JP2006505520A5 - - Google Patents
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- Publication number
- JP2006505520A5 JP2006505520A5 JP2004526900A JP2004526900A JP2006505520A5 JP 2006505520 A5 JP2006505520 A5 JP 2006505520A5 JP 2004526900 A JP2004526900 A JP 2004526900A JP 2004526900 A JP2004526900 A JP 2004526900A JP 2006505520 A5 JP2006505520 A5 JP 2006505520A5
- Authority
- JP
- Japan
- Prior art keywords
- imidazo
- pyrazin
- phenyl
- dihydro
- bromo
- 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.)
- Granted
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- 150000001875 compounds Chemical class 0.000 claims description 40
- 239000000203 mixture Substances 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 17
- 108010009911 Cytochrome P-450 CYP11B2 Proteins 0.000 claims description 10
- 102100024329 Cytochrome P450 11B2, mitochondrial Human genes 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- -1 9H-carbazol-2-yl Chemical group 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 239000000883 anti-obesity agent Substances 0.000 claims description 5
- 239000002220 antihypertensive agent Substances 0.000 claims description 5
- 229940030600 antihypertensive agent Drugs 0.000 claims description 5
- 239000003524 antilipemic agent Substances 0.000 claims description 5
- 229940125710 antiobesity agent Drugs 0.000 claims description 5
- 239000000496 cardiotonic agent Substances 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims 53
- 229910052739 hydrogen Inorganic materials 0.000 claims 53
- 150000002431 hydrogen Chemical class 0.000 claims 43
- 230000003287 optical effect Effects 0.000 claims 26
- 125000003118 aryl group Chemical group 0.000 claims 23
- 125000000547 substituted alkyl group Chemical group 0.000 claims 22
- 125000003710 aryl alkyl group Chemical group 0.000 claims 19
- 125000001072 heteroaryl group Chemical group 0.000 claims 16
- 125000004475 heteroaralkyl group Chemical group 0.000 claims 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims 10
- 239000003814 drug Substances 0.000 claims 10
- 125000000217 alkyl group Chemical group 0.000 claims 8
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 7
- 125000000623 heterocyclic group Chemical group 0.000 claims 7
- 239000001301 oxygen Substances 0.000 claims 7
- 206010020772 Hypertension Diseases 0.000 claims 6
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims 6
- 229910052736 halogen Inorganic materials 0.000 claims 6
- 150000002367 halogens Chemical class 0.000 claims 6
- 229940079593 drug Drugs 0.000 claims 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 4
- 201000001320 Atherosclerosis Diseases 0.000 claims 3
- 206010007559 Cardiac failure congestive Diseases 0.000 claims 3
- 102000008186 Collagen Human genes 0.000 claims 3
- 108010035532 Collagen Proteins 0.000 claims 3
- 206010016654 Fibrosis Diseases 0.000 claims 3
- 206010019280 Heart failures Diseases 0.000 claims 3
- 208000019025 Hypokalemia Diseases 0.000 claims 3
- 208000008589 Obesity Diseases 0.000 claims 3
- 125000003342 alkenyl group Chemical group 0.000 claims 3
- 125000000304 alkynyl group Chemical group 0.000 claims 3
- 230000015572 biosynthetic process Effects 0.000 claims 3
- 229920001436 collagen Polymers 0.000 claims 3
- 208000029078 coronary artery disease Diseases 0.000 claims 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims 3
- 230000004761 fibrosis Effects 0.000 claims 3
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 3
- 208000017169 kidney disease Diseases 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 3
- 235000020824 obesity Nutrition 0.000 claims 3
- 208000024896 potassium deficiency disease Diseases 0.000 claims 3
- 238000007634 remodeling Methods 0.000 claims 3
- 208000037803 restenosis Diseases 0.000 claims 3
- 208000011580 syndromic disease Diseases 0.000 claims 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 3
- BDWRUIAZTZPLSN-UHFFFAOYSA-N 7-[(4-methoxyphenyl)methyl]-5-(4-thiophen-3-ylphenyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C(C=2C=CC(=CC=2)C2=CSC=C2)N2C=NC=C2C1 BDWRUIAZTZPLSN-UHFFFAOYSA-N 0.000 claims 2
- 208000021866 Dressler syndrome Diseases 0.000 claims 2
- 206010048554 Endothelial dysfunction Diseases 0.000 claims 2
- 241000124008 Mammalia Species 0.000 claims 2
- 208000001647 Renal Insufficiency Diseases 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 230000004064 dysfunction Effects 0.000 claims 2
- 230000008694 endothelial dysfunction Effects 0.000 claims 2
- 201000006370 kidney failure Diseases 0.000 claims 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 230000007170 pathology Effects 0.000 claims 2
- IUIFCWCDEZGVLL-AUUYWEPGSA-N (5r)-5-(3-bromophenyl)-7-[(1r)-1-phenylethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1([C@H]2N3C=NC=C3CN(C2=O)[C@H](C)C=2C=CC=CC=2)=CC=CC(Br)=C1 IUIFCWCDEZGVLL-AUUYWEPGSA-N 0.000 claims 1
- IUIFCWCDEZGVLL-IFXJQAMLSA-N (5r)-5-(3-bromophenyl)-7-[(1s)-1-phenylethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1([C@H]2N3C=NC=C3CN(C2=O)[C@@H](C)C=2C=CC=CC=2)=CC=CC(Br)=C1 IUIFCWCDEZGVLL-IFXJQAMLSA-N 0.000 claims 1
- BNPIELKFNYKKES-AUUYWEPGSA-N (5r)-5-(4-bromophenyl)-7-[(1r)-1-phenylethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1([C@H]2N3C=NC=C3CN(C2=O)[C@H](C)C=2C=CC=CC=2)=CC=C(Br)C=C1 BNPIELKFNYKKES-AUUYWEPGSA-N 0.000 claims 1
- BNPIELKFNYKKES-IFXJQAMLSA-N (5r)-5-(4-bromophenyl)-7-[(1s)-1-phenylethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1([C@H]2N3C=NC=C3CN(C2=O)[C@@H](C)C=2C=CC=CC=2)=CC=C(Br)C=C1 BNPIELKFNYKKES-IFXJQAMLSA-N 0.000 claims 1
- IUIFCWCDEZGVLL-KUHUBIRLSA-N (5s)-5-(3-bromophenyl)-7-[(1r)-1-phenylethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1([C@@H]2N3C=NC=C3CN(C2=O)[C@H](C)C=2C=CC=CC=2)=CC=CC(Br)=C1 IUIFCWCDEZGVLL-KUHUBIRLSA-N 0.000 claims 1
- IUIFCWCDEZGVLL-LIRRHRJNSA-N (5s)-5-(3-bromophenyl)-7-[(1s)-1-phenylethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1([C@@H]2N3C=NC=C3CN(C2=O)[C@@H](C)C=2C=CC=CC=2)=CC=CC(Br)=C1 IUIFCWCDEZGVLL-LIRRHRJNSA-N 0.000 claims 1
- BNPIELKFNYKKES-KUHUBIRLSA-N (5s)-5-(4-bromophenyl)-7-[(1r)-1-phenylethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1([C@@H]2N3C=NC=C3CN(C2=O)[C@H](C)C=2C=CC=CC=2)=CC=C(Br)C=C1 BNPIELKFNYKKES-KUHUBIRLSA-N 0.000 claims 1
- BNPIELKFNYKKES-LIRRHRJNSA-N (5s)-5-(4-bromophenyl)-7-[(1s)-1-phenylethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1([C@@H]2N3C=NC=C3CN(C2=O)[C@@H](C)C=2C=CC=CC=2)=CC=C(Br)C=C1 BNPIELKFNYKKES-LIRRHRJNSA-N 0.000 claims 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- HUTNOYOBQPAKIA-UHFFFAOYSA-N 1h-pyrazin-2-one Chemical compound OC1=CN=CC=N1 HUTNOYOBQPAKIA-UHFFFAOYSA-N 0.000 claims 1
- WXWMJWIKOZGKGJ-UHFFFAOYSA-N 3-(7-benzyl-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl)benzonitrile Chemical compound N12C=NC=C2CN(CC=2C=CC=CC=2)C(=O)C1C1=CC=CC(C#N)=C1 WXWMJWIKOZGKGJ-UHFFFAOYSA-N 0.000 claims 1
- WRKVACHBUWUICF-UHFFFAOYSA-N 3-[6-oxo-7-(2-phenylethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound N12C=NC=C2CN(CCC=2C=CC=CC=2)C(=O)C1C1=CC=CC(C#N)=C1 WRKVACHBUWUICF-UHFFFAOYSA-N 0.000 claims 1
- VSKNOKVRTWBFLL-UHFFFAOYSA-N 3-[7-(cyclopropylmethyl)-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound N12C=NC=C2CN(CC2CC2)C(=O)C1C1=CC=CC(C#N)=C1 VSKNOKVRTWBFLL-UHFFFAOYSA-N 0.000 claims 1
- ZPBYJBITGDQVIN-UHFFFAOYSA-N 3-[7-[(4-chlorophenyl)methyl]-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound C1=CC(Cl)=CC=C1CN1C(=O)C(C=2C=C(C=CC=2)C#N)N2C=NC=C2C1 ZPBYJBITGDQVIN-UHFFFAOYSA-N 0.000 claims 1
- MVFLAAVOKSKJRU-UHFFFAOYSA-N 3-[7-[(4-methoxyphenyl)methyl]-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C(C=2C=C(C=CC=2)C#N)N2C=NC=C2C1 MVFLAAVOKSKJRU-UHFFFAOYSA-N 0.000 claims 1
- BZZMMPNIBLLWGA-UHFFFAOYSA-N 3-[7-[(4-methylphenyl)methyl]-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound C1=CC(C)=CC=C1CN1C(=O)C(C=2C=C(C=CC=2)C#N)N2C=NC=C2C1 BZZMMPNIBLLWGA-UHFFFAOYSA-N 0.000 claims 1
- MYVJDBWAFMABLJ-UHFFFAOYSA-N 3-[7-[2-(4-fluorophenyl)ethyl]-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound C1=CC(F)=CC=C1CCN1C(=O)C(C=2C=C(C=CC=2)C#N)N2C=NC=C2C1 MYVJDBWAFMABLJ-UHFFFAOYSA-N 0.000 claims 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims 1
- MKFSDWNOOOLJOR-UHFFFAOYSA-N 4-(5,7-dibenzyl-6-oxo-8h-imidazo[1,5-a]pyrazin-5-yl)benzonitrile Chemical compound C1C2=CN=CN2C(C=2C=CC(=CC=2)C#N)(CC=2C=CC=CC=2)C(=O)N1CC1=CC=CC=C1 MKFSDWNOOOLJOR-UHFFFAOYSA-N 0.000 claims 1
- BQZVGLJZGCOXHP-UHFFFAOYSA-N 4-(6-oxo-7-propan-2-yl-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl)benzonitrile Chemical compound O=C1N(C(C)C)CC2=CN=CN2C1C1=CC=C(C#N)C=C1 BQZVGLJZGCOXHP-UHFFFAOYSA-N 0.000 claims 1
- OLCNWVADTAJHOT-UHFFFAOYSA-N 4-(6-oxo-7-propyl-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl)benzonitrile Chemical compound O=C1N(CCC)CC2=CN=CN2C1C1=CC=C(C#N)C=C1 OLCNWVADTAJHOT-UHFFFAOYSA-N 0.000 claims 1
- ULAXZIVKDTZOBZ-UHFFFAOYSA-N 4-(7-benzyl-5-methyl-6-oxo-8h-imidazo[1,5-a]pyrazin-5-yl)benzonitrile Chemical compound C1C2=CN=CN2C(C)(C=2C=CC(=CC=2)C#N)C(=O)N1CC1=CC=CC=C1 ULAXZIVKDTZOBZ-UHFFFAOYSA-N 0.000 claims 1
- PKHXGYUUXXTTBL-UHFFFAOYSA-N 4-(7-benzyl-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl)benzonitrile Chemical compound N12C=NC=C2CN(CC=2C=CC=CC=2)C(=O)C1C1=CC=C(C#N)C=C1 PKHXGYUUXXTTBL-UHFFFAOYSA-N 0.000 claims 1
- VPUFUFPRJUQJHH-UHFFFAOYSA-N 4-(7-cyclohexyl-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl)benzonitrile Chemical compound N12C=NC=C2CN(C2CCCCC2)C(=O)C1C1=CC=C(C#N)C=C1 VPUFUFPRJUQJHH-UHFFFAOYSA-N 0.000 claims 1
- ZOGZGMGAXWRWSP-UHFFFAOYSA-N 4-(7-cyclopentyl-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl)benzonitrile Chemical compound N12C=NC=C2CN(C2CCCC2)C(=O)C1C1=CC=C(C#N)C=C1 ZOGZGMGAXWRWSP-UHFFFAOYSA-N 0.000 claims 1
- XVCMZAPPMHDIET-UHFFFAOYSA-N 4-(7-cyclopropyl-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl)benzonitrile Chemical compound N12C=NC=C2CN(C2CC2)C(=O)C1C1=CC=C(C#N)C=C1 XVCMZAPPMHDIET-UHFFFAOYSA-N 0.000 claims 1
- LFZXYWKNICMEKP-UHFFFAOYSA-N 4-(7-methyl-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl)benzonitrile Chemical compound O=C1N(C)CC2=CN=CN2C1C1=CC=C(C#N)C=C1 LFZXYWKNICMEKP-UHFFFAOYSA-N 0.000 claims 1
- OQEIHCXNKZOMQH-UHFFFAOYSA-N 4-(8-benzyl-7-oxo-6,9-dihydro-5h-imidazo[1,5-a][1,4]diazepin-5-yl)benzonitrile Chemical compound N12C=NC=C2CN(CC=2C=CC=CC=2)C(=O)CC1C1=CC=C(C#N)C=C1 OQEIHCXNKZOMQH-UHFFFAOYSA-N 0.000 claims 1
- SQFQHGKMQIYCCT-MGPUTAFESA-N 4-[(5r)-6-oxo-7-[(1s)-1-phenylethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound C1([C@H]2N3C=NC=C3CN(C2=O)[C@@H](C)C=2C=CC=CC=2)=CC=C(C#N)C=C1 SQFQHGKMQIYCCT-MGPUTAFESA-N 0.000 claims 1
- YHNWKZKJEKZJOC-OYHNWAKOSA-N 4-[(5r)-7-[(1s)-1-(4-fluorophenyl)ethyl]-5-methyl-6-oxo-8h-imidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound C1([C@@]2(C)N3C=NC=C3CN(C2=O)[C@@H](C)C=2C=CC(F)=CC=2)=CC=C(C#N)C=C1 YHNWKZKJEKZJOC-OYHNWAKOSA-N 0.000 claims 1
- SQFQHGKMQIYCCT-YWZLYKJASA-N 4-[(5s)-6-oxo-7-[(1s)-1-phenylethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound C1([C@@H]2N3C=NC=C3CN(C2=O)[C@@H](C)C=2C=CC=CC=2)=CC=C(C#N)C=C1 SQFQHGKMQIYCCT-YWZLYKJASA-N 0.000 claims 1
- YHNWKZKJEKZJOC-NYHFZMIOSA-N 4-[(5s)-7-[(1s)-1-(4-fluorophenyl)ethyl]-5-methyl-6-oxo-8h-imidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound C1([C@]2(C)N3C=NC=C3CN(C2=O)[C@@H](C)C=2C=CC(F)=CC=2)=CC=C(C#N)C=C1 YHNWKZKJEKZJOC-NYHFZMIOSA-N 0.000 claims 1
- CHMZUIQHLSUIFP-UHFFFAOYSA-N 4-[5-benzyl-7-(cyclopropylmethyl)-6-oxo-8h-imidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound C1C2=CN=CN2C(C=2C=CC(=CC=2)C#N)(CC=2C=CC=CC=2)C(=O)N1CC1CC1 CHMZUIQHLSUIFP-UHFFFAOYSA-N 0.000 claims 1
- OFKHYFQCKHPTRX-UHFFFAOYSA-N 4-[6-oxo-7-(pyridin-4-ylmethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound N12C=NC=C2CN(CC=2C=CN=CC=2)C(=O)C1C1=CC=C(C#N)C=C1 OFKHYFQCKHPTRX-UHFFFAOYSA-N 0.000 claims 1
- HDIJMBNMXWMIRX-UHFFFAOYSA-N 4-[7-(2-methoxyethyl)-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound O=C1N(CCOC)CC2=CN=CN2C1C1=CC=C(C#N)C=C1 HDIJMBNMXWMIRX-UHFFFAOYSA-N 0.000 claims 1
- KXEBUJOWUNDPAY-UHFFFAOYSA-N 4-[7-(3-methoxypropyl)-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound O=C1N(CCCOC)CC2=CN=CN2C1C1=CC=C(C#N)C=C1 KXEBUJOWUNDPAY-UHFFFAOYSA-N 0.000 claims 1
- USZCRFIFTPDWOU-UHFFFAOYSA-N 4-[7-(3-morpholin-4-ylpropyl)-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound N12C=NC=C2CN(CCCN2CCOCC2)C(=O)C1C1=CC=C(C#N)C=C1 USZCRFIFTPDWOU-UHFFFAOYSA-N 0.000 claims 1
- KGROSPWRIWFUBR-UHFFFAOYSA-N 4-[7-(cyclopropylmethyl)-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound N12C=NC=C2CN(CC2CC2)C(=O)C1C1=CC=C(C#N)C=C1 KGROSPWRIWFUBR-UHFFFAOYSA-N 0.000 claims 1
- JOLXPHHHSCJPNO-UHFFFAOYSA-N 4-[7-[(4-chlorophenyl)methyl]-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound C1=CC(Cl)=CC=C1CN1C(=O)C(C=2C=CC(=CC=2)C#N)N2C=NC=C2C1 JOLXPHHHSCJPNO-UHFFFAOYSA-N 0.000 claims 1
- ANCYWORHVHQAIZ-UHFFFAOYSA-N 4-[7-[(4-fluorophenyl)methyl]-5-methyl-6-oxo-8h-imidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound C1C2=CN=CN2C(C)(C=2C=CC(=CC=2)C#N)C(=O)N1CC1=CC=C(F)C=C1 ANCYWORHVHQAIZ-UHFFFAOYSA-N 0.000 claims 1
- CDUVZWMJORAJOJ-UHFFFAOYSA-N 4-[7-[2-(4-fluorophenyl)ethyl]-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound C1=CC(F)=CC=C1CCN1C(=O)C(C=2C=CC(=CC=2)C#N)N2C=NC=C2C1 CDUVZWMJORAJOJ-UHFFFAOYSA-N 0.000 claims 1
- REWJFOIXMYASRH-UHFFFAOYSA-N 4-[8-(cyclopropylmethyl)-7-oxo-6,9-dihydro-5h-imidazo[1,5-a][1,4]diazepin-5-yl]benzonitrile Chemical compound N12C=NC=C2CN(CC2CC2)C(=O)CC1C1=CC=C(C#N)C=C1 REWJFOIXMYASRH-UHFFFAOYSA-N 0.000 claims 1
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims 1
- FANADPDZEHHCKT-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(2-phenylethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound BrC1=CC=CC(C2N3C=NC=C3CN(CCC=3C=CC=CC=3)C2=O)=C1 FANADPDZEHHCKT-UHFFFAOYSA-N 0.000 claims 1
- ZSAPBGNHZNJUBA-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(4-methoxyphenyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(OC)=CC=C1N1C(=O)C(C=2C=C(Br)C=CC=2)N2C=NC=C2C1 ZSAPBGNHZNJUBA-UHFFFAOYSA-N 0.000 claims 1
- IFDMLYRAZYXDPL-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(cyclohexylmethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound BrC1=CC=CC(C2N3C=NC=C3CN(CC3CCCCC3)C2=O)=C1 IFDMLYRAZYXDPL-UHFFFAOYSA-N 0.000 claims 1
- JEPUCKBOKLMEPM-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(cyclopropylmethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound BrC1=CC=CC(C2N3C=NC=C3CN(CC3CC3)C2=O)=C1 JEPUCKBOKLMEPM-UHFFFAOYSA-N 0.000 claims 1
- YVFGHDUZENEISF-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(cyclopropylmethyl)-5-methyl-8h-imidazo[1,5-a]pyrazin-6-one Chemical compound C1C2=CN=CN2C(C)(C=2C=C(Br)C=CC=2)C(=O)N1CC1CC1 YVFGHDUZENEISF-UHFFFAOYSA-N 0.000 claims 1
- VANATMKOEOJRAZ-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(furan-2-ylmethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound BrC1=CC=CC(C2N3C=NC=C3CN(CC=3OC=CC=3)C2=O)=C1 VANATMKOEOJRAZ-UHFFFAOYSA-N 0.000 claims 1
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| CN1997643A (zh) * | 2004-05-28 | 2007-07-11 | 斯皮德尔实验股份公司 | 杂环化合物及其作为醛固酮合酶抑制剂的应用 |
| TW200611897A (en) * | 2004-07-09 | 2006-04-16 | Speedel Experimenta Ag | Organic compounds |
| TW200716634A (en) * | 2005-05-31 | 2007-05-01 | Speedel Experimenta Ag | Heterocyclic spiro-compounds |
| TW200716636A (en) * | 2005-05-31 | 2007-05-01 | Speedel Experimenta Ag | Heterocyclic spiro-compounds |
| EP1842543A1 (en) | 2006-04-05 | 2007-10-10 | Speedel Pharma AG | Pharmaceutical composition coprising an aldosterone synthase inhibitor and a mineralcorticoid receptor antagonist |
| TW200813071A (en) * | 2006-04-12 | 2008-03-16 | Speedel Experimenta Ag | Spiro-imidazo compounds |
| TW200808813A (en) | 2006-04-12 | 2008-02-16 | Speedel Experimenta Ag | Imidazo compounds |
| TW200808812A (en) * | 2006-04-12 | 2008-02-16 | Speedel Experimenta Ag | Imidazo compounds |
| MX2008015008A (es) * | 2006-05-26 | 2008-12-05 | Novartis Ag | INHIBIDORES DE SINTASA DE ALDOSTERONA Y/O DE 11ß-HIDROXILASA. |
| JP2010501573A (ja) * | 2006-08-25 | 2010-01-21 | ノバルティス アクチエンゲゼルシャフト | アルドステロン合成酵素および／または１１−β−ヒドロキシラーゼおよび／またはアロマターゼが介在する疾患の処置のための縮合イミダゾール誘導体 |
| ATE545647T1 (de) * | 2006-12-22 | 2012-03-15 | Actelion Pharmaceuticals Ltd | 5,6,7,8-tetrahydro-imidazoä1,5-aüpyrazinderivat |
| US8859538B2 (en) * | 2007-06-21 | 2014-10-14 | Cara Therapeutics, Inc. | Uses of substituted imidazoheterocycles |
| EP2170350B1 (en) | 2007-06-21 | 2013-09-11 | Cara Therapeutics, Inc. | Substituted imidazoheterocycles |
| KR20110036069A (ko) | 2008-06-25 | 2011-04-06 | 액테리온 파마슈티칼 리미티드 | 5,6,7,8-테트라히드로-이미다조[1,5-ａ]피라진 화합물 |
| CN103896796B (zh) | 2009-05-28 | 2016-04-27 | 诺华股份有限公司 | 作为脑啡肽酶抑制剂的取代的氨基丙酸衍生物 |
| EP2435402B1 (en) | 2009-05-28 | 2016-04-13 | Novartis AG | Substituted aminobutyric derivatives as neprilysin inhibitors |
| JO2967B1 (en) | 2009-11-20 | 2016-03-15 | نوفارتس ايه جي | Acetic acid derivatives of carbamoyl methyl amino are substituted as new NEP inhibitors |
| US10065960B2 (en) | 2010-04-02 | 2018-09-04 | Ogeda Sa | NK-3 receptor selective antagonist compounds, pharmaceutical composition and methods for use in NK-3 receptors mediated disorders |
| EP2552920B1 (en) | 2010-04-02 | 2017-03-15 | Ogeda Sa | Novel nk-3 receptor selective antagonist compounds, pharmaceutical composition and methods for use in nk-3 receptors mediated disorders |
| US8673974B2 (en) | 2010-11-16 | 2014-03-18 | Novartis Ag | Substituted amino bisphenyl pentanoic acid derivatives as NEP inhibitors |
| US8877815B2 (en) | 2010-11-16 | 2014-11-04 | Novartis Ag | Substituted carbamoylcycloalkyl acetic acid derivatives as NEP |
| ES2683350T3 (es) | 2011-07-08 | 2018-09-26 | Novartis Ag | Método para tratar la aterosclerosis en sujetos con alto nivel de triglicéridos |
| WO2013050424A1 (en) | 2011-10-03 | 2013-04-11 | Euroscreen S.A. | NOVEL CHIRAL N-ACYL-5,6,7,(8-SUBSTITUTED)-TETRAHYDRO-[1,2,4]TRIAZOLO[4,3-a]PYRAZINES AS SELECTIVE NK-3 RECEPTOR ANTAGONISTS, PHARMACEUTICAL COMPOSITION, METHODS FOR USE IN NK-3 RECEPTOR MEDIATED DISORDERS AND CHIRAL SYNTHESIS THEREOF |
| UY35144A (es) | 2012-11-20 | 2014-06-30 | Novartis Ag | Miméticos lineales sintéticos de apelina para el tratamiento de insuficiencia cardiaca |
| CU24330B1 (es) | 2013-02-14 | 2018-03-13 | Novartis Ag | Derivados del ácido 4-((1,1) bifenil-4-il)-3-(3-fosfonopropanamido) butanoico, activos como inhibidores de nep (endopeptidasa neutral) |
| MX2016001020A (es) | 2013-07-25 | 2016-08-03 | Novartis Ag | Polipeptidos ciclicos para el tratamiento de insuficiencia cardiaca. |
| CN105705167A (zh) | 2013-07-25 | 2016-06-22 | 诺华股份有限公司 | 合成的apelin多肽的生物缀合物 |
| NZ730295A (en) | 2014-09-25 | 2023-05-26 | Ogeda Sa | Novel chiral synthesis of n-acyl-(3-substituted)-(8-substituted)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazines |
| CR20170338A (es) | 2015-01-23 | 2017-09-12 | Novartis Ag | Conjugados de ácidos grasos y apelina sintética con mayor vida media |
| US10189841B2 (en) | 2015-11-20 | 2019-01-29 | Forma Therapeutics, Inc. | Purinones as ubiquitin-specific protease 1 inhibitors |
| JOP20190086A1 (ar) | 2016-10-21 | 2019-04-18 | Novartis Ag | مشتقات نافثيريدينون جديدة واستخدامها في معالجة عدم انتظام ضربات القلب |
| UY38072A (es) | 2018-02-07 | 2019-10-01 | Novartis Ag | Compuestos derivados de éster butanoico sustituido con bisfenilo como inhibidores de nep, composiciones y combinaciones de los mismos |
| AU2019245403B2 (en) | 2018-03-29 | 2025-02-06 | Board Of Regents, The University Of Texas System | Imidazopiperazine inhibitors of transcription activating proteins |
| WO2019195846A1 (en) * | 2018-04-06 | 2019-10-10 | Board Of Regents, The University Of Texas System | Imidazopiperazinone inhibitors of transcription activating proteins |
| UY38485A (es) | 2018-11-27 | 2020-06-30 | Novartis Ag | Compuestos tetrámeros cíclicos como inhibidores de proproteína convertasa subtilisina/kexina tipo 9 (pcsk9), método de tratamiento, uso y su preparación |
| JP7657151B2 (ja) | 2018-11-27 | 2025-04-04 | ノバルティス アーゲー | 代謝性障害の処置のためのプロタンパク質コンバターゼスブチリシン／ケキシン９型（ｐｃｓｋ９）阻害剤としての環状ペプチド |
| US20230089867A1 (en) | 2018-11-27 | 2023-03-23 | Novartis Ag | Cyclic pentamer compounds as proprotein convertase subtilisin/kexin type 9 (pcsk9) inhibitors for the treatment of metabolic disorder |
| WO2022072648A1 (en) | 2020-10-02 | 2022-04-07 | Board Of Regents, The University Of Texas System | Imidazopiperazine inhibitors of transcription activating proteins |
| JP7777131B2 (ja) | 2020-10-02 | 2025-11-27 | ボード オブ レジェンツ，ザ ユニバーシティ オブ テキサス システム | 転写活性化タンパク質のイミダゾピペラジン阻害剤 |
| US12115154B2 (en) | 2020-12-16 | 2024-10-15 | Srx Cardio, Llc | Compounds for the modulation of proprotein convertase subtilisin/kexin type 9 (PCSK9) |
| WO2023084449A1 (en) | 2021-11-12 | 2023-05-19 | Novartis Ag | Diaminocyclopentylpyridine derivatives for the treatment of a disease or disorder |
| AR127698A1 (es) | 2021-11-23 | 2024-02-21 | Novartis Ag | Derivados de naftiridinona para el tratamiento de una enfermedad o un trastorno |
| KR20260015867A (ko) | 2023-05-24 | 2026-02-03 | 노파르티스 아게 | 질환 또는 장애 치료용 나프티리디논 유도체 |
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| US3582315A (en) * | 1968-03-22 | 1971-06-01 | Lilly Co Eli | Methods and compositions for inhibiting plant growth |
| US4617307A (en) | 1984-06-20 | 1986-10-14 | Ciba-Geigy Corporation | Substituted imidazo[1,5-A]pyridine derivatives as aromatase inhibitors |
| US4889861A (en) | 1982-12-21 | 1989-12-26 | Ciba-Geigy Corp. | Substituted imidazo[1,5-a]pyridine derivatives and other substituted bicyclic derivatives and their use as aromatase inhibitors |
| US5529992A (en) | 1992-04-21 | 1996-06-25 | Curators Of The University Of Missouri | Method for inhibiting myocardial fibrosis by administering an aldosterone antagonist which suppresses aldoster one receptors |
| US6150347A (en) | 1992-04-21 | 2000-11-21 | The Curators Of The University Of Missouri | Use of aldosterone antagonists to inhibit myocardial fibrosis |
| DE4237656A1 (de) * | 1992-06-13 | 1993-12-16 | Merck Patent Gmbh | Benzimidazolderivate |
| JPH07101959A (ja) * | 1993-09-30 | 1995-04-18 | Sankyo Co Ltd | １−メチルカルバペネム誘導体 |
| DE4341453A1 (de) * | 1993-12-06 | 1995-06-08 | Merck Patent Gmbh | Imidazopyridine |
| WO1997000257A1 (en) | 1995-06-14 | 1997-01-03 | Yamanouchi Pharmaceutical Co., Ltd. | Fused imidazole derivatives and medicinal composition thereof |
| US20050014939A1 (en) * | 1999-08-31 | 2005-01-20 | Neurogen Corporation | Fused pyrrolecarboxamides: GABA brain receptor ligands |
| GB0206033D0 (en) * | 2002-03-14 | 2002-04-24 | Pfizer Ltd | Compounds useful in therapy |
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- 2003-08-06 BR BR0313293-5A patent/BR0313293A/pt not_active IP Right Cessation
- 2003-08-06 AU AU2003253387A patent/AU2003253387A1/en not_active Abandoned
- 2003-08-06 JP JP2004526900A patent/JP4533139B2/ja not_active Expired - Fee Related
- 2003-08-06 CN CNB038238780A patent/CN100404535C/zh not_active Expired - Lifetime
- 2003-08-06 AT AT03784194T patent/ATE335744T1/de not_active IP Right Cessation
- 2003-08-06 PT PT03784194T patent/PT1537114E/pt unknown
- 2003-08-06 DE DE60307483T patent/DE60307483T2/de not_active Expired - Lifetime
- 2003-08-06 DK DK03784194T patent/DK1537114T3/da active
- 2003-08-06 US US10/523,870 patent/US7732603B2/en not_active Expired - Fee Related
- 2003-08-06 WO PCT/EP2003/008720 patent/WO2004014914A1/en not_active Ceased
- 2003-08-06 ES ES03784194T patent/ES2270143T3/es not_active Expired - Lifetime
- 2003-08-06 CA CA002494636A patent/CA2494636A1/en not_active Abandoned
-
2006
- 2006-10-24 CY CY20061101527T patent/CY1106217T1/el unknown
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