208000000718 duodenal ulcer Diseases 0.000 description 1
210000001198 duodenum Anatomy 0.000 description 1
230000004064 dysfunction Effects 0.000 description 1
239000003221 ear drop Substances 0.000 description 1
229940047652 ear drops Drugs 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
NYURFOITSAPYLU-UHFFFAOYSA-N ethyl 3-chloro-4-fluorobenzoate Chemical compound CCOC(=O)C1=CC=C(F)C(Cl)=C1 NYURFOITSAPYLU-UHFFFAOYSA-N 0.000 description 1
UMPRJGKLMUDRHL-UHFFFAOYSA-N ethyl 4-fluorobenzoate Chemical compound CCOC(=O)C1=CC=C(F)C=C1 UMPRJGKLMUDRHL-UHFFFAOYSA-N 0.000 description 1
230000005284 excitation Effects 0.000 description 1
239000003889 eye drop Substances 0.000 description 1
229940012356 eye drops Drugs 0.000 description 1
239000003885 eye ointment Substances 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
239000012530 fluid Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
239000006260 foam Substances 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
230000006870 function Effects 0.000 description 1
238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
239000000499 gel Substances 0.000 description 1
230000014509 gene expression Effects 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
206010061989 glomerulosclerosis Diseases 0.000 description 1
239000008103 glucose Substances 0.000 description 1
125000005456 glyceride group Chemical group 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
239000008187 granular material Substances 0.000 description 1
230000035876 healing Effects 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
150000002460 imidazoles Chemical class 0.000 description 1
125000002632 imidazolidinyl group Chemical group 0.000 description 1
125000002636 imidazolinyl group Chemical group 0.000 description 1
150000005232 imidazopyridines Chemical class 0.000 description 1
125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000000099 in vitro assay Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
239000000893 inhibin Substances 0.000 description 1
ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
208000014674 injury Diseases 0.000 description 1
102000006495 integrins Human genes 0.000 description 1
108010044426 integrins Proteins 0.000 description 1
UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229940045996 isethionic acid Drugs 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
229940043355 kinase inhibitor Drugs 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
229960000448 lactic acid Drugs 0.000 description 1
229940099563 lactobionic acid Drugs 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
208000019423 liver disease Diseases 0.000 description 1
239000003589 local anesthetic agent Substances 0.000 description 1
229960005015 local anesthetics Drugs 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000008176 lyophilized powder Substances 0.000 description 1
239000012139 lysis buffer Substances 0.000 description 1
210000002540 macrophage Anatomy 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
235000019359 magnesium stearate Nutrition 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
238000005259 measurement Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000028161 membrane depolarization Effects 0.000 description 1
210000003584 mesangial cell Anatomy 0.000 description 1
108020004999 messenger RNA Proteins 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
XRDRKVPNHIWTBX-UHFFFAOYSA-N methyl 3-chlorobenzoate Chemical compound COC(=O)C1=CC=CC(Cl)=C1 XRDRKVPNHIWTBX-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
210000001616 monocyte Anatomy 0.000 description 1
ZOPBEWUNCNLYSD-UHFFFAOYSA-N morpholin-4-yl-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanone Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(C(=O)N2CCOCC2)C=C1 ZOPBEWUNCNLYSD-UHFFFAOYSA-N 0.000 description 1
LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
ZEWYGORJLGSZNO-UHFFFAOYSA-N n,n-dimethyl-2-[4-[4-[2-(6-methylpyridin-2-yl)ethynyl]pyridin-2-yl]phenoxy]ethanamine Chemical compound C1=CC(OCCN(C)C)=CC=C1C1=CC(C#CC=2N=C(C)C=CC=2)=CC=N1 ZEWYGORJLGSZNO-UHFFFAOYSA-N 0.000 description 1
RKZVMZDIJYKSJK-UHFFFAOYSA-N n-(3-methoxypropyl)-4-[4-[2-(6-methylpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]pyridin-2-yl]benzamide Chemical compound C1=CC(C(=O)NCCCOC)=CC=C1C1=CC(C=2N3C=CC=CC3=NC=2C=2N=C(C)C=CC=2)=CC=N1 RKZVMZDIJYKSJK-UHFFFAOYSA-N 0.000 description 1
LEYWRYHAZXRHIB-UHFFFAOYSA-N n-(oxan-4-yl)benzamide Chemical compound C=1C=CC=CC=1C(=O)NC1CCOCC1 LEYWRYHAZXRHIB-UHFFFAOYSA-N 0.000 description 1
NPSPNWPZDXQYAC-UHFFFAOYSA-N n-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanesulfonamide Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(NS(C)(=O)=O)C=C1 NPSPNWPZDXQYAC-UHFFFAOYSA-N 0.000 description 1
VORLCVJQGAXZES-UHFFFAOYSA-N n-[diphenoxyphosphoryl-[2-(4-ethylsulfonylphenyl)pyridin-4-yl]methyl]aniline Chemical compound C1=CC(S(=O)(=O)CC)=CC=C1C1=CC(C(NC=2C=CC=CC=2)P(=O)(OC=2C=CC=CC=2)OC=2C=CC=CC=2)=CC=N1 VORLCVJQGAXZES-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
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000003472 neutralizing effect Effects 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
239000002687 nonaqueous vehicle Substances 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
239000002674 ointment Substances 0.000 description 1
239000003883 ointment base Substances 0.000 description 1
XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
229940055577 oleyl alcohol Drugs 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
238000005457 optimization Methods 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
230000002018 overexpression Effects 0.000 description 1
125000001715 oxadiazolyl group Chemical group 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
239000003182 parenteral nutrition solution Substances 0.000 description 1
230000035515 penetration Effects 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
125000005010 perfluoroalkyl group Chemical group 0.000 description 1
239000012071 phase Substances 0.000 description 1
229910000073 phosphorus hydride Inorganic materials 0.000 description 1
239000003757 phosphotransferase inhibitor Substances 0.000 description 1
230000008845 photoaging Effects 0.000 description 1
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
230000010287 polarization Effects 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920001155 polypropylene Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
238000003825 pressing Methods 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
238000012545 processing Methods 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
235000013772 propylene glycol Nutrition 0.000 description 1
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
235000018102 proteins Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
239000003586 protic polar solvent 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
125000002098 pyridazinyl group Chemical group 0.000 description 1
JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000001422 pyrrolinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
230000005855 radiation Effects 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
238000011084 recovery Methods 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
238000007789 sealing Methods 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000003355 serines Chemical group 0.000 description 1
125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
230000009759 skin aging Effects 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
239000007790 solid phase Substances 0.000 description 1
238000010532 solid phase synthesis reaction Methods 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
239000001593 sorbitan monooleate Substances 0.000 description 1
235000011069 sorbitan monooleate Nutrition 0.000 description 1
229940035049 sorbitan monooleate Drugs 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000002511 suppository base Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 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
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000005308 thiazepinyl group Chemical group S1N=C(C=CC=C1)* 0.000 description 1
125000002769 thiazolinyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
125000005505 thiomorpholino group Chemical group 0.000 description 1
238000004448 titration Methods 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
239000012049 topical pharmaceutical composition Substances 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1
238000001890 transfection Methods 0.000 description 1
238000011830 transgenic mouse model Methods 0.000 description 1
229960001727 tretinoin Drugs 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
WRTMQOHKMFDUKX-UHFFFAOYSA-N triiodide Chemical compound I[I-]I WRTMQOHKMFDUKX-UHFFFAOYSA-N 0.000 description 1
KRCRFMUDDJJGCS-UHFFFAOYSA-N trimethyl-[2-(6-methylpyridin-2-yl)ethynyl]silane Chemical compound CC1=CC=CC(C#C[Si](C)(C)C)=N1 KRCRFMUDDJJGCS-UHFFFAOYSA-N 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
238000005406 washing Methods 0.000 description 1
230000037314 wound repair Effects 0.000 description 1