KR20040094908A - 트리-치환된 헤테로아릴 및 이를 제조 및 사용하는 방법 - Google Patents
트리-치환된 헤테로아릴 및 이를 제조 및 사용하는 방법 Download PDFInfo
- Publication number
- KR20040094908A KR20040094908A KR10-2004-7015706A KR20047015706A KR20040094908A KR 20040094908 A KR20040094908 A KR 20040094908A KR 20047015706 A KR20047015706 A KR 20047015706A KR 20040094908 A KR20040094908 A KR 20040094908A
- Authority
- KR
- South Korea
- Prior art keywords
- methyl
- benzo
- imidazol
- pyridin
- dioxol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 125000001072 heteroaryl group Chemical class 0.000 title claims description 44
- 238000000034 method Methods 0.000 title claims description 29
- 150000001875 compounds Chemical class 0.000 claims abstract description 161
- 230000003176 fibrotic effect Effects 0.000 claims abstract description 13
- -1 hydroxy, amino, nitro, oxo, thioxo Chemical group 0.000 claims description 190
- 125000000217 alkyl group Chemical group 0.000 claims description 70
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 57
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims description 56
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 46
- 125000003118 aryl group Chemical group 0.000 claims description 41
- 210000004027 cell Anatomy 0.000 claims description 36
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 36
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 27
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 23
- 239000002253 acid Substances 0.000 claims description 22
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 20
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 20
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
- 150000002431 hydrogen Chemical class 0.000 claims description 18
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 17
- 125000003342 alkenyl group Chemical group 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 15
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 13
- 125000000304 alkynyl group Chemical group 0.000 claims description 13
- 125000005843 halogen group Chemical group 0.000 claims description 13
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 12
- 230000019491 signal transduction Effects 0.000 claims description 12
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 claims description 11
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 claims description 11
- 206010028980 Neoplasm Diseases 0.000 claims description 11
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 11
- 125000004414 alkyl thio group Chemical group 0.000 claims description 11
- 210000002744 extracellular matrix Anatomy 0.000 claims description 11
- 230000002401 inhibitory effect Effects 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 10
- 125000004104 aryloxy group Chemical group 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 10
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 10
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 claims description 10
- GPRLTFBKWDERLU-UHFFFAOYSA-N bicyclo[2.2.2]octane Chemical group C1CC2CCC1CC2 GPRLTFBKWDERLU-UHFFFAOYSA-N 0.000 claims description 9
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 9
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 8
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 8
- 230000001404 mediated effect Effects 0.000 claims description 8
- 125000004193 piperazinyl group Chemical group 0.000 claims description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 201000009030 Carcinoma Diseases 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000003435 aroyl group Chemical group 0.000 claims description 7
- 239000004202 carbamide Substances 0.000 claims description 7
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 7
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 230000002018 overexpression Effects 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 6
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 6
- 210000004881 tumor cell Anatomy 0.000 claims description 6
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 208000017169 kidney disease Diseases 0.000 claims description 5
- 210000004185 liver Anatomy 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- KOJILNLSRNSDPE-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]bicyclo[2.2.2]octane-4-carboxylic acid Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)C(O)=O)C=2C=C3OCOC3=CC=2)=N1 KOJILNLSRNSDPE-UHFFFAOYSA-N 0.000 claims description 4
- YUOCFEKWIWPITK-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-(1-benzylsulfonylpiperidin-4-yl)-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)S(=O)(=O)CC=2C=CC=CC=2)C=2C=C3OCOC3=CC=2)=N1 YUOCFEKWIWPITK-UHFFFAOYSA-N 0.000 claims description 4
- NLYMASABUDSJAK-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-(1-benzylsulfonylpiperidin-4-yl)-1h-imidazol-5-yl]pyridine Chemical compound C1CC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CCN1S(=O)(=O)CC1=CC=CC=C1 NLYMASABUDSJAK-UHFFFAOYSA-N 0.000 claims description 4
- PBQVYGAFMWMPQG-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-(1-methylsulfonylpiperidin-4-yl)-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)S(C)(=O)=O)C=2C=C3OCOC3=CC=2)=N1 PBQVYGAFMWMPQG-UHFFFAOYSA-N 0.000 claims description 4
- KPUSZZFAYGWAHZ-UHFFFAOYSA-N 3-azabicyclo[2.2.2]octane Chemical group C1CC2CCC1NC2 KPUSZZFAYGWAHZ-UHFFFAOYSA-N 0.000 claims description 4
- CJQNJRRDTPULTL-UHFFFAOYSA-N 3-azabicyclo[3.2.1]octane Chemical group C1C2CCC1CNC2 CJQNJRRDTPULTL-UHFFFAOYSA-N 0.000 claims description 4
- CONVAEXWACQJSA-UHFFFAOYSA-N 3-oxabicyclo[2.2.2]octane Chemical group C1CC2CCC1OC2 CONVAEXWACQJSA-UHFFFAOYSA-N 0.000 claims description 4
- 201000008808 Fibrosarcoma Diseases 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 238000009825 accumulation Methods 0.000 claims description 4
- LPCWKMYWISGVSK-UHFFFAOYSA-N bicyclo[3.2.1]octane Chemical group C1C2CCC1CCC2 LPCWKMYWISGVSK-UHFFFAOYSA-N 0.000 claims description 4
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 4
- 210000004072 lung Anatomy 0.000 claims description 4
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- VPRBGKHSSMMFKG-UHFFFAOYSA-N n-[4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]cyclohexyl]-1-phenylmethanesulfonamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCC(CC2)NS(=O)(=O)CC=2C=CC=CC=2)C=2C=C3OCOC3=CC=2)=N1 VPRBGKHSSMMFKG-UHFFFAOYSA-N 0.000 claims description 4
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical group C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- UREOYJDBSNWAOP-UHFFFAOYSA-N 4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]cyclohexan-1-amine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCC(N)CC2)C=2C=C3OCOC3=CC=2)=N1 UREOYJDBSNWAOP-UHFFFAOYSA-N 0.000 claims description 3
- 206010001233 Adenoma benign Diseases 0.000 claims description 3
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 3
- 208000007659 Fibroadenoma 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
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 3
- 206010061216 Infarction Diseases 0.000 claims description 3
- 206010027476 Metastases 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
- HJTDQRHNNVDYNJ-UHFFFAOYSA-N benzyl 4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]piperidine-1-carboxylate Chemical compound C1CC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CCN1C(=O)OCC1=CC=CC=C1 HJTDQRHNNVDYNJ-UHFFFAOYSA-N 0.000 claims description 3
- KYTOWRQDSUTQEP-UHFFFAOYSA-N benzyl n-[1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-4-bicyclo[2.2.2]octanyl]carbamate Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)NC(=O)OCC=2C=CC=CC=2)C=2C=C3OCOC3=CC=2)=N1 KYTOWRQDSUTQEP-UHFFFAOYSA-N 0.000 claims description 3
- HKDZSCRAUDDTJO-UHFFFAOYSA-N benzyl n-[4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]cyclohexyl]carbamate Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCC(CC2)NC(=O)OCC=2C=CC=CC=2)C=2C=C3OCOC3=CC=2)=N1 HKDZSCRAUDDTJO-UHFFFAOYSA-N 0.000 claims description 3
- 210000000481 breast Anatomy 0.000 claims description 3
- 201000003149 breast fibroadenoma Diseases 0.000 claims description 3
- 230000009787 cardiac fibrosis Effects 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 3
- 208000005017 glioblastoma Diseases 0.000 claims description 3
- 210000003128 head Anatomy 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 3
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- 230000009401 metastasis Effects 0.000 claims description 3
- MLNIHAZFATZMLC-UHFFFAOYSA-N methyl 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]bicyclo[2.2.2]octane-4-carboxylate Chemical compound C1CC(C(=O)OC)(CC2)CCC12C(N1)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CC(C)=N1 MLNIHAZFATZMLC-UHFFFAOYSA-N 0.000 claims description 3
- 210000003739 neck Anatomy 0.000 claims description 3
- 210000000496 pancreas Anatomy 0.000 claims description 3
- 210000002307 prostate Anatomy 0.000 claims description 3
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical group C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- TWFAJNXORPXXHJ-UHFFFAOYSA-N (2-chlorophenyl)methyl 4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]piperidine-1-carboxylate Chemical compound ClC1=CC=CC=C1COC(=O)N1CCC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CC1 TWFAJNXORPXXHJ-UHFFFAOYSA-N 0.000 claims description 2
- SPIRDUBGWMKCEE-UHFFFAOYSA-N 1-[4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=NC(C=2C=C3OCOC3=CC=2)=C(C=2N=CC=CC=2)N1 SPIRDUBGWMKCEE-UHFFFAOYSA-N 0.000 claims description 2
- SNYRGCFIRFHTBD-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-(1-methylsulfonylpiperidin-4-yl)-1h-imidazol-5-yl]pyridine Chemical compound C1CN(S(=O)(=O)C)CCC1C1=NC(C=2C=C3OCOC3=CC=2)=C(C=2N=CC=CC=2)N1 SNYRGCFIRFHTBD-UHFFFAOYSA-N 0.000 claims description 2
- 208000028006 Corneal injury Diseases 0.000 claims description 2
- 206010011044 Corneal scar Diseases 0.000 claims description 2
- 150000001204 N-oxides Chemical class 0.000 claims description 2
- 206010069351 acute lung injury Diseases 0.000 claims description 2
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 2
- 125000006383 alkylpyridyl group Chemical group 0.000 claims description 2
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 2
- 125000005163 aryl sulfanyl group Chemical group 0.000 claims description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000005872 benzooxazolyl group Chemical group 0.000 claims description 2
- 125000005874 benzothiadiazolyl group Chemical group 0.000 claims description 2
- 210000003445 biliary tract Anatomy 0.000 claims description 2
- 125000005171 cycloalkylsulfanyl group Chemical group 0.000 claims description 2
- 206010016629 fibroma Diseases 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- 206010025135 lupus erythematosus Diseases 0.000 claims description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004998 naphthylethyl group Chemical group C1(=CC=CC2=CC=CC=C12)CC* 0.000 claims description 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 2
- 231100000241 scar Toxicity 0.000 claims description 2
- BDCDBMMOQZVEQQ-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-cyclopropylpyridin-2-yl)-1h-imidazol-2-yl]bicyclo[2.2.2]octane-4-carboxylic acid Chemical compound C1CC(C(=O)O)(CC2)CCC12C(NC=1C=2C=C3OCOC3=CC=2)=NC=1C(N=1)=CC=CC=1C1CC1 BDCDBMMOQZVEQQ-UHFFFAOYSA-N 0.000 claims 3
- TYKPSDLNBWREBQ-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-n,n-dimethylbicyclo[2.2.2]octane-4-carboxamide Chemical compound C1CC(C(=O)N(C)C)(CC2)CCC12C(N1)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CC(C)=N1 TYKPSDLNBWREBQ-UHFFFAOYSA-N 0.000 claims 3
- OYLSBWOMVFQWKV-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-n-(1-methyl-5-methylsulfanyl-1,2,4-triazol-3-yl)bicyclo[2.2.2]octane-4-carboxamide Chemical compound CN1C(SC)=NC(NC(=O)C23CCC(CC2)(CC3)C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=C(C)C=CC=2)=N1 OYLSBWOMVFQWKV-UHFFFAOYSA-N 0.000 claims 3
- OLKOQFCACIBBJG-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-n-hydroxybicyclo[2.2.2]octane-4-carboxamide Chemical compound CC1=CC=CC(C2=C(NC(=N2)C23CCC(CC2)(CC3)C(=O)NO)C=2C=C3OCOC3=CC=2)=N1 OLKOQFCACIBBJG-UHFFFAOYSA-N 0.000 claims 3
- RFHKQZKAHKOHRP-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-n-methoxybicyclo[2.2.2]octane-4-carboxamide Chemical compound C1CC(C(=O)NOC)(CC2)CCC12C(NC=1C=2C=C3OCOC3=CC=2)=NC=1C1=CC=CC(C)=N1 RFHKQZKAHKOHRP-UHFFFAOYSA-N 0.000 claims 3
- HDYXSERXYSWHPR-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-n-methylbicyclo[2.2.2]octane-4-carboxamide Chemical compound C1CC(C(=O)NC)(CC2)CCC12C(N1)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CC(C)=N1 HDYXSERXYSWHPR-UHFFFAOYSA-N 0.000 claims 3
- XEDYDXQBBLLNLV-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]bicyclo[2.2.2]octan-4-ol Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(O)(CC2)CC3)C=2C=C3OCOC3=CC=2)=N1 XEDYDXQBBLLNLV-UHFFFAOYSA-N 0.000 claims 3
- FQKPLAVROJGWCP-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]bicyclo[2.2.2]octane-4-carbohydrazide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)C(=O)NN)C=2C=C3OCOC3=CC=2)=N1 FQKPLAVROJGWCP-UHFFFAOYSA-N 0.000 claims 3
- JUHTXZGCTPDXRU-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]bicyclo[2.2.2]octane-4-carboxamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)C(N)=O)C=2C=C3OCOC3=CC=2)=N1 JUHTXZGCTPDXRU-UHFFFAOYSA-N 0.000 claims 3
- MPBWLALQULSSSD-UHFFFAOYSA-N 1-[4-(3-methyl-4-oxoquinazolin-6-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]bicyclo[2.2.2]octane-4-carboxamide Chemical compound CC1=CC=CC(C2=C(NC(=N2)C23CCC(CC2)(CC3)C(N)=O)C=2C=C3C(=O)N(C)C=NC3=CC=2)=N1 MPBWLALQULSSSD-UHFFFAOYSA-N 0.000 claims 3
- XDONAADVYDVOCU-UHFFFAOYSA-N 1-[4-(3-methyl-4-oxoquinazolin-6-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]bicyclo[2.2.2]octane-4-carboxylic acid Chemical compound CC1=CC=CC(C2=C(NC(=N2)C23CCC(CC2)(CC3)C(O)=O)C=2C=C3C(=O)N(C)C=NC3=CC=2)=N1 XDONAADVYDVOCU-UHFFFAOYSA-N 0.000 claims 3
- YGHSVVBPXIXHSF-UHFFFAOYSA-N 1-[5-(6-cyclopropylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-1h-imidazol-2-yl]-n-hydroxybicyclo[2.2.2]octane-4-carboxamide Chemical compound C1CC(C(=O)NO)(CC2)CCC12C(NC=1C2=CN3N=CN=C3C=C2)=NC=1C(N=1)=CC=CC=1C1CC1 YGHSVVBPXIXHSF-UHFFFAOYSA-N 0.000 claims 3
- WJADENHXXXGFQC-UHFFFAOYSA-N 1-[5-(6-cyclopropylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-1h-imidazol-2-yl]bicyclo[2.2.2]octane-4-carboxamide Chemical compound C1CC(C(=O)N)(CC2)CCC12C(NC=1C2=CN3N=CN=C3C=C2)=NC=1C(N=1)=CC=CC=1C1CC1 WJADENHXXXGFQC-UHFFFAOYSA-N 0.000 claims 3
- NVJLNUFBDYBWQY-UHFFFAOYSA-N 1-[5-(6-cyclopropylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-1h-imidazol-2-yl]bicyclo[2.2.2]octane-4-carboxylic acid Chemical compound C1CC(C(=O)O)(CC2)CCC12C(NC=1C2=CN3N=CN=C3C=C2)=NC=1C(N=1)=CC=CC=1C1CC1 NVJLNUFBDYBWQY-UHFFFAOYSA-N 0.000 claims 3
- HBTUBFWKPRCCGB-UHFFFAOYSA-N 1-[5-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-1h-imidazol-2-yl]bicyclo[2.2.2]octane-4-carboxamide Chemical compound CC1=CC=CC(C2=C(NC(=N2)C23CCC(CC2)(CC3)C(N)=O)C2=CN3N=CN=C3C=C2)=N1 HBTUBFWKPRCCGB-UHFFFAOYSA-N 0.000 claims 3
- YURRESDVZOTIIE-UHFFFAOYSA-N 1-[5-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-1h-imidazol-2-yl]bicyclo[2.2.2]octane-4-carboxylic acid Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)C(O)=O)C2=CN3N=CN=C3C=C2)=N1 YURRESDVZOTIIE-UHFFFAOYSA-N 0.000 claims 3
- SDJBBSCKFMBPRN-UHFFFAOYSA-N 1-[5-(6-methylpyridin-2-yl)-4-quinoxalin-6-yl-1h-imidazol-2-yl]bicyclo[2.2.2]octane-4-carboxamide Chemical class CC1=CC=CC(C2=C(NC(=N2)C23CCC(CC2)(CC3)C(N)=O)C=2C=C3N=CC=NC3=CC=2)=N1 SDJBBSCKFMBPRN-UHFFFAOYSA-N 0.000 claims 3
- YIBGSDUTNZLXET-UHFFFAOYSA-N 1-[5-(6-methylpyridin-2-yl)-4-quinoxalin-6-yl-1h-imidazol-2-yl]bicyclo[2.2.2]octane-4-carboxylic acid Chemical compound CC1=CC=CC(C2=C(NC(=N2)C23CCC(CC2)(CC3)C(O)=O)C=2C=C3N=CC=NC3=CC=2)=N1 YIBGSDUTNZLXET-UHFFFAOYSA-N 0.000 claims 3
- KSZCAGWHZCZJLZ-UHFFFAOYSA-N 1-methylimidazole-4-sulfonic acid Chemical compound CN1C=NC(S(O)(=O)=O)=C1 KSZCAGWHZCZJLZ-UHFFFAOYSA-N 0.000 claims 3
- MZJSZQWWQZFBNG-UHFFFAOYSA-N 2,2,2-trifluoro-n-[4-[5-(6-methylpyridin-2-yl)-4-quinoxalin-6-yl-1h-imidazol-2-yl]cyclohexyl]acetamide Chemical compound CC1=CC=CC(C2=C(NC(=N2)C2CCC(CC2)NC(=O)C(F)(F)F)C=2C=C3N=CC=NC3=CC=2)=N1 MZJSZQWWQZFBNG-UHFFFAOYSA-N 0.000 claims 3
- RDGCFSQXZFOYHX-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-(1-benzylsulfonylpiperidin-4-yl)-1h-imidazol-5-yl]-6-ethylpyridine Chemical compound CCC1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)S(=O)(=O)CC=2C=CC=CC=2)C=2C=C3OCOC3=CC=2)=N1 RDGCFSQXZFOYHX-UHFFFAOYSA-N 0.000 claims 3
- HQNAVRIDVCVQQZ-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-(1-butylsulfonylpiperidin-4-yl)-1h-imidazol-5-yl]-6-methylpyridine Chemical compound C1CN(S(=O)(=O)CCCC)CCC1C1=NC(C=2C=C3OCOC3=CC=2)=C(C=2N=C(C)C=CC=2)N1 HQNAVRIDVCVQQZ-UHFFFAOYSA-N 0.000 claims 3
- IEMNRBMFCIUNGS-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-(1-butylsulfonylpiperidin-4-yl)-1h-imidazol-5-yl]pyridine Chemical compound C1CN(S(=O)(=O)CCCC)CCC1C1=NC(C=2C=C3OCOC3=CC=2)=C(C=2N=CC=CC=2)N1 IEMNRBMFCIUNGS-UHFFFAOYSA-N 0.000 claims 3
- DXBVGXRVODZVNR-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-(1-propan-2-ylsulfonylpiperidin-4-yl)-1h-imidazol-5-yl]-6-methylpyridine Chemical compound C1CN(S(=O)(=O)C(C)C)CCC1C1=NC(C=2C=C3OCOC3=CC=2)=C(C=2N=C(C)C=CC=2)N1 DXBVGXRVODZVNR-UHFFFAOYSA-N 0.000 claims 3
- WFAFZVJXDCKORT-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-(1-propylsulfonylpiperidin-4-yl)-1h-imidazol-5-yl]-6-methylpyridine Chemical compound C1CN(S(=O)(=O)CCC)CCC1C1=NC(C=2C=C3OCOC3=CC=2)=C(C=2N=C(C)C=CC=2)N1 WFAFZVJXDCKORT-UHFFFAOYSA-N 0.000 claims 3
- AQCMMAOQMOKPJQ-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-(1-thiophen-2-ylsulfonylpiperidin-4-yl)-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)S(=O)(=O)C=2SC=CC=2)C=2C=C3OCOC3=CC=2)=N1 AQCMMAOQMOKPJQ-UHFFFAOYSA-N 0.000 claims 3
- PBXFIFABKLKBKE-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-(1-thiophen-3-ylsulfonylpiperidin-4-yl)-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)S(=O)(=O)C2=CSC=C2)C=2C=C3OCOC3=CC=2)=N1 PBXFIFABKLKBKE-UHFFFAOYSA-N 0.000 claims 3
- ZFHPVSVBYUVQQV-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-(1-methylimidazol-4-yl)sulfonylpiperidin-4-yl]-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)S(=O)(=O)C=2N=CN(C)C=2)C=2C=C3OCOC3=CC=2)=N1 ZFHPVSVBYUVQQV-UHFFFAOYSA-N 0.000 claims 3
- HGSNZSXZNFRRKD-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-(2-phenylethylsulfonyl)piperidin-4-yl]-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)S(=O)(=O)CCC=2C=CC=CC=2)C=2C=C3OCOC3=CC=2)=N1 HGSNZSXZNFRRKD-UHFFFAOYSA-N 0.000 claims 3
- DKBOGMRTFOKIEM-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-(2-phenylethylsulfonyl)piperidin-4-yl]-1h-imidazol-5-yl]pyridine Chemical compound C1CC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CCN1S(=O)(=O)CCC1=CC=CC=C1 DKBOGMRTFOKIEM-UHFFFAOYSA-N 0.000 claims 3
- FJTQBZQIVAMWKJ-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-(4-chlorophenyl)sulfonylpiperidin-4-yl]-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)S(=O)(=O)C=2C=CC(Cl)=CC=2)C=2C=C3OCOC3=CC=2)=N1 FJTQBZQIVAMWKJ-UHFFFAOYSA-N 0.000 claims 3
- MPSCSDJNRHTYAK-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-[(3,5-dichlorophenyl)methylsulfonyl]piperidin-4-yl]-1h-imidazol-5-yl]pyridine Chemical compound ClC1=CC(Cl)=CC(CS(=O)(=O)N2CCC(CC2)C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)=C1 MPSCSDJNRHTYAK-UHFFFAOYSA-N 0.000 claims 3
- XCFZTCGAQOLULN-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-[(4-fluorophenyl)methylsulfonyl]piperidin-4-yl]-1h-imidazol-5-yl]pyridine Chemical compound C1=CC(F)=CC=C1CS(=O)(=O)N1CCC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CC1 XCFZTCGAQOLULN-UHFFFAOYSA-N 0.000 claims 3
- VTNZDIXVWUFWCR-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[4-(2h-tetrazol-5-yl)-1-bicyclo[2.2.2]octanyl]-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)C=2NN=NN=2)C=2C=C3OCOC3=CC=2)=N1 VTNZDIXVWUFWCR-UHFFFAOYSA-N 0.000 claims 3
- HTLSOALCDIEOBI-UHFFFAOYSA-N 2-[4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-1-bicyclo[2.2.2]octanyl]acetic acid Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC(O)=O)(CC2)CC3)C=2C=C3OCOC3=CC=2)=N1 HTLSOALCDIEOBI-UHFFFAOYSA-N 0.000 claims 3
- WTMCRVJVKGKDOO-UHFFFAOYSA-N 2-[4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-1-bicyclo[2.2.2]octanyl]acetonitrile Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC#N)(CC2)CC3)C=2C=C3OCOC3=CC=2)=N1 WTMCRVJVKGKDOO-UHFFFAOYSA-N 0.000 claims 3
- FVJFPPZGRCXFRL-UHFFFAOYSA-N 2-[[4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]piperidin-1-yl]sulfonylmethyl]aniline Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)S(=O)(=O)CC=2C(=CC=CC=2)N)C=2C=C3OCOC3=CC=2)=N1 FVJFPPZGRCXFRL-UHFFFAOYSA-N 0.000 claims 3
- IHUYHJOWTKRENW-UHFFFAOYSA-N 2-[[4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]piperidin-1-yl]sulfonylmethyl]pyridine Chemical compound C1CC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CCN1S(=O)(=O)CC1=CC=CC=N1 IHUYHJOWTKRENW-UHFFFAOYSA-N 0.000 claims 3
- GKODTPGEVLRHGQ-UHFFFAOYSA-N 4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]bicyclo[2.2.2]octane-1-carbonitrile Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)C#N)C=2C=C3OCOC3=CC=2)=N1 GKODTPGEVLRHGQ-UHFFFAOYSA-N 0.000 claims 3
- DFMXDYMTTUZLHC-UHFFFAOYSA-N 4-[4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]piperidin-1-yl]sulfonyl-5-methyl-1,2-oxazole Chemical compound O1N=CC(S(=O)(=O)N2CCC(CC2)C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=C(C)C=CC=2)=C1C DFMXDYMTTUZLHC-UHFFFAOYSA-N 0.000 claims 3
- QRRMLTSYWBBKFI-UHFFFAOYSA-N 4-[4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]piperidin-1-yl]sulfonylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1S(=O)(=O)N1CCC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CC1 QRRMLTSYWBBKFI-UHFFFAOYSA-N 0.000 claims 3
- BQRGKTFOVBEAPO-UHFFFAOYSA-N 4-[[4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]piperidin-1-yl]sulfonylmethyl]-7,7-dimethylbicyclo[2.2.1]heptan-3-one Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)S(=O)(=O)CC23C(CC(CC2)C3(C)C)=O)C=2C=C3OCOC3=CC=2)=N1 BQRGKTFOVBEAPO-UHFFFAOYSA-N 0.000 claims 3
- XPCUDTLFGOVKAW-UHFFFAOYSA-N [1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-4-bicyclo[2.2.2]octanyl] sulfamate Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)OS(N)(=O)=O)C=2C=C3OCOC3=CC=2)=N1 XPCUDTLFGOVKAW-UHFFFAOYSA-N 0.000 claims 3
- BYAKYGFYMNEJPP-UHFFFAOYSA-N [4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-1-bicyclo[2.2.2]octanyl]methanol Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CO)(CC2)CC3)C=2C=C3OCOC3=CC=2)=N1 BYAKYGFYMNEJPP-UHFFFAOYSA-N 0.000 claims 3
- BTAJRCJWIJOGDV-UHFFFAOYSA-N [4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]piperidin-1-yl]-(3-chlorophenyl)methanone Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)C(=O)C=2C=C(Cl)C=CC=2)C=2C=C3OCOC3=CC=2)=N1 BTAJRCJWIJOGDV-UHFFFAOYSA-N 0.000 claims 3
- BFSIPABIKNTDAL-UHFFFAOYSA-N benzyl n-[4-[5-(6-methylpyridin-2-yl)-4-quinoxalin-6-yl-1h-imidazol-2-yl]cyclohexyl]carbamate Chemical compound CC1=CC=CC(C2=C(NC(=N2)C2CCC(CC2)NC(=O)OCC=2C=CC=CC=2)C=2C=C3N=CC=NC3=CC=2)=N1 BFSIPABIKNTDAL-UHFFFAOYSA-N 0.000 claims 3
- NTKOFBLZGJHQLV-UHFFFAOYSA-N benzyl n-[[4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]cyclohexyl]methyl]carbamate Chemical class CC1=CC=CC(C2=C(N=C(N2)C2CCC(CNC(=O)OCC=3C=CC=CC=3)CC2)C=2C=C3OCOC3=CC=2)=N1 NTKOFBLZGJHQLV-UHFFFAOYSA-N 0.000 claims 3
- YNWJWINZGPMSOV-UHFFFAOYSA-N methyl 1-[4-(3-methyl-4-oxoquinazolin-6-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]bicyclo[2.2.2]octane-4-carboxylate Chemical compound C1CC(C(=O)OC)(CC2)CCC12C(NC=1C=2C=C3C(=O)N(C)C=NC3=CC=2)=NC=1C1=CC=CC(C)=N1 YNWJWINZGPMSOV-UHFFFAOYSA-N 0.000 claims 3
- VDOQHHCXPVJPQV-UHFFFAOYSA-N methyl 1-[5-(5-fluoro-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-1h-imidazol-2-yl]bicyclo[2.2.2]octane-4-carboxylate Chemical compound C1CC(C(=O)OC)(CC2)CCC12C(NC=1C2=CN3N=CN=C3C=C2)=NC=1C1=CC=C(F)C(C)=N1 VDOQHHCXPVJPQV-UHFFFAOYSA-N 0.000 claims 3
- DFMWOFQKSBDAJT-UHFFFAOYSA-N methyl 1-[5-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-1h-imidazol-2-yl]bicyclo[2.2.2]octane-4-carboxylate Chemical compound C1CC(C(=O)OC)(CC2)CCC12C(N1)=NC(C2=CN3N=CN=C3C=C2)=C1C1=CC=CC(C)=N1 DFMWOFQKSBDAJT-UHFFFAOYSA-N 0.000 claims 3
- FDJOWQXTDJWMPC-UHFFFAOYSA-N methyl 1-[5-(6-methylpyridin-2-yl)-4-quinoxalin-6-yl-1h-imidazol-2-yl]bicyclo[2.2.2]octane-4-carboxylate Chemical class C1CC(C(=O)OC)(CC2)CCC12C(NC=1C=2C=C3N=CC=NC3=CC=2)=NC=1C1=CC=CC(C)=N1 FDJOWQXTDJWMPC-UHFFFAOYSA-N 0.000 claims 3
- LZZKVZNLUYDCJN-UHFFFAOYSA-N n-[1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-4-bicyclo[2.2.2]octanyl]-1-methylimidazole-4-sulfonamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)NS(=O)(=O)C=2N=CN(C)C=2)C=2C=C3OCOC3=CC=2)=N1 LZZKVZNLUYDCJN-UHFFFAOYSA-N 0.000 claims 3
- FZEJDYTUUDDWPT-UHFFFAOYSA-N n-[1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-4-bicyclo[2.2.2]octanyl]thiophene-2-sulfonamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)NS(=O)(=O)C=2SC=CC=2)C=2C=C3OCOC3=CC=2)=N1 FZEJDYTUUDDWPT-UHFFFAOYSA-N 0.000 claims 3
- FLFUCQHZGVBFDA-UHFFFAOYSA-N n-[1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-4-bicyclo[2.2.2]octanyl]thiophene-3-sulfonamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)NS(=O)(=O)C2=CSC=C2)C=2C=C3OCOC3=CC=2)=N1 FLFUCQHZGVBFDA-UHFFFAOYSA-N 0.000 claims 3
- GATOOMWOKQPQIA-UHFFFAOYSA-N n-[4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]cyclohexyl]-1-pyridin-2-ylmethanesulfonamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCC(CC2)NS(=O)(=O)CC=2N=CC=CC=2)C=2C=C3OCOC3=CC=2)=N1 GATOOMWOKQPQIA-UHFFFAOYSA-N 0.000 claims 3
- BNRHAYBJQHUPFO-UHFFFAOYSA-N n-[4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]cyclohexyl]butane-1-sulfonamide Chemical compound C1CC(NS(=O)(=O)CCCC)CCC1C1=NC(C=2C=C3OCOC3=CC=2)=C(C=2N=C(C)C=CC=2)N1 BNRHAYBJQHUPFO-UHFFFAOYSA-N 0.000 claims 3
- SQAMQHSJXJSQPS-UHFFFAOYSA-N n-[4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]cyclohexyl]thiophene-2-sulfonamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCC(CC2)NS(=O)(=O)C=2SC=CC=2)C=2C=C3OCOC3=CC=2)=N1 SQAMQHSJXJSQPS-UHFFFAOYSA-N 0.000 claims 3
- SSOWKIPDUUSTQR-UHFFFAOYSA-N n-[4-[5-(6-methylpyridin-2-yl)-4-quinoxalin-6-yl-1h-imidazol-2-yl]cyclohexyl]methanesulfonamide Chemical compound CC1=CC=CC(C2=C(NC(=N2)C2CCC(CC2)NS(C)(=O)=O)C=2C=C3N=CC=NC3=CC=2)=N1 SSOWKIPDUUSTQR-UHFFFAOYSA-N 0.000 claims 3
- HLEPPLCYOPROMT-UHFFFAOYSA-N n-[[4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]cyclohexyl]methyl]-1-phenylmethanesulfonamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCC(CNS(=O)(=O)CC=3C=CC=CC=3)CC2)C=2C=C3OCOC3=CC=2)=N1 HLEPPLCYOPROMT-UHFFFAOYSA-N 0.000 claims 3
- ILVOUIRNTYMOBH-UHFFFAOYSA-N n-[[4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]cyclohexyl]methyl]-1-pyridin-2-ylmethanesulfonamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCC(CNS(=O)(=O)CC=3N=CC=CC=3)CC2)C=2C=C3OCOC3=CC=2)=N1 ILVOUIRNTYMOBH-UHFFFAOYSA-N 0.000 claims 3
- OGDDSGBJTFBANP-UHFFFAOYSA-N n-[[4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]cyclohexyl]methyl]acetamide Chemical compound C1CC(CNC(=O)C)CCC1C1=NC(C=2C=C3OCOC3=CC=2)=C(C=2N=C(C)C=CC=2)N1 OGDDSGBJTFBANP-UHFFFAOYSA-N 0.000 claims 3
- FPVNUKSAQKMDQL-UHFFFAOYSA-N n-[[4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]cyclohexyl]methyl]butane-1-sulfonamide Chemical compound C1CC(CNS(=O)(=O)CCCC)CCC1C1=NC(C=2C=C3OCOC3=CC=2)=C(C=2N=C(C)C=CC=2)N1 FPVNUKSAQKMDQL-UHFFFAOYSA-N 0.000 claims 3
- YPDUTSPYVABKFP-UHFFFAOYSA-N n-[[4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]cyclohexyl]methyl]methanesulfonamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCC(CNS(C)(=O)=O)CC2)C=2C=C3OCOC3=CC=2)=N1 YPDUTSPYVABKFP-UHFFFAOYSA-N 0.000 claims 3
- HNZSKMMZMZQUQM-UHFFFAOYSA-N n-[[4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]cyclohexyl]methyl]propane-2-sulfonamide Chemical compound C1CC(CNS(=O)(=O)C(C)C)CCC1C1=NC(C=2C=C3OCOC3=CC=2)=C(C=2N=C(C)C=CC=2)N1 HNZSKMMZMZQUQM-UHFFFAOYSA-N 0.000 claims 3
- HPDIJGLJVPCQPX-UHFFFAOYSA-N n-hydroxy-1-[5-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-1h-imidazol-2-yl]bicyclo[2.2.2]octane-4-carboxamide Chemical compound CC1=CC=CC(C2=C(NC(=N2)C23CCC(CC2)(CC3)C(=O)NO)C2=CN3N=CN=C3C=C2)=N1 HPDIJGLJVPCQPX-UHFFFAOYSA-N 0.000 claims 3
- SJVMSBCSXJCECY-UHFFFAOYSA-N n-hydroxy-1-[5-(6-methylpyridin-2-yl)-4-quinoxalin-6-yl-1h-imidazol-2-yl]bicyclo[2.2.2]octane-4-carboxamide Chemical class CC1=CC=CC(C2=C(NC(=N2)C23CCC(CC2)(CC3)C(=O)NO)C=2C=C3N=CC=NC3=CC=2)=N1 SJVMSBCSXJCECY-UHFFFAOYSA-N 0.000 claims 3
- JBVFHFGCUCLBAC-UHFFFAOYSA-N (4-nitrophenyl)methyl 4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]piperidine-1-carboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)N1CCC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CC1 JBVFHFGCUCLBAC-UHFFFAOYSA-N 0.000 claims 2
- PSFNVZCUNRDLSM-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-n,n-diethylbicyclo[2.2.2]octane-4-carboxamide Chemical compound C1CC(C(=O)N(CC)CC)(CC2)CCC12C(N1)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CC(C)=N1 PSFNVZCUNRDLSM-UHFFFAOYSA-N 0.000 claims 2
- RGNMSMJXVJXJIK-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-n-(3-imidazol-1-ylpropyl)bicyclo[2.2.2]octane-4-carboxamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)C(=O)NCCCN2C=NC=C2)C=2C=C3OCOC3=CC=2)=N1 RGNMSMJXVJXJIK-UHFFFAOYSA-N 0.000 claims 2
- KKVJMMSITMLWCO-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-n-(furan-2-ylmethyl)bicyclo[2.2.2]octane-4-carboxamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)C(=O)NCC=2OC=CC=2)C=2C=C3OCOC3=CC=2)=N1 KKVJMMSITMLWCO-UHFFFAOYSA-N 0.000 claims 2
- ZNHHQIKDYUGVDY-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-n-(pyridin-2-ylmethyl)bicyclo[2.2.2]octane-4-carboxamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)C(=O)NCC=2N=CC=CC=2)C=2C=C3OCOC3=CC=2)=N1 ZNHHQIKDYUGVDY-UHFFFAOYSA-N 0.000 claims 2
- SXNCKMDMFDMHGZ-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-n-butylbicyclo[2.2.2]octane-4-carboxamide Chemical compound C1CC(C(=O)NCCCC)(CC2)CCC12C(N1)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CC(C)=N1 SXNCKMDMFDMHGZ-UHFFFAOYSA-N 0.000 claims 2
- XZZCGMDSLJGNSF-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-n-ethylbicyclo[2.2.2]octane-4-carboxamide Chemical compound C1CC(C(=O)NCC)(CC2)CCC12C(N1)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CC(C)=N1 XZZCGMDSLJGNSF-UHFFFAOYSA-N 0.000 claims 2
- CFAJOGKZNGBSHP-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-n-propan-2-ylbicyclo[2.2.2]octane-4-carboxamide Chemical compound C1CC(C(=O)NC(C)C)(CC2)CCC12C(N1)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CC(C)=N1 CFAJOGKZNGBSHP-UHFFFAOYSA-N 0.000 claims 2
- KXENDECZPMIZLE-UHFFFAOYSA-N 1-[4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]piperidin-1-yl]-3-phenylpropan-1-one Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)C(=O)CCC=2C=CC=CC=2)C=2C=C3OCOC3=CC=2)=N1 KXENDECZPMIZLE-UHFFFAOYSA-N 0.000 claims 2
- YHDUMDBRUMICHF-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-(1-benzylsulfonylpiperidin-3-yl)-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CN(CCC2)S(=O)(=O)CC=2C=CC=CC=2)C=2C=C3OCOC3=CC=2)=N1 YHDUMDBRUMICHF-UHFFFAOYSA-N 0.000 claims 2
- SGQKTIWTZZVBHS-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-(1-benzylsulfonylpyrrolidin-3-yl)-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CN(CC2)S(=O)(=O)CC=2C=CC=CC=2)C=2C=C3OCOC3=CC=2)=N1 SGQKTIWTZZVBHS-UHFFFAOYSA-N 0.000 claims 2
- GUTRQDMDMYZGES-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-(1-butylsulfonylpiperidin-3-yl)-1h-imidazol-5-yl]-6-methylpyridine Chemical compound C1N(S(=O)(=O)CCCC)CCCC1C1=NC(C=2C=C3OCOC3=CC=2)=C(C=2N=C(C)C=CC=2)N1 GUTRQDMDMYZGES-UHFFFAOYSA-N 0.000 claims 2
- CWPONJIVPGFGOA-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-(1-butylsulfonylpyrrolidin-3-yl)-1h-imidazol-5-yl]-6-methylpyridine Chemical compound C1N(S(=O)(=O)CCCC)CCC1C1=NC(C=2C=C3OCOC3=CC=2)=C(C=2N=C(C)C=CC=2)N1 CWPONJIVPGFGOA-UHFFFAOYSA-N 0.000 claims 2
- BXUBKWMJQNIVNK-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-(1-methylsulfonylpyrrolidin-3-yl)-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CN(CC2)S(C)(=O)=O)C=2C=C3OCOC3=CC=2)=N1 BXUBKWMJQNIVNK-UHFFFAOYSA-N 0.000 claims 2
- SBOQNZCQEFSIBJ-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-(1-propylsulfonylpiperidin-4-yl)-1h-imidazol-5-yl]pyridine Chemical compound C1CN(S(=O)(=O)CCC)CCC1C1=NC(C=2C=C3OCOC3=CC=2)=C(C=2N=CC=CC=2)N1 SBOQNZCQEFSIBJ-UHFFFAOYSA-N 0.000 claims 2
- JWWQUDKZMQCNNI-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-(1-methylimidazol-4-yl)sulfonylpyrrolidin-3-yl]-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CN(CC2)S(=O)(=O)C=2N=CN(C)C=2)C=2C=C3OCOC3=CC=2)=N1 JWWQUDKZMQCNNI-UHFFFAOYSA-N 0.000 claims 2
- NIVOFZWVKLYSMZ-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-(2-phenylethenylsulfonyl)piperidin-4-yl]-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)S(=O)(=O)C=CC=2C=CC=CC=2)C=2C=C3OCOC3=CC=2)=N1 NIVOFZWVKLYSMZ-UHFFFAOYSA-N 0.000 claims 2
- ZTIDOCNVLREPJM-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-(3,4-dichlorophenyl)sulfonylpiperidin-4-yl]-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)S(=O)(=O)C=2C=C(Cl)C(Cl)=CC=2)C=2C=C3OCOC3=CC=2)=N1 ZTIDOCNVLREPJM-UHFFFAOYSA-N 0.000 claims 2
- DDWDJRWPMOQIFD-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-(4-chlorophenyl)sulfonylpiperidin-4-yl]-1h-imidazol-5-yl]pyridine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1CCC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CC1 DDWDJRWPMOQIFD-UHFFFAOYSA-N 0.000 claims 2
- IZSKNMHGLYPANF-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-(4-methylphenyl)sulfonylpiperidin-4-yl]-1h-imidazol-5-yl]pyridine Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1CCC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CC1 IZSKNMHGLYPANF-UHFFFAOYSA-N 0.000 claims 2
- XHVXAVMCXRSSIJ-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-[(3,4-dichlorophenyl)methylsulfonyl]piperidin-4-yl]-1h-imidazol-5-yl]pyridine Chemical compound C1=C(Cl)C(Cl)=CC=C1CS(=O)(=O)N1CCC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CC1 XHVXAVMCXRSSIJ-UHFFFAOYSA-N 0.000 claims 2
- CTYCYBCAYNIGGD-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-[5-methyl-2-(trifluoromethyl)furan-3-yl]sulfonylpiperidin-4-yl]-1h-imidazol-5-yl]-6-methylpyridine Chemical compound O1C(C)=CC(S(=O)(=O)N2CCC(CC2)C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=C(C)C=CC=2)=C1C(F)(F)F CTYCYBCAYNIGGD-UHFFFAOYSA-N 0.000 claims 2
- VCZVKWZFYAUTMB-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-[[3-(trifluoromethyl)phenyl]methylsulfonyl]piperidin-4-yl]-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)S(=O)(=O)CC=2C=C(C=CC=2)C(F)(F)F)C=2C=C3OCOC3=CC=2)=N1 VCZVKWZFYAUTMB-UHFFFAOYSA-N 0.000 claims 2
- PCCZEQHMOCIYSN-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-[[3-(trifluoromethyl)phenyl]methylsulfonyl]piperidin-4-yl]-1h-imidazol-5-yl]pyridine Chemical compound FC(F)(F)C1=CC=CC(CS(=O)(=O)N2CCC(CC2)C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)=C1 PCCZEQHMOCIYSN-UHFFFAOYSA-N 0.000 claims 2
- QTIQBUCPHAGXIX-UHFFFAOYSA-N 4-[2-(1-benzylsulfonylpiperidin-4-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-4-yl]-n-[(4-methoxyphenyl)methyl]pyridin-2-amine Chemical compound C1=CC(OC)=CC=C1CNC1=CC(C2=C(NC(=N2)C2CCN(CC2)S(=O)(=O)CC=2C=CC=CC=2)C=2N=C(C)C=CC=2)=CC=N1 QTIQBUCPHAGXIX-UHFFFAOYSA-N 0.000 claims 2
- HQTYIMWMJZWTMU-UHFFFAOYSA-N 4-[2-(1-butylsulfonylpiperidin-4-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-4-yl]-n-[(4-methoxyphenyl)methyl]pyridin-2-amine Chemical compound C1CN(S(=O)(=O)CCCC)CCC1C1=NC(C=2C=C(NCC=3C=CC(OC)=CC=3)N=CC=2)=C(C=2N=C(C)C=CC=2)N1 HQTYIMWMJZWTMU-UHFFFAOYSA-N 0.000 claims 2
- ZJRFSDKQGLOMFX-UHFFFAOYSA-N 4-[2-(1-butylsulfonylpiperidin-4-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-4-yl]pyridin-2-amine Chemical compound C1CN(S(=O)(=O)CCCC)CCC1C1=NC(C=2C=C(N)N=CC=2)=C(C=2N=C(C)C=CC=2)N1 ZJRFSDKQGLOMFX-UHFFFAOYSA-N 0.000 claims 2
- VQLOYGTZJBJXHP-UHFFFAOYSA-N [1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-4-bicyclo[2.2.2]octanyl]-pyrrolidin-1-ylmethanone Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)C(=O)N2CCCC2)C=2C=C3OCOC3=CC=2)=N1 VQLOYGTZJBJXHP-UHFFFAOYSA-N 0.000 claims 2
- JMDJSUXTQIQLKM-UHFFFAOYSA-N [4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]piperidin-1-yl]-(4-fluorophenyl)methanone Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)C(=O)C=2C=CC(F)=CC=2)C=2C=C3OCOC3=CC=2)=N1 JMDJSUXTQIQLKM-UHFFFAOYSA-N 0.000 claims 2
- UYVSVOPNRWVWOK-UHFFFAOYSA-N benzyl 3-[4-(1,3-benzodioxol-5-yl)-1-hydroxy-5-(6-methylpyridin-2-yl)imidazol-2-yl]pyrrolidine-1-carboxylate Chemical compound CC1=CC=CC(C=2N(C(C3CN(CC3)C(=O)OCC=3C=CC=CC=3)=NC=2C=2C=C3OCOC3=CC=2)O)=N1 UYVSVOPNRWVWOK-UHFFFAOYSA-N 0.000 claims 2
- WMRUYLMASOAKIX-UHFFFAOYSA-N benzyl 3-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]piperidine-1-carboxylate Chemical compound C1CCC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CN1C(=O)OCC1=CC=CC=C1 WMRUYLMASOAKIX-UHFFFAOYSA-N 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- VMRGJYKFCNTJKM-UHFFFAOYSA-N n-[4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]cyclohexyl]methanesulfonamide Chemical class CC1=CC=CC(C2=C(N=C(N2)C2CCC(CC2)NS(C)(=O)=O)C=2C=C3OCOC3=CC=2)=N1 VMRGJYKFCNTJKM-UHFFFAOYSA-N 0.000 claims 2
- WDETXUVGXDZSND-UHFFFAOYSA-N n-[4-[5-(6-methylpyridin-2-yl)-4-quinoxalin-6-yl-1h-imidazol-2-yl]cyclohexyl]acetamide Chemical compound C1CC(NC(=O)C)CCC1C1=NC(C=2N=C(C)C=CC=2)=C(C=2C=C3N=CC=NC3=CC=2)N1 WDETXUVGXDZSND-UHFFFAOYSA-N 0.000 claims 2
- AVBSRIGBTOAPCC-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-n,n-dipropylbicyclo[2.2.2]octane-4-carboxamide Chemical compound C1CC(C(=O)N(CCC)CCC)(CC2)CCC12C(N1)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CC(C)=N1 AVBSRIGBTOAPCC-UHFFFAOYSA-N 0.000 claims 1
- SCLUKIYIEQXKPC-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-n-(1,3-benzothiazol-2-yl)bicyclo[2.2.2]octane-4-carboxamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)C(=O)NC=2SC3=CC=CC=C3N=2)C=2C=C3OCOC3=CC=2)=N1 SCLUKIYIEQXKPC-UHFFFAOYSA-N 0.000 claims 1
- WQGFGKHYEZFVEL-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-n-(1-hydroxy-1-phenylpropan-2-yl)bicyclo[2.2.2]octane-4-carboxamide Chemical compound C=1C=CC=CC=1C(O)C(C)NC(=O)C(CC1)(CC2)CCC12C(N1)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CC(C)=N1 WQGFGKHYEZFVEL-UHFFFAOYSA-N 0.000 claims 1
- YKNSIFNFRJZJNZ-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-n-(5,7-difluoro-1,3-benzothiazol-2-yl)bicyclo[2.2.2]octane-4-carboxamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)C(=O)NC=2SC3=C(F)C=C(F)C=C3N=2)C=2C=C3OCOC3=CC=2)=N1 YKNSIFNFRJZJNZ-UHFFFAOYSA-N 0.000 claims 1
- IDMSXJAGKSMKAQ-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-n-(pyridin-4-ylmethyl)bicyclo[2.2.2]octane-4-carboxamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)C(=O)NCC=2C=CN=CC=2)C=2C=C3OCOC3=CC=2)=N1 IDMSXJAGKSMKAQ-UHFFFAOYSA-N 0.000 claims 1
- ZRTGIBNKIAKGJK-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-n-[(3-chloro-4-fluorophenyl)methyl]bicyclo[2.2.2]octane-4-carboxamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)C(=O)NCC=2C=C(Cl)C(F)=CC=2)C=2C=C3OCOC3=CC=2)=N1 ZRTGIBNKIAKGJK-UHFFFAOYSA-N 0.000 claims 1
- ZUTIQUZCDSCVSY-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-n-benzylbicyclo[2.2.2]octane-4-carboxamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)C(=O)NCC=2C=CC=CC=2)C=2C=C3OCOC3=CC=2)=N1 ZUTIQUZCDSCVSY-UHFFFAOYSA-N 0.000 claims 1
- JJNJCSWAUNUNME-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]-n-cyclohexylbicyclo[2.2.2]octane-4-carboxamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)C(=O)NC2CCCCC2)C=2C=C3OCOC3=CC=2)=N1 JJNJCSWAUNUNME-UHFFFAOYSA-N 0.000 claims 1
- DKSAUIAQFZUDED-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]bicyclo[2.2.2]octan-4-amine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(N)(CC2)CC3)C=2C=C3OCOC3=CC=2)=N1 DKSAUIAQFZUDED-UHFFFAOYSA-N 0.000 claims 1
- YCEVMAIOGXNBBQ-UHFFFAOYSA-N 1-[4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]piperidin-1-yl]-2-methylpropan-2-ol Chemical compound C1CN(CC(C)(O)C)CCC1C1=NC(C=2C=C3OCOC3=CC=2)=C(C=2N=CC=CC=2)N1 YCEVMAIOGXNBBQ-UHFFFAOYSA-N 0.000 claims 1
- QNTZUABGHJBFPJ-UHFFFAOYSA-N 1-[4-[4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]piperidin-1-yl]sulfonylphenyl]ethanone Chemical compound C1=CC(C(=O)C)=CC=C1S(=O)(=O)N1CCC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CC1 QNTZUABGHJBFPJ-UHFFFAOYSA-N 0.000 claims 1
- BOZGZZYIXMPCOR-UHFFFAOYSA-N 2-(3-amino-6-iminoxanthen-9-yl)-4-[4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]piperidine-1-carbonyl]benzoic acid Chemical compound C=12C=CC(=N)C=C2OC2=CC(N)=CC=C2C=1C(C(=CC=1)C(O)=O)=CC=1C(=O)N(CC1)CCC1C(N1)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CC=N1 BOZGZZYIXMPCOR-UHFFFAOYSA-N 0.000 claims 1
- HXKYYFMLJPHFTP-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-(1-benzylsulfonylpiperidin-3-yl)-1h-imidazol-5-yl]pyridine Chemical compound C1CCC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CN1S(=O)(=O)CC1=CC=CC=C1 HXKYYFMLJPHFTP-UHFFFAOYSA-N 0.000 claims 1
- YBQSOTUUSVQSDX-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-(1-propan-2-ylsulfonylpiperidin-4-yl)-1h-imidazol-5-yl]pyridine Chemical compound C1CN(S(=O)(=O)C(C)C)CCC1C1=NC(C=2C=C3OCOC3=CC=2)=C(C=2N=CC=CC=2)N1 YBQSOTUUSVQSDX-UHFFFAOYSA-N 0.000 claims 1
- WIESZJDBWQBFCO-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-(2-naphthalen-1-ylethylsulfonyl)piperidin-4-yl]-1h-imidazol-5-yl]pyridine Chemical compound C=1C=CC2=CC=CC=C2C=1CCS(=O)(=O)N(CC1)CCC1C(N1)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CC=N1 WIESZJDBWQBFCO-UHFFFAOYSA-N 0.000 claims 1
- CHISAJWFSHSAGP-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-(2-naphthalen-2-ylethylsulfonyl)piperidin-4-yl]-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)S(=O)(=O)CCC=2C=C3C=CC=CC3=CC=2)C=2C=C3OCOC3=CC=2)=N1 CHISAJWFSHSAGP-UHFFFAOYSA-N 0.000 claims 1
- HLLZYGDCAIEDSD-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-(2-phenylethenylsulfonyl)piperidin-4-yl]-1h-imidazol-5-yl]pyridine Chemical compound C1CC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CCN1S(=O)(=O)C=CC1=CC=CC=C1 HLLZYGDCAIEDSD-UHFFFAOYSA-N 0.000 claims 1
- UYMPGKGTHHSJND-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-(3,4-dichlorophenyl)sulfonylpiperidin-4-yl]-1h-imidazol-5-yl]pyridine Chemical compound C1=C(Cl)C(Cl)=CC=C1S(=O)(=O)N1CCC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CC1 UYMPGKGTHHSJND-UHFFFAOYSA-N 0.000 claims 1
- WQRSAMRRRMOASD-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-(4-chlorophenyl)sulfonylpyrrolidin-3-yl]-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CN(CC2)S(=O)(=O)C=2C=CC(Cl)=CC=2)C=2C=C3OCOC3=CC=2)=N1 WQRSAMRRRMOASD-UHFFFAOYSA-N 0.000 claims 1
- JMKJVYXTWYNLEK-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-(4-phenylphenyl)sulfonylpiperidin-4-yl]-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)S(=O)(=O)C=2C=CC(=CC=2)C=2C=CC=CC=2)C=2C=C3OCOC3=CC=2)=N1 JMKJVYXTWYNLEK-UHFFFAOYSA-N 0.000 claims 1
- IMZJDTDYZJVIDZ-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-(4-phenylphenyl)sulfonylpiperidin-4-yl]-4h-imidazol-5-yl]pyridine Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1S(=O)(=O)N(CC1)CCC1C(N=1)=NC(C=2C=C3OCOC3=CC=2)C=1C1=CC=CC=N1 IMZJDTDYZJVIDZ-UHFFFAOYSA-N 0.000 claims 1
- QNWJZGWOVACKLE-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-(cyclohexylmethyl)piperidin-4-yl]-1h-imidazol-5-yl]pyridine Chemical compound C1CC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CCN1CC1CCCCC1 QNWJZGWOVACKLE-UHFFFAOYSA-N 0.000 claims 1
- VONCCHSJBDBVLX-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-(furan-2-ylmethyl)piperidin-4-yl]-1h-imidazol-5-yl]pyridine Chemical compound C=1C=COC=1CN(CC1)CCC1C(N1)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CC=N1 VONCCHSJBDBVLX-UHFFFAOYSA-N 0.000 claims 1
- DJUINZOSOCXBAC-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-(pyridin-4-ylmethyl)piperidin-4-yl]-1h-imidazol-5-yl]pyridine Chemical compound C=1C=NC=CC=1CN(CC1)CCC1C(N1)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CC=N1 DJUINZOSOCXBAC-UHFFFAOYSA-N 0.000 claims 1
- LRAVQICQOUSVKQ-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-[(3-phenoxyphenyl)methylsulfonyl]piperidin-4-yl]-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)S(=O)(=O)CC=2C=C(OC=3C=CC=CC=3)C=CC=2)C=2C=C3OCOC3=CC=2)=N1 LRAVQICQOUSVKQ-UHFFFAOYSA-N 0.000 claims 1
- QPDBYYHHNUCVME-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-[(4-methylphenyl)methyl]piperidin-4-yl]-1h-imidazol-5-yl]pyridine Chemical compound C1=CC(C)=CC=C1CN1CCC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CC1 QPDBYYHHNUCVME-UHFFFAOYSA-N 0.000 claims 1
- CFNZVCJCUGTYBR-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-[(4-methylphenyl)methylsulfonyl]piperidin-4-yl]-1h-imidazol-5-yl]pyridine Chemical compound C1=CC(C)=CC=C1CS(=O)(=O)N1CCC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CC1 CFNZVCJCUGTYBR-UHFFFAOYSA-N 0.000 claims 1
- OGRVREHRYLXFIJ-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-[[3,5-bis(trifluoromethyl)phenyl]methylsulfonyl]piperidin-4-yl]-1h-imidazol-5-yl]pyridine Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(CS(=O)(=O)N2CCC(CC2)C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)=C1 OGRVREHRYLXFIJ-UHFFFAOYSA-N 0.000 claims 1
- QOLBRKVCDJBHLM-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-1h-imidazol-5-yl]pyridine Chemical compound FC(F)(F)C1=CC(F)=CC(CN2CCC(CC2)C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)=C1 QOLBRKVCDJBHLM-UHFFFAOYSA-N 0.000 claims 1
- KHDKNUGNYWMNRU-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-piperidin-4-yl-1h-imidazol-5-yl]pyridine Chemical compound C1=C2OCOC2=CC=C1C=1N=C(C2CCNCC2)NC=1C1=CC=CC=N1 KHDKNUGNYWMNRU-UHFFFAOYSA-N 0.000 claims 1
- JLVJKUWRYNTZKQ-UHFFFAOYSA-N 4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]-n-[(2-chlorophenyl)methyl]piperidine-1-carboxamide Chemical class ClC1=CC=CC=C1CNC(=O)N1CCC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CC1 JLVJKUWRYNTZKQ-UHFFFAOYSA-N 0.000 claims 1
- HHTYORXLPPYWAD-UHFFFAOYSA-N 4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]-n-[(3-fluorophenyl)methyl]piperidine-1-carboxamide Chemical compound FC1=CC=CC(CNC(=O)N2CCC(CC2)C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)=C1 HHTYORXLPPYWAD-UHFFFAOYSA-N 0.000 claims 1
- PYXXJCQYVKRWTJ-UHFFFAOYSA-N 4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]-n-[(4-fluorophenyl)methyl]piperidine-1-carboxamide Chemical compound C1=CC(F)=CC=C1CNC(=O)N1CCC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CC1 PYXXJCQYVKRWTJ-UHFFFAOYSA-N 0.000 claims 1
- LDQVZEVRSYWYTL-UHFFFAOYSA-N 4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]-n-[(4-methoxyphenyl)methyl]piperidine-1-carboxamide Chemical compound C1=CC(OC)=CC=C1CNC(=O)N1CCC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CC1 LDQVZEVRSYWYTL-UHFFFAOYSA-N 0.000 claims 1
- ISBORYSXADEHMA-UHFFFAOYSA-N 4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]-n-[(4-methylphenyl)methyl]piperidine-1-carboxamide Chemical class C1=CC(C)=CC=C1CNC(=O)N1CCC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CC1 ISBORYSXADEHMA-UHFFFAOYSA-N 0.000 claims 1
- BCYZNZMXANPOKW-UHFFFAOYSA-N 4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]-n-benzylpiperidine-1-carboxamide Chemical compound C1CC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CCN1C(=O)NCC1=CC=CC=C1 BCYZNZMXANPOKW-UHFFFAOYSA-N 0.000 claims 1
- FRJGDMVGTXTZSH-UHFFFAOYSA-N 4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]piperidine-1-carboxamide Chemical compound C1CN(C(=O)N)CCC1C1=NC(C=2C=C3OCOC3=CC=2)=C(C=2N=CC=CC=2)N1 FRJGDMVGTXTZSH-UHFFFAOYSA-N 0.000 claims 1
- KRRCEHFMQSRQEX-UHFFFAOYSA-N 4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1C1=NC(C=2C=C3OCOC3=CC=2)=C(C=2N=CC=CC=2)N1 KRRCEHFMQSRQEX-UHFFFAOYSA-N 0.000 claims 1
- CXJKVETXNJOEHR-UHFFFAOYSA-N 4-[[4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]piperidin-1-yl]sulfonylmethyl]-7,7-dimethylbicyclo[2.2.1]heptan-3-one Chemical compound CC1(C)C(CC2=O)CCC12CS(=O)(=O)N(CC1)CCC1C(N1)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CC=N1 CXJKVETXNJOEHR-UHFFFAOYSA-N 0.000 claims 1
- FOIDCTICLKCJAX-UHFFFAOYSA-N 5-[4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]piperidin-1-yl]sulfonyl-n,n-dimethylnaphthalen-1-amine Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(=O)(=O)N(CC1)CCC1C(N1)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CC=N1 FOIDCTICLKCJAX-UHFFFAOYSA-N 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- XLRLGDAZZOAPBN-UHFFFAOYSA-N [4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]piperidin-1-yl]-(4-methoxyphenyl)methanone Chemical compound C1=CC(OC)=CC=C1C(=O)N1CCC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=C(C)C=CC=2)CC1 XLRLGDAZZOAPBN-UHFFFAOYSA-N 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 1
- FLPVZFWPLBCBPW-UHFFFAOYSA-N benzyl 3-[4-(1,3-benzodioxol-5-yl)-1-hydroxy-5-(6-methylpyridin-2-yl)imidazol-2-yl]piperidine-1-carboxylate Chemical compound CC1=CC=CC(C=2N(C(C3CN(CCC3)C(=O)OCC=3C=CC=CC=3)=NC=2C=2C=C3OCOC3=CC=2)O)=N1 FLPVZFWPLBCBPW-UHFFFAOYSA-N 0.000 claims 1
- YYAWRRQXTYRTBM-UHFFFAOYSA-N benzyl 3-[4-(1,3-benzodioxol-5-yl)-1-hydroxy-5-pyridin-2-ylimidazol-2-yl]piperidine-1-carboxylate Chemical class ON1C(C2CN(CCC2)C(=O)OCC=2C=CC=CC=2)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CC=N1 YYAWRRQXTYRTBM-UHFFFAOYSA-N 0.000 claims 1
- MXPBQVSQKIJLBS-UHFFFAOYSA-N benzyl 4-[4-(1,3-benzodioxol-5-yl)-1-methyl-5-(6-methylpyridin-2-yl)imidazol-2-yl]piperidine-1-carboxylate Chemical compound CC1=CC=CC(C=2N(C(C3CCN(CC3)C(=O)OCC=3C=CC=CC=3)=NC=2C=2C=C3OCOC3=CC=2)C)=N1 MXPBQVSQKIJLBS-UHFFFAOYSA-N 0.000 claims 1
- RCCQRLHHHFFQTG-UHFFFAOYSA-N benzyl 4-[4-(1,3-benzodioxol-5-yl)-5-[6-(trifluoromethyl)pyridin-2-yl]-1h-imidazol-2-yl]piperidine-1-carboxylate Chemical class FC(F)(F)C1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)C(=O)OCC=2C=CC=CC=2)C=2C=C3OCOC3=CC=2)=N1 RCCQRLHHHFFQTG-UHFFFAOYSA-N 0.000 claims 1
- HBEIOFRPWWAEOL-UHFFFAOYSA-N benzyl 4-[4-(2-chloropyridin-4-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]piperidine-1-carboxylate Chemical class CC1=CC=CC(C2=C(N=C(N2)C2CCN(CC2)C(=O)OCC=2C=CC=CC=2)C=2C=C(Cl)N=CC=2)=N1 HBEIOFRPWWAEOL-UHFFFAOYSA-N 0.000 claims 1
- PBPHCFMNDCXBPN-UHFFFAOYSA-N benzyl 4-[5-(1,3-benzodioxol-5-yl)-1-hydroxy-4-(6-methylpyridin-2-yl)imidazol-2-yl]piperidine-1-carboxylate Chemical compound CC1=CC=CC(C2=C(N(O)C(C3CCN(CC3)C(=O)OCC=3C=CC=CC=3)=N2)C=2C=C3OCOC3=CC=2)=N1 PBPHCFMNDCXBPN-UHFFFAOYSA-N 0.000 claims 1
- ZEMXQOXSUMNQJR-UHFFFAOYSA-N benzyl 4-[5-(1,3-benzodioxol-5-yl)-1-methyl-4-(6-methylpyridin-2-yl)imidazol-2-yl]piperidine-1-carboxylate Chemical compound CC1=CC=CC(C2=C(N(C)C(C3CCN(CC3)C(=O)OCC=3C=CC=CC=3)=N2)C=2C=C3OCOC3=CC=2)=N1 ZEMXQOXSUMNQJR-UHFFFAOYSA-N 0.000 claims 1
- FGLYBAMPQJQWRN-UHFFFAOYSA-N benzyl 4-[5-(1,3-benzodioxol-5-yl)-4-(6-bromopyridin-2-yl)-1-hydroxyimidazol-2-yl]piperidine-1-carboxylate Chemical compound C=1C=C2OCOC2=CC=1C=1N(O)C(C2CCN(CC2)C(=O)OCC=2C=CC=CC=2)=NC=1C1=CC=CC(Br)=N1 FGLYBAMPQJQWRN-UHFFFAOYSA-N 0.000 claims 1
- NUNPIJGMCBURAP-UHFFFAOYSA-N benzyl n-[4-[4-(1,3-benzodioxol-5-yl)-1-hydroxy-5-(6-methylpyridin-2-yl)imidazol-2-yl]cyclohexyl]carbamate Chemical compound CC1=CC=CC(C=2N(C(C3CCC(CC3)NC(=O)OCC=3C=CC=CC=3)=NC=2C=2C=C3OCOC3=CC=2)O)=N1 NUNPIJGMCBURAP-UHFFFAOYSA-N 0.000 claims 1
- BUIXBCZZDTVZGU-UHFFFAOYSA-N benzyl n-[[4-[4-(1,3-benzodioxol-5-yl)-1-hydroxy-5-(6-methylpyridin-2-yl)imidazol-2-yl]cyclohexyl]methyl]carbamate Chemical compound CC1=CC=CC(C=2N(C(C3CCC(CNC(=O)OCC=4C=CC=CC=4)CC3)=NC=2C=2C=C3OCOC3=CC=2)O)=N1 BUIXBCZZDTVZGU-UHFFFAOYSA-N 0.000 claims 1
- 208000019065 cervical carcinoma Diseases 0.000 claims 1
- UDYZIFHYNMPZCV-UHFFFAOYSA-N ethyl 2-[[4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1h-imidazol-2-yl]piperidin-1-yl]methyl]cyclopropane-1-carboxylate Chemical compound CCOC(=O)C1CC1CN1CCC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CC1 UDYZIFHYNMPZCV-UHFFFAOYSA-N 0.000 claims 1
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 claims 1
- 201000003911 head and neck carcinoma Diseases 0.000 claims 1
- ATZVYFZDGMLQDL-UHFFFAOYSA-N n-(1h-benzimidazol-2-yl)-1-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]bicyclo[2.2.2]octane-4-carboxamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C23CCC(CC2)(CC3)C(=O)NC=2NC3=CC=CC=C3N=2)C=2C=C3OCOC3=CC=2)=N1 ATZVYFZDGMLQDL-UHFFFAOYSA-N 0.000 claims 1
- KAYVCFMKCMLIDK-UHFFFAOYSA-N n-[[4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]cyclohexyl]methyl]-1-pyridin-4-ylmethanesulfonamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCC(CNS(=O)(=O)CC=3C=CN=CC=3)CC2)C=2C=C3OCOC3=CC=2)=N1 KAYVCFMKCMLIDK-UHFFFAOYSA-N 0.000 claims 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 201000001514 prostate carcinoma Diseases 0.000 claims 1
- 125000001425 triazolyl group Chemical group 0.000 claims 1
- 230000005856 abnormality Effects 0.000 abstract description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 14
- 201000010099 disease Diseases 0.000 abstract description 13
- 238000011282 treatment Methods 0.000 abstract description 9
- 239000005557 antagonist Substances 0.000 abstract description 7
- 230000002265 prevention Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 88
- 239000000203 mixture Substances 0.000 description 63
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 57
- 239000000243 solution Substances 0.000 description 56
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 51
- 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 description 50
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- 235000019439 ethyl acetate Nutrition 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 108010059616 Activins Proteins 0.000 description 29
- 102000005606 Activins Human genes 0.000 description 29
- 239000000488 activin Substances 0.000 description 29
- 102000005962 receptors Human genes 0.000 description 28
- 108020003175 receptors Proteins 0.000 description 28
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 27
- 239000007787 solid Substances 0.000 description 23
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 22
- 239000012267 brine Substances 0.000 description 20
- 229910052938 sodium sulfate Inorganic materials 0.000 description 20
- 235000011152 sodium sulphate Nutrition 0.000 description 20
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
- 230000000694 effects Effects 0.000 description 18
- 238000000746 purification Methods 0.000 description 18
- 238000004128 high performance liquid chromatography Methods 0.000 description 17
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
- 239000002904 solvent Substances 0.000 description 15
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 14
- 206010016654 Fibrosis Diseases 0.000 description 13
- 239000007864 aqueous solution Substances 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 230000004761 fibrosis Effects 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- 229910021529 ammonia Inorganic materials 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000002024 ethyl acetate extract Substances 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 150000001299 aldehydes Chemical class 0.000 description 8
- SOIRQISQWQDGSN-UHFFFAOYSA-N benzyl n-(4-formylcyclohexyl)carbamate Chemical compound C1CC(C=O)CCC1NC(=O)OCC1=CC=CC=C1 SOIRQISQWQDGSN-UHFFFAOYSA-N 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 125000005126 aryl alkyl carbonyl amino group Chemical group 0.000 description 7
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 7
- 125000004658 aryl carbonyl amino group Chemical group 0.000 description 7
- 230000027455 binding Effects 0.000 description 7
- 125000005169 cycloalkylcarbonylamino group Chemical group 0.000 description 7
- 125000005224 heteroarylcarbonylamino group Chemical group 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- AICIYIDUYNFPRY-UHFFFAOYSA-N 1,3-dihydro-2H-imidazol-2-one Chemical compound O=C1NC=CN1 AICIYIDUYNFPRY-UHFFFAOYSA-N 0.000 description 6
- GXJVMVJKUHLUEM-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-yl)-2-hydroxyimino-2-(6-methylpyridin-2-yl)ethanone Chemical compound CC1=CC=CC(C(=NO)C(=O)C=2C=C3OCOC3=CC=2)=N1 GXJVMVJKUHLUEM-UHFFFAOYSA-N 0.000 description 6
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 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
- 238000002953 preparative HPLC Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 125000003396 thiol group Chemical class [H]S* 0.000 description 6
- 239000005089 Luciferase Substances 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 125000004181 carboxyalkyl group Chemical group 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 125000001188 haloalkyl group Chemical group 0.000 description 5
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- HQYHJVWXCZOELK-UHFFFAOYSA-N 1-(6-methylpyridin-2-yl)-2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)ethanone Chemical compound CC1=CC=CC(C(=O)CC2=CN3N=CN=C3C=C2)=N1 HQYHJVWXCZOELK-UHFFFAOYSA-N 0.000 description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 4
- 239000005695 Ammonium acetate Substances 0.000 description 4
- 102000008186 Collagen Human genes 0.000 description 4
- 108010035532 Collagen Proteins 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 102100033456 TGF-beta receptor type-1 Human genes 0.000 description 4
- 108010011702 Transforming Growth Factor-beta Type I Receptor Proteins 0.000 description 4
- 125000001931 aliphatic group Chemical group 0.000 description 4
- 235000019257 ammonium acetate Nutrition 0.000 description 4
- 229940043376 ammonium acetate Drugs 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 229920001436 collagen Polymers 0.000 description 4
- 239000006274 endogenous ligand Substances 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 239000005090 green fluorescent protein Substances 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 125000006413 ring segment Chemical group 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- SYSRNUAOBOQPPX-UHFFFAOYSA-N 2-bromo-6-(1,3-dioxolan-2-yl)pyridine Chemical compound BrC1=CC=CC(C2OCCO2)=N1 SYSRNUAOBOQPPX-UHFFFAOYSA-N 0.000 description 3
- CHMLCFAYQCGYFX-UHFFFAOYSA-N 2-cyclopropyl-6-(1,3-dioxolan-2-yl)pyridine Chemical compound C1CC1C1=CC=CC(C2OCCO2)=N1 CHMLCFAYQCGYFX-UHFFFAOYSA-N 0.000 description 3
- ZVMICQYOGWAOSU-UHFFFAOYSA-N 4-(phenylmethoxycarbonylamino)cyclohexane-1-carboxylic acid Chemical compound C1CC(C(=O)O)CCC1NC(=O)OCC1=CC=CC=C1 ZVMICQYOGWAOSU-UHFFFAOYSA-N 0.000 description 3
- OEBPATOPDYFHIV-UHFFFAOYSA-N 6-cyclopropylpyridine-2-carbaldehyde Chemical compound O=CC1=CC=CC(C2CC2)=N1 OEBPATOPDYFHIV-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-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
- 108091005682 Receptor kinases Proteins 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- 230000035578 autophosphorylation Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 125000002837 carbocyclic group Chemical group 0.000 description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 125000005114 heteroarylalkoxy group Chemical group 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 3
- 210000004969 inflammatory cell Anatomy 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- OAHKWDDSKCRNFE-UHFFFAOYSA-N phenylmethanesulfonyl chloride Chemical compound ClS(=O)(=O)CC1=CC=CC=C1 OAHKWDDSKCRNFE-UHFFFAOYSA-N 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 210000002536 stromal cell Anatomy 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 229910052722 tritium Inorganic materials 0.000 description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- UIIOVRFUJRDPLJ-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-yl)-2-(6-methylpyridin-2-yl)ethanone Chemical compound CC1=CC=CC(CC(=O)C=2C=C3OCOC3=CC=2)=N1 UIIOVRFUJRDPLJ-UHFFFAOYSA-N 0.000 description 2
- XXZKYLQGXQYXME-UHFFFAOYSA-N 1-(1,3-dioxol-4-yl)-2-hydroxyimino-2-(6-methylpyridin-2-yl)ethanone Chemical compound O1COC=C1C(C(=NO)C1=NC(=CC=C1)C)=O XXZKYLQGXQYXME-UHFFFAOYSA-N 0.000 description 2
- PRRPUEWAMYRKPC-UHFFFAOYSA-N 2-hydroxyiminoacetaldehyde Chemical compound ON=CC=O PRRPUEWAMYRKPC-UHFFFAOYSA-N 0.000 description 2
- 101150101604 ACVR1B gene Proteins 0.000 description 2
- 102100034111 Activin receptor type-1 Human genes 0.000 description 2
- 101710105225 Activin receptor type-1 Proteins 0.000 description 2
- RYVZYACBVYKUHD-UHFFFAOYSA-N Alk5 Natural products CC#CC#CCCCCC=CC(=O)NCC(C)C RYVZYACBVYKUHD-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 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
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- IBCXZJCWDGCXQT-UHFFFAOYSA-N LY 364947 Chemical compound C=1C=NC2=CC=CC=C2C=1C1=CNN=C1C1=CC=CC=N1 IBCXZJCWDGCXQT-UHFFFAOYSA-N 0.000 description 2
- 101710128836 Large T antigen Proteins 0.000 description 2
- 241000270322 Lepidosauria Species 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- 102100025751 Mothers against decapentaplegic homolog 2 Human genes 0.000 description 2
- 101710143123 Mothers against decapentaplegic homolog 2 Proteins 0.000 description 2
- 102100025748 Mothers against decapentaplegic homolog 3 Human genes 0.000 description 2
- 101710143111 Mothers against decapentaplegic homolog 3 Proteins 0.000 description 2
- 102100025725 Mothers against decapentaplegic homolog 4 Human genes 0.000 description 2
- 101710143112 Mothers against decapentaplegic homolog 4 Proteins 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 102000043168 TGF-beta family Human genes 0.000 description 2
- 108091085018 TGF-beta family Proteins 0.000 description 2
- 101710084191 TGF-beta receptor type-1 Proteins 0.000 description 2
- 108091005735 TGF-beta receptors Proteins 0.000 description 2
- 102000016715 Transforming Growth Factor beta Receptors Human genes 0.000 description 2
- 102000014172 Transforming Growth Factor-beta Type I Receptor Human genes 0.000 description 2
- 102000009618 Transforming Growth Factors Human genes 0.000 description 2
- 108010009583 Transforming Growth Factors Proteins 0.000 description 2
- 206010046798 Uterine leiomyoma Diseases 0.000 description 2
- SYLGZKAGHAOGFM-UHFFFAOYSA-N [1,2,4]triazolo[1,5-a]pyridine-6-carbaldehyde Chemical compound C1=C(C=O)C=CC2=NC=NN21 SYLGZKAGHAOGFM-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- ZJQMLJFHCKTCSF-UHFFFAOYSA-N benzyl 4-formylpiperidine-1-carboxylate Chemical compound C1CC(C=O)CCN1C(=O)OCC1=CC=CC=C1 ZJQMLJFHCKTCSF-UHFFFAOYSA-N 0.000 description 2
- KEPVPNRFMVTTKV-UHFFFAOYSA-N benzyl n-[4-[methoxy(methyl)carbamoyl]cyclohexyl]carbamate Chemical compound C1CC(C(=O)N(C)OC)CCC1NC(=O)OCC1=CC=CC=C1 KEPVPNRFMVTTKV-UHFFFAOYSA-N 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 210000000013 bile duct Anatomy 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 210000003679 cervix uteri Anatomy 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 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
- 230000006378 damage Effects 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003797 essential amino acid Substances 0.000 description 2
- 235000020776 essential amino acid Nutrition 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 201000010260 leiomyoma Diseases 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 2
- ISWNUAFRSGDCAH-UHFFFAOYSA-N n-methoxy-n-methyl-1,3-benzodioxole-5-carboxamide Chemical compound CON(C)C(=O)C1=CC=C2OCOC2=C1 ISWNUAFRSGDCAH-UHFFFAOYSA-N 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 238000010992 reflux Methods 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
- 239000011734 sodium Substances 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- 229940054269 sodium pyruvate Drugs 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000003756 stirring 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
- 230000004083 survival effect Effects 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 230000000699 topical effect Effects 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
- GCCKNHYFOVQZRG-UHFFFAOYSA-N (2-chlorophenyl)methyl carbonochloridate Chemical compound ClC(=O)OCC1=CC=CC=C1Cl GCCKNHYFOVQZRG-UHFFFAOYSA-N 0.000 description 1
- YUXKOWPNKJSTPQ-AXWWPMSFSA-N (2s,3r)-2-amino-3-hydroxybutanoic acid;(2s)-2-amino-3-hydroxypropanoic acid Chemical compound OC[C@H](N)C(O)=O.C[C@@H](O)[C@H](N)C(O)=O YUXKOWPNKJSTPQ-AXWWPMSFSA-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
- NWGPLYYBECWONP-UHFFFAOYSA-N (carbamoylamino) hydrogen sulfate Chemical compound NC(=O)NOS(O)(=O)=O NWGPLYYBECWONP-UHFFFAOYSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- IIIWZUTUDDZCIM-UHFFFAOYSA-N 1,2-dichloro-3-(isocyanatomethyl)benzene Chemical compound ClC1=CC=CC(CN=C=O)=C1Cl IIIWZUTUDDZCIM-UHFFFAOYSA-N 0.000 description 1
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-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
- SCDVYRNVAAKKEO-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(NC=N2)C=2C=C3OCOC3=CC=2)=N1 SCDVYRNVAAKKEO-UHFFFAOYSA-N 0.000 description 1
- JMYMOBAFZUSNHT-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-[1-(furan-2-yl)-2-methylpiperidin-4-yl]-1h-imidazol-5-yl]pyridine Chemical compound CC1CC(C=2NC(=C(N=2)C=2C=C3OCOC3=CC=2)C=2N=CC=CC=2)CCN1C1=CC=CO1 JMYMOBAFZUSNHT-UHFFFAOYSA-N 0.000 description 1
- SARWAMFCNRRZTD-UHFFFAOYSA-N 2-[4-(1,3-benzodioxol-5-yl)-2-piperidin-4-yl-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C2CCNCC2)C=2C=C3OCOC3=CC=2)=N1 SARWAMFCNRRZTD-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 description 1
- 125000006040 2-hexenyl group Chemical group 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
- 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
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- DRNGLYHKYPNTEA-UHFFFAOYSA-N 4-azaniumylcyclohexane-1-carboxylate Chemical compound NC1CCC(C(O)=O)CC1 DRNGLYHKYPNTEA-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
- 125000004608 5,6,7,8-tetrahydroquinolinyl group Chemical group N1=C(C=CC=2CCCCC12)* 0.000 description 1
- DWSUJONSJJTODA-UHFFFAOYSA-N 5-(chloromethyl)-1,3-benzodioxole Chemical compound ClCC1=CC=C2OCOC2=C1 DWSUJONSJJTODA-UHFFFAOYSA-N 0.000 description 1
- IVILGUFRMDBUEQ-UHFFFAOYSA-N 5-iodopyridin-2-amine Chemical compound NC1=CC=C(I)C=N1 IVILGUFRMDBUEQ-UHFFFAOYSA-N 0.000 description 1
- IVGTZFKULNOQTI-UHFFFAOYSA-N 6-bromopiperidine-2-carbaldehyde Chemical compound BrC1CCCC(C=O)N1 IVGTZFKULNOQTI-UHFFFAOYSA-N 0.000 description 1
- QWFHFNGMCPMOCD-UHFFFAOYSA-N 6-bromopyridine-2-carbaldehyde Chemical compound BrC1=CC=CC(C=O)=N1 QWFHFNGMCPMOCD-UHFFFAOYSA-N 0.000 description 1
- CDWWPXNAXCMGFV-UHFFFAOYSA-N 6-iodo-[1,2,4]triazolo[1,5-a]pyridine Chemical compound C1=C(I)C=CC2=NC=NN21 CDWWPXNAXCMGFV-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
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-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
- 240000000662 Anethum graveolens Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- PSXLCTPHDAEPLK-UHFFFAOYSA-N CC(C)[Mg] Chemical compound CC(C)[Mg] PSXLCTPHDAEPLK-UHFFFAOYSA-N 0.000 description 1
- 206010006895 Cachexia Diseases 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
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 208000032544 Cicatrix 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
- 239000004593 Epoxy Substances 0.000 description 1
- 241000283086 Equidae Species 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
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 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
- 241000238631 Hexapoda Species 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 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
- 208000020060 Increased inflammatory response Diseases 0.000 description 1
- 108010004250 Inhibins Proteins 0.000 description 1
- OWYWGLHRNBIFJP-UHFFFAOYSA-N Ipazine Chemical compound CCN(CC)C1=NC(Cl)=NC(NC(C)C)=N1 OWYWGLHRNBIFJP-UHFFFAOYSA-N 0.000 description 1
- 208000005777 Lupus Nephritis Diseases 0.000 description 1
- 244000294411 Mirabilis expansa Species 0.000 description 1
- 235000015429 Mirabilis expansa Nutrition 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000282339 Mustela Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 101150003085 Pdcl gene Proteins 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
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
- 206010037211 Psychomotor hyperactivity Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 101100437153 Rattus norvegicus Acvr2b gene Proteins 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 102000007614 Thrombospondin 1 Human genes 0.000 description 1
- 108010046722 Thrombospondin 1 Proteins 0.000 description 1
- 208000031737 Tissue Adhesions Diseases 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 206010058990 Venous occlusion Diseases 0.000 description 1
- 208000010399 Wasting Syndrome Diseases 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
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 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
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 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
- 150000001412 amines Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 238000003491 array Methods 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
- 230000001363 autoimmune Effects 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- QKGTVOXHDCVOAW-UHFFFAOYSA-N benzyl 3-formylpiperidine-1-carboxylate Chemical compound C1C(C=O)CCCN1C(=O)OCC1=CC=CC=C1 QKGTVOXHDCVOAW-UHFFFAOYSA-N 0.000 description 1
- GDPSCBPOCONUDM-UHFFFAOYSA-N benzyl 3-formylpyrrolidine-1-carboxylate Chemical compound C1C(C=O)CCN1C(=O)OCC1=CC=CC=C1 GDPSCBPOCONUDM-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000000090 biomarker Substances 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
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 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
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*: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
- 230000010261 cell growth Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 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
- 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
- 239000012351 deprotecting agent Substances 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- KUMNEOGIHFCNQW-UHFFFAOYSA-N diphenyl phosphite Chemical compound C=1C=CC=CC=1OP([O-])OC1=CC=CC=C1 KUMNEOGIHFCNQW-UHFFFAOYSA-N 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 239000003221 ear drop Substances 0.000 description 1
- 229940047652 ear drops Drugs 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 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
- 238000010195 expression analysis Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 150000004665 fatty acids Chemical group 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 125000004967 formylalkyl group Chemical group 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- QFWPJPIVLCBXFJ-UHFFFAOYSA-N glymidine Chemical compound N1=CC(OCCOC)=CN=C1NS(=O)(=O)C1=CC=CC=C1 QFWPJPIVLCBXFJ-UHFFFAOYSA-N 0.000 description 1
- 150000002343 gold Chemical class 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000008629 immune suppression Effects 0.000 description 1
- 210000000987 immune system Anatomy 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
- 230000006698 induction Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000000893 inhibin Substances 0.000 description 1
- 108010019691 inhibin beta A subunit Proteins 0.000 description 1
- 239000003112 inhibitor 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
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000006525 intracellular process Effects 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 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
- 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
- 210000004324 lymphatic system Anatomy 0.000 description 1
- VFZXMEQGIIWBFJ-UHFFFAOYSA-M magnesium;cyclopropane;bromide Chemical compound [Mg+2].[Br-].C1C[CH-]1 VFZXMEQGIIWBFJ-UHFFFAOYSA-M 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
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000009681 mesenchymal cell proliferation Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- KNSYWHCOJRHWRP-UHFFFAOYSA-N methyl 1-formylbicyclo[2.2.2]octane-4-carboxylate Chemical compound C1CC2(C=O)CCC1(C(=O)OC)CC2 KNSYWHCOJRHWRP-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 235000013536 miso Nutrition 0.000 description 1
- 238000000329 molecular dynamics simulation Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000000651 myofibroblast Anatomy 0.000 description 1
- 210000001087 myotubule Anatomy 0.000 description 1
- CXKJPVJQTPRXRT-UHFFFAOYSA-N n-[diphenoxyphosphoryl-(6-methylpyridin-2-yl)methyl]aniline Chemical compound CC1=CC=CC(C(NC=2C=CC=CC=2)P(=O)(OC=2C=CC=CC=2)OC=2C=CC=CC=2)=N1 CXKJPVJQTPRXRT-UHFFFAOYSA-N 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
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 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
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 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
- 230000001590 oxidative effect Effects 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
- 230000002085 persistent effect Effects 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 229950000688 phenothiazine Drugs 0.000 description 1
- 229940012957 plasmin Drugs 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
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 102000037983 regulatory factors Human genes 0.000 description 1
- 108091008025 regulatory factors Proteins 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000037387 scars 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
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000002294 steroidal antiinflammatory agent Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 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
- 238000012546 transfer Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Ophthalmology & Optometry (AREA)
- Pulmonology (AREA)
- Neurology (AREA)
- Heart & Thoracic Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36979302P | 2002-04-04 | 2002-04-04 | |
| US60/369.793 | 2002-04-04 | ||
| PCT/US2003/010440 WO2003087304A2 (en) | 2002-04-04 | 2003-04-04 | Tri-substituted heteroaryls and methods of making and using the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20040094908A true KR20040094908A (ko) | 2004-11-10 |
Family
ID=29250467
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR10-2004-7015706A Ceased KR20040094908A (ko) | 2002-04-04 | 2003-04-04 | 트리-치환된 헤테로아릴 및 이를 제조 및 사용하는 방법 |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US7612094B2 (https=) |
| EP (1) | EP1499308A4 (https=) |
| JP (1) | JP2005527590A (https=) |
| KR (1) | KR20040094908A (https=) |
| CN (1) | CN100448868C (https=) |
| AR (1) | AR039241A1 (https=) |
| AU (1) | AU2003228446B2 (https=) |
| CA (1) | CA2480860A1 (https=) |
| EA (1) | EA010418B1 (https=) |
| IL (1) | IL164295A0 (https=) |
| IS (1) | IS7475A (https=) |
| MX (1) | MXPA04009546A (https=) |
| NO (1) | NO20044779L (https=) |
| NZ (1) | NZ536202A (https=) |
| PL (1) | PL373502A1 (https=) |
| RS (1) | RS95904A (https=) |
| UA (1) | UA81624C2 (https=) |
| WO (1) | WO2003087304A2 (https=) |
| ZA (1) | ZA200407902B (https=) |
Families Citing this family (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR039241A1 (es) | 2002-04-04 | 2005-02-16 | Biogen Inc | Heteroarilos trisustituidos y metodos para su produccion y uso de los mismos |
| GB0217787D0 (en) * | 2002-07-31 | 2002-09-11 | Glaxo Group Ltd | C ompounds |
| CA2497971A1 (en) | 2002-09-18 | 2004-04-01 | Pfizer Products Inc. | Triazole derivatives as transforming growth factor (tgf) inhibitors |
| MXPA05002332A (es) | 2002-09-18 | 2005-06-08 | Pfizer Prod Inc | Nuevos compuestos de oxazol y tiazol como inhibidores del factor de crecimiento transformador (tgf). |
| JP4547271B2 (ja) | 2002-09-18 | 2010-09-22 | ファイザー・プロダクツ・インク | トランスフォーミング増殖因子（ｔｇｆ）阻害剤としての新規イミダゾール化合物 |
| PL375973A1 (en) | 2002-09-18 | 2005-12-12 | Pfizer Products Inc. | Novel isothiazole and isoxazole compounds as transforming growth factor (tgf) inhibitors |
| HRP20050247A2 (en) | 2002-09-18 | 2005-10-31 | Pfizer Products Inc. | Pyrazole derivatives as transforming growth factor (tgf) inhibitors |
| PA8595001A1 (es) | 2003-03-04 | 2004-09-28 | Pfizer Prod Inc | Nuevos compuestos heteroaromaticos condensados que son inhibidores del factor de crecimiento transforante (tgf) |
| CN1921864A (zh) * | 2003-12-24 | 2007-02-28 | 西奥斯公司 | 使用TGF－β抑制剂治疗神经胶质瘤 |
| NZ549003A (en) * | 2004-03-05 | 2009-07-31 | Taisho Pharmaceutical Co Ltd | Thiazole derivative as an ALK5 inhibitor |
| US20080319012A1 (en) | 2004-04-21 | 2008-12-25 | In2Gen Co., Ltd. | 2-Pyridyl substituted imidazoles as ALK5 and/or ALK4 inhibitors |
| CA2578630A1 (en) * | 2004-08-31 | 2006-03-09 | Wen-Cherng Lee | Pyrimidinylimidazoles as tgf-beta inhibitors |
| WO2006028029A1 (ja) * | 2004-09-07 | 2006-03-16 | Sankyo Company, Limited | 置換ビフェニル誘導体 |
| CA2581426A1 (en) | 2004-09-24 | 2006-04-06 | Janssen Pharmaceutica, N.V. | Sulfonamide compounds |
| EP1804801A2 (en) * | 2004-10-15 | 2007-07-11 | Biogen Idec MA, Inc. | Methods of treating vascular injuries |
| GB0510141D0 (en) | 2005-05-18 | 2005-06-22 | Addex Pharmaceuticals Sa | Novel compounds B3 |
| EP1973914A2 (en) | 2005-12-22 | 2008-10-01 | Biogen Idec MA Inc. | Transforming growth factor modulators |
| DK2083863T3 (da) | 2006-10-03 | 2015-06-22 | Genzyme Corp | Antistoffer mod tgf-beta til anvendelse til behandling af spædbørn med risiko for udvikling af bronkopulmonal dysplasi |
| WO2009009059A1 (en) * | 2007-07-09 | 2009-01-15 | Biogen Idec Ma Inc. | Spiro compounds as antagonists of tgf-beta |
| US8138168B1 (en) | 2007-09-26 | 2012-03-20 | Takeda Pharmaceutical Company Limited | Renin inhibitors |
| AU2009227013B2 (en) * | 2008-03-21 | 2013-01-10 | Novartis Ag | Novel heterocyclic compounds and uses therof |
| US8865732B2 (en) | 2008-03-21 | 2014-10-21 | Novartis Ag | Heterocyclic compounds and uses thereof |
| CL2009000904A1 (es) * | 2008-04-21 | 2010-04-30 | Shionogi & Co | Compuestos derivados de ciclohexil sulfonamidas que tienen actividad antagonista en el receptor npy y5, composicion farmaceutica y formulacion farmaceutica que los comprende. |
| UA103319C2 (en) | 2008-05-06 | 2013-10-10 | Глаксосмитклайн Ллк | Thiazole- and oxazole-benzene sulfonamide compounds |
| JP2011521969A (ja) * | 2008-05-30 | 2011-07-28 | スムマ ヘルス システムズ エルエルシー | 眼疾患を治療するためのＴＧＦ−β受容体阻害剤又はアクチビン様キナーゼ（ＡＬＫ）５阻害剤、Ａ−８３−０１及びＳＢ−４３１５４２の使用方法及び創傷治療条件 |
| WO2010011917A1 (en) * | 2008-07-25 | 2010-01-28 | Glaxosmithkline Llc | SEH AND 11β-HSD1 DUAL INHIBITORS |
| WO2010121162A1 (en) * | 2009-04-17 | 2010-10-21 | Summa Health Systems Llc | Use of transforming growth factor-b receptor inhibitors to suppress ocular scarring |
| US8513222B2 (en) | 2010-06-29 | 2013-08-20 | EWHA University—Industry Collaboration Foundation | Methods of treating fibrosis, cancer and vascular injuries |
| USRE47141E1 (en) | 2010-06-29 | 2018-11-27 | EWHA University—Industry Collaboration Foundation | Methods of treating fibrosis, cancer and vascular injuries |
| US8080568B1 (en) | 2010-06-29 | 2011-12-20 | Ewha University - Industry Collaboration Foundation | 2-pyridyl substituted imidazoles as therapeutic ALK5 and/or ALK4 inhibitors |
| US8871744B2 (en) | 2010-07-21 | 2014-10-28 | B & G Partyers, LLC | Compounds and methods for selectively targeting tumor-associated mucins |
| DK2731949T3 (en) | 2011-07-13 | 2018-06-14 | Tiumbio Co Ltd | 2-PYRIDYL-SUBSTITUTED IMIDAZOLS AS ALK5 AND / OR ALK4 INHIBITORS |
| US20140308275A1 (en) | 2011-07-27 | 2014-10-16 | Inserm (Institut National De La Sante Et De La Recherche Medicale | Methods for diagnosing and treating myhre syndrome |
| WO2013062544A1 (en) | 2011-10-26 | 2013-05-02 | Seattle Children's Research Institute | Cysteamine in the treatment of fibrotic disease |
| MX394360B (es) | 2013-03-14 | 2025-03-24 | Sumitomo Pharma Oncology Inc | Inhibidores de jak2 y alk2 y metodos para su uso. |
| US9242969B2 (en) | 2013-03-14 | 2016-01-26 | Novartis Ag | Biaryl amide compounds as kinase inhibitors |
| CN106456578B (zh) | 2014-02-07 | 2020-02-18 | 匈牙利科学院大学及其他机构附属研究所 | Sigma-1受体激动剂化合物的用途 |
| US10842794B2 (en) | 2014-02-07 | 2020-11-24 | Támogatott Kutatócsoportok Irodája | Use of Sigma-1 receptor agonist compounds |
| UY36294A (es) | 2014-09-12 | 2016-04-29 | Novartis Ag | Compuestos y composiciones como inhibidores de quinasa |
| WO2017151409A1 (en) | 2016-02-29 | 2017-09-08 | University Of Florida Research Foundation, Incorporated | Chemotherapeutic methods |
| AU2017329090B9 (en) | 2016-09-19 | 2019-09-05 | Novartis Ag | Therapeutic combinations comprising a RAF inhibitor and a ERK inhibitor |
| ES2952265T3 (es) | 2017-05-02 | 2023-10-30 | Novartis Ag | Terapia combinada que comprende un inhibidor de Raf y trametinib |
| US20210154188A1 (en) * | 2018-04-02 | 2021-05-27 | Silverback Therapeutics, Inc. | Alk5 inhibitors, conjugates, and uses thereof |
| MX2021000977A (es) | 2018-07-26 | 2021-04-12 | Sumitomo Pharma Oncology Inc | Metodos para tratar enfermedades asociadas con expresion anormal de receptor de activina a tipo 1 (acvr1) e inhibidores de acvr1 para uso en los mismos. |
| MX2021008678A (es) * | 2019-01-22 | 2021-10-26 | Bisichem Co Ltd | Compuesto de heteroarilo de anillo fusionado como inhibidor del receptor de tipo i de la activina (alk4) y/o el receptor de tipo i del factor beta de crecimiento transformante (tgf-beta) (alk5). |
| JP2022527972A (ja) | 2019-04-02 | 2022-06-07 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | 前悪性病変を有する患者において癌を予測及び予防する方法 |
| ES3025633T3 (en) | 2019-05-13 | 2025-06-09 | Novartis Ag | New crystalline forms of n-(3-(2-(2-hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methvlphenyl)-2(trifluoromethyl)isonicotinamide as raf inhibitors for the treatment of cancer |
| AU2021205893A1 (en) | 2020-01-08 | 2022-06-23 | Synthis Therapeutics, Inc. | ALK5 inhibitor conjugates and uses thereof |
| KR20230041003A (ko) | 2020-07-15 | 2023-03-23 | 키에시 파르마슈티시 엣스. 피. 에이. | Alk5 억제제로서 피리도 옥사진 아미노 유도체 |
| PT4182308T (pt) | 2020-07-15 | 2024-12-04 | Chiesi Farm Spa | Derivados de piridazinil amino como inibidores de alk5 |
| ES2982017T3 (es) | 2020-07-15 | 2024-10-14 | Chiesi Farm Spa | Derivados de pirido-oxazina como inhibidores de ALK5 |
| US20240116948A1 (en) | 2020-12-23 | 2024-04-11 | Chiesi Farmaceutici S.P.A. | Pyrido oxazine derivatives as alk5 inhibitors |
| CN112759592A (zh) * | 2021-02-01 | 2021-05-07 | 无锡鸣鹭医药科技有限公司 | 一种6-碘[1,2,3]三唑并[1,5-a]吡啶的合成方法 |
| CN114105975A (zh) * | 2021-02-25 | 2022-03-01 | 无锡海伦生物科技有限公司 | 一种[1,2,4]三氮唑[1,5-a]吡啶-6-甲醛的合成方法 |
| AU2022351219A1 (en) | 2021-09-21 | 2024-05-02 | Chiesi Farmaceutici S.P.A. | Pyridazinyl amino derivatives as alk5 inhibitors |
| US20250270215A1 (en) | 2022-04-27 | 2025-08-28 | Chiesi Farmaceutici S.P.A. | Imidazole derivatives as alk5 inhibitors |
| WO2024111626A1 (ja) * | 2022-11-25 | 2024-05-30 | カルナバイオサイエンス株式会社 | 新規チアゾール誘導体 |
| CN121712526A (zh) | 2023-06-13 | 2026-03-20 | 辛瑟斯治疗股份有限公司 | 抗cd5抗体及其用途 |
| CN121181544A (zh) * | 2025-07-07 | 2025-12-23 | 无锡海伦生物科技有限公司 | 一种三唑并吡啶化合物的制备方法 |
Family Cites Families (142)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3940486A (en) | 1971-05-10 | 1976-02-24 | Ciba-Geigy Corporation | Imidazole derivatives in the treatment of pain |
| DE3029376A1 (de) | 1980-07-31 | 1982-03-18 | Nepera Chemical Co. Inc., Harriman, N.Y. | Verfahren zur herstellung von 2,4,5-tris-pyridylimidazolen |
| US4302464A (en) | 1980-10-16 | 1981-11-24 | Pfizer Inc. | Imidazolylpyridine therapeutic agents |
| JPH01181187U (https=) | 1988-06-13 | 1989-12-27 | ||
| DE68925011T2 (de) | 1988-09-16 | 1996-06-27 | Philips Electronics Nv | Hochauflösungs-Fersehsystem. |
| JPH02216969A (ja) | 1989-02-16 | 1990-08-29 | Nec Corp | ファクシミリ端末 |
| AU1422392A (en) | 1991-03-22 | 1992-10-21 | Nippon Soda Co., Ltd. | 2-substituted pyridine derivative, production thereof, and agrohorticultural bactericide |
| US5916891A (en) | 1992-01-13 | 1999-06-29 | Smithkline Beecham Corporation | Pyrimidinyl imidazoles |
| US5656644A (en) | 1994-07-20 | 1997-08-12 | Smithkline Beecham Corporation | Pyridyl imidazoles |
| MX9300141A (es) | 1992-01-13 | 1994-07-29 | Smithkline Beecham Corp | Compuestos de imidazol novedosos, procedimiento para su preparacion y composiciones farmaceuticas que lo contienen. |
| DK64592D0 (da) * | 1992-05-14 | 1992-05-14 | Carlbiotech Ltd As | Peptider til terapeutisk behandling |
| US5593992A (en) | 1993-07-16 | 1997-01-14 | Smithkline Beecham Corporation | Compounds |
| IL110296A (en) | 1993-07-16 | 1999-12-31 | Smithkline Beecham Corp | Imidazole compounds process for their preparation and pharmaceutical compositions containing them |
| US5670527A (en) | 1993-07-16 | 1997-09-23 | Smithkline Beecham Corporation | Pyridyl imidazole compounds and compositions |
| US5593991A (en) | 1993-07-16 | 1997-01-14 | Adams; Jerry L. | Imidazole compounds, use and process of making |
| WO1995003297A1 (en) | 1993-07-21 | 1995-02-02 | Smithkline Beecham Corporation | Imidazoles for treating cytokine mediated disease |
| US5559137A (en) | 1994-05-16 | 1996-09-24 | Smithkline Beecham Corp. | Compounds |
| GB9423460D0 (en) | 1994-11-21 | 1995-01-11 | Merck Sharp & Dohme | Therapeutic agents |
| DK0797575T3 (da) | 1994-12-13 | 2004-02-16 | Hoffmann La Roche | Imidazolderivater som proteinkinase-inhibitorer, især EGF-R-tyrosinkinase |
| JP3734180B2 (ja) | 1994-12-28 | 2006-01-11 | エーザイ株式会社 | 新規ピラゾール誘導体 |
| US5514505A (en) | 1995-05-15 | 1996-05-07 | Xerox Corporation | Method for obtaining improved image contrast in migration imaging members |
| IL118544A (en) | 1995-06-07 | 2001-08-08 | Smithkline Beecham Corp | History of imidazole, the process for their preparation and the pharmaceutical preparations containing them |
| US5739143A (en) | 1995-06-07 | 1998-04-14 | Smithkline Beecham Corporation | Imidazole compounds and compositions |
| US6369068B1 (en) | 1995-06-07 | 2002-04-09 | Smithkline Beecham Corporation | Amino substituted pyrimidine containing compounds |
| EP0846699A1 (en) | 1995-06-29 | 1998-06-10 | Fujisawa Pharmaceutical Co., Ltd. | Substance wf16616, process for production thereof, and use thereof |
| US5792778A (en) | 1995-08-10 | 1998-08-11 | Merck & Co., Inc. | 2-substituted aryl pyrroles, compositions containing such compounds and methods of use |
| US5837719A (en) | 1995-08-10 | 1998-11-17 | Merck & Co., Inc. | 2,5-substituted aryl pyrroles, compositions containing such compounds and methods of use |
| US5717100A (en) | 1995-10-06 | 1998-02-10 | Merck & Co., Inc. | Substituted imidazoles having anti-cancer and cytokine inhibitory activity |
| US6083949A (en) | 1995-10-06 | 2000-07-04 | Merck & Co., Inc. | Substituted imidazoles having anti-cancer and cytokine inhibitory activity |
| GB2306108A (en) | 1995-10-13 | 1997-04-30 | Merck & Co Inc | Treatment of Raf-mediated cancers with imidazole derivatives |
| AU7529096A (en) | 1995-10-31 | 1997-05-22 | Merck & Co., Inc. | Substituted aryl pyrroles, compositions containing such compounds and methods of use |
| WO1997016441A1 (en) | 1995-10-31 | 1997-05-09 | Merck & Co., Inc. | Substituted aryl pyrroles, compositions containing such compounds and methods of use |
| ZA9610687B (en) | 1995-12-22 | 1997-09-29 | Smithkline Beecham Corp | Novel synthesis. |
| ZA97175B (en) | 1996-01-11 | 1997-11-04 | Smithkline Beecham Corp | Novel substituted imidazole compounds. |
| US6046208A (en) | 1996-01-11 | 2000-04-04 | Smithkline Beecham Corporation | Substituted imidazole compounds |
| PL187516B1 (pl) | 1996-01-11 | 2004-07-30 | Smithkline Beecham Corp | Nowe podstawione pochodne imidazolu, sposób ich wytwarzania oraz kompozycja farmaceutyczna zawierająca te związki |
| WO1997028160A1 (en) | 1996-02-01 | 1997-08-07 | Smithkline Beecham Corporation | Endothelin receptor antagonists |
| WO1997032583A1 (en) | 1996-03-08 | 1997-09-12 | Smithkline Beecham Corporation | Use of csaidtm compounds as inhibitors of angiogenesis |
| US6096748A (en) | 1996-03-13 | 2000-08-01 | Smithkline Beecham Corporation | Pyrimidine compounds useful in treating cytokine mediated diseases |
| US6235760B1 (en) | 1996-03-25 | 2001-05-22 | Smithkline Beecham Corporation | Treatment for CNS injuries |
| JP2000507558A (ja) | 1996-03-25 | 2000-06-20 | スミスクライン・ビーチャム・コーポレイション | Ｃｎｓ損傷についての新規な治療 |
| DE19613172A1 (de) | 1996-04-02 | 1997-10-09 | Bayer Ag | Verwendung von substituierten Aryl-imidazolen |
| US5872136A (en) | 1996-04-03 | 1999-02-16 | Merck & Co., Inc. | Arylheteroaryl inhibitors of farnesyl-protein transferase |
| US5939557A (en) | 1996-04-03 | 1999-08-17 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| US5880140A (en) | 1996-04-03 | 1999-03-09 | Merck & Co., Inc. | Biheteroaryl inhibitors of farnesyl-protein transferase |
| US6080870A (en) | 1996-04-03 | 2000-06-27 | Merck & Co., Inc. | Biaryl substituted imidazole compounds useful as farnesyl-protein transferase inhibitors |
| US5883105A (en) | 1996-04-03 | 1999-03-16 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| US5854265A (en) | 1996-04-03 | 1998-12-29 | Merck & Co., Inc. | Biheteroaryl inhibitors of farnesyl-protein transferase |
| EP0906307B1 (en) | 1996-06-10 | 2005-04-27 | Merck & Co., Inc. | Substituted imidazoles having cytokine inhibitory activity |
| US5854264A (en) | 1996-07-24 | 1998-12-29 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| DE69728688T2 (de) | 1996-11-19 | 2004-08-19 | Amgen Inc., Thousand Oaks | Aryl und heteroaryl substituierte kondensierte pyrrole als entzündunghemmende mittel |
| US6410729B1 (en) | 1996-12-05 | 2002-06-25 | Amgen Inc. | Substituted pyrimidine compounds and methods of use |
| US6096753A (en) | 1996-12-05 | 2000-08-01 | Amgen Inc. | Substituted pyrimidinone and pyridone compounds and methods of use |
| ZA9711092B (en) | 1996-12-11 | 1999-07-22 | Smithkline Beecham Corp | Novel compounds. |
| US5939439A (en) | 1996-12-30 | 1999-08-17 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| RU2222534C2 (ru) | 1997-04-24 | 2004-01-27 | Орто-Макнейл Фармасьютикал, Инк. | Замещенные имидазолы, способ их получения, фармацевтическая композиция на их основе, способы лечения цитокин-опосредованных заболеваний |
| US6514977B1 (en) | 1997-05-22 | 2003-02-04 | G.D. Searle & Company | Substituted pyrazoles as p38 kinase inhibitors |
| EP0983260A2 (en) | 1997-05-22 | 2000-03-08 | G.D. Searle & Co. | 3(5)-HETEROARYL SUBSTITUTED PYRAZOLES AS p38 KINASE INHIBITORS |
| US6087496A (en) | 1998-05-22 | 2000-07-11 | G. D. Searle & Co. | Substituted pyrazoles suitable as p38 kinase inhibitors |
| AU7726898A (en) | 1997-05-22 | 1998-12-11 | G.D. Searle & Co. | Pyrazole derivatives as p38 kinase inhibitors |
| KR100704059B1 (ko) | 1997-06-12 | 2007-04-05 | 롱프랑 로라 리미티드 | 이미다졸릴-사이클릭 아세탈 |
| CA2294057A1 (en) | 1997-06-13 | 1998-12-17 | Smithkline Beecham Corporation | Novel pyrazole and pyrazoline substituted compounds |
| AU8154998A (en) | 1997-06-19 | 1999-01-04 | Smithkline Beecham Corporation | Novel aryloxy substituted pyrimidine imidazole compounds |
| GB9713726D0 (en) | 1997-06-30 | 1997-09-03 | Ciba Geigy Ag | Organic compounds |
| EP0994858A1 (en) | 1997-06-30 | 2000-04-26 | Ortho-McNeil Pharmaceutical, Inc. | 2-substituted imidazoles useful in the treatment of inflammatory diseases |
| TW517055B (en) | 1997-07-02 | 2003-01-11 | Smithkline Beecham Corp | Novel substituted imidazole compounds |
| US6562832B1 (en) | 1997-07-02 | 2003-05-13 | Smithkline Beecham Corporation | Substituted imidazole compounds |
| US7301021B2 (en) | 1997-07-02 | 2007-11-27 | Smithkline Beecham Corporation | Substituted imidazole compounds |
| WO1999003480A1 (en) | 1997-07-17 | 1999-01-28 | William Harvey Research Limited | Use of adenosine tri- or tetra-phosphates and their analogues for the treatment of cerebral infarction |
| EP1021173A1 (en) | 1997-10-10 | 2000-07-26 | Imperial College Innovations Limited | Use of csaid?tm compounds for the management of uterine contractions |
| WO1999032121A1 (en) | 1997-12-19 | 1999-07-01 | Smithkline Beecham Corporation | Compounds of heteroaryl substituted imidazole, their pharmaceutical compositions and uses |
| GB9809869D0 (en) | 1998-05-09 | 1998-07-08 | Medical Res Council | Inhibition of protein kinases |
| CN1548436A (zh) | 1998-05-22 | 2004-11-24 | ʷ��˿�������ȳ�ķ����˾ | 新的2-烷基取代咪唑化合物 |
| WO2000001688A1 (en) | 1998-07-02 | 2000-01-13 | Sankyo Company, Limited | Five-membered heteroaryl compounds |
| JP2003525201A (ja) | 1998-08-20 | 2003-08-26 | スミスクライン・ビーチャム・コーポレイション | 新規な置換トリアゾール化合物 |
| WO2000023444A1 (en) | 1998-10-21 | 2000-04-27 | Abbott Laboratories | 5,7-disubstituted-4-aminopyrido[2,3-d]pyrimidine compounds |
| AU6476599A (en) | 1998-11-03 | 2000-05-22 | Novartis Ag | Anti-inflammatory 4-phenyl-5-pyrimidinyl-imidazoles |
| WO2000025791A1 (en) | 1998-11-04 | 2000-05-11 | Smithkline Beecham Corporation | Pyridin-4-yl or pyrimidin-4-yl substituted pyrazines |
| US6239279B1 (en) | 1998-12-16 | 2001-05-29 | Smithkline Beecham Corporation | Synthesis for 4-aryl-5-pyrimidine imidazole substituted derivatives |
| US6288089B1 (en) | 1998-12-21 | 2001-09-11 | Michael Zawada | Use of kinase inhibitors for treating neurodegenerative diseases |
| AU765492B2 (en) | 1998-12-25 | 2003-09-18 | Teikoku Hormone Mfg. Co., Ltd. | Aminopyrazole derivatives |
| WO2000059902A2 (en) | 1999-04-02 | 2000-10-12 | Du Pont Pharmaceuticals Company | Aryl sulfonyls as factor xa inhibitors |
| DE60001229T2 (de) | 1999-04-09 | 2003-10-30 | Smithkline Beecham Corp., Philadelphia | Triarylimidazole |
| CO5170501A1 (es) | 1999-04-14 | 2002-06-27 | Novartis Ag | AZOLES SUSTITUIDOS UTILES PARA EL TRATAMIENTO DE ENFERMEDADES MEDIADAS POR TNFa eIL-1 Y ENFERMEDADES DEL METABOLISMO OSEO |
| CN1178931C (zh) | 1999-06-03 | 2004-12-08 | 帝国脏器制药株式会社 | 取代吡唑化合物 |
| WO2001001986A1 (en) | 1999-07-02 | 2001-01-11 | Lipton Stuart A | Method of reducing neuronal injury or apoptosis |
| WO2001022965A1 (en) | 1999-09-28 | 2001-04-05 | Merck & Co., Inc. | Substituted imidazoles having cytokine inhibitory activity |
| TR200201364T2 (tr) | 1999-11-22 | 2002-10-21 | Smithkline Beecham P. L. C. | Yeni bileşikler. |
| US20030109428A1 (en) | 1999-12-01 | 2003-06-12 | John Bertin | Novel molecules of the card-related protein family and uses thereof |
| WO2001046196A1 (en) | 1999-12-21 | 2001-06-28 | Sugen, Inc. | 4-substituted 7-aza-indolin-2-ones and their use as protein kinase inhibitors |
| AR029803A1 (es) | 2000-02-21 | 2003-07-16 | Smithkline Beecham Plc | Imidazoles sustituidos con piridilo y composiciones farmaceuticas que las comprenden |
| ES2218391T3 (es) | 2000-03-06 | 2004-11-16 | Smithkline Beecham Plc | Derivados de imidazol como inhibidores de raf-cinasa. |
| GB0007405D0 (en) | 2000-03-27 | 2000-05-17 | Smithkline Beecham Corp | Compounds |
| GB0011092D0 (en) | 2000-05-08 | 2000-06-28 | Black James Foundation | Gastrin and cholecystokinin receptor ligands (III) |
| CA2410475A1 (en) | 2000-06-01 | 2001-12-06 | Merck & Co., Inc. | Use of (di-substituted-phenyl)-pyrimidinyl-imidazole derivatives as jnk-inhibitors |
| AU2001268711A1 (en) | 2000-06-23 | 2002-01-08 | Bristol-Myers Squibb Pharma Company | Heteroaryl-phenyl substituted factor xa inhibitors |
| WO2002000651A2 (en) | 2000-06-27 | 2002-01-03 | Bristol-Myers Squibb Pharma Company | Factor xa inhibitors |
| PE20020506A1 (es) | 2000-08-22 | 2002-07-09 | Glaxo Group Ltd | Derivados de pirazol fusionados como inhibidores de la proteina cinasa |
| GB0021726D0 (en) | 2000-09-05 | 2000-10-18 | Astrazeneca Ab | Chemical compounds |
| US7199137B2 (en) | 2000-09-21 | 2007-04-03 | Smithkline Beecham Plc | Imidazole derivatives as Raf kinase inhibitors |
| US6755497B2 (en) * | 2000-09-26 | 2004-06-29 | Canon Kabushiki Kaisha | Ink-jet printing apparatus, control method thereof, and data processing apparatus and method |
| JP2002114780A (ja) * | 2000-10-11 | 2002-04-16 | Taisho Pharmaceut Co Ltd | ４−（３−インドリル）イミダゾール誘導体 |
| CA2426337A1 (en) | 2000-10-18 | 2002-04-25 | Ortho-Mcneil Pharmaceutical, Inc. | Substituted imidazoles useful in the treatment of inflammatory diseases |
| US6630325B1 (en) | 2000-10-19 | 2003-10-07 | Maine Medical Center Research Institute | Compositions, methods and kits relating to remodel |
| GB0027987D0 (en) | 2000-11-16 | 2001-01-03 | Smithkline Beecham Plc | Compounds |
| JP2004517068A (ja) | 2000-11-16 | 2004-06-10 | スミスクライン・ビーチャム・コーポレイション | 化合物 |
| ES2289004T3 (es) | 2000-11-20 | 2008-02-01 | Smithkline Beecham Corporation | Nuevos compuestos. |
| GB0100762D0 (en) * | 2001-01-11 | 2001-02-21 | Smithkline Beecham Plc | Novel use |
| JP2004521915A (ja) | 2001-02-02 | 2004-07-22 | グラクソ グループ リミテッド | Ｔｇｆ過剰発現に対するピラゾール誘導体 |
| GB0102673D0 (en) | 2001-02-02 | 2001-03-21 | Glaxo Group Ltd | Compounds |
| WO2002062787A1 (en) | 2001-02-02 | 2002-08-15 | Glaxo Group Limited | Pyrazoles as tgf inhibitors |
| GB0102668D0 (en) | 2001-02-02 | 2001-03-21 | Glaxo Group Ltd | Compounds |
| GB0102672D0 (en) | 2001-02-02 | 2001-03-21 | Glaxo Group Ltd | Compounds |
| GB0102665D0 (en) | 2001-02-02 | 2001-03-21 | Glaxo Group Ltd | Compounds |
| ITMI20010821A1 (it) | 2001-04-17 | 2002-10-17 | Gienne Pharma S P A | Impiego di composti derivati dallo spirolattone per inibire l'azione pro-fibrigenetica delle cellule stellate epatiche e delle cellule musco |
| US7074801B1 (en) | 2001-04-26 | 2006-07-11 | Eisai Co., Ltd. | Nitrogen-containing condensed cyclic compound having a pyrazolyl group as a substituent group and pharmaceutical composition thereof |
| JP2004532234A (ja) | 2001-04-27 | 2004-10-21 | バーテックス ファーマシューティカルズ インコーポレイテッド | トリアゾール由来キナーゼインヒビターおよびその使用 |
| US6727364B2 (en) | 2001-04-30 | 2004-04-27 | The Procter & Gamble Company | Triazole compounds useful in treating diseases associated with unwanted cytokine activity |
| US6787555B2 (en) | 2001-04-30 | 2004-09-07 | The Procter & Gamble Company | Triazole compounds useful in treating diseases associated with unwanted cytokine activity |
| JP2005022972A (ja) | 2001-05-16 | 2005-01-27 | Teikoku Hormone Mfg Co Ltd | ４−（４−ピリダジニル）ピラゾール誘導体 |
| EP1406573A4 (en) * | 2001-06-07 | 2005-03-30 | Skinmedica Inc | CONDITIONED CELL CULTURE MEDIA AND ITS USES |
| US7300442B2 (en) * | 2001-07-11 | 2007-11-27 | Daniel Cherfas | Method of destroying formations in a body |
| WO2003015781A1 (en) | 2001-08-15 | 2003-02-27 | Sankyo Company, Limited | Novel antidiabetic pharmaceutical compositions |
| GB0127433D0 (en) | 2001-11-15 | 2002-01-09 | Smithkline Beecham Corp | Compounds |
| JP2005516916A (ja) | 2001-12-11 | 2005-06-09 | スミスクライン ビーチャム コーポレーション | 抗ヘルペス薬としてのピラゾロ−ピリジン誘導体 |
| AR039241A1 (es) | 2002-04-04 | 2005-02-16 | Biogen Inc | Heteroarilos trisustituidos y metodos para su produccion y uso de los mismos |
| KR100755577B1 (ko) | 2002-04-26 | 2007-09-12 | 일라이 릴리 앤드 캄파니 | 타키키닌 수용체 길항제로서의 트리아졸 유도체 |
| EP1511738A4 (en) | 2002-05-17 | 2007-05-09 | Scios Inc | TREATMENT OF FIBROPROLIFERATIVE DISEASES USING TGF BETA INHIBITORS |
| GB0215844D0 (en) | 2002-07-09 | 2002-08-14 | Novartis Ag | Organic compounds |
| GB0217783D0 (en) | 2002-07-31 | 2002-09-11 | Glaxo Group Ltd | Compounds |
| GB0217786D0 (en) | 2002-07-31 | 2002-09-11 | Glaxo Group Ltd | Compounds |
| GB0217780D0 (en) | 2002-07-31 | 2002-09-11 | Glaxo Group Ltd | Compounds |
| WO2004013135A1 (en) | 2002-07-31 | 2004-02-12 | Smithkline Beecham Corporation | 2-phenylpyridin-4-yl derivatives as alk5 inhibitors |
| JP4547271B2 (ja) * | 2002-09-18 | 2010-09-22 | ファイザー・プロダクツ・インク | トランスフォーミング増殖因子（ｔｇｆ）阻害剤としての新規イミダゾール化合物 |
| MXPA05002332A (es) | 2002-09-18 | 2005-06-08 | Pfizer Prod Inc | Nuevos compuestos de oxazol y tiazol como inhibidores del factor de crecimiento transformador (tgf). |
| CA2497971A1 (en) | 2002-09-18 | 2004-04-01 | Pfizer Products Inc. | Triazole derivatives as transforming growth factor (tgf) inhibitors |
| EP1553096B1 (en) | 2002-09-25 | 2012-10-31 | Ube Industries, Ltd. | Pyrazole compounds |
| UA80571C2 (en) | 2002-11-22 | 2007-10-10 | Lilly Co Eli | Quinolinyl-pyrrolopyrazoles |
| US7361669B2 (en) | 2003-01-02 | 2008-04-22 | Millennium Pharmaceuticals, Inc. | Compositions and method for inhibiting TGF-β |
| WO2004065392A1 (en) | 2003-01-24 | 2004-08-05 | Smithkline Beecham Corporation | Condensed pyridines and pyrimidines and their use as alk-5 receptor ligands |
| GB0313914D0 (en) | 2003-06-16 | 2003-07-23 | Smithkline Beecham Corp | Compounds |
| GB0313915D0 (en) | 2003-06-16 | 2003-07-23 | Smithkline Beecham Corp | Compounds |
-
2003
- 2003-04-03 AR ARP030101166A patent/AR039241A1/es unknown
- 2003-04-04 NZ NZ536202A patent/NZ536202A/en not_active IP Right Cessation
- 2003-04-04 UA UA20041108993A patent/UA81624C2/ru unknown
- 2003-04-04 AU AU2003228446A patent/AU2003228446B2/en not_active Ceased
- 2003-04-04 EP EP03726198A patent/EP1499308A4/en not_active Withdrawn
- 2003-04-04 IL IL16429503A patent/IL164295A0/xx unknown
- 2003-04-04 RS YU95904A patent/RS95904A/sr unknown
- 2003-04-04 CA CA002480860A patent/CA2480860A1/en not_active Abandoned
- 2003-04-04 JP JP2003584248A patent/JP2005527590A/ja active Pending
- 2003-04-04 PL PL03373502A patent/PL373502A1/xx not_active Application Discontinuation
- 2003-04-04 KR KR10-2004-7015706A patent/KR20040094908A/ko not_active Ceased
- 2003-04-04 US US10/510,459 patent/US7612094B2/en not_active Expired - Lifetime
- 2003-04-04 MX MXPA04009546A patent/MXPA04009546A/es unknown
- 2003-04-04 EA EA200401309A patent/EA010418B1/ru not_active IP Right Cessation
- 2003-04-04 WO PCT/US2003/010440 patent/WO2003087304A2/en not_active Ceased
- 2003-04-04 CN CNB038126990A patent/CN100448868C/zh not_active Expired - Fee Related
-
2004
- 2004-09-28 IS IS7475A patent/IS7475A/is unknown
- 2004-09-30 ZA ZA200407902A patent/ZA200407902B/en unknown
- 2004-11-03 NO NO20044779A patent/NO20044779L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP1499308A2 (en) | 2005-01-26 |
| CN100448868C (zh) | 2009-01-07 |
| JP2005527590A (ja) | 2005-09-15 |
| WO2003087304A2 (en) | 2003-10-23 |
| AU2003228446B2 (en) | 2009-08-06 |
| AU2003228446A1 (en) | 2003-10-27 |
| US7612094B2 (en) | 2009-11-03 |
| EA200401309A1 (ru) | 2005-08-25 |
| RS95904A (sr) | 2006-10-27 |
| IL164295A0 (en) | 2005-12-18 |
| UA81624C2 (ru) | 2008-01-25 |
| EP1499308A4 (en) | 2006-05-24 |
| NZ536202A (en) | 2009-08-28 |
| PL373502A1 (en) | 2005-09-05 |
| IS7475A (is) | 2004-09-28 |
| ZA200407902B (en) | 2005-09-22 |
| MXPA04009546A (es) | 2005-01-25 |
| NO20044779L (no) | 2005-01-04 |
| EA010418B1 (ru) | 2008-08-29 |
| AR039241A1 (es) | 2005-02-16 |
| US20060063809A1 (en) | 2006-03-23 |
| CN1658866A (zh) | 2005-08-24 |
| CA2480860A1 (en) | 2003-10-23 |
| WO2003087304A3 (en) | 2004-07-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7612094B2 (en) | Tri-substituted heteroaryls and methods of making and using the same | |
| EP2731949B1 (en) | 2-pyridyl substituted imidazoles as alk5 and/or alk4 inhibitors | |
| US20060264440A1 (en) | Pyrazoles and methods of making and using the same | |
| US7691865B2 (en) | Pyrazolopyridines and methods of making and using the same | |
| WO2006026306A1 (en) | Pyrimidinylimidazoles as tgf-beta inhibitors | |
| US20080171755A1 (en) | Pyrimidinylpyrazoles as Tgf-Beta Inhibitors | |
| US20080319022A1 (en) | 2-Pyridyl substituted imidazoles as ALK5 and/or ALK4 inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20041002 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20080404 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20100723 Patent event code: PE09021S01D |
|
| E601 | Decision to refuse application | ||
| PE0601 | Decision on rejection of patent |
Patent event date: 20101028 Comment text: Decision to Refuse Application Patent event code: PE06012S01D Patent event date: 20100723 Comment text: Notification of reason for refusal Patent event code: PE06011S01I |