CA2351488C - Substituted 4-amino-2-arylcyclopenta[d]pyrimidines, their preparation, their use and pharmaceutical preparations comprising them - Google Patents
Substituted 4-amino-2-arylcyclopenta[d]pyrimidines, their preparation, their use and pharmaceutical preparations comprising them Download PDFInfo
- Publication number
- CA2351488C CA2351488C CA002351488A CA2351488A CA2351488C CA 2351488 C CA2351488 C CA 2351488C CA 002351488 A CA002351488 A CA 002351488A CA 2351488 A CA2351488 A CA 2351488A CA 2351488 C CA2351488 C CA 2351488C
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- substituted
- pyrimidine
- cyclopenta
- dihydro
- 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 - Fee Related
Links
- 239000000825 pharmaceutical preparation Substances 0.000 title claims abstract description 12
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 150000003230 pyrimidines Chemical class 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 91
- 238000011321 prophylaxis Methods 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 12
- 206010002383 Angina Pectoris Diseases 0.000 claims abstract description 5
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 5
- 206010020772 Hypertension Diseases 0.000 claims abstract description 5
- 208000007536 Thrombosis Diseases 0.000 claims abstract description 5
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 4
- 206010019280 Heart failures Diseases 0.000 claims abstract description 4
- -1 4-hydroxycyclohexyl Chemical group 0.000 claims description 89
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 69
- 125000001424 substituent group Chemical group 0.000 claims description 69
- 150000003839 salts Chemical class 0.000 claims description 51
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 40
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 28
- 125000000623 heterocyclic group Chemical group 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 25
- 102000007637 Soluble Guanylyl Cyclase Human genes 0.000 claims description 22
- 108010007205 Soluble Guanylyl Cyclase Proteins 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 19
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 125000001624 naphthyl group Chemical group 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
- 125000005842 heteroatom Chemical group 0.000 claims description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
- 238000002560 therapeutic procedure Methods 0.000 claims description 11
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 125000002950 monocyclic group Chemical group 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical group O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 4
- 125000002619 bicyclic group Chemical group 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- YFFIDZJIZDLWDB-WKILWMFISA-N C1=CC(C)=CC=C1C(N=C1N[C@@H]2CC[C@@H](O)CC2)=NC2=C1CCC2 Chemical compound C1=CC(C)=CC=C1C(N=C1N[C@@H]2CC[C@@H](O)CC2)=NC2=C1CCC2 YFFIDZJIZDLWDB-WKILWMFISA-N 0.000 claims description 3
- UYSQYXCWLRFPRE-SHTZXODSSA-N C1C[C@@H](O)CC[C@@H]1NC1=NC(C=2C=CC(Cl)=CC=2)=NC2=C1CCC2 Chemical compound C1C[C@@H](O)CC[C@@H]1NC1=NC(C=2C=CC(Cl)=CC=2)=NC2=C1CCC2 UYSQYXCWLRFPRE-SHTZXODSSA-N 0.000 claims description 3
- 206010048554 Endothelial dysfunction Diseases 0.000 claims description 3
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- 230000008694 endothelial dysfunction Effects 0.000 claims description 3
- 201000001881 impotence Diseases 0.000 claims description 3
- 208000010125 myocardial infarction Diseases 0.000 claims description 3
- WUFCJZLKDBWTBT-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-n-(3-methoxypropyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C=2CCCC=2C(NCCCOC)=NC=1C1=CC=C(OC)C(OC)=C1 WUFCJZLKDBWTBT-UHFFFAOYSA-N 0.000 claims description 2
- MDLRUXNZLBAKEZ-UHFFFAOYSA-N 2-(3,5-dichlorophenyl)-n-(pyridin-3-ylmethyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound ClC1=CC(Cl)=CC(C=2N=C(NCC=3C=NC=CC=3)C=3CCCC=3N=2)=C1 MDLRUXNZLBAKEZ-UHFFFAOYSA-N 0.000 claims description 2
- KNMVHYWDSWWOKN-UHFFFAOYSA-N 2-(3-chlorophenyl)-n-(pyridin-3-ylmethyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(C=2N=C(NCC=3C=NC=CC=3)C=3CCCC=3N=2)=C1 KNMVHYWDSWWOKN-UHFFFAOYSA-N 0.000 claims description 2
- XRTIEINWNWWLLV-UHFFFAOYSA-N 2-(3-chlorophenyl)-n-cyclopentyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(C=2N=C(NC3CCCC3)C=3CCCC=3N=2)=C1 XRTIEINWNWWLLV-UHFFFAOYSA-N 0.000 claims description 2
- WZWVYYXJHMVYNN-UHFFFAOYSA-N 2-(4-chlorophenyl)-n-(2-methylpropyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C=2CCCC=2C(NCC(C)C)=NC=1C1=CC=C(Cl)C=C1 WZWVYYXJHMVYNN-UHFFFAOYSA-N 0.000 claims description 2
- NDHSLSZOESUPPN-UHFFFAOYSA-N 2-(4-chlorophenyl)-n-cyclopentyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound C1=CC(Cl)=CC=C1C(N=C1NC2CCCC2)=NC2=C1CCC2 NDHSLSZOESUPPN-UHFFFAOYSA-N 0.000 claims description 2
- VNYUDZMBULFXAH-UHFFFAOYSA-N 2-[[2-(4-methylphenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]amino]ethanol Chemical compound C1=CC(C)=CC=C1C(N=C1NCCO)=NC2=C1CCC2 VNYUDZMBULFXAH-UHFFFAOYSA-N 0.000 claims description 2
- ASALTPIJADNPFQ-UHFFFAOYSA-N 3-[[2-(4-methoxyphenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]amino]propan-1-ol Chemical compound C1=CC(OC)=CC=C1C(N=C1NCCCO)=NC2=C1CCC2 ASALTPIJADNPFQ-UHFFFAOYSA-N 0.000 claims description 2
- LAXAXXLEFJERMU-UHFFFAOYSA-N 4-[4-(3-methoxypropylamino)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-2-yl]benzonitrile Chemical compound N=1C=2CCCC=2C(NCCCOC)=NC=1C1=CC=C(C#N)C=C1 LAXAXXLEFJERMU-UHFFFAOYSA-N 0.000 claims description 2
- JUTHAFDLHUNZBH-UHFFFAOYSA-N 4-[4-(benzylamino)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-2-yl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1C(N=C1NCC=2C=CC=CC=2)=NC2=C1CCC2 JUTHAFDLHUNZBH-UHFFFAOYSA-N 0.000 claims description 2
- JSNYFSFWTAUTFR-UHFFFAOYSA-N 4-[4-(pyridin-3-ylmethylamino)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-2-yl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1C(N=C1NCC=2C=NC=CC=2)=NC2=C1CCC2 JSNYFSFWTAUTFR-UHFFFAOYSA-N 0.000 claims description 2
- ISSVEEMYWVLUBE-UHFFFAOYSA-N 4-[[2-(3,5-dichlorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]amino]butan-1-ol Chemical compound N=1C=2CCCC=2C(NCCCCO)=NC=1C1=CC(Cl)=CC(Cl)=C1 ISSVEEMYWVLUBE-UHFFFAOYSA-N 0.000 claims description 2
- 206010052337 Diastolic dysfunction Diseases 0.000 claims description 2
- 208000011514 Familial renal glucosuria Diseases 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 208000020832 chronic kidney disease Diseases 0.000 claims description 2
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 2
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 2
- MEVSBTPHUHIQMQ-UHFFFAOYSA-N n-[2-(2-chlorophenyl)ethyl]-2-(4-methoxyphenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1C(N=C1NCCC=2C(=CC=CC=2)Cl)=NC2=C1CCC2 MEVSBTPHUHIQMQ-UHFFFAOYSA-N 0.000 claims description 2
- HXKXDHGVMNKZKN-UHFFFAOYSA-N n-butyl-2-(3,4-dimethoxyphenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C=2CCCC=2C(NCCCC)=NC=1C1=CC=C(OC)C(OC)=C1 HXKXDHGVMNKZKN-UHFFFAOYSA-N 0.000 claims description 2
- BMQFHIMGDYQPLP-UHFFFAOYSA-N n-butyl-2-(3,5-dichlorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C=2CCCC=2C(NCCCC)=NC=1C1=CC(Cl)=CC(Cl)=C1 BMQFHIMGDYQPLP-UHFFFAOYSA-N 0.000 claims description 2
- RMEBDWFOJDIDCG-UHFFFAOYSA-N n-butyl-2-(4-chlorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C=2CCCC=2C(NCCCC)=NC=1C1=CC=C(Cl)C=C1 RMEBDWFOJDIDCG-UHFFFAOYSA-N 0.000 claims description 2
- XBTOUXZSDWFOJV-UHFFFAOYSA-N n-butyl-2-(4-methoxyphenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C=2CCCC=2C(NCCCC)=NC=1C1=CC=C(OC)C=C1 XBTOUXZSDWFOJV-UHFFFAOYSA-N 0.000 claims description 2
- YLOXCZMZUXEPAK-UHFFFAOYSA-N n-butyl-2-(4-methylphenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C=2CCCC=2C(NCCCC)=NC=1C1=CC=C(C)C=C1 YLOXCZMZUXEPAK-UHFFFAOYSA-N 0.000 claims description 2
- XKNJKKXCPOGINE-UHFFFAOYSA-N n-cyclohexyl-2-(3,4-dimethoxyphenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound C1=C(OC)C(OC)=CC=C1C(N=C1NC2CCCCC2)=NC2=C1CCC2 XKNJKKXCPOGINE-UHFFFAOYSA-N 0.000 claims description 2
- AZVDCNKFNRCARM-UHFFFAOYSA-N n-cyclohexyl-2-(4-methoxyphenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1C(N=C1NC2CCCCC2)=NC2=C1CCC2 AZVDCNKFNRCARM-UHFFFAOYSA-N 0.000 claims description 2
- PPRZHPKKDVNLTJ-UHFFFAOYSA-N n-cyclohexyl-2-(4-methylphenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound C1=CC(C)=CC=C1C(N=C1NC2CCCCC2)=NC2=C1CCC2 PPRZHPKKDVNLTJ-UHFFFAOYSA-N 0.000 claims description 2
- MQXYGWJHOABDIK-UHFFFAOYSA-N n-cyclopentyl-2-(3,4-dimethoxyphenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound C1=C(OC)C(OC)=CC=C1C(N=C1NC2CCCC2)=NC2=C1CCC2 MQXYGWJHOABDIK-UHFFFAOYSA-N 0.000 claims description 2
- XOTUXHUSCXTYQE-UHFFFAOYSA-N n-cyclopentyl-2-(3,5-dichlorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound ClC1=CC(Cl)=CC(C=2N=C(NC3CCCC3)C=3CCCC=3N=2)=C1 XOTUXHUSCXTYQE-UHFFFAOYSA-N 0.000 claims description 2
- HHYMRWQLZNNEGY-UHFFFAOYSA-N n-cyclopentyl-2-(4-methoxyphenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1C(N=C1NC2CCCC2)=NC2=C1CCC2 HHYMRWQLZNNEGY-UHFFFAOYSA-N 0.000 claims description 2
- ZGRLBUXNONOKGU-UHFFFAOYSA-N n-cyclopentyl-2-(4-methylphenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound C1=CC(C)=CC=C1C(N=C1NC2CCCC2)=NC2=C1CCC2 ZGRLBUXNONOKGU-UHFFFAOYSA-N 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 2
- 208000007278 renal glycosuria Diseases 0.000 claims description 2
- 125000006763 (C3-C9) cycloalkyl group Chemical group 0.000 claims 9
- 125000005843 halogen group Chemical group 0.000 claims 3
- 150000002431 hydrogen Chemical class 0.000 claims 3
- YCGULRPNRQSLEY-SHTZXODSSA-N C1C[C@@H](O)CC[C@@H]1NC1=NC(C=2C=C(Cl)C=C(Cl)C=2)=NC2=C1CCC2 Chemical compound C1C[C@@H](O)CC[C@@H]1NC1=NC(C=2C=C(Cl)C=C(Cl)C=2)=NC2=C1CCC2 YCGULRPNRQSLEY-SHTZXODSSA-N 0.000 claims 2
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 claims 1
- PHUWLVRHWFFLJZ-UHFFFAOYSA-N 2-(3-chlorophenyl)-n-[2-(3-methoxyphenyl)ethyl]-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound COC1=CC=CC(CCNC=2C=3CCCC=3N=C(N=2)C=2C=C(Cl)C=CC=2)=C1 PHUWLVRHWFFLJZ-UHFFFAOYSA-N 0.000 claims 1
- KSPPZEBFPYJWBT-UHFFFAOYSA-N 2-(4-chlorophenyl)-n-(2-methoxyethyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C=2CCCC=2C(NCCOC)=NC=1C1=CC=C(Cl)C=C1 KSPPZEBFPYJWBT-UHFFFAOYSA-N 0.000 claims 1
- ISSNZDSDJWQCPL-UHFFFAOYSA-N 2-(4-chlorophenyl)-n-[2-(3-methoxyphenyl)ethyl]-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound COC1=CC=CC(CCNC=2C=3CCCC=3N=C(N=2)C=2C=CC(Cl)=CC=2)=C1 ISSNZDSDJWQCPL-UHFFFAOYSA-N 0.000 claims 1
- CGYLYGPMMOXDKO-UHFFFAOYSA-N 2-(4-methylphenyl)-n-(pyridin-3-ylmethyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound C1=CC(C)=CC=C1C(N=C1NCC=2C=NC=CC=2)=NC2=C1CCC2 CGYLYGPMMOXDKO-UHFFFAOYSA-N 0.000 claims 1
- 230000003213 activating effect Effects 0.000 claims 1
- 239000012190 activator Substances 0.000 claims 1
- ZOOGRGPOEVQQDX-KHLHZJAASA-N cyclic guanosine monophosphate Chemical compound C([C@H]1O2)O[P@](O)(=O)O[C@@H]1[C@H](O)[C@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-KHLHZJAASA-N 0.000 abstract description 26
- 201000010099 disease Diseases 0.000 abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 11
- 239000003814 drug Substances 0.000 abstract description 11
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 238000011282 treatment Methods 0.000 abstract description 6
- 239000013543 active substance Substances 0.000 abstract 1
- 230000001771 impaired effect Effects 0.000 abstract 1
- 150000003254 radicals Chemical class 0.000 description 38
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical group O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 12
- 239000000126 substance Substances 0.000 description 11
- 230000004913 activation Effects 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 230000000638 stimulation Effects 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 230000009471 action Effects 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 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 4
- 108010078321 Guanylate Cyclase Proteins 0.000 description 4
- 102000014469 Guanylate cyclase Human genes 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- 150000001409 amidines Chemical class 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- XKMLYUALXHKNFT-UUOKFMHZSA-N Guanosine-5'-triphosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XKMLYUALXHKNFT-UUOKFMHZSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000003795 chemical substances by application Substances 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
- 239000007903 gelatin capsule Substances 0.000 description 3
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- YNGQOTJHZOCSLT-UHFFFAOYSA-N 1,3-dihydrocyclopenta[d]pyrimidin-2-one Chemical compound N1C(O)=NC=C2C=CC=C21 YNGQOTJHZOCSLT-UHFFFAOYSA-N 0.000 description 2
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- RWJQVBUXAYSOCF-UHFFFAOYSA-N 4-(4-oxo-1,5,6,7-tetrahydrocyclopenta[d]pyrimidin-2-yl)benzamide Chemical compound C1=CC(C(=O)N)=CC=C1C(N=C1O)=NC2=C1CCC2 RWJQVBUXAYSOCF-UHFFFAOYSA-N 0.000 description 2
- RAFNPOPFXZECJN-UHFFFAOYSA-N 4-chloro-2-(3,5-dichlorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidine Chemical compound ClC1=CC(Cl)=CC(C=2N=C(Cl)C=3CCCC=3N=2)=C1 RAFNPOPFXZECJN-UHFFFAOYSA-N 0.000 description 2
- RENVKOKCEONDMA-UHFFFAOYSA-N 4-chloro-2-(4-chlorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidine Chemical compound C1=CC(Cl)=CC=C1C(N=C1Cl)=NC2=C1CCC2 RENVKOKCEONDMA-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-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
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 208000007718 Stable Angina Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 208000007814 Unstable Angina Diseases 0.000 description 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 2
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical compound [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 2
- AYLIEDQYYJIGDP-UHFFFAOYSA-N [C]1=CC=CS1 Chemical compound [C]1=CC=CS1 AYLIEDQYYJIGDP-UHFFFAOYSA-N 0.000 description 2
- FIULGFJIHJJXMT-UHFFFAOYSA-N [C]1[N]C=CC=C1 Chemical compound [C]1[N]C=CC=C1 FIULGFJIHJJXMT-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 150000005840 aryl radicals Chemical class 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 150000003278 haem Chemical class 0.000 description 2
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000007922 nasal spray Substances 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 150000002829 nitrogen Chemical class 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 238000010606 normalization Methods 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 2
- 230000010118 platelet activation Effects 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- RXAOGVQDNBYURA-UHFFFAOYSA-N (4-chlorobenzenecarboximidoyl)azanium;chloride Chemical compound Cl.NC(=N)C1=CC=C(Cl)C=C1 RXAOGVQDNBYURA-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- CRPTXKKKIGGDBX-UHFFFAOYSA-N (z)-but-2-ene Chemical compound [CH2]C=CC CRPTXKKKIGGDBX-UHFFFAOYSA-N 0.000 description 1
- 0 *c1nc(N(*)*)c(CCC2)c2n1 Chemical compound *c1nc(N(*)*)c(CCC2)c2n1 0.000 description 1
- KZKRRZFCAYOXQE-UHFFFAOYSA-N 1$l^{2}-azinane Chemical compound C1CC[N]CC1 KZKRRZFCAYOXQE-UHFFFAOYSA-N 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- HTJMXYRLEDBSLT-UHFFFAOYSA-N 1,2,4,5-tetrazine Chemical compound C1=NN=CN=N1 HTJMXYRLEDBSLT-UHFFFAOYSA-N 0.000 description 1
- FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 1
- LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 1
- JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 description 1
- ABADUMLIAZCWJD-UHFFFAOYSA-N 1,3-dioxole Chemical compound C1OC=CO1 ABADUMLIAZCWJD-UHFFFAOYSA-N 0.000 description 1
- JUYWDXUELATAOI-UHFFFAOYSA-N 1,3-oxazepine Chemical compound O1C=CC=CN=C1 JUYWDXUELATAOI-UHFFFAOYSA-N 0.000 description 1
- SIMIXFVGSWZJJV-UHFFFAOYSA-N 1,3-thiazepine Chemical compound S1C=CC=CN=C1 SIMIXFVGSWZJJV-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- KVGZZAHHUNAVKZ-UHFFFAOYSA-N 1,4-Dioxin Chemical compound O1C=COC=C1 KVGZZAHHUNAVKZ-UHFFFAOYSA-N 0.000 description 1
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- POXWDTQUDZUOGP-UHFFFAOYSA-N 1h-1,4-diazepine Chemical compound N1C=CC=NC=C1 POXWDTQUDZUOGP-UHFFFAOYSA-N 0.000 description 1
- NPULTOPKCMEZGG-UHFFFAOYSA-N 1h-cyclopenta[d]pyrimidin-4-ol Chemical compound N1=CNC2=CC=CC2=C1O NPULTOPKCMEZGG-UHFFFAOYSA-N 0.000 description 1
- LTFBFZBWUKWXID-UHFFFAOYSA-N 1h-cyclopenta[d]pyrimidine Chemical class N1=CNC2=CC=CC2=C1 LTFBFZBWUKWXID-UHFFFAOYSA-N 0.000 description 1
- NFEZOYIKZXDOAJ-UHFFFAOYSA-N 2,4-bis(trifluoromethyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine;hydrochloride Chemical compound Cl.C1NCCC2=C1N=C(C(F)(F)F)N=C2C(F)(F)F NFEZOYIKZXDOAJ-UHFFFAOYSA-N 0.000 description 1
- BPIRPBAWOOYVCF-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-1,5,6,7-tetrahydrocyclopenta[d]pyrimidin-4-one Chemical compound C1=C(OC)C(OC)=CC=C1C(N=C1O)=NC2=C1CCC2 BPIRPBAWOOYVCF-UHFFFAOYSA-N 0.000 description 1
- FQMZSCOGPBCPEE-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-n,n-dipropyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C=2CCCC=2C(N(CCC)CCC)=NC=1C1=CC=C(OC)C(OC)=C1 FQMZSCOGPBCPEE-UHFFFAOYSA-N 0.000 description 1
- BGTLRFAIWJMSNT-UHFFFAOYSA-N 2-(3,5-dichlorophenyl)-1,5,6,7-tetrahydrocyclopenta[d]pyrimidin-4-one Chemical compound N=1C=2CCCC=2C(O)=NC=1C1=CC(Cl)=CC(Cl)=C1 BGTLRFAIWJMSNT-UHFFFAOYSA-N 0.000 description 1
- OHWKZLXJLCCRPR-UHFFFAOYSA-N 2-(3,5-dichlorophenyl)-4-piperidin-1-yl-6,7-dihydro-5h-cyclopenta[d]pyrimidine Chemical compound ClC1=CC(Cl)=CC(C=2N=C(C=3CCCC=3N=2)N2CCCCC2)=C1 OHWKZLXJLCCRPR-UHFFFAOYSA-N 0.000 description 1
- BMMWEYFISHCLAI-UHFFFAOYSA-N 2-(3,5-dichlorophenyl)-n,n-dipropyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C=2CCCC=2C(N(CCC)CCC)=NC=1C1=CC(Cl)=CC(Cl)=C1 BMMWEYFISHCLAI-UHFFFAOYSA-N 0.000 description 1
- BEVYZRJHFFNZBW-UHFFFAOYSA-N 2-(3-chlorophenyl)-1,5,6,7-tetrahydrocyclopenta[d]pyrimidin-4-one Chemical compound N=1C=2CCCC=2C(O)=NC=1C1=CC=CC(Cl)=C1 BEVYZRJHFFNZBW-UHFFFAOYSA-N 0.000 description 1
- PHQSYFJNXUDQFB-UHFFFAOYSA-N 2-(3-chlorophenyl)-4-pyrrolidin-1-yl-6,7-dihydro-5h-cyclopenta[d]pyrimidine Chemical compound ClC1=CC=CC(C=2N=C(C=3CCCC=3N=2)N2CCCC2)=C1 PHQSYFJNXUDQFB-UHFFFAOYSA-N 0.000 description 1
- PGXLZGYMYIJTMK-UHFFFAOYSA-N 2-(3-chlorophenyl)-n,n-diethyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.N=1C=2CCCC=2C(N(CC)CC)=NC=1C1=CC=CC(Cl)=C1 PGXLZGYMYIJTMK-UHFFFAOYSA-N 0.000 description 1
- FZNRUOUCTOVNNQ-UHFFFAOYSA-N 2-(3-chlorophenyl)-n-(2,2,6,6-tetramethylpiperidin-4-yl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(C=2C=C(Cl)C=CC=2)=NC2=C1CCC2 FZNRUOUCTOVNNQ-UHFFFAOYSA-N 0.000 description 1
- KAHLZBRYVBIJBZ-UHFFFAOYSA-N 2-(3-chlorophenyl)-n-[2-(3-methoxyphenyl)ethyl]-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.COC1=CC=CC(CCNC=2C=3CCCC=3N=C(N=2)C=2C=C(Cl)C=CC=2)=C1 KAHLZBRYVBIJBZ-UHFFFAOYSA-N 0.000 description 1
- DEBMGALIVVKFNL-UHFFFAOYSA-N 2-(4-chlorophenyl)-1,5,6,7-tetrahydrocyclopenta[d]pyrimidin-4-one Chemical compound N=1C=2CCCC=2C(O)=NC=1C1=CC=C(Cl)C=C1 DEBMGALIVVKFNL-UHFFFAOYSA-N 0.000 description 1
- YPQBOYHGAIAPCN-UHFFFAOYSA-N 2-(4-chlorophenyl)-n,n-dipropyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C=2CCCC=2C(N(CCC)CCC)=NC=1C1=CC=C(Cl)C=C1 YPQBOYHGAIAPCN-UHFFFAOYSA-N 0.000 description 1
- AUHNZVAMELYTCO-UHFFFAOYSA-N 2-(4-chlorophenyl)-n-(2-methoxyethyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.N=1C=2CCCC=2C(NCCOC)=NC=1C1=CC=C(Cl)C=C1 AUHNZVAMELYTCO-UHFFFAOYSA-N 0.000 description 1
- WUVABPFJWBDSNL-UHFFFAOYSA-N 2-(4-chlorophenyl)-n-[2-(3-methoxyphenyl)ethyl]-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.COC1=CC=CC(CCNC=2C=3CCCC=3N=C(N=2)C=2C=CC(Cl)=CC=2)=C1 WUVABPFJWBDSNL-UHFFFAOYSA-N 0.000 description 1
- HVAGQCGMYPRMCE-UHFFFAOYSA-N 2-(4-methoxyphenyl)-n,n-dipropyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C=2CCCC=2C(N(CCC)CCC)=NC=1C1=CC=C(OC)C=C1 HVAGQCGMYPRMCE-UHFFFAOYSA-N 0.000 description 1
- OHMNXVUHKFUNHH-UHFFFAOYSA-N 2-(4-methylphenyl)-1,5,6,7-tetrahydrocyclopenta[d]pyrimidin-4-one Chemical compound C1=CC(C)=CC=C1C(N=C1O)=NC2=C1CCC2 OHMNXVUHKFUNHH-UHFFFAOYSA-N 0.000 description 1
- CZIJSOUMZAUBHO-UHFFFAOYSA-N 2-(4-methylphenyl)-4-pyrrolidin-1-yl-6,7-dihydro-5h-cyclopenta[d]pyrimidine Chemical compound C1=CC(C)=CC=C1C(N=C1N2CCCC2)=NC2=C1CCC2 CZIJSOUMZAUBHO-UHFFFAOYSA-N 0.000 description 1
- LDLHAMRLNJYYHK-UHFFFAOYSA-N 2-(4-methylphenyl)-n,n-dipropyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C=2CCCC=2C(N(CCC)CCC)=NC=1C1=CC=C(C)C=C1 LDLHAMRLNJYYHK-UHFFFAOYSA-N 0.000 description 1
- OXQGTIUCKGYOAA-UHFFFAOYSA-N 2-Ethylbutanoic acid Chemical compound CCC(CC)C(O)=O OXQGTIUCKGYOAA-UHFFFAOYSA-N 0.000 description 1
- QZZZIWCTHRRLHS-UHFFFAOYSA-N 2-[[2-(3-chlorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]amino]ethanol Chemical compound N=1C=2CCCC=2C(NCCO)=NC=1C1=CC=CC(Cl)=C1 QZZZIWCTHRRLHS-UHFFFAOYSA-N 0.000 description 1
- SAQGBDRYBGEFIG-UHFFFAOYSA-N 2-[[2-(4-chlorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]amino]ethanol Chemical compound N=1C=2CCCC=2C(NCCO)=NC=1C1=CC=C(Cl)C=C1 SAQGBDRYBGEFIG-UHFFFAOYSA-N 0.000 description 1
- GLVYLTSKTCWWJR-UHFFFAOYSA-N 2-carbonoperoxoylbenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1C(O)=O GLVYLTSKTCWWJR-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- MSRJJSCOWHWGGX-UHFFFAOYSA-N 2h-1,3-diazepine Chemical compound C1N=CC=CC=N1 MSRJJSCOWHWGGX-UHFFFAOYSA-N 0.000 description 1
- KGWNRZLPXLBMPS-UHFFFAOYSA-N 2h-1,3-oxazine Chemical compound C1OC=CC=N1 KGWNRZLPXLBMPS-UHFFFAOYSA-N 0.000 description 1
- NTYABNDBNKVWOO-UHFFFAOYSA-N 2h-1,3-thiazine Chemical compound C1SC=CC=N1 NTYABNDBNKVWOO-UHFFFAOYSA-N 0.000 description 1
- YHWMFDLNZGIJSD-UHFFFAOYSA-N 2h-1,4-oxazine Chemical compound C1OC=CN=C1 YHWMFDLNZGIJSD-UHFFFAOYSA-N 0.000 description 1
- ZAISDHPZTZIFQF-UHFFFAOYSA-N 2h-1,4-thiazine Chemical compound C1SC=CN=C1 ZAISDHPZTZIFQF-UHFFFAOYSA-N 0.000 description 1
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- XQJFSRYBSBZTRX-UHFFFAOYSA-N 4-(4-chloro-6,7-dihydro-5h-cyclopenta[d]pyrimidin-2-yl)benzonitrile Chemical compound N=1C=2CCCC=2C(Cl)=NC=1C1=CC=C(C#N)C=C1 XQJFSRYBSBZTRX-UHFFFAOYSA-N 0.000 description 1
- WLFGAKKAGKFIDC-UHFFFAOYSA-N 4-(4-morpholin-4-yl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-2-yl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1C(N=C1N2CCOCC2)=NC2=C1CCC2 WLFGAKKAGKFIDC-UHFFFAOYSA-N 0.000 description 1
- LYNJGGUWZYHZCS-UHFFFAOYSA-N 4-(4-piperidin-1-yl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-2-yl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1C(N=C1N2CCCCC2)=NC2=C1CCC2 LYNJGGUWZYHZCS-UHFFFAOYSA-N 0.000 description 1
- IERYPIRDVQUALW-UHFFFAOYSA-N 4-(azepan-1-yl)-2-(3-chlorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidine;hydrochloride Chemical compound Cl.ClC1=CC=CC(C=2N=C(C=3CCCC=3N=2)N2CCCCCC2)=C1 IERYPIRDVQUALW-UHFFFAOYSA-N 0.000 description 1
- MSGPLXICXJOIQT-UHFFFAOYSA-N 4-(azepan-1-yl)-2-(4-methoxyphenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidine Chemical compound C1=CC(OC)=CC=C1C(N=C1N2CCCCCC2)=NC2=C1CCC2 MSGPLXICXJOIQT-UHFFFAOYSA-N 0.000 description 1
- XFMQAKHLNXCHBR-UHFFFAOYSA-N 4-[2-(3,4-dimethoxyphenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]-2,6-dimethylmorpholine Chemical compound C1=C(OC)C(OC)=CC=C1C(N=C1N2CC(C)OC(C)C2)=NC2=C1CCC2 XFMQAKHLNXCHBR-UHFFFAOYSA-N 0.000 description 1
- VBBNHCLZUHIACP-UHFFFAOYSA-N 4-[2-(3-chlorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]morpholine Chemical compound ClC1=CC=CC(C=2N=C(C=3CCCC=3N=2)N2CCOCC2)=C1 VBBNHCLZUHIACP-UHFFFAOYSA-N 0.000 description 1
- VJPOPMMOFYJMFI-UHFFFAOYSA-N 4-[2-(3-chlorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]thiomorpholine Chemical compound ClC1=CC=CC(C=2N=C(C=3CCCC=3N=2)N2CCSCC2)=C1 VJPOPMMOFYJMFI-UHFFFAOYSA-N 0.000 description 1
- CSJWINZHHVTCEL-UHFFFAOYSA-N 4-[2-(4-chlorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]thiomorpholine Chemical compound C1=CC(Cl)=CC=C1C(N=C1N2CCSCC2)=NC2=C1CCC2 CSJWINZHHVTCEL-UHFFFAOYSA-N 0.000 description 1
- DMLJKDKTFOIQNC-UHFFFAOYSA-N 4-[2-(4-methoxyphenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]morpholine Chemical compound C1=CC(OC)=CC=C1C(N=C1N2CCOCC2)=NC2=C1CCC2 DMLJKDKTFOIQNC-UHFFFAOYSA-N 0.000 description 1
- UGCWHGZDATVJKM-UHFFFAOYSA-N 4-[2-(4-methylphenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]thiomorpholine Chemical compound C1=CC(C)=CC=C1C(N=C1N2CCSCC2)=NC2=C1CCC2 UGCWHGZDATVJKM-UHFFFAOYSA-N 0.000 description 1
- QQFNWDMODQUPIP-UHFFFAOYSA-N 4-[4-(diethylamino)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-2-yl]benzonitrile Chemical compound N=1C=2CCCC=2C(N(CC)CC)=NC=1C1=CC=C(C#N)C=C1 QQFNWDMODQUPIP-UHFFFAOYSA-N 0.000 description 1
- RKTQEVMZBCBOSB-UHFFFAOYSA-N 4-aminocyclohexan-1-ol;hydron;chloride Chemical compound Cl.NC1CCC(O)CC1 RKTQEVMZBCBOSB-UHFFFAOYSA-N 0.000 description 1
- PSZQIUNRGLXOHO-UHFFFAOYSA-N 4-chloro-2-(3,4-dimethoxyphenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidine Chemical compound C1=C(OC)C(OC)=CC=C1C(N=C1Cl)=NC2=C1CCC2 PSZQIUNRGLXOHO-UHFFFAOYSA-N 0.000 description 1
- DINPDNYECZHUBO-UHFFFAOYSA-N 4-chloro-2-(3-chlorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidine Chemical compound ClC1=CC=CC(C=2N=C(Cl)C=3CCCC=3N=2)=C1 DINPDNYECZHUBO-UHFFFAOYSA-N 0.000 description 1
- CBDCXGHPYNIGFE-UHFFFAOYSA-N 4-chloro-2-(4-methoxyphenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidine Chemical compound C1=CC(OC)=CC=C1C(N=C1Cl)=NC2=C1CCC2 CBDCXGHPYNIGFE-UHFFFAOYSA-N 0.000 description 1
- BHGRLNAAQVHUHS-UHFFFAOYSA-N 4-chloro-2-(4-methylphenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidine Chemical compound C1=CC(C)=CC=C1C(N=C1Cl)=NC2=C1CCC2 BHGRLNAAQVHUHS-UHFFFAOYSA-N 0.000 description 1
- VNWDSIFDOVILCV-UHFFFAOYSA-N 4-chloro-3h-cyclopenta[d]pyrimidine Chemical compound N1=CNC2=CC=CC2=C1Cl VNWDSIFDOVILCV-UHFFFAOYSA-N 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- 102000002723 Atrial Natriuretic Factor Human genes 0.000 description 1
- 101800001288 Atrial natriuretic factor Proteins 0.000 description 1
- 101800001890 Atrial natriuretic peptide Proteins 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- KSFOVUSSGSKXFI-GAQDCDSVSA-N CC1=C/2NC(\C=C3/N=C(/C=C4\N\C(=C/C5=N/C(=C\2)/C(C=C)=C5C)C(C=C)=C4C)C(C)=C3CCC(O)=O)=C1CCC(O)=O Chemical compound CC1=C/2NC(\C=C3/N=C(/C=C4\N\C(=C/C5=N/C(=C\2)/C(C=C)=C5C)C(C=C)=C4C)C(C)=C3CCC(O)=O)=C1CCC(O)=O KSFOVUSSGSKXFI-GAQDCDSVSA-N 0.000 description 1
- OPVUZHYUVBJDFQ-ZGTDKVADSA-N CS(O)(=O)=O.C1C[C@@H](O)CC[C@@H]1NC1=NC(C=2C=C(Cl)C=C(Cl)C=2)=NC2=C1CCC2 Chemical compound CS(O)(=O)=O.C1C[C@@H](O)CC[C@@H]1NC1=NC(C=2C=C(Cl)C=C(Cl)C=2)=NC2=C1CCC2 OPVUZHYUVBJDFQ-ZGTDKVADSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 108010003591 Cyclic GMP-Dependent Protein Kinases Proteins 0.000 description 1
- 102000004654 Cyclic GMP-Dependent Protein Kinases Human genes 0.000 description 1
- 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 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 229940121891 Dopamine receptor antagonist Drugs 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
- 238000011891 EIA kit Methods 0.000 description 1
- 102000004300 GABA-A Receptors Human genes 0.000 description 1
- 108090000839 GABA-A Receptors Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 108010089792 Hemeproteins Proteins 0.000 description 1
- 102000008015 Hemeproteins Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 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 1
- 241000270322 Lepidosauria Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 108020001621 Natriuretic Peptide Proteins 0.000 description 1
- 102000004571 Natriuretic peptide Human genes 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 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
- 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 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- RMRFFCXPLWYOOY-UHFFFAOYSA-N allyl radical Chemical compound [CH2]C=C RMRFFCXPLWYOOY-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000000909 amidinium group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000005122 aminoalkylamino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000003262 carboxylic acid ester group Chemical group [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- NSQLIUXCMFBZME-MPVJKSABSA-N carperitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 NSQLIUXCMFBZME-MPVJKSABSA-N 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000017455 cell-cell adhesion Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 125000006547 cyclononyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- RQFCJASXJCIDSX-UUOKFMHZSA-N guanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O RQFCJASXJCIDSX-UUOKFMHZSA-N 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000008282 halocarbons Chemical class 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
- 239000000833 heterodimer Substances 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
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 125000003453 indazolyl group Chemical class N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000023404 leukocyte cell-cell adhesion Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- PZBBESSUKAHBHD-UHFFFAOYSA-N methyl 2-oxocyclopentane-1-carboxylate Chemical compound COC(=O)C1CCCC1=O PZBBESSUKAHBHD-UHFFFAOYSA-N 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- PMPOELUYAFWYBN-UHFFFAOYSA-N n-butyl-2-(3-chlorophenyl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-amine Chemical compound N=1C=2CCCC=2C(NCCCC)=NC=1C1=CC=CC(Cl)=C1 PMPOELUYAFWYBN-UHFFFAOYSA-N 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical class C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- 150000005054 naphthyridines Chemical class 0.000 description 1
- 239000000692 natriuretic peptide Substances 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 230000006715 negative regulation of smooth muscle cell proliferation Effects 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910017604 nitric acid Inorganic materials 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
- 239000002674 ointment Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229940082615 organic nitrates used in cardiac disease Drugs 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229950000688 phenothiazine Drugs 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000003375 plant hormone Substances 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 125000004585 polycyclic heterocycle group Chemical group 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229950003776 protoporphyrin Drugs 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical class [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000004648 relaxation of smooth muscle Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940121356 serotonin receptor antagonist Drugs 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229940127296 soluble guanylate cyclase stimulator Drugs 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000000101 thioether group Chemical group 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 description 1
- 125000000464 thioxo group Chemical group S=* 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- ORGHESHFQPYLAO-UHFFFAOYSA-N vinyl radical Chemical compound C=[CH] ORGHESHFQPYLAO-UHFFFAOYSA-N 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Pulmonology (AREA)
- Endocrinology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Obesity (AREA)
- Vascular Medicine (AREA)
- Hematology (AREA)
- Psychiatry (AREA)
- Emergency Medicine (AREA)
- Gynecology & Obstetrics (AREA)
- Reproductive Health (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19853278A DE19853278A1 (de) | 1998-11-19 | 1998-11-19 | Substituierte 4-Amino-2-aryl-cyclopenta[d]pyrimidine, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
| DE19853278.4 | 1998-11-19 | ||
| PCT/EP1999/008382 WO2000031047A1 (de) | 1998-11-19 | 1999-11-03 | Substituierte 4-amino-2-aryl-cyclopenta[d]pyrimidine, ihre herstellung, ihre verwendung und sie enthaltende pharmazeutische präparate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2351488A1 CA2351488A1 (en) | 2000-06-02 |
| CA2351488C true CA2351488C (en) | 2009-12-29 |
Family
ID=7888276
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002351488A Expired - Fee Related CA2351488C (en) | 1998-11-19 | 1999-11-03 | Substituted 4-amino-2-arylcyclopenta[d]pyrimidines, their preparation, their use and pharmaceutical preparations comprising them |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US6627628B1 (https=) |
| EP (1) | EP1131302B1 (https=) |
| JP (1) | JP4695262B2 (https=) |
| AT (1) | ATE316964T1 (https=) |
| AU (1) | AU1159400A (https=) |
| CA (1) | CA2351488C (https=) |
| DE (2) | DE19853278A1 (https=) |
| ES (1) | ES2257103T3 (https=) |
| PT (1) | PT1131302E (https=) |
| WO (1) | WO2000031047A1 (https=) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19853278A1 (de) * | 1998-11-19 | 2000-05-25 | Aventis Pharma Gmbh | Substituierte 4-Amino-2-aryl-cyclopenta[d]pyrimidine, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
| DE19904710A1 (de) | 1999-02-05 | 2000-08-10 | Aventis Pharma Gmbh | Substituierte 4-Amino-2-aryl-tetrahydrochinazoline, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
| US7031977B2 (en) * | 2002-02-28 | 2006-04-18 | Plumtree Software, Inc. | Efficiently storing indented threads in a threaded discussion application |
| WO2004052862A1 (ja) * | 2002-12-10 | 2004-06-24 | Ono Pharmaceutical Co., Ltd. | 含窒素複素環化合物およびその医薬用途 |
| ZA200601859B (en) * | 2003-08-05 | 2008-03-26 | Vertex Pharma | Condensed pyrimidine compounds as inhibitors of voltagegated ion channels |
| CA2545422C (en) | 2003-12-03 | 2015-06-02 | Cytopia Research Pty Ltd | Tubulin inhibitors |
| TW200621257A (en) * | 2004-10-20 | 2006-07-01 | Astellas Pharma Inc | Pyrimidine derivative fused with nonaromatic ring |
| ATE532789T1 (de) | 2006-07-06 | 2011-11-15 | Array Biopharma Inc | Dihydrothienopyrimidine als akt-proteinkinase- inhibitoren |
| US8329701B2 (en) | 2006-07-06 | 2012-12-11 | Array Biopharma Inc. | Dihydrofuro pyrimidines as AKT protein kinase inhibitors |
| US8063050B2 (en) * | 2006-07-06 | 2011-11-22 | Array Biopharma Inc. | Hydroxylated and methoxylated pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
| EP2049500B1 (en) * | 2006-07-06 | 2011-09-07 | Array Biopharma, Inc. | Cyclopenta [d] pyrimidines as akt protein kinase inhibitors |
| US9409886B2 (en) | 2007-07-05 | 2016-08-09 | Array Biopharma Inc. | Pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
| CN101918373B (zh) * | 2007-07-05 | 2013-06-05 | 阵列生物制药公司 | 作为akt蛋白激酶抑制剂的嘧啶基环戊烷 |
| CN103396409B (zh) | 2007-07-05 | 2015-03-11 | 阵列生物制药公司 | 作为akt蛋白激酶抑制剂的嘧啶基环戊烷 |
| US8846683B2 (en) | 2007-07-05 | 2014-09-30 | Array Biopharma, Inc. | Pyrimidyl cyclopentanes as Akt protein kinase inhibitors |
| US8841304B2 (en) | 2008-01-08 | 2014-09-23 | Array Biopharma, Inc. | Pyrrolopyridines as kinase inhibitors |
| US8853216B2 (en) | 2008-01-09 | 2014-10-07 | Array Biopharma, Inc. | Hydroxylated pyrimidyl cyclopentane as AKT protein kinase inhibitor |
| NZ586346A (en) * | 2008-01-09 | 2012-02-24 | Array Biopharma Inc | Hydroxylated pyrimidyl cyclopentanes as akt protein kinase inhibitors |
| CN101965347B (zh) | 2008-01-09 | 2013-01-02 | 阵列生物制药公司 | 作为激酶抑制剂的吡唑并吡啶 |
| KR102021157B1 (ko) | 2011-04-01 | 2019-09-11 | 제넨테크, 인크. | Ａｋｔ 억제제 화합물 및 아비라테론의 조합물, 및 사용 방법 |
| TR201815685T4 (tr) | 2011-04-01 | 2018-11-21 | Genentech Inc | Kanser tedavisi için akt ve mek inhibe edici bileşiklerin kombinasyonları. |
| CA2896731A1 (en) | 2012-12-28 | 2014-07-03 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Inhibitors of the usp1/uaf1 deubiquitinase complex and uses thereof |
| EP4142732B1 (en) * | 2020-04-28 | 2026-04-22 | Global Blood Therapeutics, Inc. | Methods of use for pyrimidines as ferroportin inhibitors |
| EP4011873A1 (en) | 2020-12-10 | 2022-06-15 | Bayer Aktiengesellschaft | Substituted pyrazolo piperidine carboxylic acids |
| CN113880859B (zh) * | 2021-11-16 | 2022-06-21 | 江西科技师范大学 | 2-芳基-4-芳甲胺基嘧啶类化合物及其应用 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3346452A (en) | 1963-08-19 | 1967-10-10 | Ciba Geigy Corp | 5, 6-lower alkylene-pyrimidines |
| DE4029654A1 (de) * | 1990-09-19 | 1992-04-02 | Hoechst Ag | 2-phenyl-pyrimidine, verfahren zu ihrer herstellung, sie enthaltende mittel und ihre verwendung als fungizide |
| JP2928079B2 (ja) | 1994-02-14 | 1999-07-28 | 永信薬品工業股▲ふん▼有限公司 | １−（置換ベンジル）−３−（置換アリール）縮合ピラゾール類、その製造法及びその用途 |
| JPH07228573A (ja) * | 1994-02-16 | 1995-08-29 | Dainippon Pharmaceut Co Ltd | ２−フェニルシクロアルカノピリミジン誘導体 |
| IL117659A (en) | 1995-04-13 | 2000-12-06 | Dainippon Pharmaceutical Co | Substituted 2-phenyl pyrimidino amino acetamide derivative process for preparing the same and a pharmaceutical composition containing same |
| JP3531169B2 (ja) | 1996-06-11 | 2004-05-24 | 三菱ウェルファーマ株式会社 | 縮合ヘテロ環化合物およびその医薬用途 |
| DE19642255A1 (de) | 1996-10-14 | 1998-04-16 | Bayer Ag | Verwendung von 1-Benzyl-3-(substituierten-hetaryl) -kondensierten Pyrazol-Derivaten |
| IL129416A0 (en) | 1996-10-14 | 2000-02-17 | Bayer Ag | New heterocyclylmethyl-substituted pyrazol derivatives |
| DE19836697A1 (de) | 1998-08-13 | 2000-02-17 | Hoechst Marion Roussel De Gmbh | Substituierte 4-Amino-2-aryl-pyrimidine, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
| DE19853278A1 (de) * | 1998-11-19 | 2000-05-25 | Aventis Pharma Gmbh | Substituierte 4-Amino-2-aryl-cyclopenta[d]pyrimidine, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
-
1998
- 1998-11-19 DE DE19853278A patent/DE19853278A1/de not_active Withdrawn
-
1999
- 1999-11-03 DE DE59913103T patent/DE59913103D1/de not_active Expired - Lifetime
- 1999-11-03 AU AU11594/00A patent/AU1159400A/en not_active Abandoned
- 1999-11-03 AT AT99972626T patent/ATE316964T1/de active
- 1999-11-03 US US09/856,069 patent/US6627628B1/en not_active Expired - Lifetime
- 1999-11-03 EP EP99972626A patent/EP1131302B1/de not_active Expired - Lifetime
- 1999-11-03 JP JP2000583875A patent/JP4695262B2/ja not_active Expired - Fee Related
- 1999-11-03 CA CA002351488A patent/CA2351488C/en not_active Expired - Fee Related
- 1999-11-03 ES ES99972626T patent/ES2257103T3/es not_active Expired - Lifetime
- 1999-11-03 WO PCT/EP1999/008382 patent/WO2000031047A1/de not_active Ceased
- 1999-11-03 PT PT99972626T patent/PT1131302E/pt unknown
-
2003
- 2003-09-12 US US10/660,489 patent/US7138398B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| WO2000031047A1 (de) | 2000-06-02 |
| PT1131302E (pt) | 2006-05-31 |
| ES2257103T3 (es) | 2006-07-16 |
| CA2351488A1 (en) | 2000-06-02 |
| DE59913103D1 (de) | 2006-04-13 |
| US7138398B2 (en) | 2006-11-21 |
| US20040048850A1 (en) | 2004-03-11 |
| EP1131302A1 (de) | 2001-09-12 |
| US6627628B1 (en) | 2003-09-30 |
| JP2002530385A (ja) | 2002-09-17 |
| DE19853278A1 (de) | 2000-05-25 |
| JP4695262B2 (ja) | 2011-06-08 |
| AU1159400A (en) | 2000-06-13 |
| EP1131302B1 (de) | 2006-02-01 |
| ATE316964T1 (de) | 2006-02-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2351488C (en) | Substituted 4-amino-2-arylcyclopenta[d]pyrimidines, their preparation, their use and pharmaceutical preparations comprising them | |
| CA2340405C (en) | Substituted 4-amino-2-aryl-pyrimidines, their production and use and pharmaceutical preparations containing same | |
| US6613772B1 (en) | Substituted 2-aryl-4-amino-chinazolines, method for the production and use thereof as medicaments | |
| RU2234497C2 (ru) | Серозамещенные n-ариламиды сульфониламинокарбоновой кислоты, способ их получения (варианты), фармацевтическая композиция и способ лечения | |
| EP1150963B1 (en) | Substituted 4-amino-2-aryltetrahydroquinazolines, their preparation, their use and pharmaceutical compositions comprising them | |
| RU2378267C2 (ru) | Новые пиримидинамидные производные и их применение | |
| NO327755B1 (no) | Svovelsubstituerte sulfonylaminokarboksylsyre N-arylamider, deres fremstilling og anvendelse samt farmasoytiske preparater inneholdende forbindelsene | |
| US6809089B2 (en) | Sulfonylaminocarboxylic acid N-arylamides as guanylate cyclase activators | |
| MXPA01001411A (en) | Substituted 4-amino-2-aryl-pyrimidines, their production and use and pharmaceutical preparations containing same | |
| MXPA00012966A (es) | N-arilamidas de acido sulfonilaminocarboxilico con sustitucion de azufre, su preparacion, su uso y preparaciones farmaceuticas que las contienen |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20161103 |