TW200808321A - Certain chemical entities, compositions and methods - Google Patents
Certain chemical entities, compositions and methods Download PDFInfo
- Publication number
- TW200808321A TW200808321A TW095146918A TW95146918A TW200808321A TW 200808321 A TW200808321 A TW 200808321A TW 095146918 A TW095146918 A TW 095146918A TW 95146918 A TW95146918 A TW 95146918A TW 200808321 A TW200808321 A TW 200808321A
- Authority
- TW
- Taiwan
- Prior art keywords
- methyl
- amino
- phenyl
- fluoro
- optionally substituted
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims description 95
- 238000000034 method Methods 0.000 title claims description 47
- 150000005829 chemical entities Chemical class 0.000 title 1
- 206010019280 Heart failures Diseases 0.000 claims abstract description 26
- 206010007559 Cardiac failure congestive Diseases 0.000 claims abstract description 20
- 238000011282 treatment Methods 0.000 claims abstract description 18
- 230000000747 cardiac effect Effects 0.000 claims abstract description 11
- 208000008253 Systolic Heart Failure Diseases 0.000 claims abstract 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 729
- -1 cyano, hydroxy Chemical group 0.000 claims description 708
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 519
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 209
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 197
- 125000000217 alkyl group Chemical group 0.000 claims description 171
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 163
- 229910052739 hydrogen Inorganic materials 0.000 claims description 133
- 239000001257 hydrogen Substances 0.000 claims description 133
- 125000001072 heteroaryl group Chemical group 0.000 claims description 86
- 150000001875 compounds Chemical class 0.000 claims description 85
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 84
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 76
- 239000002253 acid Substances 0.000 claims description 68
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 65
- 239000000126 substance Substances 0.000 claims description 61
- 125000004076 pyridyl group Chemical group 0.000 claims description 59
- 125000003386 piperidinyl group Chemical group 0.000 claims description 55
- 125000001041 indolyl group Chemical group 0.000 claims description 54
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 claims description 54
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 52
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 51
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 48
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 48
- 125000001153 fluoro group Chemical group F* 0.000 claims description 47
- 125000005843 halogen group Chemical group 0.000 claims description 47
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 46
- 125000003118 aryl group Chemical group 0.000 claims description 44
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 43
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 42
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 41
- MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 claims description 41
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 41
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 41
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 40
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 39
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 38
- 150000001412 amines Chemical class 0.000 claims description 34
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 34
- 210000002216 heart Anatomy 0.000 claims description 33
- 150000004702 methyl esters Chemical class 0.000 claims description 31
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 31
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 30
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 30
- VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 claims description 29
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 28
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 27
- 239000004202 carbamide Substances 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 27
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 26
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 25
- 125000003107 substituted aryl group Chemical group 0.000 claims description 25
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 24
- 125000003277 amino group Chemical group 0.000 claims description 24
- 235000013877 carbamide Nutrition 0.000 claims description 22
- 239000007789 gas Substances 0.000 claims description 22
- 239000000052 vinegar Substances 0.000 claims description 22
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 21
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
- YKFLJYAKACCWMH-UHFFFAOYSA-N methyl piperidine-1-carboxylate Chemical compound COC(=O)N1CCCCC1 YKFLJYAKACCWMH-UHFFFAOYSA-N 0.000 claims description 21
- 235000021419 vinegar Nutrition 0.000 claims description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 20
- 125000005842 heteroatom Chemical group 0.000 claims description 19
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 19
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 claims description 18
- 235000019253 formic acid Nutrition 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 18
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 15
- 229930182817 methionine Natural products 0.000 claims description 15
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 14
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 208000019622 heart disease Diseases 0.000 claims description 14
- 230000001965 increasing effect Effects 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 239000011737 fluorine Substances 0.000 claims description 13
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 13
- IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical compound C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 claims description 12
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 12
- 241000124008 Mammalia Species 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 12
- 125000004494 ethyl ester group Chemical group 0.000 claims description 12
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 12
- 230000008602 contraction Effects 0.000 claims description 11
- 239000002689 soil Substances 0.000 claims description 11
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 claims description 11
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 10
- 150000002148 esters Chemical class 0.000 claims description 10
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
- 229910021653 sulphate ion Inorganic materials 0.000 claims description 10
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 9
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 9
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 9
- 229910052786 argon Inorganic materials 0.000 claims description 8
- 125000004429 atom Chemical group 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims description 8
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 8
- 150000002923 oximes Chemical class 0.000 claims description 8
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 7
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 7
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 7
- 241000009298 Trigla lyra Species 0.000 claims description 7
- 230000010247 heart contraction Effects 0.000 claims description 7
- 229960003194 meglumine Drugs 0.000 claims description 7
- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical compound CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- YSPVHAUJXLGZHP-UHFFFAOYSA-N ethyl piperidine-1-carboxylate Chemical compound CCOC(=O)N1CCCCC1 YSPVHAUJXLGZHP-UHFFFAOYSA-N 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 6
- 239000000651 prodrug Substances 0.000 claims description 6
- 229940002612 prodrug Drugs 0.000 claims description 6
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 5
- ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 claims description 5
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- GZUXJHMPEANEGY-UHFFFAOYSA-N methyl bromide Substances BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 claims description 5
- 239000002243 precursor Substances 0.000 claims description 5
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 4
- 241001465754 Metazoa Species 0.000 claims description 4
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical group [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 4
- 230000008901 benefit Effects 0.000 claims description 4
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 4
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- TWFZGCMQGLPBSX-UHFFFAOYSA-N Carbendazim Natural products C1=CC=C2NC(NC(=O)OC)=NC2=C1 TWFZGCMQGLPBSX-UHFFFAOYSA-N 0.000 claims description 3
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 3
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 3
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 3
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 3
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 3
- 239000000443 aerosol Substances 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 239000006013 carbendazim Substances 0.000 claims description 3
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 3
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 3
- 229940102396 methyl bromide Drugs 0.000 claims description 3
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 229930192474 thiophene Natural products 0.000 claims description 3
- 230000009278 visceral effect Effects 0.000 claims description 3
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 2
- HVSACIINGLQLCS-UHFFFAOYSA-N 2-methoxyethyl formate Chemical compound COCCOC=O HVSACIINGLQLCS-UHFFFAOYSA-N 0.000 claims description 2
- XUYPXLNMDZIRQH-LURJTMIESA-N N-acetyl-L-methionine Chemical compound CSCC[C@@H](C(O)=O)NC(C)=O XUYPXLNMDZIRQH-LURJTMIESA-N 0.000 claims description 2
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- JNPZQRQPIHJYNM-UHFFFAOYSA-N carbendazim Chemical compound C1=C[CH]C2=NC(NC(=O)OC)=NC2=C1 JNPZQRQPIHJYNM-UHFFFAOYSA-N 0.000 claims description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
- WHRIKZCFRVTHJH-UHFFFAOYSA-N ethylhydrazine Chemical compound CCNN WHRIKZCFRVTHJH-UHFFFAOYSA-N 0.000 claims description 2
- LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 claims description 2
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 2
- 239000012530 fluid Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 239000007937 lozenge Substances 0.000 claims description 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 claims description 2
- 235000019260 propionic acid Nutrition 0.000 claims description 2
- 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 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 22
- BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 claims 4
- 125000005577 anthracene group Chemical group 0.000 claims 2
- GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthrene Natural products C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 claims 2
- CRSOQBOWXPBRES-UHFFFAOYSA-N neopentane Chemical compound CC(C)(C)C CRSOQBOWXPBRES-UHFFFAOYSA-N 0.000 claims 2
- SARMGXPVOFNNNG-UHFFFAOYSA-N 1-[amino-(4-chloroanilino)methylidene]-2-propan-2-ylguanidine;hydron;chloride Chemical group Cl.CC(C)N=C(N)N=C(N)NC1=CC=C(Cl)C=C1 SARMGXPVOFNNNG-UHFFFAOYSA-N 0.000 claims 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 1
- UKQJDWBNQNAJHB-UHFFFAOYSA-N 2-hydroxyethyl formate Chemical compound OCCOC=O UKQJDWBNQNAJHB-UHFFFAOYSA-N 0.000 claims 1
- YVDQSNMOVRWOSU-UHFFFAOYSA-N 2-hydroxyethyl piperidine-1-carboxylate Chemical compound OCCOC(=O)N1CCCCC1 YVDQSNMOVRWOSU-UHFFFAOYSA-N 0.000 claims 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims 1
- YSIKHBWUBSFBRZ-UHFFFAOYSA-N 3-methoxypropanoic acid Chemical compound COCCC(O)=O YSIKHBWUBSFBRZ-UHFFFAOYSA-N 0.000 claims 1
- VUTBELPREDJDDH-UHFFFAOYSA-N 4-amino-5-hydroxymethyl-2-methylpyrimidine Chemical compound CC1=NC=C(CO)C(N)=N1 VUTBELPREDJDDH-UHFFFAOYSA-N 0.000 claims 1
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 claims 1
- RMOUBSOVHSONPZ-UHFFFAOYSA-N Isopropyl formate Chemical compound CC(C)OC=O RMOUBSOVHSONPZ-UHFFFAOYSA-N 0.000 claims 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims 1
- 241000207929 Scutellaria Species 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- RDJGWRFTDZZXSM-RNWLQCGYSA-N benzylmorphine Chemical compound O([C@@H]1[C@]23CCN([C@H](C4)[C@@H]3C=C[C@@H]1O)C)C1=C2C4=CC=C1OCC1=CC=CC=C1 RDJGWRFTDZZXSM-RNWLQCGYSA-N 0.000 claims 1
- 229910021386 carbon form Inorganic materials 0.000 claims 1
- 238000005266 casting Methods 0.000 claims 1
- 239000006071 cream Substances 0.000 claims 1
- 239000007933 dermal patch Substances 0.000 claims 1
- RGXWDWUGBIJHDO-UHFFFAOYSA-N ethyl decanoate Chemical compound CCCCCCCCCC(=O)OCC RGXWDWUGBIJHDO-UHFFFAOYSA-N 0.000 claims 1
- 239000012535 impurity Substances 0.000 claims 1
- GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Natural products CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 claims 1
- 229960003105 metformin Drugs 0.000 claims 1
- 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 claims 1
- VTHOTOFWYDBNID-UHFFFAOYSA-N n-decylaniline Chemical compound CCCCCCCCCCNC1=CC=CC=C1 VTHOTOFWYDBNID-UHFFFAOYSA-N 0.000 claims 1
- IKVDMBQGHZVMRN-UHFFFAOYSA-N n-methyldecan-1-amine Chemical compound CCCCCCCCCCNC IKVDMBQGHZVMRN-UHFFFAOYSA-N 0.000 claims 1
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 claims 1
- TYRGSDXYMNTMML-UHFFFAOYSA-N propyl hydrogen sulfate Chemical compound CCCOS(O)(=O)=O TYRGSDXYMNTMML-UHFFFAOYSA-N 0.000 claims 1
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- RSPCKAHMRANGJZ-UHFFFAOYSA-N thiohydroxylamine Chemical compound SN RSPCKAHMRANGJZ-UHFFFAOYSA-N 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 238000003971 tillage Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 229940117013 triethanolamine oleate Drugs 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- UPCXAARSWVHVLY-UHFFFAOYSA-N tris(2-hydroxyethyl)azanium;acetate Chemical compound CC(O)=O.OCCN(CCO)CCO UPCXAARSWVHVLY-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000010455 vermiculite Substances 0.000 description 1
- 229910052902 vermiculite Inorganic materials 0.000 description 1
- 235000019354 vermiculite Nutrition 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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- 229940075420 xanthine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Medicinal Preparation (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (3)
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| US75635606P | 2006-01-04 | 2006-01-04 | |
| US81797506P | 2006-06-29 | 2006-06-29 |
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| TW095146918A TW200808321A (en) | 2005-12-15 | 2006-12-14 | Certain chemical entities, compositions and methods |
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| EP (1) | EP1959960B1 (enExample) |
| JP (1) | JP5301284B2 (enExample) |
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| ES (1) | ES2419007T3 (enExample) |
| PE (1) | PE20071161A1 (enExample) |
| TW (1) | TW200808321A (enExample) |
| WO (1) | WO2007070683A2 (enExample) |
Cited By (1)
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| TWI847144B (zh) * | 2017-06-30 | 2024-07-01 | 美商安進公司 | 奧美卡替莫卡必爾的合成 |
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| WO2004064730A2 (en) * | 2003-01-14 | 2004-08-05 | Cytokinetics, Inc. | Compounds, compositions and methods |
| AU2005264988B2 (en) | 2004-06-17 | 2011-09-22 | Cytokinetics, Inc. | Substituted urea derivatives for treating cardiac diseases |
| US20070208000A1 (en) * | 2005-12-15 | 2007-09-06 | Morgan Bradley P | Certain chemical entities, compositions and methods |
| EP1959960B1 (en) * | 2005-12-15 | 2013-04-10 | Cytokinetics, Inc. | Certain chemical entities, compositions and methods |
| EP1959947A2 (en) * | 2005-12-15 | 2008-08-27 | Cytokinetics, Inc. | Certain chemical entities, compositions and methods |
| US7825120B2 (en) * | 2005-12-15 | 2010-11-02 | Cytokinetics, Inc. | Certain substituted ((piperazin-1-ylmethyl)benzyl)ureas |
| EP1959962A2 (en) | 2005-12-16 | 2008-08-27 | Cytokinetics, Inc. | Certain chemical entities, compositions, and methods |
| US7989455B2 (en) * | 2005-12-19 | 2011-08-02 | Cytokinetics, Inc. | Compounds, compositions and methods |
| US9895308B2 (en) * | 2013-03-14 | 2018-02-20 | Amgen Inc. | Heterocyclic compounds and their uses |
| DK2970123T3 (da) * | 2013-03-14 | 2019-10-21 | Amgen Inc | Salt af omecamtiv mecarbil og fremgangsmåde til fremstilling heraf |
| DK3645002T3 (da) | 2017-06-30 | 2024-12-16 | Amgen Inc | Fremgangsmåder til behandling af hjertesvigt med hjerte-sarkomer-aktivatorer |
| AU2018332887B2 (en) | 2017-09-13 | 2022-12-08 | Amgen Inc. | Bisamide sarcomere activating compounds and uses thereof |
| HUE052049T2 (hu) | 2018-07-09 | 2021-04-28 | Fis Fabbrica Italiana Sintetici Spa | Kristályos 2-fluor-3-nitrotoluol és eljárás annak elõállítására |
| WO2020037164A1 (en) | 2018-08-17 | 2020-02-20 | Amgen Inc. | Salts and crystal forms of omecamtiv mecarbil |
| US12442027B2 (en) | 2018-12-18 | 2025-10-14 | Amgen Inc. | Method of reducing aromatic nitro compounds |
| CN110124046B (zh) * | 2019-06-11 | 2023-04-07 | 辽宁大学 | 一种氧化石墨烯负载双氯芬酸二乙胺及其制备方法 |
| CA3168513A1 (en) * | 2020-02-10 | 2021-08-19 | Amgen Inc. | Omecamtiv mecarbil tablet |
| US12194039B2 (en) | 2020-11-12 | 2025-01-14 | Amgen Inc | Methods of treating heart failure by administering omecamtiv mecarbil |
| TW202300479A (zh) | 2021-03-10 | 2023-01-01 | 美商安進公司 | 奧美卡替莫卡必爾之合成 |
| US11986474B1 (en) | 2023-06-27 | 2024-05-21 | Cytokinetics, Incorporated | Methods for treating heart failure by administering cardiac sarcomere activators |
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-
2006
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- 2006-12-14 US US11/640,438 patent/US20070161617A1/en not_active Abandoned
- 2006-12-14 AR ARP060105509A patent/AR058347A1/es unknown
- 2006-12-14 WO PCT/US2006/047976 patent/WO2007070683A2/en not_active Ceased
- 2006-12-14 JP JP2008545855A patent/JP5301284B2/ja active Active
- 2006-12-14 TW TW095146918A patent/TW200808321A/zh unknown
- 2006-12-14 ES ES06839401T patent/ES2419007T3/es active Active
- 2006-12-15 PE PE2006001613A patent/PE20071161A1/es not_active Application Discontinuation
-
2009
- 2009-06-11 US US12/483,093 patent/US8445495B2/en active Active
-
2013
- 2013-05-17 US US13/897,086 patent/US8871768B2/en active Active
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI847144B (zh) * | 2017-06-30 | 2024-07-01 | 美商安進公司 | 奧美卡替莫卡必爾的合成 |
Also Published As
| Publication number | Publication date |
|---|---|
| JP5301284B2 (ja) | 2013-09-25 |
| EP1959960A2 (en) | 2008-08-27 |
| AR058347A1 (es) | 2008-01-30 |
| US8445495B2 (en) | 2013-05-21 |
| WO2007070683A3 (en) | 2008-11-20 |
| JP2009519951A (ja) | 2009-05-21 |
| US20130324549A1 (en) | 2013-12-05 |
| PE20071161A1 (es) | 2008-02-03 |
| EP1959960A4 (en) | 2010-08-04 |
| ES2419007T3 (es) | 2013-08-19 |
| US20070161617A1 (en) | 2007-07-12 |
| EP1959960B1 (en) | 2013-04-10 |
| US20100029680A1 (en) | 2010-02-04 |
| US8871768B2 (en) | 2014-10-28 |
| WO2007070683A2 (en) | 2007-06-21 |
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