DE60307483T2 - Organische verbindungen als mittel zur behandlung von aldosteronbedingten zuständen - Google Patents
Organische verbindungen als mittel zur behandlung von aldosteronbedingten zuständen Download PDFInfo
- Publication number
- DE60307483T2 DE60307483T2 DE60307483T DE60307483T DE60307483T2 DE 60307483 T2 DE60307483 T2 DE 60307483T2 DE 60307483 T DE60307483 T DE 60307483T DE 60307483 T DE60307483 T DE 60307483T DE 60307483 T2 DE60307483 T2 DE 60307483T2
- Authority
- DE
- Germany
- 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.)
- Expired - Lifetime
Links
- 150000002894 organic compounds Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 227
- 108010009911 Cytochrome P-450 CYP11B2 Proteins 0.000 claims abstract description 21
- 102100024329 Cytochrome P450 11B2, mitochondrial Human genes 0.000 claims abstract description 20
- 206010020772 Hypertension Diseases 0.000 claims abstract description 19
- 230000000694 effects Effects 0.000 claims abstract description 18
- 208000008589 Obesity Diseases 0.000 claims abstract description 10
- 235000020824 obesity Nutrition 0.000 claims abstract description 10
- 206010007559 Cardiac failure congestive Diseases 0.000 claims abstract description 8
- 102000008186 Collagen Human genes 0.000 claims abstract description 8
- 108010035532 Collagen Proteins 0.000 claims abstract description 8
- 206010048554 Endothelial dysfunction Diseases 0.000 claims abstract description 8
- 206010016654 Fibrosis Diseases 0.000 claims abstract description 8
- 206010019280 Heart failures Diseases 0.000 claims abstract description 8
- 208000001647 Renal Insufficiency Diseases 0.000 claims abstract description 8
- 229920001436 collagen Polymers 0.000 claims abstract description 8
- 230000008694 endothelial dysfunction Effects 0.000 claims abstract description 8
- 230000004761 fibrosis Effects 0.000 claims abstract description 8
- 208000017169 kidney disease Diseases 0.000 claims abstract description 8
- 201000006370 kidney failure Diseases 0.000 claims abstract description 8
- 208000037803 restenosis Diseases 0.000 claims abstract description 8
- 208000011580 syndromic disease Diseases 0.000 claims abstract description 8
- 208000019025 Hypokalemia Diseases 0.000 claims abstract description 7
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 7
- 238000007634 remodeling Methods 0.000 claims abstract description 7
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 5
- 208000024896 potassium deficiency disease Diseases 0.000 claims abstract description 4
- 208000010125 myocardial infarction Diseases 0.000 claims abstract 2
- -1 9H-carbazol-2-yl Chemical group 0.000 claims description 88
- 239000001257 hydrogen Substances 0.000 claims description 81
- 229910052739 hydrogen Inorganic materials 0.000 claims description 81
- 239000000203 mixture Substances 0.000 claims description 72
- 125000000217 alkyl group Chemical group 0.000 claims description 57
- 150000002431 hydrogen Chemical class 0.000 claims description 56
- 125000003118 aryl group Chemical group 0.000 claims description 52
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 52
- 230000003287 optical effect Effects 0.000 claims description 50
- 150000003839 salts Chemical class 0.000 claims description 49
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 34
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 34
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 32
- 229910052736 halogen Inorganic materials 0.000 claims description 31
- 150000002367 halogens Chemical class 0.000 claims description 31
- 125000000623 heterocyclic group Chemical group 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 24
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 22
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 17
- 125000003282 alkyl amino group Chemical group 0.000 claims description 16
- 125000004414 alkyl thio group Chemical group 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 16
- 239000001301 oxygen Substances 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 16
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 14
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 14
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 13
- 125000002252 acyl group Chemical group 0.000 claims description 12
- 125000004423 acyloxy group Chemical group 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 12
- 125000004442 acylamino group Chemical group 0.000 claims description 11
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 125000005110 aryl thio group Chemical group 0.000 claims description 10
- 125000002619 bicyclic group Chemical group 0.000 claims description 10
- 125000004104 aryloxy group Chemical group 0.000 claims description 9
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
- 125000002950 monocyclic group Chemical group 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000001589 carboacyl group Chemical group 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 239000004041 inotropic agent Substances 0.000 claims description 8
- 125000004043 oxo group Chemical group O=* 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
- 239000002220 antihypertensive agent Substances 0.000 claims description 7
- 239000003524 antilipemic agent Substances 0.000 claims description 7
- 208000019622 heart disease Diseases 0.000 claims description 7
- 125000002883 imidazolyl group Chemical group 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 206010061216 Infarction Diseases 0.000 claims description 6
- 229940030600 antihypertensive agent Drugs 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 230000007574 infarction Effects 0.000 claims description 6
- 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 description 5
- 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 description 5
- JNSHAFSIADREGA-UHFFFAOYSA-N 5-(4-bromophenyl)-7-[(4-methoxyphenyl)methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C(C=2C=CC(Br)=CC=2)N2C=NC=C2C1 JNSHAFSIADREGA-UHFFFAOYSA-N 0.000 claims description 5
- 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 description 5
- 125000005333 aroyloxy group Chemical group 0.000 claims description 5
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000004470 heterocyclooxy group Chemical group 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 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 description 4
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 4
- MHFSWEVJOIPGPC-UHFFFAOYSA-N 7-benzyl-5-(4-bromophenyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(Br)=CC=C1C1N2C=NC=C2CN(CC=2C=CC=CC=2)C1=O MHFSWEVJOIPGPC-UHFFFAOYSA-N 0.000 claims description 4
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 230000009466 transformation Effects 0.000 claims description 4
- HUTNOYOBQPAKIA-UHFFFAOYSA-N 1h-pyrazin-2-one Chemical compound OC1=CN=CC=N1 HUTNOYOBQPAKIA-UHFFFAOYSA-N 0.000 claims description 3
- 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 description 3
- 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 description 3
- 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 description 3
- 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 description 3
- 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 description 3
- 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 description 3
- 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 description 3
- 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 description 3
- 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 description 3
- VLUHNNONLXRLDP-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(furan-3-ylmethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound BrC1=CC=CC(C2N3C=NC=C3CN(CC3=COC=C3)C2=O)=C1 VLUHNNONLXRLDP-UHFFFAOYSA-N 0.000 claims description 3
- ZVDLMGVYQXTJGB-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(pyridin-2-ylmethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound BrC1=CC=CC(C2N3C=NC=C3CN(CC=3N=CC=CC=3)C2=O)=C1 ZVDLMGVYQXTJGB-UHFFFAOYSA-N 0.000 claims description 3
- WDQGXPYKAOIHAH-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(pyridin-3-ylmethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound BrC1=CC=CC(C2N3C=NC=C3CN(CC=3C=NC=CC=3)C2=O)=C1 WDQGXPYKAOIHAH-UHFFFAOYSA-N 0.000 claims description 3
- DUZSCKPDZXTNHU-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(pyridin-4-ylmethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound BrC1=CC=CC(C2N3C=NC=C3CN(CC=3C=CN=CC=3)C2=O)=C1 DUZSCKPDZXTNHU-UHFFFAOYSA-N 0.000 claims description 3
- JPRUCAHFHQKXSJ-UHFFFAOYSA-N 5-(4-bromophenyl)-7-methyl-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound O=C1N(C)CC2=CN=CN2C1C1=CC=C(Br)C=C1 JPRUCAHFHQKXSJ-UHFFFAOYSA-N 0.000 claims description 3
- YTJRDFYHQUXXCN-UHFFFAOYSA-N 5-benzyl-5-(4-bromophenyl)-7-[(4-fluorophenyl)methyl]-8h-imidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(F)=CC=C1CN1C(=O)C(CC=2C=CC=CC=2)(C=2C=CC(Br)=CC=2)N2C=NC=C2C1 YTJRDFYHQUXXCN-UHFFFAOYSA-N 0.000 claims description 3
- MVDJFHIGCJKAKH-UHFFFAOYSA-N 7-[(4-fluorophenyl)methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(F)=CC=C1CN1C(=O)CN2C=NC=C2C1 MVDJFHIGCJKAKH-UHFFFAOYSA-N 0.000 claims description 3
- UCDBANUXQWESGO-UHFFFAOYSA-N 7-[(4-fluorophenyl)methyl]-5-(4-phenylphenyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(F)=CC=C1CN1C(=O)C(C=2C=CC(=CC=2)C=2C=CC=CC=2)N2C=NC=C2C1 UCDBANUXQWESGO-UHFFFAOYSA-N 0.000 claims description 3
- GHBPBVBYHXDIFZ-UHFFFAOYSA-N 7-[(4-methylphenyl)methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(C)=CC=C1CN1C(=O)CN2C=NC=C2C1 GHBPBVBYHXDIFZ-UHFFFAOYSA-N 0.000 claims description 3
- DBNHJIYTPWCCOH-UHFFFAOYSA-N 7-benzyl-5-(3-bromophenyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound BrC1=CC=CC(C2N3C=NC=C3CN(CC=3C=CC=CC=3)C2=O)=C1 DBNHJIYTPWCCOH-UHFFFAOYSA-N 0.000 claims description 3
- LHQHSTYXNKDXTC-UHFFFAOYSA-N 7-benzyl-5-(3-phenylphenyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound N12C=NC=C2CN(CC=2C=CC=CC=2)C(=O)C1C(C=1)=CC=CC=1C1=CC=CC=C1 LHQHSTYXNKDXTC-UHFFFAOYSA-N 0.000 claims description 3
- XBQGXUALPAFHIM-UHFFFAOYSA-N 7-methyl-5-phenyl-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound O=C1N(C)CC2=CN=CN2C1C1=CC=CC=C1 XBQGXUALPAFHIM-UHFFFAOYSA-N 0.000 claims description 3
- 239000000883 anti-obesity agent Substances 0.000 claims description 3
- 229940125710 antiobesity agent Drugs 0.000 claims description 3
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000005226 heteroaryloxycarbonyl group Chemical group 0.000 claims description 3
- 125000005936 piperidyl group Chemical group 0.000 claims description 3
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 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
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- VUYDZKKRXNRQSM-UHFFFAOYSA-N 3-[7-[(4-fluorophenyl)methyl]-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound C1=CC(F)=CC=C1CN1C(=O)C(C=2C=C(C=CC=2)C#N)N2C=NC=C2C1 VUYDZKKRXNRQSM-UHFFFAOYSA-N 0.000 claims description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- NSKMOZAZMUBKEJ-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(piperidin-4-ylmethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound BrC1=CC=CC(C2N3C=NC=C3CN(CC3CCNCC3)C2=O)=C1 NSKMOZAZMUBKEJ-UHFFFAOYSA-N 0.000 claims description 2
- LUUMGPGDVOJSJM-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(thiophen-2-ylmethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound BrC1=CC=CC(C2N3C=NC=C3CN(CC=3SC=CC=3)C2=O)=C1 LUUMGPGDVOJSJM-UHFFFAOYSA-N 0.000 claims description 2
- CXJIKIOJRDNKRH-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(thiophen-3-ylmethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound BrC1=CC=CC(C2N3C=NC=C3CN(CC3=CSC=C3)C2=O)=C1 CXJIKIOJRDNKRH-UHFFFAOYSA-N 0.000 claims description 2
- XAIXUBGPVIVPOO-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[(3-fluorophenyl)methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound FC1=CC=CC(CN2C(C(N3C=NC=C3C2)C=2C=C(Br)C=CC=2)=O)=C1 XAIXUBGPVIVPOO-UHFFFAOYSA-N 0.000 claims description 2
- HVNXIUUIXBJKRM-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[(3-methylphenyl)methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound CC1=CC=CC(CN2C(C(N3C=NC=C3C2)C=2C=C(Br)C=CC=2)=O)=C1 HVNXIUUIXBJKRM-UHFFFAOYSA-N 0.000 claims description 2
- ZGKLSEYDYQHFQG-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[(4-chlorophenyl)methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(Cl)=CC=C1CN1C(=O)C(C=2C=C(Br)C=CC=2)N2C=NC=C2C1 ZGKLSEYDYQHFQG-UHFFFAOYSA-N 0.000 claims description 2
- MOIFHPFTYNPRPV-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[(4-fluorophenyl)methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(F)=CC=C1CN1C(=O)C(C=2C=C(Br)C=CC=2)N2C=NC=C2C1 MOIFHPFTYNPRPV-UHFFFAOYSA-N 0.000 claims description 2
- APKLLSXECGEEDD-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[(4-methylphenyl)methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(C)=CC=C1CN1C(=O)C(C=2C=C(Br)C=CC=2)N2C=NC=C2C1 APKLLSXECGEEDD-UHFFFAOYSA-N 0.000 claims description 2
- OVDYMLUTPKLPKZ-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[2-(3-chlorophenyl)ethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound ClC1=CC=CC(CCN2C(C(N3C=NC=C3C2)C=2C=C(Br)C=CC=2)=O)=C1 OVDYMLUTPKLPKZ-UHFFFAOYSA-N 0.000 claims description 2
- KYYRSZHHGNBBEP-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[2-(4-chlorophenyl)ethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(Cl)=CC=C1CCN1C(=O)C(C=2C=C(Br)C=CC=2)N2C=NC=C2C1 KYYRSZHHGNBBEP-UHFFFAOYSA-N 0.000 claims description 2
- BIHIJYVAWZCWRW-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[2-(4-fluorophenyl)ethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(F)=CC=C1CCN1C(=O)C(C=2C=C(Br)C=CC=2)N2C=NC=C2C1 BIHIJYVAWZCWRW-UHFFFAOYSA-N 0.000 claims description 2
- GGNMFIOEXAYJBB-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[2-(4-methoxyphenyl)ethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(OC)=CC=C1CCN1C(=O)C(C=2C=C(Br)C=CC=2)N2C=NC=C2C1 GGNMFIOEXAYJBB-UHFFFAOYSA-N 0.000 claims description 2
- NVLYNXBWZMIGSZ-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[2-(4-methylphenyl)ethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(C)=CC=C1CCN1C(=O)C(C=2C=C(Br)C=CC=2)N2C=NC=C2C1 NVLYNXBWZMIGSZ-UHFFFAOYSA-N 0.000 claims description 2
- HMACKOWEQJLSOU-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[[3-(trifluoromethyl)phenyl]methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound FC(F)(F)C1=CC=CC(CN2C(C(N3C=NC=C3C2)C=2C=C(Br)C=CC=2)=O)=C1 HMACKOWEQJLSOU-UHFFFAOYSA-N 0.000 claims description 2
- VLQUDWXZXSWBNT-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[[4-(trifluoromethyl)phenyl]methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(C(F)(F)F)=CC=C1CN1C(=O)C(C=2C=C(Br)C=CC=2)N2C=NC=C2C1 VLQUDWXZXSWBNT-UHFFFAOYSA-N 0.000 claims description 2
- JTRTUICSPPQURP-UHFFFAOYSA-N 5-(3-bromophenyl)-7-cyclohexyl-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound BrC1=CC=CC(C2N3C=NC=C3CN(C2=O)C2CCCCC2)=C1 JTRTUICSPPQURP-UHFFFAOYSA-N 0.000 claims description 2
- MDEQEPGEWJZZKJ-UHFFFAOYSA-N 5-(3-bromophenyl)-7-methyl-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound O=C1N(C)CC2=CN=CN2C1C1=CC=CC(Br)=C1 MDEQEPGEWJZZKJ-UHFFFAOYSA-N 0.000 claims description 2
- VGGBGEMTNNWEPE-UHFFFAOYSA-N 5-(4-bromophenyl)-7-(4-methoxyphenyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(OC)=CC=C1N1C(=O)C(C=2C=CC(Br)=CC=2)N2C=NC=C2C1 VGGBGEMTNNWEPE-UHFFFAOYSA-N 0.000 claims description 2
- PVINFKAGXJWKAW-UHFFFAOYSA-N 5-(4-bromophenyl)-7-(cyclopropylmethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(Br)=CC=C1C1N2C=NC=C2CN(CC2CC2)C1=O PVINFKAGXJWKAW-UHFFFAOYSA-N 0.000 claims description 2
- QSMJOOJEOTWELD-UHFFFAOYSA-N 5-(4-bromophenyl)-7-(cyclopropylmethyl)-5-methyl-8h-imidazo[1,5-a]pyrazin-6-one Chemical compound C1C2=CN=CN2C(C)(C=2C=CC(Br)=CC=2)C(=O)N1CC1CC1 QSMJOOJEOTWELD-UHFFFAOYSA-N 0.000 claims description 2
- GVYRBVAXFAOEFT-UHFFFAOYSA-N 5-(4-bromophenyl)-7-[(4-chlorophenyl)methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(Cl)=CC=C1CN1C(=O)C(C=2C=CC(Br)=CC=2)N2C=NC=C2C1 GVYRBVAXFAOEFT-UHFFFAOYSA-N 0.000 claims description 2
- KZQBSCBXVWQAIU-UHFFFAOYSA-N 5-(4-bromophenyl)-7-[(4-fluorophenyl)methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(F)=CC=C1CN1C(=O)C(C=2C=CC(Br)=CC=2)N2C=NC=C2C1 KZQBSCBXVWQAIU-UHFFFAOYSA-N 0.000 claims description 2
- FMWIADMBURQFPR-UHFFFAOYSA-N 5-(4-bromophenyl)-7-[(4-methoxyphenyl)methyl]-6,8-dihydro-5h-imidazo[1,5-a]pyrazine Chemical compound C1=CC(OC)=CC=C1CN1CC2=CN=CN2C(C=2C=CC(Br)=CC=2)C1 FMWIADMBURQFPR-UHFFFAOYSA-N 0.000 claims description 2
- PCDNGPVCHFKGGP-UHFFFAOYSA-N 5-(4-bromophenyl)-7-[2-(4-fluorophenyl)ethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(F)=CC=C1CCN1C(=O)C(C=2C=CC(Br)=CC=2)N2C=NC=C2C1 PCDNGPVCHFKGGP-UHFFFAOYSA-N 0.000 claims description 2
- SQYQWCMLHXLANN-UHFFFAOYSA-N 5-(4-bromophenyl)-7-[[4-(trifluoromethyl)phenyl]methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(C(F)(F)F)=CC=C1CN1C(=O)C(C=2C=CC(Br)=CC=2)N2C=NC=C2C1 SQYQWCMLHXLANN-UHFFFAOYSA-N 0.000 claims description 2
- MGGVICIZANYYQK-UHFFFAOYSA-N 5-[4-(4-chlorophenyl)phenyl]-7-[(4-methoxyphenyl)methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C(C=2C=CC(=CC=2)C=2C=CC(Cl)=CC=2)N2C=NC=C2C1 MGGVICIZANYYQK-UHFFFAOYSA-N 0.000 claims description 2
- JVZWSPJIGBCUCC-UHFFFAOYSA-N 7-(cyclopropylmethyl)-5-(4-thiophen-3-ylphenyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound N12C=NC=C2CN(CC2CC2)C(=O)C1C(C=C1)=CC=C1C=1C=CSC=1 JVZWSPJIGBCUCC-UHFFFAOYSA-N 0.000 claims description 2
- FAYQLFDMZVWUHN-UHFFFAOYSA-N 7-benzyl-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound O=C1CN2C=NC=C2CN1CC1=CC=CC=C1 FAYQLFDMZVWUHN-UHFFFAOYSA-N 0.000 claims description 2
- RAHSKDGRTKKFLT-UHFFFAOYSA-N 7-benzyl-5-[3-(4-fluorophenyl)phenyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound C1=CC(F)=CC=C1C1=CC=CC(C2N3C=NC=C3CN(CC=3C=CC=CC=3)C2=O)=C1 RAHSKDGRTKKFLT-UHFFFAOYSA-N 0.000 claims description 2
- UHAXVXOZRHDNAF-UHFFFAOYSA-N 7-benzyl-5-phenyl-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound N12C=NC=C2CN(CC=2C=CC=CC=2)C(=O)C1C1=CC=CC=C1 UHAXVXOZRHDNAF-UHFFFAOYSA-N 0.000 claims description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 2
- 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
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims 1
- ZNAHNGZDLLLXRF-UHFFFAOYSA-N 5-(4-bromophenyl)-7-[(4-fluorophenyl)methyl]-5-methyl-8h-imidazo[1,5-a]pyrazin-6-one Chemical compound C1C2=CN=CN2C(C)(C=2C=CC(Br)=CC=2)C(=O)N1CC1=CC=C(F)C=C1 ZNAHNGZDLLLXRF-UHFFFAOYSA-N 0.000 claims 1
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 abstract description 14
- 230000005764 inhibitory process Effects 0.000 abstract description 6
- 208000020832 chronic kidney disease Diseases 0.000 abstract description 5
- 208000022831 chronic renal failure syndrome Diseases 0.000 abstract description 5
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 abstract description 4
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 abstract description 4
- 229960002478 aldosterone Drugs 0.000 abstract description 4
- 230000002265 prevention Effects 0.000 abstract description 4
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 abstract description 3
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 abstract description 3
- 230000001404 mediated effect Effects 0.000 abstract description 3
- 229940124639 Selective inhibitor Drugs 0.000 abstract description 2
- 208000029078 coronary artery disease Diseases 0.000 abstract 1
- 239000002831 pharmacologic agent Substances 0.000 abstract 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 105
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 96
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 91
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 64
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 60
- 235000019439 ethyl acetate Nutrition 0.000 description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
- 239000000243 solution Substances 0.000 description 39
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 25
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 239000000741 silica gel Substances 0.000 description 21
- 229910002027 silica gel Inorganic materials 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 20
- 239000002904 solvent Substances 0.000 description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 239000012267 brine Substances 0.000 description 17
- 238000000034 method Methods 0.000 description 17
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
- 239000007787 solid Substances 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 239000002253 acid Substances 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- 239000012074 organic phase Substances 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 125000006239 protecting group Chemical group 0.000 description 12
- 229910052727 yttrium Inorganic materials 0.000 description 12
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- 239000002585 base Substances 0.000 description 11
- 239000003960 organic solvent Substances 0.000 description 11
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 238000003818 flash chromatography Methods 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- KCWZGJVSDFYRIX-YFKPBYRVSA-N N(gamma)-nitro-L-arginine methyl ester Chemical compound COC(=O)[C@@H](N)CCCN=C(N)N[N+]([O-])=O KCWZGJVSDFYRIX-YFKPBYRVSA-N 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 8
- 0 Cc1cc(C*C(CC2=C*=C*2C2c3ccc(*)cc3)C2=O)ccc1 Chemical compound Cc1cc(C*C(CC2=C*=C*2C2c3ccc(*)cc3)C2=O)ccc1 0.000 description 7
- 239000002168 alkylating agent Substances 0.000 description 7
- 229940100198 alkylating agent Drugs 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 229940002612 prodrug Drugs 0.000 description 7
- 239000000651 prodrug Substances 0.000 description 7
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 241001295925 Gegenes Species 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 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 5
- 241000124008 Mammalia Species 0.000 description 5
- 125000002947 alkylene group Chemical group 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 150000002430 hydrocarbons Chemical group 0.000 description 5
- WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
- 235000015424 sodium Nutrition 0.000 description 5
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- DVQYFYUODSFBFS-UHFFFAOYSA-N (1-tritylimidazol-4-yl)methanol Chemical compound C1=NC(CO)=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 DVQYFYUODSFBFS-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 102100030988 Angiotensin-converting enzyme Human genes 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 125000005907 alkyl ester group Chemical group 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 125000004665 trialkylsilyl group Chemical group 0.000 description 4
- YNVRNJRVLZDDPH-UHFFFAOYSA-N (1-tritylimidazol-4-yl)methyl acetate Chemical compound C1=NC(COC(=O)C)=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 YNVRNJRVLZDDPH-UHFFFAOYSA-N 0.000 description 3
- NXFFJDQHYLNEJK-UHFFFAOYSA-N 2-[4-[(4-chlorophenyl)methyl]-7-fluoro-5-methylsulfonyl-2,3-dihydro-1h-cyclopenta[b]indol-3-yl]acetic acid Chemical compound C1=2C(S(=O)(=O)C)=CC(F)=CC=2C=2CCC(CC(O)=O)C=2N1CC1=CC=C(Cl)C=C1 NXFFJDQHYLNEJK-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- 206010003210 Arteriosclerosis Diseases 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- OMFXVFTZEKFJBZ-UHFFFAOYSA-N Corticosterone Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 OMFXVFTZEKFJBZ-UHFFFAOYSA-N 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 102000003729 Neprilysin Human genes 0.000 description 3
- 108090000028 Neprilysin Proteins 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Natural products OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 230000003579 anti-obesity Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 229910000085 borane Inorganic materials 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 150000001735 carboxylic acids Chemical class 0.000 description 3
- 239000000460 chlorine Chemical group 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 239000011976 maleic acid Substances 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- KPQQGTQMINZUFF-UHFFFAOYSA-N methyl 3-(4-cyanophenyl)-3-(5-formylimidazol-1-yl)propanoate Chemical compound C1=NC=C(C=O)N1C(CC(=O)OC)C1=CC=C(C#N)C=C1 KPQQGTQMINZUFF-UHFFFAOYSA-N 0.000 description 3
- CKPIUNMQZFJXNL-UHFFFAOYSA-N methyl 3-(4-cyanophenyl)-3-[5-(hydroxymethyl)imidazol-1-yl]propanoate Chemical compound C1=NC=C(CO)N1C(CC(=O)OC)C1=CC=C(C#N)C=C1 CKPIUNMQZFJXNL-UHFFFAOYSA-N 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 230000003204 osmotic effect Effects 0.000 description 3
- 230000003169 placental effect Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229960004793 sucrose Drugs 0.000 description 3
- LJXGESHWGFHORY-UHFFFAOYSA-N tert-butyl-dimethyl-[(1-tritylimidazol-4-yl)methoxy]silane Chemical compound C1=NC(CO[Si](C)(C)C(C)(C)C)=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 LJXGESHWGFHORY-UHFFFAOYSA-N 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 150000003573 thiols Chemical class 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 3
- XQWBDIAGTOWOOU-UHFFFAOYSA-K trisodium;dioxido-oxo-sulfanylidene-$l^{6}-sulfane;hydrogen carbonate Chemical compound [Na+].[Na+].[Na+].OC([O-])=O.[O-]S([O-])(=O)=S XQWBDIAGTOWOOU-UHFFFAOYSA-K 0.000 description 3
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
- 102100029077 3-hydroxy-3-methylglutaryl-coenzyme A reductase Human genes 0.000 description 2
- 101710158485 3-hydroxy-3-methylglutaryl-coenzyme A reductase Proteins 0.000 description 2
- YSRXDZXPBMRNHT-UHFFFAOYSA-N 4-(7-benzyl-5-methyl-6-oxo-8h-imidazo[1,5-a]pyrazin-5-yl)benzonitrile;hydrochloride Chemical compound Cl.C1C2=CN=CN2C(C)(C=2C=CC(=CC=2)C#N)C(=O)N1CC1=CC=CC=C1 YSRXDZXPBMRNHT-UHFFFAOYSA-N 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 2
- YQMPDRSBLSFKHG-UHFFFAOYSA-N 5-(4-bromophenyl)-7-[(4-methoxyphenyl)methyl]-6,8-dihydro-5h-imidazo[1,5-a]pyrazine;dihydrochloride Chemical compound Cl.Cl.C1=CC(OC)=CC=C1CN1CC2=CN=CN2C(C=2C=CC(Br)=CC=2)C1 YQMPDRSBLSFKHG-UHFFFAOYSA-N 0.000 description 2
- VJEDIARBUAXACT-UHFFFAOYSA-N 5-[4-(4-chlorophenyl)phenyl]-7-[(4-methoxyphenyl)methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1CN1C(=O)C(C=2C=CC(=CC=2)C=2C=CC(Cl)=CC=2)N2C=NC=C2C1 VJEDIARBUAXACT-UHFFFAOYSA-N 0.000 description 2
- QKXYZPAVZKASTQ-UHFFFAOYSA-N 7-benzyl-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.O=C1CN2C=NC=C2CN1CC1=CC=CC=C1 QKXYZPAVZKASTQ-UHFFFAOYSA-N 0.000 description 2
- FEUXFSLNGDCYGA-UHFFFAOYSA-N 7-benzyl-5-phenyl-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.N12C=NC=C2CN(CC=2C=CC=CC=2)C(=O)C1C1=CC=CC=C1 FEUXFSLNGDCYGA-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 239000004072 C09CA03 - Valsartan Substances 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-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
- 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 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Natural products OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N Lactic Acid Natural products CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 125000005236 alkanoylamino group Chemical group 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 125000003435 aroyl group Chemical group 0.000 description 2
- 125000005239 aroylamino group Chemical group 0.000 description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- MRAHIVCBBZNVHV-UHFFFAOYSA-N benzonitrile;hydrobromide Chemical compound Br.N#CC1=CC=CC=C1 MRAHIVCBBZNVHV-UHFFFAOYSA-N 0.000 description 2
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 2
- 229960005156 digoxin Drugs 0.000 description 2
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 229940088679 drug related substance Drugs 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 125000004404 heteroalkyl group Chemical group 0.000 description 2
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- RKOJNHMAUOGYSD-UHFFFAOYSA-N methyl 2-(5-formylimidazol-1-yl)-2-phenylacetate Chemical compound C1=NC=C(C=O)N1C(C(=O)OC)C1=CC=CC=C1 RKOJNHMAUOGYSD-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 230000003228 microsomal effect Effects 0.000 description 2
- OKDQKPLMQBXTNH-UHFFFAOYSA-N n,n-dimethyl-2h-pyridin-1-amine Chemical compound CN(C)N1CC=CC=C1 OKDQKPLMQBXTNH-UHFFFAOYSA-N 0.000 description 2
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 238000005192 partition Methods 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 229940049953 phenylacetate Drugs 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 230000003014 reinforcing effect Effects 0.000 description 2
- 230000008521 reorganization Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 150000003460 sulfonic acids Chemical class 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 2
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 2
- 125000001425 triazolyl group Chemical group 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical class OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 229960004699 valsartan Drugs 0.000 description 2
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical group C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 1
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
- LPUDGHQMOAHMMF-JBACZVJFSA-N (2s)-2-[[[(2s)-6-amino-2-(methanesulfonamido)hexanoyl]amino]methyl]-3-[1-[[(1s)-1-carboxy-2-(4-hydroxyphenyl)ethyl]carbamoyl]cyclopentyl]propanoic acid Chemical compound N([C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C(=O)C1(C[C@@H](CNC(=O)[C@H](CCCCN)NS(=O)(=O)C)C(O)=O)CCCC1 LPUDGHQMOAHMMF-JBACZVJFSA-N 0.000 description 1
- BIDNLKIUORFRQP-XYGFDPSESA-N (2s,4s)-4-cyclohexyl-1-[2-[[(1s)-2-methyl-1-propanoyloxypropoxy]-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C([P@@](=O)(O[C@H](OC(=O)CC)C(C)C)CC(=O)N1[C@@H](C[C@H](C1)C1CCCCC1)C(O)=O)CCCC1=CC=CC=C1 BIDNLKIUORFRQP-XYGFDPSESA-N 0.000 description 1
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 1
- CAYQIZIAYYNFCS-UHFFFAOYSA-N (4-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1 CAYQIZIAYYNFCS-UHFFFAOYSA-N 0.000 description 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 125000006088 2-oxoazepinyl group Chemical group 0.000 description 1
- 125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
- 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
- 125000006087 2-oxopyrrolodinyl group Chemical group 0.000 description 1
- 125000004610 3,4-dihydro-4-oxo-quinazolinyl group Chemical group O=C1NC(=NC2=CC=CC=C12)* 0.000 description 1
- XEEAXBWCPKLDAW-UHFFFAOYSA-N 3-[6-oxo-7-(2-phenylethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile;hydrochloride Chemical compound Cl.N12C=NC=C2CN(CCC=2C=CC=CC=2)C(=O)C1C1=CC=CC(C#N)=C1 XEEAXBWCPKLDAW-UHFFFAOYSA-N 0.000 description 1
- NURSGWUXVIFRLX-UHFFFAOYSA-N 3-[7-(cyclopropylmethyl)-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile;hydrochloride Chemical compound Cl.N12C=NC=C2CN(CC2CC2)C(=O)C1C1=CC=CC(C#N)=C1 NURSGWUXVIFRLX-UHFFFAOYSA-N 0.000 description 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 description 1
- HTPPIWRQQBXHEZ-UHFFFAOYSA-N 3-[7-[(4-chlorophenyl)methyl]-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile;hydrochloride Chemical compound Cl.C1=CC(Cl)=CC=C1CN1C(=O)C(C=2C=C(C=CC=2)C#N)N2C=NC=C2C1 HTPPIWRQQBXHEZ-UHFFFAOYSA-N 0.000 description 1
- OHWHFDMWTQYCOR-UHFFFAOYSA-N 3-[7-[(4-fluorophenyl)methyl]-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1CN1C(=O)C(C=2C=C(C=CC=2)C#N)N2C=NC=C2C1 OHWHFDMWTQYCOR-UHFFFAOYSA-N 0.000 description 1
- DNIGOEDJVYJHER-UHFFFAOYSA-N 3-[7-[(4-methoxyphenyl)methyl]-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1CN1C(=O)C(C=2C=C(C=CC=2)C#N)N2C=NC=C2C1 DNIGOEDJVYJHER-UHFFFAOYSA-N 0.000 description 1
- LPFMIEOZUOUNPE-UHFFFAOYSA-N 3-[7-[(4-methylphenyl)methyl]-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile;hydrochloride Chemical compound Cl.C1=CC(C)=CC=C1CN1C(=O)C(C=2C=C(C=CC=2)C#N)N2C=NC=C2C1 LPFMIEOZUOUNPE-UHFFFAOYSA-N 0.000 description 1
- DSEHVFZMEOMZGG-UHFFFAOYSA-N 3-[7-[2-(4-fluorophenyl)ethyl]-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1CCN1C(=O)C(C=2C=C(C=CC=2)C#N)N2C=NC=C2C1 DSEHVFZMEOMZGG-UHFFFAOYSA-N 0.000 description 1
- UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 description 1
- PLMAQZARXYJJPX-UHFFFAOYSA-N 4-(7-methyl-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl)benzonitrile;hydrochloride Chemical compound Cl.O=C1N(C)CC2=CN=CN2C1C1=CC=C(C#N)C=C1 PLMAQZARXYJJPX-UHFFFAOYSA-N 0.000 description 1
- UMLFTCYAQPPZER-UHFFFAOYSA-N 4-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=C(C#N)C=C1 UMLFTCYAQPPZER-UHFFFAOYSA-N 0.000 description 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 description 1
- SQFQHGKMQIYCCT-OOJLDXBWSA-N 4-[6-oxo-7-[(1s)-1-phenylethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound O=C1N([C@@H](C)C=2C=CC=CC=2)CC2=CN=CN2C1C1=CC=C(C#N)C=C1 SQFQHGKMQIYCCT-OOJLDXBWSA-N 0.000 description 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 description 1
- YHNWKZKJEKZJOC-UEDXYCIISA-N 4-[7-[(1s)-1-(4-fluorophenyl)ethyl]-5-methyl-6-oxo-8h-imidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound O=C1N([C@@H](C)C=2C=CC(F)=CC=2)CC2=CN=CN2C1(C)C1=CC=C(C#N)C=C1 YHNWKZKJEKZJOC-UEDXYCIISA-N 0.000 description 1
- RXLGVXWTYGDMSL-UHFFFAOYSA-N 4-[7-[(4-chlorophenyl)methyl]-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile;hydrochloride Chemical compound Cl.C1=CC(Cl)=CC=C1CN1C(=O)C(C=2C=CC(=CC=2)C#N)N2C=NC=C2C1 RXLGVXWTYGDMSL-UHFFFAOYSA-N 0.000 description 1
- OIROBOQKTCGSMC-UHFFFAOYSA-N 4-[7-[(4-fluorophenyl)methyl]-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile Chemical compound C1=CC(F)=CC=C1CN1C(=O)C(C=2C=CC(=CC=2)C#N)N2C=NC=C2C1 OIROBOQKTCGSMC-UHFFFAOYSA-N 0.000 description 1
- SXIDKHNTWVBOIJ-UHFFFAOYSA-N 4-[7-[2-(4-fluorophenyl)ethyl]-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-5-yl]benzonitrile;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1CCN1C(=O)C(C=2C=CC(=CC=2)C#N)N2C=NC=C2C1 SXIDKHNTWVBOIJ-UHFFFAOYSA-N 0.000 description 1
- BIGLBUBIECIISY-UHFFFAOYSA-N 4-[[5-(3-bromophenyl)-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-7-yl]methyl]piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1CN1C(=O)C(C=2C=C(Br)C=CC=2)N2C=NC=C2C1 BIGLBUBIECIISY-UHFFFAOYSA-N 0.000 description 1
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 1
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000005986 4-piperidonyl group Chemical group 0.000 description 1
- LJAWPSUNBYZFBY-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(2-phenylethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.BrC1=CC=CC(C2N3C=NC=C3CN(CCC=3C=CC=CC=3)C2=O)=C1 LJAWPSUNBYZFBY-UHFFFAOYSA-N 0.000 description 1
- ABQVXNPGWUXXNZ-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(cyclopropylmethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.BrC1=CC=CC(C2N3C=NC=C3CN(CC3CC3)C2=O)=C1 ABQVXNPGWUXXNZ-UHFFFAOYSA-N 0.000 description 1
- NZVIPQZNYMKUBW-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(cyclopropylmethyl)-5-methyl-8h-imidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1C2=CN=CN2C(C)(C=2C=C(Br)C=CC=2)C(=O)N1CC1CC1 NZVIPQZNYMKUBW-UHFFFAOYSA-N 0.000 description 1
- CMJUVFMWVRUOPA-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(furan-2-ylmethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.BrC1=CC=CC(C2N3C=NC=C3CN(CC=3OC=CC=3)C2=O)=C1 CMJUVFMWVRUOPA-UHFFFAOYSA-N 0.000 description 1
- TWFAHJRTFIVDDO-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(piperidin-4-ylmethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;dihydrochloride Chemical compound Cl.Cl.BrC1=CC=CC(C2N3C=NC=C3CN(CC3CCNCC3)C2=O)=C1 TWFAHJRTFIVDDO-UHFFFAOYSA-N 0.000 description 1
- LDRQVLJGCVAAFS-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(thiophen-2-ylmethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.BrC1=CC=CC(C2N3C=NC=C3CN(CC=3SC=CC=3)C2=O)=C1 LDRQVLJGCVAAFS-UHFFFAOYSA-N 0.000 description 1
- IUIFCWCDEZGVLL-MJTSIZKDSA-N 5-(3-bromophenyl)-7-[(1r)-1-phenylethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound O=C1N([C@H](C)C=2C=CC=CC=2)CC2=CN=CN2C1C1=CC=CC(Br)=C1 IUIFCWCDEZGVLL-MJTSIZKDSA-N 0.000 description 1
- IUIFCWCDEZGVLL-KTQQKIMGSA-N 5-(3-bromophenyl)-7-[(1s)-1-phenylethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound O=C1N([C@@H](C)C=2C=CC=CC=2)CC2=CN=CN2C1C1=CC=CC(Br)=C1 IUIFCWCDEZGVLL-KTQQKIMGSA-N 0.000 description 1
- SWWHZAUDUYZNEI-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[(3-fluorophenyl)methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.FC1=CC=CC(CN2C(C(N3C=NC=C3C2)C=2C=C(Br)C=CC=2)=O)=C1 SWWHZAUDUYZNEI-UHFFFAOYSA-N 0.000 description 1
- FWBBDTXPYYERMR-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[(3-methylphenyl)methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.CC1=CC=CC(CN2C(C(N3C=NC=C3C2)C=2C=C(Br)C=CC=2)=O)=C1 FWBBDTXPYYERMR-UHFFFAOYSA-N 0.000 description 1
- HZKYQBFNSQFRSD-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[(4-chlorophenyl)methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1=CC(Cl)=CC=C1CN1C(=O)C(C=2C=C(Br)C=CC=2)N2C=NC=C2C1 HZKYQBFNSQFRSD-UHFFFAOYSA-N 0.000 description 1
- YLUFLZYCCHCTJB-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[(4-fluorophenyl)methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1CN1C(=O)C(C=2C=C(Br)C=CC=2)N2C=NC=C2C1 YLUFLZYCCHCTJB-UHFFFAOYSA-N 0.000 description 1
- PFYVYRPNGUWJMY-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[(4-methoxyphenyl)methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1CN1C(=O)C(C=2C=C(Br)C=CC=2)N2C=NC=C2C1 PFYVYRPNGUWJMY-UHFFFAOYSA-N 0.000 description 1
- LLCBOOLDFBVBBS-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[(4-methylphenyl)methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1=CC(C)=CC=C1CN1C(=O)C(C=2C=C(Br)C=CC=2)N2C=NC=C2C1 LLCBOOLDFBVBBS-UHFFFAOYSA-N 0.000 description 1
- MFGPEWFYVZEDME-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[2-(3-chlorophenyl)ethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.ClC1=CC=CC(CCN2C(C(N3C=NC=C3C2)C=2C=C(Br)C=CC=2)=O)=C1 MFGPEWFYVZEDME-UHFFFAOYSA-N 0.000 description 1
- CEQCFKNRWNCDQN-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[2-(4-chlorophenyl)ethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1=CC(Cl)=CC=C1CCN1C(=O)C(C=2C=C(Br)C=CC=2)N2C=NC=C2C1 CEQCFKNRWNCDQN-UHFFFAOYSA-N 0.000 description 1
- DRBBHHBJIDPZKA-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[2-(4-fluorophenyl)ethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1CCN1C(=O)C(C=2C=C(Br)C=CC=2)N2C=NC=C2C1 DRBBHHBJIDPZKA-UHFFFAOYSA-N 0.000 description 1
- SAZKYEPYUZWYPH-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[2-(4-methoxyphenyl)ethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1CCN1C(=O)C(C=2C=C(Br)C=CC=2)N2C=NC=C2C1 SAZKYEPYUZWYPH-UHFFFAOYSA-N 0.000 description 1
- GMSPGDUVJZCGCN-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[2-(4-methylphenyl)ethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1=CC(C)=CC=C1CCN1C(=O)C(C=2C=C(Br)C=CC=2)N2C=NC=C2C1 GMSPGDUVJZCGCN-UHFFFAOYSA-N 0.000 description 1
- RQEBNQFSOVTFDY-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[[3-(trifluoromethyl)phenyl]methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.FC(F)(F)C1=CC=CC(CN2C(C(N3C=NC=C3C2)C=2C=C(Br)C=CC=2)=O)=C1 RQEBNQFSOVTFDY-UHFFFAOYSA-N 0.000 description 1
- FDFOSYQTVGDHDA-UHFFFAOYSA-N 5-(3-bromophenyl)-7-[[4-(trifluoromethyl)phenyl]methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1=CC(C(F)(F)F)=CC=C1CN1C(=O)C(C=2C=C(Br)C=CC=2)N2C=NC=C2C1 FDFOSYQTVGDHDA-UHFFFAOYSA-N 0.000 description 1
- YLHLDMJWLHUXEA-UHFFFAOYSA-N 5-(3-bromophenyl)-7-cyclohexyl-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;oxalic acid Chemical compound OC(=O)C(O)=O.BrC1=CC=CC(C2N3C=NC=C3CN(C2=O)C2CCCCC2)=C1 YLHLDMJWLHUXEA-UHFFFAOYSA-N 0.000 description 1
- GTFYEYKRZTTWOC-UHFFFAOYSA-N 5-(3-bromophenyl)-7-methyl-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.O=C1N(C)CC2=CN=CN2C1C1=CC=CC(Br)=C1 GTFYEYKRZTTWOC-UHFFFAOYSA-N 0.000 description 1
- WDKUDQANCZBOLA-UHFFFAOYSA-N 5-(4-bromophenyl)-7-(4-methoxyphenyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1N1C(=O)C(C=2C=CC(Br)=CC=2)N2C=NC=C2C1 WDKUDQANCZBOLA-UHFFFAOYSA-N 0.000 description 1
- XTRQTOSOBPPCNC-UHFFFAOYSA-N 5-(4-bromophenyl)-7-(4-methoxyphenyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;oxalic acid Chemical compound OC(=O)C(O)=O.C1=CC(OC)=CC=C1N1C(=O)C(C=2C=CC(Br)=CC=2)N2C=NC=C2C1 XTRQTOSOBPPCNC-UHFFFAOYSA-N 0.000 description 1
- WOSQEMUUIALFBT-UHFFFAOYSA-N 5-(4-bromophenyl)-7-(cyclopropylmethyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1=CC(Br)=CC=C1C1N2C=NC=C2CN(CC2CC2)C1=O WOSQEMUUIALFBT-UHFFFAOYSA-N 0.000 description 1
- PFUTUWXDFUIQKF-UHFFFAOYSA-N 5-(4-bromophenyl)-7-(cyclopropylmethyl)-5-methyl-8h-imidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1C2=CN=CN2C(C)(C=2C=CC(Br)=CC=2)C(=O)N1CC1CC1 PFUTUWXDFUIQKF-UHFFFAOYSA-N 0.000 description 1
- BNPIELKFNYKKES-MJTSIZKDSA-N 5-(4-bromophenyl)-7-[(1r)-1-phenylethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound O=C1N([C@H](C)C=2C=CC=CC=2)CC2=CN=CN2C1C1=CC=C(Br)C=C1 BNPIELKFNYKKES-MJTSIZKDSA-N 0.000 description 1
- BNPIELKFNYKKES-KTQQKIMGSA-N 5-(4-bromophenyl)-7-[(1s)-1-phenylethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one Chemical compound O=C1N([C@@H](C)C=2C=CC=CC=2)CC2=CN=CN2C1C1=CC=C(Br)C=C1 BNPIELKFNYKKES-KTQQKIMGSA-N 0.000 description 1
- GSPUJAFNWBZPDX-UHFFFAOYSA-N 5-(4-bromophenyl)-7-[(4-chlorophenyl)methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1=CC(Cl)=CC=C1CN1C(=O)C(C=2C=CC(Br)=CC=2)N2C=NC=C2C1 GSPUJAFNWBZPDX-UHFFFAOYSA-N 0.000 description 1
- MVKIRNCLBUFFCS-UHFFFAOYSA-N 5-(4-bromophenyl)-7-[(4-fluorophenyl)methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1CN1C(=O)C(C=2C=CC(Br)=CC=2)N2C=NC=C2C1 MVKIRNCLBUFFCS-UHFFFAOYSA-N 0.000 description 1
- JIOJCRHLRWXBRD-UHFFFAOYSA-N 5-(4-bromophenyl)-7-[(4-fluorophenyl)methyl]-5-methyl-8h-imidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1C2=CN=CN2C(C)(C=2C=CC(Br)=CC=2)C(=O)N1CC1=CC=C(F)C=C1 JIOJCRHLRWXBRD-UHFFFAOYSA-N 0.000 description 1
- UTMLHWAGKHYUKP-UHFFFAOYSA-N 5-(4-bromophenyl)-7-[2-(4-fluorophenyl)ethyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1CCN1C(=O)C(C=2C=CC(Br)=CC=2)N2C=NC=C2C1 UTMLHWAGKHYUKP-UHFFFAOYSA-N 0.000 description 1
- UOQSLIAFUIFRIP-UHFFFAOYSA-N 5-(4-bromophenyl)-7-[[4-(trifluoromethyl)phenyl]methyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1=CC(C(F)(F)F)=CC=C1CN1C(=O)C(C=2C=CC(Br)=CC=2)N2C=NC=C2C1 UOQSLIAFUIFRIP-UHFFFAOYSA-N 0.000 description 1
- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 description 1
- HXFLZWAZSSPLCO-UHFFFAOYSA-N 6,6-dimethylbicyclo[3.1.1]heptyl Chemical group C1[C-]2C([CH2+])([CH2-])[C+]1CCC2 HXFLZWAZSSPLCO-UHFFFAOYSA-N 0.000 description 1
- QFXPGURMNBWIHP-UHFFFAOYSA-N 7-(cyclopropylmethyl)-5-(4-thiophen-3-ylphenyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.N12C=NC=C2CN(CC2CC2)C(=O)C1C(C=C1)=CC=C1C=1C=CSC=1 QFXPGURMNBWIHP-UHFFFAOYSA-N 0.000 description 1
- WQJBRSWBZQYPLZ-UHFFFAOYSA-N 7-benzyl-5-(3-bromophenyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.BrC1=CC=CC(C2N3C=NC=C3CN(CC=3C=CC=CC=3)C2=O)=C1 WQJBRSWBZQYPLZ-UHFFFAOYSA-N 0.000 description 1
- CWHNKRMEYFBEOM-UHFFFAOYSA-N 7-benzyl-5-(4-bromophenyl)-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1=CC(Br)=CC=C1C1N2C=NC=C2CN(CC=2C=CC=CC=2)C1=O CWHNKRMEYFBEOM-UHFFFAOYSA-N 0.000 description 1
- SOEFQNZGDQSARK-UHFFFAOYSA-N 7-benzyl-5-(4-bromophenyl)-6,8-dihydro-5h-imidazo[1,5-a]pyrazine;4-methylbenzenesulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.C1=CC(Br)=CC=C1C1N2C=NC=C2CN(CC=2C=CC=CC=2)C1 SOEFQNZGDQSARK-UHFFFAOYSA-N 0.000 description 1
- MYZQLPKUAKEGJD-UHFFFAOYSA-N 7-benzyl-5-[3-(4-fluorophenyl)phenyl]-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1C1=CC=CC(C2N3C=NC=C3CN(CC=3C=CC=CC=3)C2=O)=C1 MYZQLPKUAKEGJD-UHFFFAOYSA-N 0.000 description 1
- RPNPOWUPMOMOII-UHFFFAOYSA-N 7-methyl-5-phenyl-5,8-dihydroimidazo[1,5-a]pyrazin-6-one;hydrochloride Chemical compound Cl.O=C1N(C)CC2=CN=CN2C1C1=CC=CC=C1 RPNPOWUPMOMOII-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 108091006112 ATPases Proteins 0.000 description 1
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 229940123338 Aldosterone synthase inhibitor Drugs 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 229940123413 Angiotensin II antagonist Drugs 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 108010078554 Aromatase Proteins 0.000 description 1
- 102000014654 Aromatase Human genes 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- PLVDVHNPWFJJHC-DYUKFFQPSA-N C/C=C(/CC(Cc1ccccc1)C(C1c(cc2)ccc2Br)=O)\N1C=C Chemical compound C/C=C(/CC(Cc1ccccc1)C(C1c(cc2)ccc2Br)=O)\N1C=C PLVDVHNPWFJJHC-DYUKFFQPSA-N 0.000 description 1
- 239000002083 C09CA01 - Losartan Substances 0.000 description 1
- 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
- 239000002053 C09CA06 - Candesartan Substances 0.000 description 1
- 239000005537 C09CA07 - Telmisartan Substances 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- CLOFIHCTVXABBC-UHFFFAOYSA-N Cc(cc(CN(Cc1cnc[n]1C1c(cc2)ccc2C#N)C1O)cc1)c1Cl Chemical compound Cc(cc(CN(Cc1cnc[n]1C1c(cc2)ccc2C#N)C1O)cc1)c1Cl CLOFIHCTVXABBC-UHFFFAOYSA-N 0.000 description 1
- GWJRBAKNDYEMCG-UHFFFAOYSA-N Cc1cc(C(C(N(Cc2ccccc2)C2)=O)[n]3c2cnc3)ccc1 Chemical compound Cc1cc(C(C(N(Cc2ccccc2)C2)=O)[n]3c2cnc3)ccc1 GWJRBAKNDYEMCG-UHFFFAOYSA-N 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- JRWZLRBJNMZMFE-UHFFFAOYSA-N Dobutamine Chemical compound C=1C=C(O)C(O)=CC=1CCNC(C)CCC1=CC=C(O)C=C1 JRWZLRBJNMZMFE-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 108010061435 Enalapril Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000013038 Hypocalcemia Diseases 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 108010007859 Lisinopril Proteins 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- UWWDHYUMIORJTA-HSQYWUDLSA-N Moexipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC(OC)=C(OC)C=C2C1)C(O)=O)CC1=CC=CC=C1 UWWDHYUMIORJTA-HSQYWUDLSA-N 0.000 description 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- IKQCLNBRIBUYHU-UHFFFAOYSA-N N#Cc1cc(C(C(C(Cc2ccccc2)C2)=O)[n]3c2cnc3)ccc1 Chemical compound N#Cc1cc(C(C(C(Cc2ccccc2)C2)=O)[n]3c2cnc3)ccc1 IKQCLNBRIBUYHU-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 229910003251 Na K Inorganic materials 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 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
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- NGBFQHCMQULJNZ-UHFFFAOYSA-N Torsemide Chemical compound CC(C)NC(=O)NS(=O)(=O)C1=CN=CC=C1NC1=CC=CC(C)=C1 NGBFQHCMQULJNZ-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- VXFJYXUZANRPDJ-WTNASJBWSA-N Trandopril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@H]2CCCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 VXFJYXUZANRPDJ-WTNASJBWSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 229960002122 acebutolol Drugs 0.000 description 1
- GOEMGAFJFRBGGG-UHFFFAOYSA-N acebutolol Chemical compound CCCC(=O)NC1=CC=C(OCC(O)CNC(C)C)C(C(C)=O)=C1 GOEMGAFJFRBGGG-UHFFFAOYSA-N 0.000 description 1
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 description 1
- 125000004670 alkyl amino thio carbonyl group Chemical group 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
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229960000528 amlodipine Drugs 0.000 description 1
- ZPBWCRDSRKPIDG-UHFFFAOYSA-N amlodipine benzenesulfonate Chemical compound OS(=O)(=O)C1=CC=CC=C1.CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl ZPBWCRDSRKPIDG-UHFFFAOYSA-N 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229960005471 androstenedione Drugs 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 239000012223 aqueous fraction Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 125000005140 aralkylsulfonyl group Chemical group 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000004659 aryl alkyl thio group Chemical group 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 229960002274 atenolol Drugs 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- 125000002785 azepinyl group Chemical group 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 229960004530 benazepril Drugs 0.000 description 1
- 125000005870 benzindolyl group Chemical group 0.000 description 1
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 1
- KKBIUAUSZKGNOA-HNAYVOBHSA-N benzyl (2s)-2-[[(2s)-2-(acetylsulfanylmethyl)-3-(1,3-benzodioxol-5-yl)propanoyl]amino]propanoate Chemical compound O=C([C@@H](NC(=O)[C@@H](CSC(C)=O)CC=1C=C2OCOC2=CC=1)C)OCC1=CC=CC=C1 KKBIUAUSZKGNOA-HNAYVOBHSA-N 0.000 description 1
- UIEATEWHFDRYRU-UHFFFAOYSA-N bepridil Chemical compound C1CCCN1C(COCC(C)C)CN(C=1C=CC=CC=1)CC1=CC=CC=C1 UIEATEWHFDRYRU-UHFFFAOYSA-N 0.000 description 1
- 229960003665 bepridil Drugs 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229960004324 betaxolol Drugs 0.000 description 1
- CHDPSNLJFOQTRK-UHFFFAOYSA-N betaxolol hydrochloride Chemical compound [Cl-].C1=CC(OCC(O)C[NH2+]C(C)C)=CC=C1CCOCC1CC1 CHDPSNLJFOQTRK-UHFFFAOYSA-N 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 229960002781 bisoprolol Drugs 0.000 description 1
- VHYCDWMUTMEGQY-UHFFFAOYSA-N bisoprolol Chemical compound CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1 VHYCDWMUTMEGQY-UHFFFAOYSA-N 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 229960000932 candesartan Drugs 0.000 description 1
- SGZAIDDFHDDFJU-UHFFFAOYSA-N candesartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SGZAIDDFHDDFJU-UHFFFAOYSA-N 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 125000004623 carbolinyl group Chemical group 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000003683 cardiac damage Effects 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229960005110 cerivastatin Drugs 0.000 description 1
- SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 description 1
- GPUADMRJQVPIAS-QCVDVZFFSA-M cerivastatin sodium Chemical compound [Na+].COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 GPUADMRJQVPIAS-QCVDVZFFSA-M 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000004617 chromonyl group Chemical group O1C(=CC(C2=CC=CC=C12)=O)* 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical compound NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 125000004652 decahydroisoquinolinyl group Chemical group C1(NCCC2CCCCC12)* 0.000 description 1
- 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000013681 dietary sucrose Nutrition 0.000 description 1
- 150000005332 diethylamines Chemical class 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-O diethylammonium Chemical compound CC[NH2+]CC HPNMFZURTQLUMO-UHFFFAOYSA-O 0.000 description 1
- 125000001070 dihydroindolyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000004611 dihydroisoindolyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000004609 dihydroquinazolinyl group Chemical group N1(CN=CC2=CC=CC=C12)* 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 229960004166 diltiazem Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000012153 distilled water Substances 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
- 229960001089 dobutamine Drugs 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229960000873 enalapril Drugs 0.000 description 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 description 1
- AVOLMBLBETYQHX-UHFFFAOYSA-N etacrynic acid Chemical compound CCC(=C)C(=O)C1=CC=C(OCC(O)=O)C(Cl)=C1Cl AVOLMBLBETYQHX-UHFFFAOYSA-N 0.000 description 1
- 229960003199 etacrynic acid Drugs 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 229950005203 fasidotril Drugs 0.000 description 1
- 229960003580 felodipine Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229960002490 fosinopril Drugs 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000004615 furo[2,3-b]pyridinyl group Chemical group O1C(=CC=2C1=NC=CC2)* 0.000 description 1
- 125000004613 furo[2,3-c]pyridinyl group Chemical group O1C(=CC=2C1=CN=CC2)* 0.000 description 1
- 125000006086 furo[3,2-b]pyridinyl] group Chemical group 0.000 description 1
- 125000004612 furopyridinyl group Chemical group O1C(=CC2=C1C=CC=N2)* 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 229960003883 furosemide Drugs 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 210000002837 heart atrium Anatomy 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000000705 hypocalcaemia Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- QDYTUZCWBJRHKK-UHFFFAOYSA-N imidazole-4-methanol Chemical compound OCC1=CNC=N1 QDYTUZCWBJRHKK-UHFFFAOYSA-N 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 239000011630 iodine Chemical group 0.000 description 1
- 229910052740 iodine Chemical group 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229960002198 irbesartan Drugs 0.000 description 1
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 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
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 125000003971 isoxazolinyl group Chemical group 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 229960002394 lisinopril Drugs 0.000 description 1
- CZRQXSDBMCMPNJ-ZUIPZQNBSA-N lisinopril dihydrate Chemical compound O.O.C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 CZRQXSDBMCMPNJ-ZUIPZQNBSA-N 0.000 description 1
- 239000002171 loop diuretic Substances 0.000 description 1
- 229960004773 losartan Drugs 0.000 description 1
- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- 235000014659 low sodium diet Nutrition 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- ALRMKMDZZIJTFD-UHFFFAOYSA-N methyl 2-[5-[[tert-butyl(dimethyl)silyl]oxymethyl]imidazol-1-yl]-2-(4-cyanophenyl)acetate Chemical compound COC(=O)C(c1ccc(cc1)C#N)n1cncc1CO[Si](C)(C)C(C)(C)C ALRMKMDZZIJTFD-UHFFFAOYSA-N 0.000 description 1
- NHFBYYMNJUMVOT-UHFFFAOYSA-N methyl 2-bromo-2-phenylacetate Chemical compound COC(=O)C(Br)C1=CC=CC=C1 NHFBYYMNJUMVOT-UHFFFAOYSA-N 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- VKQFCGNPDRICFG-UHFFFAOYSA-N methyl 2-methylpropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)C)C1C1=CC=CC=C1[N+]([O-])=O VKQFCGNPDRICFG-UHFFFAOYSA-N 0.000 description 1
- OBWFJXLKRAFEDI-UHFFFAOYSA-N methyl cyanoformate Chemical compound COC(=O)C#N OBWFJXLKRAFEDI-UHFFFAOYSA-N 0.000 description 1
- 229960002237 metoprolol Drugs 0.000 description 1
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 1
- AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 description 1
- 229950009116 mevastatin Drugs 0.000 description 1
- BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 description 1
- 238000004452 microanalysis Methods 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- PZRHRDRVRGEVNW-UHFFFAOYSA-N milrinone Chemical compound N1C(=O)C(C#N)=CC(C=2C=CN=CC=2)=C1C PZRHRDRVRGEVNW-UHFFFAOYSA-N 0.000 description 1
- 229960003574 milrinone Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229960005170 moexipril Drugs 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- 230000003680 myocardial damage Effects 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- VWPOSFSPZNDTMJ-UCWKZMIHSA-N nadolol Chemical compound C1[C@@H](O)[C@@H](O)CC2=C1C=CC=C2OCC(O)CNC(C)(C)C VWPOSFSPZNDTMJ-UCWKZMIHSA-N 0.000 description 1
- 229960004255 nadolol Drugs 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 229960001783 nicardipine Drugs 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 229960000715 nimodipine Drugs 0.000 description 1
- 229960000227 nisoldipine Drugs 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- LVRLSYPNFFBYCZ-VGWMRTNUSA-N omapatrilat Chemical compound C([C@H](S)C(=O)N[C@H]1CCS[C@H]2CCC[C@H](N2C1=O)C(=O)O)C1=CC=CC=C1 LVRLSYPNFFBYCZ-VGWMRTNUSA-N 0.000 description 1
- 229950000973 omapatrilat Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 229960001243 orlistat Drugs 0.000 description 1
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000003431 oxalo group Chemical group 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229960002797 pitavastatin Drugs 0.000 description 1
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000006085 pyrrolopyridyl group Chemical group 0.000 description 1
- 229960001455 quinapril Drugs 0.000 description 1
- JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 229960003401 ramipril Drugs 0.000 description 1
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 210000005241 right ventricle Anatomy 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229960000672 rosuvastatin Drugs 0.000 description 1
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 1
- 229950001780 sampatrilat Drugs 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002370 sotalol Drugs 0.000 description 1
- ZBMZVLHSJCTVON-UHFFFAOYSA-N sotalol Chemical compound CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 ZBMZVLHSJCTVON-UHFFFAOYSA-N 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229960005187 telmisartan Drugs 0.000 description 1
- QCIWZIYBBNEPKB-UHFFFAOYSA-N tert-butyl(dimethyl)silane Chemical compound C[SiH](C)C(C)(C)C QCIWZIYBBNEPKB-UHFFFAOYSA-N 0.000 description 1
- 125000006092 tetrahydro-1,1-dioxothienyl group Chemical group 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000006090 thiamorpholinyl sulfone group Chemical group 0.000 description 1
- 125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229960004605 timolol Drugs 0.000 description 1
- 229940024986 topical antifungal imidazole and triazole derivative Drugs 0.000 description 1
- 229960005461 torasemide Drugs 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 229960002051 trandolapril Drugs 0.000 description 1
- 125000005389 trialkylsiloxy group Chemical group 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- DRDCQJADRSJFFD-UHFFFAOYSA-N tris-hydroxymethyl-methyl-ammonium Chemical class OC[N+](C)(CO)CO DRDCQJADRSJFFD-UHFFFAOYSA-N 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 230000007279 water homeostasis Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07D487/04—Ortho-condensed systems
-
- 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
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
- A61P5/40—Mineralocorticosteroids, e.g. aldosterone; Drugs increasing or potentiating the activity of mineralocorticosteroids
-
- 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
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- A61P9/12—Antihypertensives
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US40169302P | 2002-08-07 | 2002-08-07 | |
| US401693P | 2002-08-07 | ||
| PCT/EP2003/008720 WO2004014914A1 (en) | 2002-08-07 | 2003-08-06 | Organic compounds as agents for the treatment of aldosterone mediated conditions |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60307483D1 DE60307483D1 (de) | 2006-09-21 |
| DE60307483T2 true DE60307483T2 (de) | 2007-07-05 |
Family
ID=31715720
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60307483T Expired - Lifetime DE60307483T2 (de) | 2002-08-07 | 2003-08-06 | Organische verbindungen als mittel zur behandlung von aldosteronbedingten zuständen |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US7732603B2 (enExample) |
| EP (1) | EP1537114B8 (enExample) |
| JP (1) | JP4533139B2 (enExample) |
| CN (1) | CN100404535C (enExample) |
| AT (1) | ATE335744T1 (enExample) |
| AU (1) | AU2003253387A1 (enExample) |
| BR (1) | BR0313293A (enExample) |
| CA (1) | CA2494636A1 (enExample) |
| CY (1) | CY1106217T1 (enExample) |
| DE (1) | DE60307483T2 (enExample) |
| DK (1) | DK1537114T3 (enExample) |
| ES (1) | ES2270143T3 (enExample) |
| PT (1) | PT1537114E (enExample) |
| WO (1) | WO2004014914A1 (enExample) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008500998A (ja) * | 2004-05-28 | 2008-01-17 | シュペーデル・エクスペリメンタ・アーゲー | 複素環式化合物およびアルドステロンシンターゼ阻害薬としてのそれらの使用 |
| AR049711A1 (es) * | 2004-07-09 | 2006-08-30 | Speedel Experimenta Ag | Compuestos heterociclicos condensados como inhibidores de la aldosterona sintasa; composiciones farmaceuticas que los contienen y su uso en la preparacion de un medicamento para el tratamiento o prevencion de enfermedades relacionadas con el hiperaldosterismo y por una liberacion excesiva de cortiso |
| TW200716636A (en) * | 2005-05-31 | 2007-05-01 | Speedel Experimenta Ag | Heterocyclic spiro-compounds |
| TW200716634A (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 |
| TW200808812A (en) * | 2006-04-12 | 2008-02-16 | Speedel Experimenta Ag | Imidazo compounds |
| TW200808813A (en) * | 2006-04-12 | 2008-02-16 | Speedel Experimenta Ag | Imidazo compounds |
| CA2651549A1 (en) * | 2006-05-26 | 2007-12-06 | Novartis Ag | Aldosterone synthase and/or 11.beta.-hydroxylase inhibitors |
| 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 |
| JP5485148B2 (ja) | 2007-06-21 | 2014-05-07 | カラ セラピューティクス インコーポレイテッド | 置換イミダゾ複素環 |
| US20110105514A1 (en) * | 2008-06-25 | 2011-05-05 | Hamed Aissaoui | 5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine compounds |
| BRPI1011657A2 (pt) | 2009-05-28 | 2019-04-16 | Novartis Ag | derivados aminopropiônicos substituídos como inibidores de neprilisina |
| 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 |
| MX342161B (es) | 2010-04-02 | 2016-09-19 | Euroscreen Sa | Compuestos antagonistas selectivos de receptor nk-3 novedosos, composicion farmaceutica y metodos para utilizarse en trastornos transmitidos por receptores nk-3. |
| 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 |
| 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 |
| US9867811B2 (en) | 2011-07-08 | 2018-01-16 | Novartis Ag | Method of treating atherosclerosis in high triglyceride subjects |
| MX367774B (es) | 2011-10-03 | 2019-09-04 | Ogeda S A | N-ACIL-5,6,7, (8-SUSTITUIDO)-TETRAHIDRO- [1,2,4] TRIAZOLO [4,3-a] PIRAZINAS QUIRALES, NOVEDOSAS, COMO ANTAGONISTAS SELECTIVOS DE RECEPTOR DE NK-3; COMPOSICIÓN FARMACÉUTICA, MÉTODOS PARA USO EN TRASTORNOS MEDIADOS POR RECEPTOR DE NK-3 Y SU SÍNTESIS QUIRAL. |
| UY35144A (es) | 2012-11-20 | 2014-06-30 | Novartis Ag | Miméticos lineales sintéticos de apelina para el tratamiento de insuficiencia cardiaca |
| SG11201506018PA (en) | 2013-02-14 | 2015-08-28 | Novartis Ag | Substituted bisphenyl butanoic phosphonic acid derivatives as nep (neutral endopeptidase) inhibitors |
| TW201518323A (zh) | 2013-07-25 | 2015-05-16 | Novartis Ag | 合成ａｐｅｌｉｎ多肽之生物結合物 |
| SG11201600211XA (en) | 2013-07-25 | 2016-02-26 | Novartis Ag | Cyclic polypeptides for the treatment of heart failure |
| CN107001289B (zh) | 2014-09-25 | 2019-12-31 | 欧歌达有限公司 | N-酰基-(3-取代的)-(8-取代的)-5,6-二氢-[1,2,4]三唑并[4,3-a]吡嗪的新手性合成 |
| AU2016209968B2 (en) | 2015-01-23 | 2018-11-29 | Novartis Ag | Synthetic apelin fatty acid conjugates with improved half-life |
| JP6964343B2 (ja) | 2015-11-20 | 2021-11-10 | フォーマ セラピューティクス，インコーポレイテッド | ユビキチン特異的プロテアーゼ１阻害剤としてのプリノン |
| 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 |
| BR112020019824A2 (pt) | 2018-03-29 | 2021-01-05 | Board Of Regents, The University Of Texas System | Composto de fórmula estrutural i ou um sal do mesmo, composição farmacêutica, método de inibição de cbp, método de inibição de p300, método de tratamento de uma doença mediada por cbp, método de tratamento de uma doença mediada por p300 e método para alcançar um efeito em um paciente |
| WO2019195846A1 (en) * | 2018-04-06 | 2019-10-10 | Board Of Regents, The University Of Texas System | Imidazopiperazinone inhibitors of transcription activating proteins |
| CN113166204B (zh) | 2018-11-27 | 2025-01-28 | 诺华股份有限公司 | 作为治疗代谢障碍的蛋白质原转换酶枯草杆菌蛋白酶/kexin 9型（PCSK9）抑制剂的环状肽 |
| EP3887363A1 (en) | 2018-11-27 | 2021-10-06 | Novartis AG | Cyclic pentamer compounds as proprotein convertase subtilisin/kexin type 9 (pcsk9) inhibitors for the treatment of metabolic disorder |
| 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 |
| US12115154B2 (en) | 2020-12-16 | 2024-10-15 | Srx Cardio, Llc | Compounds for the modulation of proprotein convertase subtilisin/kexin type 9 (PCSK9) |
| TW202333563A (zh) | 2021-11-12 | 2023-09-01 | 瑞士商諾華公司 | 用於治療疾病或障礙之二胺基環戊基吡啶衍生物 |
| AR127698A1 (es) | 2021-11-23 | 2024-02-21 | Novartis Ag | Derivados de naftiridinona para el tratamiento de una enfermedad o un trastorno |
| US20240391941A1 (en) | 2023-05-24 | 2024-11-28 | Novartis Ag | Naphthyridinone derivatives for the treatment of a disease or disorder |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3582315A (en) * | 1968-03-22 | 1971-06-01 | Lilly Co Eli | Methods and compositions for inhibiting plant growth |
| 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 |
| US4617307A (en) | 1984-06-20 | 1986-10-14 | Ciba-Geigy Corporation | Substituted imidazo[1,5-A]pyridine derivatives 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 |
| AU6015796A (en) * | 1995-06-14 | 1997-01-15 | 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 |
-
2003
- 2003-08-06 EP EP03784194A patent/EP1537114B8/en not_active Expired - Lifetime
- 2003-08-06 DK DK03784194T patent/DK1537114T3/da active
- 2003-08-06 ES ES03784194T patent/ES2270143T3/es not_active Expired - Lifetime
- 2003-08-06 CN CNB038238780A patent/CN100404535C/zh not_active Expired - Lifetime
- 2003-08-06 PT PT03784194T patent/PT1537114E/pt unknown
- 2003-08-06 BR BR0313293-5A patent/BR0313293A/pt not_active IP Right Cessation
- 2003-08-06 WO PCT/EP2003/008720 patent/WO2004014914A1/en not_active Ceased
- 2003-08-06 AT AT03784194T patent/ATE335744T1/de not_active IP Right Cessation
- 2003-08-06 JP JP2004526900A patent/JP4533139B2/ja not_active Expired - Fee Related
- 2003-08-06 US US10/523,870 patent/US7732603B2/en not_active Expired - Fee Related
- 2003-08-06 DE DE60307483T patent/DE60307483T2/de not_active Expired - Lifetime
- 2003-08-06 AU AU2003253387A patent/AU2003253387A1/en not_active Abandoned
- 2003-08-06 CA CA002494636A patent/CA2494636A1/en not_active Abandoned
-
2006
- 2006-10-24 CY CY20061101527T patent/CY1106217T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN100404535C (zh) | 2008-07-23 |
| WO2004014914A1 (en) | 2004-02-19 |
| ATE335744T1 (de) | 2006-09-15 |
| CN1688583A (zh) | 2005-10-26 |
| HK1080290A1 (en) | 2006-04-21 |
| BR0313293A (pt) | 2005-06-14 |
| ES2270143T3 (es) | 2007-04-01 |
| JP4533139B2 (ja) | 2010-09-01 |
| CA2494636A1 (en) | 2004-02-19 |
| EP1537114B8 (en) | 2007-10-03 |
| PT1537114E (pt) | 2006-12-29 |
| EP1537114A1 (en) | 2005-06-08 |
| CY1106217T1 (el) | 2011-06-08 |
| DK1537114T3 (da) | 2006-11-13 |
| EP1537114B1 (en) | 2006-08-09 |
| JP2006505520A (ja) | 2006-02-16 |
| DE60307483D1 (de) | 2006-09-21 |
| AU2003253387A1 (en) | 2004-02-25 |
| US20060166973A1 (en) | 2006-07-27 |
| US7732603B2 (en) | 2010-06-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE60307483T2 (de) | Organische verbindungen als mittel zur behandlung von aldosteronbedingten zuständen | |
| RU2726206C2 (ru) | Модуляторы ccr2 | |
| KR102399206B1 (ko) | 이소퀴놀린-3-일 카르복스아마이드 및 이의 제제와 용도 | |
| JP5701608B2 (ja) | 有機化合物 | |
| DE60018037T2 (de) | Substituierte 2-aryl-3-(heteroaryl)-imidazo[1,2-alpha]pyrimidine und ihren verwandten arzneimittel und verfahren | |
| DE60008372T2 (de) | Pharmazeutisch aktive verbindungen | |
| DE69331888T2 (de) | Bicyclische Pyridinderivate, Verfahren zu ihrer Herstellung, Zwischenprodukte, ihre Anwendung als Arzneimittel und diese enthaltende pharmazeutische Zusammensetzungen | |
| DE602005004287T2 (de) | Pyrrazolopyrimidinderivate | |
| DE60315062T2 (de) | Triazolverbindungen zur behandlung von dysmenorrhoe | |
| EP3010909A1 (de) | Substituierte phenyl-2,3-benzodiazepine | |
| JP2000506537A (ja) | 新規なＮ―７―ヘテロサイクリル―ピロロ［２，３―ｄ］ピリミジンおよびこれらの使用 | |
| JP7048587B2 (ja) | 架橋ピペリジン誘導体 | |
| JP2006508970A (ja) | イミダゾ［１，５ａ］ピリジン誘導体およびアルデステロンにより仲介される疾患の処置方法 | |
| CN101605792A (zh) | 氮杂-异吲哚酮和它们作为亲代谢性谷氨酸受体增效剂-613的用途 | |
| MX2013008629A (es) | Inhibidores de histona desacetilasa y composiciones y metodos para su uso. | |
| JP2004512323A (ja) | Ｃｃｒ５ケモカイン受容体活性のピロリジンモジュレーター | |
| JPH0873439A (ja) | １−ベンジル−１，３−ジヒドロ−２ｈ−ベンズイミダゾール−２−オン誘導体、これらの調製およびこれらを含有する薬学的組成物 | |
| AU2017378316B2 (en) | Cyclopropyl fused thiazine derivatives as beta-secretase inhibitors and methods of use | |
| JP6956175B2 (ja) | 二環式ヘテロアリール誘導体 | |
| EP1071670B1 (de) | Diphenyl-substituierte 5-ring-heterocyclen, verfahren zu ihrer herstellung sowie deren verwendung als arzneimittel | |
| CN109689656B (zh) | 7-取代的1-芳基二氮杂萘-3-羧酰胺及其用途 | |
| WO2003057213A2 (en) | Cyclohexano- and cycloheptapyrazole derivative compounds, for use in diseases associated with the 5-ht2c receptor | |
| DE602004003914T2 (de) | Für die therapie geeignete triazolverbindungen | |
| EP3652157B1 (en) | 1,3-diaza-spiro-[3.4]-octane derivatives | |
| WO1998043976A1 (en) | Biphenyl derivatives and medicinal compositions |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8332 | No legal effect for de | ||
| 8370 | Indication related to discontinuation of the patent is to be deleted | ||
| 8364 | No opposition during term of opposition | ||
| 8328 | Change in the person/name/address of the agent |
Representative=s name: KROHER, STROBEL RECHTS- UND PATENTANWAELTE, 80336 |
|
| 8328 | Change in the person/name/address of the agent |
Representative=s name: DR. SCHOEN & PARTNER, 80336 MUENCHEN |