UA80296C2 - Imidazolopyridines and methods of making and using the same - Google Patents

Info

Publication number

UA80296C2

UA80296C2 UAA200503149A UA2005003149A UA80296C2 UA 80296 C2 UA80296 C2 UA 80296C2 UA A200503149 A UAA200503149 A UA A200503149A UA 2005003149 A UA2005003149 A UA 2005003149A UA 80296 C2 UA80296 C2 UA 80296C2

Authority

UA

Ukraine

Prior art keywords

methylpyridin

imidazo

pyridin

pyrimidin

aminopyrimidin

Prior art date

2002-09-06

Links

• Espacenet
• Global Dossier
• Discuss

• 238000000034 method Methods 0.000 title claims description 32
• GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical class C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 145
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 38
• 201000010099 disease Diseases 0.000 claims abstract description 20
• 230000003176 fibrotic effect Effects 0.000 claims abstract description 11
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 231
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 187
• 125000000217 alkyl group Chemical group 0.000 claims description 164
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 115
• 150000001412 amines Chemical class 0.000 claims description 107
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 95
• -1 hydroxy, amino, nitro, cyano, guanidino, amidino, carboxy, sulfo, mercapto Chemical class 0.000 claims description 75
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 74
• 125000001072 heteroaryl group Chemical group 0.000 claims description 61
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 56
• LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 claims description 47
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 46
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 44
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 42
• 125000003545 alkoxy group Chemical group 0.000 claims description 37
• 150000001408 amides Chemical class 0.000 claims description 33
• DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 32
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 30
• 125000003118 aryl group Chemical group 0.000 claims description 30
• 210000004027 cell Anatomy 0.000 claims description 29
• 125000004414 alkyl thio group Chemical group 0.000 claims description 28
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 28
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 27
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 27
• 125000002252 acyl group Chemical group 0.000 claims description 26
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 24
• 229910052736 halogen Inorganic materials 0.000 claims description 24
• 150000002367 halogens Chemical class 0.000 claims description 23
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 21
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
• 206010016654 Fibrosis Diseases 0.000 claims description 20
• KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 20
• KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 claims description 20
• AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 claims description 19
• KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 claims description 18
• 125000003342 alkenyl group Chemical group 0.000 claims description 18
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 18
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 18
• 208000035475 disorder Diseases 0.000 claims description 17
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 17
• 239000002253 acid Substances 0.000 claims description 16
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 16
• 230000004761 fibrosis Effects 0.000 claims description 16
• 125000001188 haloalkyl group Chemical group 0.000 claims description 16
• 229960003966 nicotinamide Drugs 0.000 claims description 16
• 235000005152 nicotinamide Nutrition 0.000 claims description 16
• 239000011570 nicotinamide Substances 0.000 claims description 16
• 125000000304 alkynyl group Chemical group 0.000 claims description 15
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 14
• 206010028980 Neoplasm Diseases 0.000 claims description 13
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 13
• HVLUYXIJZLDNIS-UHFFFAOYSA-N 2-thiophen-2-ylethanamine Chemical compound NCCC1=CC=CS1 HVLUYXIJZLDNIS-UHFFFAOYSA-N 0.000 claims description 12
• GMPKIPWJBDOURN-UHFFFAOYSA-N Methoxyamine Chemical compound CON GMPKIPWJBDOURN-UHFFFAOYSA-N 0.000 claims description 12
• 150000004702 methyl esters Chemical class 0.000 claims description 12
• 150000003839 salts Chemical class 0.000 claims description 12
• 230000019491 signal transduction Effects 0.000 claims description 12
• NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 claims description 12
• 238000011282 treatment Methods 0.000 claims description 12
• JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 claims description 11
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 claims description 11
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 claims description 11
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 11
• 230000015572 biosynthetic process Effects 0.000 claims description 11
• HWDVTQAXQJQROO-UHFFFAOYSA-N cyclopropylazanide Chemical compound [NH-]C1CC1 HWDVTQAXQJQROO-UHFFFAOYSA-N 0.000 claims description 11
• 210000002744 extracellular matrix Anatomy 0.000 claims description 11
• 125000005224 heteroarylcarbonylamino group Chemical group 0.000 claims description 11
• LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 10
• 125000004104 aryloxy group Chemical group 0.000 claims description 10
• 239000012634 fragment Substances 0.000 claims description 10
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 10
• 229910052739 hydrogen Inorganic materials 0.000 claims description 10
• 239000001257 hydrogen Substances 0.000 claims description 10
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 10
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 9
• 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 9
• 125000004122 cyclic group Chemical group 0.000 claims description 9
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 9
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 9
• 150000002431 hydrogen Chemical class 0.000 claims description 9
• 230000002401 inhibitory effect Effects 0.000 claims description 9
• DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 claims description 9
• 235000019260 propionic acid Nutrition 0.000 claims description 9
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 9
• 125000003396 thiol group Chemical class [H]S* 0.000 claims description 9
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 8
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 8
• ZXKINMCYCKHYFR-UHFFFAOYSA-N aminooxidanide Chemical compound [O-]N ZXKINMCYCKHYFR-UHFFFAOYSA-N 0.000 claims description 8
• 239000004202 carbamide Substances 0.000 claims description 8
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 8
• 125000005169 cycloalkylcarbonylamino group Chemical group 0.000 claims description 8
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
• 210000004185 liver Anatomy 0.000 claims description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 7
• ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 claims description 7
• WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 7
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 7
• 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 7
• 125000003435 aroyl group Chemical group 0.000 claims description 7
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 7
• 210000004072 lung Anatomy 0.000 claims description 7
• 108090000623 proteins and genes Proteins 0.000 claims description 7
• VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 claims description 7
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 6
• 125000005126 aryl alkyl carbonyl amino group Chemical group 0.000 claims description 6
• 125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 6
• 208000019425 cirrhosis of liver Diseases 0.000 claims description 6
• 230000001404 mediated effect Effects 0.000 claims description 6
• 230000002018 overexpression Effects 0.000 claims description 6
• RGUUBRUFWMBQOW-UHFFFAOYSA-N 2-amino-1-pyridin-3-ylethanone Chemical compound NCC(=O)C1=CC=CN=C1 RGUUBRUFWMBQOW-UHFFFAOYSA-N 0.000 claims description 5
• 238000009825 accumulation Methods 0.000 claims description 5
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 5
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
• BBEQQKBWUHCIOU-UHFFFAOYSA-N 5-(dimethylamino)-1-naphthalenesulfonic acid(dansyl acid) Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(O)(=O)=O BBEQQKBWUHCIOU-UHFFFAOYSA-N 0.000 claims description 4
• 239000005711 Benzoic acid Substances 0.000 claims description 4
• 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 4
• 206010027476 Metastases Diseases 0.000 claims description 4
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 4
• 125000005163 aryl sulfanyl group Chemical group 0.000 claims description 4
• 235000010233 benzoic acid Nutrition 0.000 claims description 4
• 210000003445 biliary tract Anatomy 0.000 claims description 4
• 230000007882 cirrhosis Effects 0.000 claims description 4
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
• 125000005114 heteroarylalkoxy group Chemical group 0.000 claims description 4
• 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 4
• 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 4
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
• IPOVLZSJBYKHHU-UHFFFAOYSA-N piperidin-3-ylmethanamine Chemical compound NCC1CCCNC1 IPOVLZSJBYKHHU-UHFFFAOYSA-N 0.000 claims description 4
• FVUKYCZRWSQGAS-UHFFFAOYSA-N 3-carbamoylbenzoic acid Chemical compound NC(=O)C1=CC=CC(C(O)=O)=C1 FVUKYCZRWSQGAS-UHFFFAOYSA-N 0.000 claims description 3
• NOQGZXFMHARMLW-UHFFFAOYSA-N Daminozide Chemical compound CN(C)NC(=O)CCC(O)=O NOQGZXFMHARMLW-UHFFFAOYSA-N 0.000 claims description 3
• 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 3
• 208000007659 Fibroadenoma Diseases 0.000 claims description 3
• 201000008808 Fibrosarcoma Diseases 0.000 claims description 3
• 208000032612 Glial tumor Diseases 0.000 claims description 3
• 206010018338 Glioma Diseases 0.000 claims description 3
• 206010018364 Glomerulonephritis Diseases 0.000 claims description 3
• 206010020772 Hypertension Diseases 0.000 claims description 3
• 208000005777 Lupus Nephritis Diseases 0.000 claims description 3
• 208000034578 Multiple myelomas Diseases 0.000 claims description 3
• 206010035226 Plasma cell myeloma Diseases 0.000 claims description 3
• 206010039710 Scleroderma Diseases 0.000 claims description 3
• 206010046798 Uterine leiomyoma Diseases 0.000 claims description 3
• 206010069351 acute lung injury Diseases 0.000 claims description 3
• 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 3
• 229910052796 boron Inorganic materials 0.000 claims description 3
• 210000003169 central nervous system Anatomy 0.000 claims description 3
• 230000001684 chronic effect Effects 0.000 claims description 3
• 208000033679 diabetic kidney disease Diseases 0.000 claims description 3
• 239000003814 drug Substances 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 206010016629 fibroma Diseases 0.000 claims description 3
• 210000000232 gallbladder Anatomy 0.000 claims description 3
• 210000001035 gastrointestinal tract Anatomy 0.000 claims description 3
• 208000005017 glioblastoma Diseases 0.000 claims description 3
• 201000010260 leiomyoma Diseases 0.000 claims description 3
• 201000001441 melanoma Diseases 0.000 claims description 3
• 210000000496 pancreas Anatomy 0.000 claims description 3
• 239000008194 pharmaceutical composition Substances 0.000 claims description 3
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 3
• 229940080818 propionamide Drugs 0.000 claims description 3
• 210000002307 prostate Anatomy 0.000 claims description 3
• KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 claims description 3
• 229920002554 vinyl polymer Polymers 0.000 claims description 3
• 230000029663 wound healing Effects 0.000 claims description 3
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 2
• 206010001233 Adenoma benign Diseases 0.000 claims description 2
• 208000024827 Alzheimer disease Diseases 0.000 claims description 2
• 206010059245 Angiopathy Diseases 0.000 claims description 2
• 200000000007 Arterial disease Diseases 0.000 claims description 2
• 206010008609 Cholangitis sclerosing Diseases 0.000 claims description 2
• 208000016192 Demyelinating disease Diseases 0.000 claims description 2
• 206010012305 Demyelination Diseases 0.000 claims description 2
• 208000002260 Keloid Diseases 0.000 claims description 2
• 208000004852 Lung Injury Diseases 0.000 claims description 2
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
• 208000032056 Radiation Fibrosis Syndrome Diseases 0.000 claims description 2
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 2
• 206010069363 Traumatic lung injury Diseases 0.000 claims description 2
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
• 125000005018 aryl alkenyl group Chemical group 0.000 claims description 2
• 125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims description 2
• 125000005015 aryl alkynyl group Chemical group 0.000 claims description 2
• 201000003149 breast fibroadenoma Diseases 0.000 claims description 2
• 230000009787 cardiac fibrosis Effects 0.000 claims description 2
• 230000002490 cerebral effect Effects 0.000 claims description 2
• 210000003679 cervix uteri Anatomy 0.000 claims description 2
• 238000002512 chemotherapy Methods 0.000 claims description 2
• 208000018631 connective tissue disease Diseases 0.000 claims description 2
• 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 2
• 229940079593 drug Drugs 0.000 claims description 2
• 208000010706 fatty liver disease Diseases 0.000 claims description 2
• 125000005843 halogen group Chemical group 0.000 claims description 2
• 210000003128 head Anatomy 0.000 claims description 2
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 2
• 210000001117 keloid Anatomy 0.000 claims description 2
• 208000017169 kidney disease Diseases 0.000 claims description 2
• 208000032839 leukemia Diseases 0.000 claims description 2
• 231100000515 lung injury Toxicity 0.000 claims description 2
• 201000006417 multiple sclerosis Diseases 0.000 claims description 2
• 210000003739 neck Anatomy 0.000 claims description 2
• 210000002569 neuron Anatomy 0.000 claims description 2
• 201000000742 primary sclerosing cholangitis Diseases 0.000 claims description 2
• 201000002793 renal fibrosis Diseases 0.000 claims description 2
• 208000037803 restenosis Diseases 0.000 claims description 2
• 208000010157 sclerosing cholangitis Diseases 0.000 claims description 2
• 206010041823 squamous cell carcinoma Diseases 0.000 claims description 2
• 125000005171 cycloalkylsulfanyl group Chemical group 0.000 claims 3
• 230000003902 lesion Effects 0.000 claims 3
• LGRLWUINFJPLSH-UHFFFAOYSA-N methanide Chemical compound [CH3-] LGRLWUINFJPLSH-UHFFFAOYSA-N 0.000 claims 3
• QQVIHTHCMHWDBS-UHFFFAOYSA-N isophthalic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 claims 2
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 1
• 208000032544 Cicatrix Diseases 0.000 claims 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
• 230000001154 acute effect Effects 0.000 claims 1
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims 1
• 125000003282 alkyl amino group Chemical group 0.000 claims 1
• WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 claims 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
• 201000005296 lung carcinoma Diseases 0.000 claims 1
• 210000005075 mammary gland Anatomy 0.000 claims 1
• 230000000414 obstructive effect Effects 0.000 claims 1
• 210000001672 ovary Anatomy 0.000 claims 1
• 231100000241 scar Toxicity 0.000 claims 1
• 230000037387 scars Effects 0.000 claims 1
• 210000000278 spinal cord Anatomy 0.000 claims 1
• 238000012876 topography Methods 0.000 claims 1
• 239000005557 antagonist Substances 0.000 abstract description 7
• 239000011541 reaction mixture Substances 0.000 description 154
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 114
• 238000002360 preparation method Methods 0.000 description 102
• 239000007787 solid Substances 0.000 description 99
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 97
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 92
• 239000000203 mixture Substances 0.000 description 84
• 239000000243 solution Substances 0.000 description 70
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 68
• 239000000725 suspension Substances 0.000 description 57
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 44
• 238000002953 preparative HPLC Methods 0.000 description 44
• 239000003708 ampul Substances 0.000 description 37
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 34
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 31
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
• 239000000126 substance Substances 0.000 description 31
• 239000000488 activin Substances 0.000 description 30
• 239000002244 precipitate Substances 0.000 description 30
• 108010059616 Activins Proteins 0.000 description 29
• 102000005606 Activins Human genes 0.000 description 29
• 238000010992 reflux Methods 0.000 description 29
• 108020003175 receptors Proteins 0.000 description 28
• 102000005962 receptors Human genes 0.000 description 28
• 229960000583 acetic acid Drugs 0.000 description 25
• 238000003756 stirring Methods 0.000 description 25
• 238000004007 reversed phase HPLC Methods 0.000 description 24
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 22
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 22
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 22
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 20
• 230000003197 catalytic effect Effects 0.000 description 19
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 16
• 238000004128 high performance liquid chromatography Methods 0.000 description 16
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• 230000000694 effects Effects 0.000 description 15
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
• 239000000872 buffer Substances 0.000 description 12
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 12
• QWMFKVNJIYNWII-UHFFFAOYSA-N 5-bromo-2-(2,5-dimethylpyrrol-1-yl)pyridine Chemical compound CC1=CC=C(C)N1C1=CC=C(Br)C=N1 QWMFKVNJIYNWII-UHFFFAOYSA-N 0.000 description 11
• 239000004305 biphenyl Substances 0.000 description 11
• 235000010290 biphenyl Nutrition 0.000 description 11
• 229920006395 saturated elastomer Polymers 0.000 description 11
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 10
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
• 239000012074 organic phase Substances 0.000 description 10
• 125000001424 substituent group Chemical group 0.000 description 10
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 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
• 125000004093 cyano group Chemical group *C#N 0.000 description 9
• RAQQRQCODVNJCK-JLHYYAGUSA-N N-[(4-amino-2-methylpyrimidin-5-yl)methyl]-N-[(E)-5-hydroxy-3-(2-hydroxyethyldisulfanyl)pent-2-en-2-yl]formamide Chemical compound C\C(N(Cc1cnc(C)nc1N)C=O)=C(\CCO)SSCCO RAQQRQCODVNJCK-JLHYYAGUSA-N 0.000 description 8
• 230000027455 binding Effects 0.000 description 8
• 235000019439 ethyl acetate Nutrition 0.000 description 8
• 239000012362 glacial acetic acid Substances 0.000 description 8
• 229910000042 hydrogen bromide Inorganic materials 0.000 description 8
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
• 230000005764 inhibitory process Effects 0.000 description 8
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
• 239000000908 ammonium hydroxide Substances 0.000 description 7
• 125000004076 pyridyl group Chemical group 0.000 description 7
• 239000012266 salt solution Substances 0.000 description 7
• 238000012360 testing method Methods 0.000 description 7
• NWGPLYYBECWONP-UHFFFAOYSA-N (carbamoylamino) hydrogen sulfate Chemical compound NC(=O)NOS(O)(=O)=O NWGPLYYBECWONP-UHFFFAOYSA-N 0.000 description 6
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• 238000004458 analytical method Methods 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 125000004043 oxo group Chemical group O=* 0.000 description 6
• 230000002265 prevention Effects 0.000 description 6
• 230000001225 therapeutic effect Effects 0.000 description 6
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 5
• 239000008346 aqueous phase Substances 0.000 description 5
• 201000011510 cancer Diseases 0.000 description 5
• 125000004432 carbon atom Chemical group C* 0.000 description 5
• 238000006243 chemical reaction Methods 0.000 description 5
• 125000002883 imidazolyl group Chemical group 0.000 description 5
• 239000010410 layer Substances 0.000 description 5
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
• XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
• 241000282414 Homo sapiens Species 0.000 description 4
• 239000005089 Luciferase Substances 0.000 description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
• 150000007513 acids Chemical class 0.000 description 4
• 125000001931 aliphatic group Chemical group 0.000 description 4
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
• 125000000392 cycloalkenyl group Chemical group 0.000 description 4
• 239000006274 endogenous ligand Substances 0.000 description 4
• 230000014509 gene expression Effects 0.000 description 4
• 125000005842 heteroatom Chemical class 0.000 description 4
• 238000004519 manufacturing process Methods 0.000 description 4
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 4
• 229910052757 nitrogen Inorganic materials 0.000 description 4
• 239000000546 pharmaceutical excipient Substances 0.000 description 4
• 230000000750 progressive effect Effects 0.000 description 4
• 125000006413 ring segment Chemical group 0.000 description 4
• 230000011664 signaling Effects 0.000 description 4
• 235000017557 sodium bicarbonate Nutrition 0.000 description 4
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
• DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 4
• 239000002904 solvent Substances 0.000 description 4
• 125000003831 tetrazolyl group Chemical group 0.000 description 4
• 210000004881 tumor cell Anatomy 0.000 description 4
• UBWXUGDQUBIEIZ-UHFFFAOYSA-N (13-methyl-3-oxo-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-17-yl) 3-phenylpropanoate Chemical compound CC12CCC(C3CCC(=O)C=C3CC3)C3C1CCC2OC(=O)CCC1=CC=CC=C1 UBWXUGDQUBIEIZ-UHFFFAOYSA-N 0.000 description 3
• IDLHTECVNDEOIY-UHFFFAOYSA-N 2-pyridin-4-ylethanamine Chemical compound NCCC1=CC=NC=C1 IDLHTECVNDEOIY-UHFFFAOYSA-N 0.000 description 3
• XPQIPUZPSLAZDV-UHFFFAOYSA-N 2-pyridylethylamine Chemical compound NCCC1=CC=CC=N1 XPQIPUZPSLAZDV-UHFFFAOYSA-N 0.000 description 3
• UCERVHYBSTYCQS-UHFFFAOYSA-N 4-methyl-2-methylsulfanylpyrimidine Chemical compound CSC1=NC=CC(C)=N1 UCERVHYBSTYCQS-UHFFFAOYSA-N 0.000 description 3
• 102000008186 Collagen Human genes 0.000 description 3
• 108010035532 Collagen Proteins 0.000 description 3
• HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 3
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 241000124008 Mammalia Species 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 108091000080 Phosphotransferase Proteins 0.000 description 3
• 102000001708 Protein Isoforms Human genes 0.000 description 3
• 108010029485 Protein Isoforms Proteins 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• 239000007868 Raney catalyst Substances 0.000 description 3
• 229910000564 Raney nickel Inorganic materials 0.000 description 3
• SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical compound NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 230000035578 autophosphorylation Effects 0.000 description 3
• 238000009835 boiling Methods 0.000 description 3
• 230000001413 cellular effect Effects 0.000 description 3
• 229940047583 cetamide Drugs 0.000 description 3
• 239000003795 chemical substances by application Substances 0.000 description 3
• 229920001436 collagen Polymers 0.000 description 3
• 125000004366 heterocycloalkenyl group Chemical group 0.000 description 3
• 239000003446 ligand Substances 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 230000004048 modification Effects 0.000 description 3
• 238000012986 modification Methods 0.000 description 3
• RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 3
• RIVIDPPYRINTTH-UHFFFAOYSA-N n-ethylpropan-2-amine Chemical compound CCNC(C)C RIVIDPPYRINTTH-UHFFFAOYSA-N 0.000 description 3
• 239000012299 nitrogen atmosphere Substances 0.000 description 3
• 230000001575 pathological effect Effects 0.000 description 3
• 102000020233 phosphotransferase Human genes 0.000 description 3
• 102000004169 proteins and genes Human genes 0.000 description 3
• 125000003226 pyrazolyl group Chemical group 0.000 description 3
• 239000013049 sediment Substances 0.000 description 3
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 210000001519 tissue Anatomy 0.000 description 3
• IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 2
• ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
• NAHHNSMHYCLMON-UHFFFAOYSA-N 2-pyridin-3-ylethanamine Chemical compound NCCC1=CC=CN=C1 NAHHNSMHYCLMON-UHFFFAOYSA-N 0.000 description 2
• BUTKIHRNYUEGKB-UHFFFAOYSA-N 3,3-dimethylbutanoyl chloride Chemical compound CC(C)(C)CC(Cl)=O BUTKIHRNYUEGKB-UHFFFAOYSA-N 0.000 description 2
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 102000018918 Activin Receptors Human genes 0.000 description 2
• 108010052946 Activin Receptors Proteins 0.000 description 2
• 102100040439 Adenylate kinase 4, mitochondrial Human genes 0.000 description 2
• 108050004095 Adenylate kinase 4, mitochondrial Proteins 0.000 description 2
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
• 239000005695 Ammonium acetate Substances 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
• 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 2
• 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 2
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
• 206010006187 Breast cancer Diseases 0.000 description 2
• 208000026310 Breast neoplasm Diseases 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
• RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
• 241000270322 Lepidosauria Species 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 2
• 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 2
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• 241000282887 Suidae Species 0.000 description 2
• 108091079639 Type I family Proteins 0.000 description 2
• 150000001413 amino acids Chemical class 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 235000019257 ammonium acetate Nutrition 0.000 description 2
• 229940043376 ammonium acetate Drugs 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• 239000002585 base Substances 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
• 125000002619 bicyclic group Chemical group 0.000 description 2
• 229940112869 bone morphogenetic protein Drugs 0.000 description 2
• 210000000481 breast Anatomy 0.000 description 2
• 239000012267 brine Substances 0.000 description 2
• 229910052799 carbon Inorganic materials 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• 239000000460 chlorine Substances 0.000 description 2
• 229910052801 chlorine Inorganic materials 0.000 description 2
• 235000015165 citric acid Nutrition 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• 230000001086 cytosolic effect Effects 0.000 description 2
• 230000003013 cytotoxicity Effects 0.000 description 2
• 231100000135 cytotoxicity Toxicity 0.000 description 2
• 230000008021 deposition Effects 0.000 description 2
• 230000004069 differentiation Effects 0.000 description 2
• 239000012894 fetal calf serum Substances 0.000 description 2
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
• XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 2
• 208000013403 hyperactivity Diseases 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 210000004969 inflammatory cell Anatomy 0.000 description 2
• 230000004054 inflammatory process Effects 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• 230000003834 intracellular effect Effects 0.000 description 2
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
• 210000003734 kidney Anatomy 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 108020004999 messenger RNA Proteins 0.000 description 2
• 229940098779 methanesulfonic acid Drugs 0.000 description 2
• 210000000651 myofibroblast Anatomy 0.000 description 2
• 210000000056 organ Anatomy 0.000 description 2
• 239000012044 organic layer Substances 0.000 description 2
• 125000003386 piperidinyl group Chemical group 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 2
• 208000005069 pulmonary fibrosis Diseases 0.000 description 2
• 238000000746 purification Methods 0.000 description 2
• 230000005855 radiation Effects 0.000 description 2
• 238000001959 radiotherapy Methods 0.000 description 2
• 239000002994 raw material Substances 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 210000002966 serum Anatomy 0.000 description 2
• 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 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 229940054269 sodium pyruvate Drugs 0.000 description 2
• 238000001228 spectrum Methods 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 238000013518 transcription Methods 0.000 description 2
• 230000035897 transcription Effects 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• QSLPNSWXUQHVLP-UHFFFAOYSA-N $l^{1}-sulfanylmethane Chemical compound [S]C QSLPNSWXUQHVLP-UHFFFAOYSA-N 0.000 description 1
• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
• 125000004178 (C1-C4) alkyl group Chemical group 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
• DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 description 1
• PREOONMJIVUPMI-UHFFFAOYSA-N 1,4-dioxan-2-ylmethanamine Chemical compound NCC1COCCO1 PREOONMJIVUPMI-UHFFFAOYSA-N 0.000 description 1
• LHLYSNGWIOFMRY-UHFFFAOYSA-N 1-(6-methylpyridin-2-yl)-2-(2-methylsulfanylpyrimidin-4-yl)ethanone Chemical compound CSC1=NC=CC(CC(=O)C=2N=C(C)C=CC=2)=N1 LHLYSNGWIOFMRY-UHFFFAOYSA-N 0.000 description 1
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
• WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
• JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical compound NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 1
• YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
• UPEWDRCXLROYOF-UHFFFAOYSA-N 2-(2-methoxyphenyl)acetyl chloride Chemical compound COC1=CC=CC=C1CC(Cl)=O UPEWDRCXLROYOF-UHFFFAOYSA-N 0.000 description 1
• OZDGMOYKSFPLSE-UHFFFAOYSA-N 2-Methylaziridine Chemical compound CC1CN1 OZDGMOYKSFPLSE-UHFFFAOYSA-N 0.000 description 1
• QMKZZQPPJRWDED-UHFFFAOYSA-N 2-aminopyridine-4-carboxylic acid Chemical compound NC1=CC(C(O)=O)=CC=N1 QMKZZQPPJRWDED-UHFFFAOYSA-N 0.000 description 1
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
• 125000006040 2-hexenyl group Chemical group 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• WDGXIUUWINKTGP-UHFFFAOYSA-N 3-(3-pyridinyl)propanoic acid Chemical compound OC(=O)CCC1=CC=CN=C1 WDGXIUUWINKTGP-UHFFFAOYSA-N 0.000 description 1
• CWLKGDAVCFYWJK-UHFFFAOYSA-N 3-aminophenol Chemical compound NC1=CC=CC(O)=C1 CWLKGDAVCFYWJK-UHFFFAOYSA-N 0.000 description 1
• 229940018563 3-aminophenol Drugs 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• KDHWOCLBMVSZPG-UHFFFAOYSA-N 3-imidazol-1-ylpropan-1-amine Chemical compound NCCCN1C=CN=C1 KDHWOCLBMVSZPG-UHFFFAOYSA-N 0.000 description 1
• RGDQRXPEZUNWHX-UHFFFAOYSA-N 3-methylpyridin-2-amine Chemical compound CC1=CC=CN=C1N RGDQRXPEZUNWHX-UHFFFAOYSA-N 0.000 description 1
• XKTYXVDYIKIYJP-UHFFFAOYSA-N 3h-dioxole Chemical compound C1OOC=C1 XKTYXVDYIKIYJP-UHFFFAOYSA-N 0.000 description 1
• FXNSVEQMUYPYJS-UHFFFAOYSA-N 4-(2-aminoethyl)benzenesulfonamide Chemical compound NCCC1=CC=C(S(N)(=O)=O)C=C1 FXNSVEQMUYPYJS-UHFFFAOYSA-N 0.000 description 1
• BFWYZZPDZZGSLJ-UHFFFAOYSA-N 4-(aminomethyl)aniline Chemical compound NCC1=CC=C(N)C=C1 BFWYZZPDZZGSLJ-UHFFFAOYSA-N 0.000 description 1
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
• WGPZNNKPLJPQAL-UHFFFAOYSA-N 4-aminobutylcarbamic acid Chemical compound NCCCCNC(O)=O WGPZNNKPLJPQAL-UHFFFAOYSA-N 0.000 description 1
• PXACTUVBBMDKRW-UHFFFAOYSA-N 4-bromobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-N 0.000 description 1
• JMHSCWJIDIKGNZ-UHFFFAOYSA-N 4-carbamoylbenzoic acid Chemical compound NC(=O)C1=CC=C(C(O)=O)C=C1 JMHSCWJIDIKGNZ-UHFFFAOYSA-N 0.000 description 1
• RQMWVVBHJMUJNZ-UHFFFAOYSA-N 4-chloropyridin-2-amine Chemical compound NC1=CC(Cl)=CC=N1 RQMWVVBHJMUJNZ-UHFFFAOYSA-N 0.000 description 1
• GYMNCTNUNURQSP-UHFFFAOYSA-N 4-methyl-2,6-bis(methylsulfanyl)pyrimidine Chemical compound CSC1=CC(C)=NC(SC)=N1 GYMNCTNUNURQSP-UHFFFAOYSA-N 0.000 description 1
• ORLGLBZRQYOWNA-UHFFFAOYSA-N 4-methylpyridin-2-amine Chemical compound CC1=CC=NC(N)=C1 ORLGLBZRQYOWNA-UHFFFAOYSA-N 0.000 description 1
• 125000004608 5,6,7,8-tetrahydroquinolinyl group Chemical group N1=C(C=CC=2CCCCC12)* 0.000 description 1
• CMAPEUIHCLCQIX-UHFFFAOYSA-N 5-aminopentylcarbamic acid Chemical compound NCCCCCNC(O)=O CMAPEUIHCLCQIX-UHFFFAOYSA-N 0.000 description 1
• VNHBYKHXBCYPBJ-UHFFFAOYSA-N 5-ethynylimidazo[1,2-a]pyridine Chemical compound C#CC1=CC=CC2=NC=CN12 VNHBYKHXBCYPBJ-UHFFFAOYSA-N 0.000 description 1
• UQJLPBLXSJWAKG-UHFFFAOYSA-N 6-methyl-1h-pyrimidin-3-ium-2-thione;chloride Chemical compound Cl.CC1=CC=NC(=S)N1 UQJLPBLXSJWAKG-UHFFFAOYSA-N 0.000 description 1
• 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• JAJIPIAHCFBEPI-UHFFFAOYSA-N 9,10-dioxoanthracene-1-sulfonic acid Chemical compound O=C1C2=CC=CC=C2C(=O)C2=C1C=CC=C2S(=O)(=O)O JAJIPIAHCFBEPI-UHFFFAOYSA-N 0.000 description 1
• PQJUJGAVDBINPI-UHFFFAOYSA-N 9H-thioxanthene Chemical compound C1=CC=C2CC3=CC=CC=C3SC2=C1 PQJUJGAVDBINPI-UHFFFAOYSA-N 0.000 description 1
• GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
• 239000005541 ACE inhibitor Substances 0.000 description 1
• 108010005853 Anti-Mullerian Hormone Proteins 0.000 description 1
• 241000271566 Aves Species 0.000 description 1
• 206010004664 Biliary fibrosis Diseases 0.000 description 1
• 108010006654 Bleomycin Proteins 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• 201000009030 Carcinoma Diseases 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
• 201000000054 Coronary Restenosis Diseases 0.000 description 1
• 206010056489 Coronary artery restenosis Diseases 0.000 description 1
• 241000699800 Cricetinae Species 0.000 description 1
• 229920000858 Cyclodextrin Polymers 0.000 description 1
• 206010011732 Cyst Diseases 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• 101100155531 Escherichia coli (strain K12) ispU gene Proteins 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 102000016359 Fibronectins Human genes 0.000 description 1
• 108010067306 Fibronectins Proteins 0.000 description 1
• 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
• 241000699694 Gerbillinae Species 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
• 229910004373 HOAc Inorganic materials 0.000 description 1
• 206010019668 Hepatic fibrosis Diseases 0.000 description 1
• 241000238631 Hexapoda Species 0.000 description 1
• LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical class ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• 206010055171 Hypertensive nephropathy Diseases 0.000 description 1
• 201000003838 Idiopathic interstitial pneumonia Diseases 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 206010062016 Immunosuppression Diseases 0.000 description 1
• 208000020060 Increased inflammatory response Diseases 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 108010004250 Inhibins Proteins 0.000 description 1
• 102000002746 Inhibins Human genes 0.000 description 1
• 101710128836 Large T antigen Proteins 0.000 description 1
• 108060001084 Luciferase Proteins 0.000 description 1
• 229910013868 M2SO4 Inorganic materials 0.000 description 1
• RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 1
• 241000699660 Mus musculus Species 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 241000282339 Mustela Species 0.000 description 1
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
• 101150050051 OAC gene Proteins 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• 206010034665 Peritoneal fibrosis Diseases 0.000 description 1
• BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
• 206010060932 Postoperative adhesion Diseases 0.000 description 1
• 241000700159 Rattus Species 0.000 description 1
• 108091005682 Receptor kinases Proteins 0.000 description 1
• YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 1
• 206010039580 Scar Diseases 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• 101100289792 Squirrel monkey polyomavirus large T gene Proteins 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 238000006069 Suzuki reaction reaction Methods 0.000 description 1
• 102000007614 Thrombospondin 1 Human genes 0.000 description 1
• 108010046722 Thrombospondin 1 Proteins 0.000 description 1
• 102000009618 Transforming Growth Factors Human genes 0.000 description 1
• 108010009583 Transforming Growth Factors Proteins 0.000 description 1
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
• 102000002138 Type I Activin Receptors Human genes 0.000 description 1
• 108010015920 Type I Activin Receptors Proteins 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 230000009692 acute damage Effects 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 150000003973 alkyl amines Chemical class 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
• 238000005576 amination reaction Methods 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
• 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
• 239000000868 anti-mullerian hormone Substances 0.000 description 1
• 239000002246 antineoplastic agent Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• 125000005605 benzo group Chemical group 0.000 description 1
• 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
• 208000020790 biliary tract neoplasm Diseases 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 229960001561 bleomycin Drugs 0.000 description 1
• OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• 210000004899 c-terminal region Anatomy 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
• 230000025084 cell cycle arrest Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 230000004663 cell proliferation Effects 0.000 description 1
• 230000003833 cell viability Effects 0.000 description 1
• 238000012200 cell viability kit Methods 0.000 description 1
• 230000033077 cellular process Effects 0.000 description 1
• 208000019065 cervical carcinoma Diseases 0.000 description 1
• 239000003610 charcoal Substances 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 210000004087 cornea Anatomy 0.000 description 1
• 229940097362 cyclodextrins Drugs 0.000 description 1
• 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
• NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 208000031513 cyst Diseases 0.000 description 1
• 229940127089 cytotoxic agent Drugs 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 238000010537 deprotonation reaction Methods 0.000 description 1
• 238000001212 derivatisation Methods 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 238000010586 diagram Methods 0.000 description 1
• 238000000502 dialysis Methods 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• MCNKHXZIPATURB-HTQZYQBOSA-N diethyl (4r,5r)-2,2-dimethyl-1,3-dioxolane-4,5-dicarboxylate Chemical compound CCOC(=O)[C@@H]1OC(C)(C)O[C@H]1C(=O)OCC MCNKHXZIPATURB-HTQZYQBOSA-N 0.000 description 1
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
• 125000005879 dioxolanyl group Chemical group 0.000 description 1
• 239000003221 ear drop Substances 0.000 description 1
• 229940047652 ear drops Drugs 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 150000002085 enols Chemical class 0.000 description 1
• 210000002919 epithelial cell Anatomy 0.000 description 1
• 238000006266 etherification reaction Methods 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
• 230000005284 excitation Effects 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 239000003889 eye drop Substances 0.000 description 1
• 229940012356 eye drops Drugs 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• 230000009791 fibrotic reaction Effects 0.000 description 1
• 239000000706 filtrate Substances 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
• 108091006047 fluorescent proteins Proteins 0.000 description 1
• 102000034287 fluorescent proteins Human genes 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 235000013373 food additive Nutrition 0.000 description 1
• 239000002778 food additive Substances 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 229960002598 fumaric acid Drugs 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 201000010536 head and neck cancer Diseases 0.000 description 1
• 208000014829 head and neck neoplasm Diseases 0.000 description 1
• 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
• 230000002440 hepatic effect Effects 0.000 description 1
• DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
• 125000005241 heteroarylamino group Chemical group 0.000 description 1
• 150000002430 hydrocarbons Chemical group 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 229940071870 hydroiodic acid Drugs 0.000 description 1
• XPGRZDJXVKFLHQ-UHFFFAOYSA-N hydron;methyl 3-aminopropanoate;chloride Chemical compound Cl.COC(=O)CCN XPGRZDJXVKFLHQ-UHFFFAOYSA-N 0.000 description 1
• MSYBLBLAMDYKKZ-UHFFFAOYSA-N hydron;pyridine-3-carbonyl chloride;chloride Chemical compound Cl.ClC(=O)C1=CC=CN=C1 MSYBLBLAMDYKKZ-UHFFFAOYSA-N 0.000 description 1
• 230000033444 hydroxylation Effects 0.000 description 1
• 238000005805 hydroxylation reaction Methods 0.000 description 1
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 230000001506 immunosuppresive effect Effects 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 230000028709 inflammatory response Effects 0.000 description 1
• 239000000893 inhibin Substances 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 239000011630 iodine Chemical group 0.000 description 1
• 229910052740 iodine Chemical group 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
• 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
• 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
• 150000002576 ketones Chemical group 0.000 description 1
• 238000002684 laminectomy Methods 0.000 description 1
• QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
• 208000014018 liver neoplasm Diseases 0.000 description 1
• 238000011866 long-term treatment Methods 0.000 description 1
• 208000020816 lung neoplasm Diseases 0.000 description 1
• 210000004324 lymphatic system Anatomy 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 229940098895 maleic acid Drugs 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
• 230000004060 metabolic process Effects 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• 230000005012 migration Effects 0.000 description 1
• 238000013508 migration Methods 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• MKQLBNJQQZRQJU-UHFFFAOYSA-N morpholin-4-amine Chemical compound NN1CCOCC1 MKQLBNJQQZRQJU-UHFFFAOYSA-N 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 206010028537 myelofibrosis Diseases 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• HGIUNFKCNGBMMU-UHFFFAOYSA-N n-pyridin-3-ylpyrimidin-2-amine Chemical compound N=1C=CC=NC=1NC1=CC=CN=C1 HGIUNFKCNGBMMU-UHFFFAOYSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 229910052759 nickel Inorganic materials 0.000 description 1
• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 125000006574 non-aromatic ring group Chemical group 0.000 description 1
• 125000005187 nonenyl group Chemical group C(=CCCCCCCC)* 0.000 description 1
• 230000009871 nonspecific binding Effects 0.000 description 1
• 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
• 125000005060 octahydroindolyl group Chemical group N1(CCC2CCCCC12)* 0.000 description 1
• 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
• 230000008816 organ damage Effects 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 230000002611 ovarian Effects 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 150000002978 peroxides Chemical class 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 239000012071 phase Substances 0.000 description 1
• 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
• 229950000688 phenothiazine Drugs 0.000 description 1
• 229960004838 phosphoric acid Drugs 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 229940012957 plasmin Drugs 0.000 description 1
• 239000002574 poison Substances 0.000 description 1
• 231100000614 poison Toxicity 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229920002704 polyhistidine Polymers 0.000 description 1
• 102000054765 polymorphisms of proteins Human genes 0.000 description 1
• 229920001184 polypeptide Polymers 0.000 description 1
• 230000026341 positive regulation of angiogenesis Effects 0.000 description 1
• 230000030795 positive regulation of cellular component movement Effects 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 239000000047 product Substances 0.000 description 1
• 230000002062 proliferating effect Effects 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
• 125000006239 protecting group Chemical group 0.000 description 1
• YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical compound NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 description 1
• IIHQNAXFIODVDU-UHFFFAOYSA-N pyrimidine-2-carbonitrile Chemical compound N#CC1=NC=CC=N1 IIHQNAXFIODVDU-UHFFFAOYSA-N 0.000 description 1
• ZFCHNZDUMIOWFV-UHFFFAOYSA-N pyrimidine-2-carboxylic acid Chemical compound OC(=O)C1=NC=CC=N1 ZFCHNZDUMIOWFV-UHFFFAOYSA-N 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 230000037390 scarring Effects 0.000 description 1
• 230000007017 scission Effects 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
• 230000007781 signaling event Effects 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• 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 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 239000008279 sol Substances 0.000 description 1
• 239000012265 solid product Substances 0.000 description 1
• 208000020431 spinal cord injury Diseases 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000002294 steroidal antiinflammatory agent Substances 0.000 description 1
• 230000003637 steroidlike Effects 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 210000002536 stromal cell Anatomy 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
• 229940032330 sulfuric acid Drugs 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 238000011830 transgenic mouse model Methods 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1
• 210000003462 vein Anatomy 0.000 description 1
• ZFLBCEDXYQHVDO-UHFFFAOYSA-N xanthen-3-imine Chemical compound C1=CC=C2OC3=CC(=N)C=CC3=CC2=C1 ZFLBCEDXYQHVDO-UHFFFAOYSA-N 0.000 description 1