JP2010523674A5 - - Google Patents
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- JP2010523674A5 JP2010523674A5 JP2010503057A JP2010503057A JP2010523674A5 JP 2010523674 A5 JP2010523674 A5 JP 2010523674A5 JP 2010503057 A JP2010503057 A JP 2010503057A JP 2010503057 A JP2010503057 A JP 2010503057A JP 2010523674 A5 JP2010523674 A5 JP 2010523674A5
- Authority
- JP
- Japan
- Prior art keywords
- oxo
- methyl
- hydroquinazolin
- dihydroquinazolin
- dichlorophenyl
- 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.)
- Pending
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 200
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 118
- 125000000217 alkyl group Chemical group 0.000 claims description 70
- 150000001875 compounds Chemical class 0.000 claims description 69
- -1 CF 3 Chemical group 0.000 claims description 57
- 125000003118 aryl group Chemical group 0.000 claims description 36
- 125000001072 heteroaryl group Chemical group 0.000 claims description 31
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 24
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 24
- 125000001475 halogen functional group Chemical group 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- 239000001257 hydrogen Substances 0.000 claims description 24
- 125000002950 monocyclic group Chemical group 0.000 claims description 24
- 125000000623 heterocyclic group Chemical group 0.000 claims description 20
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 20
- 125000003342 alkenyl group Chemical group 0.000 claims description 18
- 125000000304 alkynyl group Chemical group 0.000 claims description 16
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 16
- 150000002431 hydrogen Chemical class 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 125000002619 bicyclic group Chemical group 0.000 claims description 7
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 6
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 6
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 6
- 125000004423 acyloxy group Chemical group 0.000 claims description 5
- 125000002947 alkylene group Chemical group 0.000 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
- 125000004442 acylamino group Chemical group 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 230000000302 ischemic effect Effects 0.000 claims description 4
- LRZFEBJUJIQVDQ-UHFFFAOYSA-N methyl 2-(dimethylamino)acetate Chemical compound COC(=O)CN(C)C LRZFEBJUJIQVDQ-UHFFFAOYSA-N 0.000 claims description 4
- 239000000651 prodrug Substances 0.000 claims description 4
- 229940002612 prodrug Drugs 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 108010087894 Fatty acid desaturases Proteins 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims description 3
- 102000016553 Stearoyl-CoA Desaturase Human genes 0.000 claims description 3
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
- 208000002249 Diabetes Complications Diseases 0.000 claims description 2
- 206010012655 Diabetic complications Diseases 0.000 claims description 2
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 2
- 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 claims description 2
- 206010020772 Hypertension Diseases 0.000 claims description 2
- 206010022489 Insulin Resistance Diseases 0.000 claims description 2
- 208000032382 Ischaemic stroke Diseases 0.000 claims description 2
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 208000008589 Obesity Diseases 0.000 claims description 2
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 2
- 208000017442 Retinal disease Diseases 0.000 claims description 2
- 206010038923 Retinopathy Diseases 0.000 claims description 2
- 208000006011 Stroke Diseases 0.000 claims description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
- WFPYLTJBIPXIMX-UHFFFAOYSA-N [2-[[3-[(3,4-difluorophenyl)methyl]-4-oxoquinazolin-6-yl]amino]-2-oxoethyl] acetate Chemical compound O=C1C2=CC(NC(=O)COC(=O)C)=CC=C2N=CN1CC1=CC=C(F)C(F)=C1 WFPYLTJBIPXIMX-UHFFFAOYSA-N 0.000 claims description 2
- UTWFKZFGFBWHOZ-UHFFFAOYSA-N [2-[[3-[(3,4-dimethylphenyl)methyl]-4-oxoquinazolin-6-yl]amino]-2-oxoethyl] acetate Chemical compound O=C1C2=CC(NC(=O)COC(=O)C)=CC=C2N=CN1CC1=CC=C(C)C(C)=C1 UTWFKZFGFBWHOZ-UHFFFAOYSA-N 0.000 claims description 2
- NWFYTGSYBSYCOU-UHFFFAOYSA-N [2-[[3-[(3-chloro-4-fluorophenyl)methyl]-4-oxoquinazolin-6-yl]amino]-2-oxoethyl] acetate Chemical compound O=C1C2=CC(NC(=O)COC(=O)C)=CC=C2N=CN1CC1=CC=C(F)C(Cl)=C1 NWFYTGSYBSYCOU-UHFFFAOYSA-N 0.000 claims description 2
- BNEZMTZHTOUGNZ-UHFFFAOYSA-N [2-[[3-[(4-chlorophenyl)methyl]-4-oxoquinazolin-6-yl]amino]-2-oxoethyl] acetate Chemical compound O=C1C2=CC(NC(=O)COC(=O)C)=CC=C2N=CN1CC1=CC=C(Cl)C=C1 BNEZMTZHTOUGNZ-UHFFFAOYSA-N 0.000 claims description 2
- PJMUWESHQUJWJQ-UHFFFAOYSA-N [2-[[3-[1-(3,4-dichlorophenyl)ethyl]-4-oxoquinazolin-7-yl]amino]-2-oxoethyl] acetate Chemical compound C1=NC2=CC(NC(=O)COC(C)=O)=CC=C2C(=O)N1C(C)C1=CC=C(Cl)C(Cl)=C1 PJMUWESHQUJWJQ-UHFFFAOYSA-N 0.000 claims description 2
- CKANCWVLJIOYEH-UHFFFAOYSA-N [2-[[3-[1-(3,4-dichlorophenyl)propyl]-4-oxoquinazolin-6-yl]amino]-2-oxoethyl] acetate Chemical compound C1=NC2=CC=C(NC(=O)COC(C)=O)C=C2C(=O)N1C(CC)C1=CC=C(Cl)C(Cl)=C1 CKANCWVLJIOYEH-UHFFFAOYSA-N 0.000 claims description 2
- HZDYPOREEKDJJF-UHFFFAOYSA-N [2-[[3-[3-(2-fluorophenoxy)propyl]-4-oxoquinazolin-6-yl]amino]-2-oxoethyl] acetate Chemical compound O=C1C2=CC(NC(=O)COC(=O)C)=CC=C2N=CN1CCCOC1=CC=CC=C1F HZDYPOREEKDJJF-UHFFFAOYSA-N 0.000 claims description 2
- GXLVMWAYEGFSIW-UHFFFAOYSA-N [2-[[3-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-4-oxoquinazolin-6-yl]amino]-2-oxoethyl] acetate Chemical compound O=C1C2=CC(NC(=O)COC(=O)C)=CC=C2N=CN1CC1=CC=C(Cl)C(C(F)(F)F)=C1 GXLVMWAYEGFSIW-UHFFFAOYSA-N 0.000 claims description 2
- ABTKFZJCNLNRCZ-UHFFFAOYSA-N [2-[[3-[[4-fluoro-3-(trifluoromethyl)phenyl]methyl]-4-oxoquinazolin-6-yl]amino]-2-oxoethyl] acetate Chemical compound O=C1C2=CC(NC(=O)COC(=O)C)=CC=C2N=CN1CC1=CC=C(F)C(C(F)(F)F)=C1 ABTKFZJCNLNRCZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
- 125000005164 aryl thioalkyl group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 claims description 2
- CTUJXHSXIAJYII-UHFFFAOYSA-N benzyl n-[3-(naphthalen-2-ylmethyl)-4-oxoquinazolin-6-yl]carbamate Chemical compound C=1C=C2N=CN(CC=3C=C4C=CC=CC4=CC=3)C(=O)C2=CC=1NC(=O)OCC1=CC=CC=C1 CTUJXHSXIAJYII-UHFFFAOYSA-N 0.000 claims description 2
- BMFOQJHODDTXBF-UHFFFAOYSA-N benzyl n-[3-[(3,4-dichlorophenyl)methyl]-2-methyl-4-oxoquinazolin-7-yl]carbamate Chemical compound C=1C=C2C(=O)N(CC=3C=C(Cl)C(Cl)=CC=3)C(C)=NC2=CC=1NC(=O)OCC1=CC=CC=C1 BMFOQJHODDTXBF-UHFFFAOYSA-N 0.000 claims description 2
- HFTPWWWEDCJNRU-UHFFFAOYSA-N benzyl n-[3-[(3,4-dimethylphenyl)methyl]-4-oxoquinazolin-6-yl]carbamate Chemical compound C1=C(C)C(C)=CC=C1CN1C(=O)C2=CC(NC(=O)OCC=3C=CC=CC=3)=CC=C2N=C1 HFTPWWWEDCJNRU-UHFFFAOYSA-N 0.000 claims description 2
- QRFSRYLIFCVTFQ-UHFFFAOYSA-N benzyl n-[3-[(3-methoxyphenyl)methyl]-4-oxoquinazolin-6-yl]carbamate Chemical compound COC1=CC=CC(CN2C(C3=CC(NC(=O)OCC=4C=CC=CC=4)=CC=C3N=C2)=O)=C1 QRFSRYLIFCVTFQ-UHFFFAOYSA-N 0.000 claims description 2
- SXHQLLQDYKSKDN-UHFFFAOYSA-N benzyl n-[3-[1-(3,4-dichlorophenyl)ethyl]-4-oxoquinazolin-7-yl]carbamate Chemical compound C1=NC2=CC(NC(=O)OCC=3C=CC=CC=3)=CC=C2C(=O)N1C(C)C1=CC=C(Cl)C(Cl)=C1 SXHQLLQDYKSKDN-UHFFFAOYSA-N 0.000 claims description 2
- LLUTVUDHDVDAOY-UHFFFAOYSA-N benzyl n-[3-[2-(2-chlorophenoxy)ethyl]-4-oxoquinazolin-6-yl]carbamate Chemical compound ClC1=CC=CC=C1OCCN1C(=O)C2=CC(NC(=O)OCC=3C=CC=CC=3)=CC=C2N=C1 LLUTVUDHDVDAOY-UHFFFAOYSA-N 0.000 claims description 2
- MJJLLTSJHOQRNF-UHFFFAOYSA-N benzyl n-[3-[3-(2,5-dichlorophenoxy)propyl]-4-oxoquinazolin-6-yl]carbamate Chemical compound ClC1=CC=C(Cl)C(OCCCN2C(C3=CC(NC(=O)OCC=4C=CC=CC=4)=CC=C3N=C2)=O)=C1 MJJLLTSJHOQRNF-UHFFFAOYSA-N 0.000 claims description 2
- FUMDPIDLTCAXBG-UHFFFAOYSA-N benzyl n-[3-[3-(2,5-dichlorophenoxy)propyl]-4-oxoquinazolin-7-yl]carbamate Chemical compound ClC1=CC=C(Cl)C(OCCCN2C(C3=CC=C(NC(=O)OCC=4C=CC=CC=4)C=C3N=C2)=O)=C1 FUMDPIDLTCAXBG-UHFFFAOYSA-N 0.000 claims description 2
- GPGOYELTXDBALG-UHFFFAOYSA-N benzyl n-[3-[3-(2-chlorophenoxy)propyl]-4-oxoquinazolin-6-yl]carbamate Chemical compound ClC1=CC=CC=C1OCCCN1C(=O)C2=CC(NC(=O)OCC=3C=CC=CC=3)=CC=C2N=C1 GPGOYELTXDBALG-UHFFFAOYSA-N 0.000 claims description 2
- PLIQHENHLVWGDF-UHFFFAOYSA-N benzyl n-[3-[3-(2-cyanophenoxy)propyl]-4-oxoquinazolin-6-yl]carbamate Chemical compound C=1C=CC=CC=1COC(=O)NC(C=C1C2=O)=CC=C1N=CN2CCCOC1=CC=CC=C1C#N PLIQHENHLVWGDF-UHFFFAOYSA-N 0.000 claims description 2
- VSTIRTAQKJYNEU-UHFFFAOYSA-N benzyl n-[3-[3-(2-fluorophenoxy)propyl]-4-oxoquinazolin-6-yl]carbamate Chemical compound FC1=CC=CC=C1OCCCN1C(=O)C2=CC(NC(=O)OCC=3C=CC=CC=3)=CC=C2N=C1 VSTIRTAQKJYNEU-UHFFFAOYSA-N 0.000 claims description 2
- BOEPPJCFWCTYSX-UHFFFAOYSA-N benzyl n-[3-[3-(2-methylphenoxy)propyl]-4-oxoquinazolin-6-yl]carbamate Chemical compound CC1=CC=CC=C1OCCCN1C(=O)C2=CC(NC(=O)OCC=3C=CC=CC=3)=CC=C2N=C1 BOEPPJCFWCTYSX-UHFFFAOYSA-N 0.000 claims description 2
- CCIWOWHZPRYXOZ-UHFFFAOYSA-N benzyl n-[3-[4-(2,5-dichlorophenoxy)butyl]-4-oxoquinazolin-6-yl]carbamate Chemical compound ClC1=CC=C(Cl)C(OCCCCN2C(C3=CC(NC(=O)OCC=4C=CC=CC=4)=CC=C3N=C2)=O)=C1 CCIWOWHZPRYXOZ-UHFFFAOYSA-N 0.000 claims description 2
- KUUODPDZRYGRLM-UHFFFAOYSA-N benzyl n-[3-[[3-[(2,5-dichlorophenoxy)methyl]phenyl]methyl]-4-oxoquinazolin-6-yl]carbamate Chemical compound ClC1=CC=C(Cl)C(OCC=2C=C(CN3C(C4=CC(NC(=O)OCC=5C=CC=CC=5)=CC=C4N=C3)=O)C=CC=2)=C1 KUUODPDZRYGRLM-UHFFFAOYSA-N 0.000 claims description 2
- OMLSHDULJUEBDA-UHFFFAOYSA-N benzyl n-[3-[[4-fluoro-3-(trifluoromethyl)phenyl]methyl]-4-oxoquinazolin-6-yl]carbamate Chemical compound C1=C(C(F)(F)F)C(F)=CC=C1CN1C(=O)C2=CC(NC(=O)OCC=3C=CC=CC=3)=CC=C2N=C1 OMLSHDULJUEBDA-UHFFFAOYSA-N 0.000 claims description 2
- MYOUMZOICPUQKY-UHFFFAOYSA-N benzyl n-[4-oxo-3-[3-[2-(trifluoromethyl)phenoxy]propyl]quinazolin-6-yl]carbamate Chemical compound FC(F)(F)C1=CC=CC=C1OCCCN1C(=O)C2=CC(NC(=O)OCC=3C=CC=CC=3)=CC=C2N=C1 MYOUMZOICPUQKY-UHFFFAOYSA-N 0.000 claims description 2
- HKTYPJGCHPMZPH-UHFFFAOYSA-N benzyl n-[4-oxo-3-[[3-(trifluoromethyl)phenyl]methyl]quinazolin-6-yl]carbamate Chemical compound FC(F)(F)C1=CC=CC(CN2C(C3=CC(NC(=O)OCC=4C=CC=CC=4)=CC=C3N=C2)=O)=C1 HKTYPJGCHPMZPH-UHFFFAOYSA-N 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 230000002490 cerebral effect Effects 0.000 claims description 2
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 2
- 208000029078 coronary artery disease Diseases 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- 208000019622 heart disease Diseases 0.000 claims description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
- AYWPACLSVIRDFY-UHFFFAOYSA-N n-(3-benzyl-4-oxoquinazolin-6-yl)-2-hydroxyacetamide Chemical compound O=C1C2=CC(NC(=O)CO)=CC=C2N=CN1CC1=CC=CC=C1 AYWPACLSVIRDFY-UHFFFAOYSA-N 0.000 claims description 2
- JMSDMPBPEGROHI-SNVBAGLBSA-N n-[3-[(1r)-1-(3,4-dichlorophenyl)ethyl]-4-oxoquinazolin-7-yl]-2-hydroxyacetamide Chemical compound C1([C@@H](C)N2C(C3=CC=C(NC(=O)CO)C=C3N=C2)=O)=CC=C(Cl)C(Cl)=C1 JMSDMPBPEGROHI-SNVBAGLBSA-N 0.000 claims description 2
- JMSDMPBPEGROHI-JTQLQIEISA-N n-[3-[(1s)-1-(3,4-dichlorophenyl)ethyl]-4-oxoquinazolin-7-yl]-2-hydroxyacetamide Chemical compound C1([C@H](C)N2C(C3=CC=C(NC(=O)CO)C=C3N=C2)=O)=CC=C(Cl)C(Cl)=C1 JMSDMPBPEGROHI-JTQLQIEISA-N 0.000 claims description 2
- XBWXBBIHXFRYOE-UHFFFAOYSA-N n-[3-[(3,4-dimethylphenyl)methyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound C1=C(C)C(C)=CC=C1CN1C(=O)C2=CC(NC(=O)CO)=CC=C2N=C1 XBWXBBIHXFRYOE-UHFFFAOYSA-N 0.000 claims description 2
- WYCXEKKLBAECDV-UHFFFAOYSA-N n-[3-[(4-chlorophenyl)methyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound O=C1C2=CC(NC(=O)CO)=CC=C2N=CN1CC1=CC=C(Cl)C=C1 WYCXEKKLBAECDV-UHFFFAOYSA-N 0.000 claims description 2
- UVNYGTQVNXJYOX-UHFFFAOYSA-N n-[3-[1-(3,4-dichlorophenyl)ethyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound C1=NC2=CC=C(NC(=O)CO)C=C2C(=O)N1C(C)C1=CC=C(Cl)C(Cl)=C1 UVNYGTQVNXJYOX-UHFFFAOYSA-N 0.000 claims description 2
- JMSDMPBPEGROHI-UHFFFAOYSA-N n-[3-[1-(3,4-dichlorophenyl)ethyl]-4-oxoquinazolin-7-yl]-2-hydroxyacetamide Chemical compound C1=NC2=CC(NC(=O)CO)=CC=C2C(=O)N1C(C)C1=CC=C(Cl)C(Cl)=C1 JMSDMPBPEGROHI-UHFFFAOYSA-N 0.000 claims description 2
- GWQNYIBHBLIXEJ-UHFFFAOYSA-N n-[3-[2-(2,4-dichlorophenyl)ethyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound O=C1C2=CC(NC(=O)CO)=CC=C2N=CN1CCC1=CC=C(Cl)C=C1Cl GWQNYIBHBLIXEJ-UHFFFAOYSA-N 0.000 claims description 2
- TVJUKCVZGFXXNM-UHFFFAOYSA-N n-[3-[2-(2,5-dichlorophenoxy)ethyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound O=C1C2=CC(NC(=O)CO)=CC=C2N=CN1CCOC1=CC(Cl)=CC=C1Cl TVJUKCVZGFXXNM-UHFFFAOYSA-N 0.000 claims description 2
- VAJCDSSORKOZGI-UHFFFAOYSA-N n-[3-[2-(3-chlorophenoxy)ethyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound O=C1C2=CC(NC(=O)CO)=CC=C2N=CN1CCOC1=CC=CC(Cl)=C1 VAJCDSSORKOZGI-UHFFFAOYSA-N 0.000 claims description 2
- REYFHLSLYNRKPX-UHFFFAOYSA-N n-[3-[2-(3-chlorophenyl)ethyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound O=C1C2=CC(NC(=O)CO)=CC=C2N=CN1CCC1=CC=CC(Cl)=C1 REYFHLSLYNRKPX-UHFFFAOYSA-N 0.000 claims description 2
- HMSNCISXSUECEB-UHFFFAOYSA-N n-[3-[2-(4-chlorophenyl)ethyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound O=C1C2=CC(NC(=O)CO)=CC=C2N=CN1CCC1=CC=C(Cl)C=C1 HMSNCISXSUECEB-UHFFFAOYSA-N 0.000 claims description 2
- IYONCBOKLGDXMJ-UHFFFAOYSA-N n-[3-[2-[(2,5-dichlorophenyl)sulfonylamino]ethyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound O=C1C2=CC(NC(=O)CO)=CC=C2N=CN1CCNS(=O)(=O)C1=CC(Cl)=CC=C1Cl IYONCBOKLGDXMJ-UHFFFAOYSA-N 0.000 claims description 2
- RORPUVRZXYZASA-UHFFFAOYSA-N n-[3-[3-(2,3-dichlorophenoxy)propyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound O=C1C2=CC(NC(=O)CO)=CC=C2N=CN1CCCOC1=CC=CC(Cl)=C1Cl RORPUVRZXYZASA-UHFFFAOYSA-N 0.000 claims description 2
- ZYBXKSWALPWWQQ-UHFFFAOYSA-N n-[3-[3-(2,5-dichlorophenoxy)propyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound O=C1C2=CC(NC(=O)CO)=CC=C2N=CN1CCCOC1=CC(Cl)=CC=C1Cl ZYBXKSWALPWWQQ-UHFFFAOYSA-N 0.000 claims description 2
- KVZYMEFWOBVJHL-UHFFFAOYSA-N n-[3-[3-(2,5-dichlorophenoxy)propyl]-4-oxoquinazolin-7-yl]-2-hydroxyacetamide Chemical compound C=1C(NC(=O)CO)=CC=C(C2=O)C=1N=CN2CCCOC1=CC(Cl)=CC=C1Cl KVZYMEFWOBVJHL-UHFFFAOYSA-N 0.000 claims description 2
- MFMVQNBXIYJAHT-UHFFFAOYSA-N n-[3-[3-(2-chlorophenoxy)propyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound O=C1C2=CC(NC(=O)CO)=CC=C2N=CN1CCCOC1=CC=CC=C1Cl MFMVQNBXIYJAHT-UHFFFAOYSA-N 0.000 claims description 2
- OLWNATBKNXAMAW-UHFFFAOYSA-N n-[3-[3-(2-chlorophenyl)propyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound O=C1C2=CC(NC(=O)CO)=CC=C2N=CN1CCCC1=CC=CC=C1Cl OLWNATBKNXAMAW-UHFFFAOYSA-N 0.000 claims description 2
- AUMYINXCQGKYQO-UHFFFAOYSA-N n-[3-[3-(4-chlorophenoxy)propyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound O=C1C2=CC(NC(=O)CO)=CC=C2N=CN1CCCOC1=CC=C(Cl)C=C1 AUMYINXCQGKYQO-UHFFFAOYSA-N 0.000 claims description 2
- KJKRJIJOIPCXSK-UHFFFAOYSA-N n-[3-[3-[(2,5-dichlorophenyl)sulfonylamino]propyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound O=C1C2=CC(NC(=O)CO)=CC=C2N=CN1CCCNS(=O)(=O)C1=CC(Cl)=CC=C1Cl KJKRJIJOIPCXSK-UHFFFAOYSA-N 0.000 claims description 2
- ZYHAOOUJIRAVKM-UHFFFAOYSA-N n-[3-[3-[2-chloro-5-(trifluoromethyl)phenoxy]propyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound O=C1C2=CC(NC(=O)CO)=CC=C2N=CN1CCCOC1=CC(C(F)(F)F)=CC=C1Cl ZYHAOOUJIRAVKM-UHFFFAOYSA-N 0.000 claims description 2
- BAJKEXWWSBUXGL-UHFFFAOYSA-N n-[3-[4-(2,5-dichlorophenoxy)butyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound O=C1C2=CC(NC(=O)CO)=CC=C2N=CN1CCCCOC1=CC(Cl)=CC=C1Cl BAJKEXWWSBUXGL-UHFFFAOYSA-N 0.000 claims description 2
- VRZJMJLEEDFBAO-UHFFFAOYSA-N n-[3-[5-(2,5-dichlorophenoxy)pentyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound O=C1C2=CC(NC(=O)CO)=CC=C2N=CN1CCCCCOC1=CC(Cl)=CC=C1Cl VRZJMJLEEDFBAO-UHFFFAOYSA-N 0.000 claims description 2
- IDYGCGYCHOUWQB-UHFFFAOYSA-N n-[3-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound O=C1C2=CC(NC(=O)CO)=CC=C2N=CN1CC1=CC=C(Cl)C(C(F)(F)F)=C1 IDYGCGYCHOUWQB-UHFFFAOYSA-N 0.000 claims description 2
- DTWKOBGWCSHUPS-UHFFFAOYSA-N n-[3-[[4-fluoro-3-(trifluoromethyl)phenyl]methyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound O=C1C2=CC(NC(=O)CO)=CC=C2N=CN1CC1=CC=C(F)C(C(F)(F)F)=C1 DTWKOBGWCSHUPS-UHFFFAOYSA-N 0.000 claims description 2
- 235000020824 obesity Nutrition 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000012453 solvate Substances 0.000 claims description 2
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 230000001052 transient effect Effects 0.000 claims description 2
- 125000004188 dichlorophenyl group Chemical group 0.000 claims 3
- 239000000203 mixture Substances 0.000 claims 3
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 1
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 150000004677 hydrates Chemical class 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- NBYHWIXZXMOEEL-UHFFFAOYSA-N benzyl n-[3-[1-(3,4-dichlorophenyl)propyl]-4-oxoquinazolin-6-yl]carbamate Chemical compound C1=NC2=CC=C(NC(=O)OCC=3C=CC=CC=3)C=C2C(=O)N1C(CC)C1=CC=C(Cl)C(Cl)=C1 NBYHWIXZXMOEEL-UHFFFAOYSA-N 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- PLLMZYHSSGPIPW-UHFFFAOYSA-N n-[3-[(3,4-difluorophenyl)methyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound O=C1C2=CC(NC(=O)CO)=CC=C2N=CN1CC1=CC=C(F)C(F)=C1 PLLMZYHSSGPIPW-UHFFFAOYSA-N 0.000 description 1
- VVTGCFSFGWYQTR-UHFFFAOYSA-N n-[3-[(4-chlorophenyl)methyl]-4-oxoquinazolin-6-yl]-2-phenoxyacetamide Chemical compound C1=CC(Cl)=CC=C1CN1C(=O)C2=CC(NC(=O)COC=3C=CC=CC=3)=CC=C2N=C1 VVTGCFSFGWYQTR-UHFFFAOYSA-N 0.000 description 1
- IBALPTMGUFTXFW-UHFFFAOYSA-N n-[3-[1-(3,4-dichlorophenyl)propyl]-4-oxoquinazolin-6-yl]-2-hydroxyacetamide Chemical compound C1=NC2=CC=C(NC(=O)CO)C=C2C(=O)N1C(CC)C1=CC=C(Cl)C(Cl)=C1 IBALPTMGUFTXFW-UHFFFAOYSA-N 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
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| CN101522676A (zh) * | 2006-10-05 | 2009-09-02 | Cv医药有限公司 | 用作硬脂酰-CoA脱氢酶抑制剂的双环含氮杂环化合物 |
| EP2131844A1 (en) * | 2007-04-09 | 2009-12-16 | CV Therapeutics Inc. | PTERIDINONE DERIVATIVES FOR USE AS STEAROYL CoA DESATURASE INHIBITORS |
| US20090105283A1 (en) * | 2007-04-11 | 2009-04-23 | Dmitry Koltun | 3-HYDROQUINAZOLIN-4-ONE DERIVATIVES FOR USE AS STEAROYL CoA DESATURASE INHIBITORS |
| EP2242367A4 (en) * | 2008-01-08 | 2012-07-04 | Univ Pennsylvania | Rel inhibitors and methods of use thereof |
| US8088792B2 (en) * | 2008-04-04 | 2012-01-03 | Gilead Sciences, Inc. | Triazolopyridinone derivatives for use as stearoyl CoA desaturase inhibitors |
| CA2719362A1 (en) * | 2008-04-04 | 2009-10-08 | Gilead Sciences, Inc. | Pyrrolotriazinone derivatives for use as stearoyl coa desaturase inhibitors |
| WO2010045374A1 (en) * | 2008-10-15 | 2010-04-22 | Gilead Palo Alto, Inc. | 3-hydroquinazolin-4-one derivatives for use as stearoyl coa desaturase inhibitors |
| WO2013056148A2 (en) | 2011-10-15 | 2013-04-18 | Genentech, Inc. | Methods of using scd1 antagonists |
| MX2014012991A (es) | 2012-04-24 | 2015-08-14 | Chugai Pharmaceutical Co Ltd | Derivado de benzamida. |
| TW201348213A (zh) | 2012-04-24 | 2013-12-01 | Chugai Pharmaceutical Co Ltd | 喹唑啉二酮衍生物 |
| JP6307088B2 (ja) * | 2013-10-23 | 2018-04-04 | 中外製薬株式会社 | キナゾリノンおよびイソキノリノン誘導体 |
| SG11201708622UA (en) | 2015-02-02 | 2017-11-29 | Forma Therapeutics Inc | 3-aryl-4-amido-bicyclic [4,5,0] hydroxamic acids as hdac inhibitors |
| WO2016126726A1 (en) | 2015-02-02 | 2016-08-11 | Forma Therapeutics, Inc. | Bicyclic [4,6,0] hydroxamic acids as hdac6 inhibitors |
| EP3472131B1 (en) | 2016-06-17 | 2020-02-19 | Forma Therapeutics, Inc. | 2-spiro-5- and 6-hydroxamic acid indanes as hdac inhibitors |
| US11970486B2 (en) | 2016-10-24 | 2024-04-30 | Janssen Pharmaceutica Nv | Compounds and uses thereof |
| EA201991650A1 (ru) | 2017-01-06 | 2020-01-20 | Юманити Терапьютикс, Инк. | Способы лечения неврологических расстройств |
| CA3083000A1 (en) | 2017-10-24 | 2019-05-02 | Yumanity Therapeutics, Inc. | Compounds and uses thereof |
| AU2019200683B2 (en) * | 2018-02-01 | 2024-05-30 | The University Of Sydney | Anti-cancer compounds |
| BR112020019191A2 (pt) | 2018-03-23 | 2021-01-05 | Yumanity Therapeutics, Inc. | Compostos e seus usos |
| MX2021008903A (es) | 2019-01-24 | 2021-11-04 | Yumanity Therapeutics Inc | Compuestos y usos de los mismos. |
| CN114269756B (zh) * | 2019-07-02 | 2024-05-14 | 效应疗法股份有限公司 | 抑制eif4e的4-氧代-3,4-二氢吡啶并[3,4-d]嘧啶化合物 |
| EA202192047A1 (ru) | 2019-11-13 | 2021-12-08 | Юманити Терапьютикс, Инк. | Соединения и их применение |
| CN110903253B (zh) * | 2019-12-13 | 2020-12-25 | 西安交通大学医学院第一附属医院 | 一种喹唑啉酮类化合物及其制备方法和应用 |
| CN113354590A (zh) * | 2020-03-05 | 2021-09-07 | 宁波康柏睿格医药科技有限公司 | 拮抗nod1/2受体信号通路的喹唑啉酮类化合物 |
| IN202011027502A (https=) * | 2020-06-29 | 2021-12-31 | Council Scient Ind Res | |
| EP4185380A4 (en) * | 2020-07-24 | 2024-08-21 | Inipharm, Inc. | Quinazolinone hsd17b13 inhibitors and uses thereof |
| CN116670118B (zh) * | 2020-11-13 | 2026-02-06 | 伊尼制药公司 | 二氯苯酚hsd17b13抑制剂及其用途 |
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| JPS5920670B2 (ja) * | 1976-04-10 | 1984-05-15 | 田辺製薬株式会社 | キナゾリノン誘導体の製法 |
| US4326525A (en) * | 1980-10-14 | 1982-04-27 | Alza Corporation | Osmotic device that improves delivery properties of agent in situ |
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| US5023252A (en) * | 1985-12-04 | 1991-06-11 | Conrex Pharmaceutical Corporation | Transdermal and trans-membrane delivery of drugs |
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| US4902514A (en) * | 1988-07-21 | 1990-02-20 | Alza Corporation | Dosage form for administering nilvadipine for treating cardiovascular symptoms |
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| PT1830869E (pt) * | 2004-12-24 | 2013-08-22 | Spinifex Pharm Pty Ltd | Método de tratamento ou profilaxia |
| CN101522676A (zh) * | 2006-10-05 | 2009-09-02 | Cv医药有限公司 | 用作硬脂酰-CoA脱氢酶抑制剂的双环含氮杂环化合物 |
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-
2008
- 2008-04-09 US US12/100,399 patent/US20080255161A1/en not_active Abandoned
- 2008-04-10 CA CA002683925A patent/CA2683925A1/en not_active Abandoned
- 2008-04-10 JP JP2010503057A patent/JP2010523674A/ja active Pending
- 2008-04-10 RU RU2009141596/04A patent/RU2009141596A/ru not_active Application Discontinuation
- 2008-04-10 BR BRPI0809551-5A patent/BRPI0809551A2/pt not_active Application Discontinuation
- 2008-04-10 WO PCT/US2008/004632 patent/WO2008127615A1/en not_active Ceased
- 2008-04-10 EP EP08742725A patent/EP2155695A1/en not_active Withdrawn
- 2008-04-10 CN CN200880011238A patent/CN101652353A/zh active Pending
- 2008-04-10 KR KR1020097023479A patent/KR20100016421A/ko not_active Withdrawn
- 2008-04-10 AU AU2008239689A patent/AU2008239689A1/en not_active Abandoned
- 2008-04-10 MX MX2009010894A patent/MX2009010894A/es unknown
-
2009
- 2009-09-23 IL IL201117A patent/IL201117A0/en unknown
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