CN117865941B - 取代哌啶化合物及其制备方法和应用 - Google Patents
取代哌啶化合物及其制备方法和应用 Download PDFInfo
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- CN117865941B CN117865941B CN202410282730.9A CN202410282730A CN117865941B CN 117865941 B CN117865941 B CN 117865941B CN 202410282730 A CN202410282730 A CN 202410282730A CN 117865941 B CN117865941 B CN 117865941B
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- cyclopropyl
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- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 238000000034 method Methods 0.000 title claims description 23
- 230000008569 process Effects 0.000 title claims description 8
- 150000003053 piperidines Chemical class 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 421
- -1 piperidine compound Chemical class 0.000 claims abstract description 73
- 230000000694 effects Effects 0.000 claims abstract description 25
- 108090000783 Renin Proteins 0.000 claims abstract description 16
- 102100028255 Renin Human genes 0.000 claims abstract description 16
- 201000010099 disease Diseases 0.000 claims abstract description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 15
- 238000011282 treatment Methods 0.000 claims abstract description 11
- 206010020772 Hypertension Diseases 0.000 claims abstract description 9
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 6
- 208000037976 chronic inflammation Diseases 0.000 claims abstract description 3
- 230000006020 chronic inflammation Effects 0.000 claims abstract description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 3
- 208000017169 kidney disease Diseases 0.000 claims abstract description 3
- 230000002265 prevention Effects 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 176
- 239000007795 chemical reaction product Substances 0.000 claims description 104
- 125000003545 alkoxy group Chemical group 0.000 claims description 70
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 61
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 57
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 53
- 125000005843 halogen group Chemical group 0.000 claims description 52
- 125000000623 heterocyclic group Chemical group 0.000 claims description 35
- 239000012467 final product Substances 0.000 claims description 32
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 30
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 30
- 125000005842 heteroatom Chemical group 0.000 claims description 27
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 26
- 125000001424 substituent group Chemical group 0.000 claims description 26
- 229910052799 carbon Inorganic materials 0.000 claims description 25
- 150000002367 halogens Chemical class 0.000 claims description 23
- 230000002829 reductive effect Effects 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 229910052805 deuterium Inorganic materials 0.000 claims description 21
- 230000000155 isotopic effect Effects 0.000 claims description 20
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 19
- 125000003277 amino group Chemical group 0.000 claims description 18
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000005347 halocycloalkyl group Chemical group 0.000 claims description 11
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 11
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 8
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims description 7
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 5
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 4
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical group O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 4
- 206010019280 Heart failures Diseases 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 238000006460 hydrolysis reaction Methods 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000006317 cyclopropyl amino group Chemical group 0.000 claims description 3
- 238000010511 deprotection reaction Methods 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 238000006467 substitution reaction Methods 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 2
- 238000006482 condensation reaction Methods 0.000 claims description 2
- 238000005649 metathesis reaction Methods 0.000 claims description 2
- 238000006462 rearrangement reaction Methods 0.000 claims description 2
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims 26
- WDWDWGRYHDPSDS-UHFFFAOYSA-N methanimine Chemical group N=C WDWDWGRYHDPSDS-UHFFFAOYSA-N 0.000 claims 3
- QDXGKRWDQCEABB-UHFFFAOYSA-N pyrimidine-5-carboxamide Chemical compound NC(=O)C1=CN=CN=C1 QDXGKRWDQCEABB-UHFFFAOYSA-N 0.000 claims 2
- 125000006311 cyclobutyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000004431 deuterium atom Chemical group 0.000 claims 1
- JZTVCHDVUWOXER-UHFFFAOYSA-N n-(trifluoromethyl)pyridine-2-carboxamide Chemical compound FC(F)(F)NC(=O)C1=CC=CC=N1 JZTVCHDVUWOXER-UHFFFAOYSA-N 0.000 claims 1
- DMYLUKNFEYWGCH-UHFFFAOYSA-N pyridazine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=N1 DMYLUKNFEYWGCH-UHFFFAOYSA-N 0.000 claims 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical group OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 claims 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 abstract description 6
- 206010007558 Cardiac failure chronic Diseases 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 description 264
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 263
- 238000003786 synthesis reaction Methods 0.000 description 174
- 230000015572 biosynthetic process Effects 0.000 description 171
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 171
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 144
- 239000000741 silica gel Substances 0.000 description 144
- 229910002027 silica gel Inorganic materials 0.000 description 144
- 239000000243 solution Substances 0.000 description 143
- 238000003818 flash chromatography Methods 0.000 description 141
- 229910052757 nitrogen Inorganic materials 0.000 description 136
- 239000007864 aqueous solution Substances 0.000 description 120
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 105
- 239000003921 oil Substances 0.000 description 99
- 235000019198 oils Nutrition 0.000 description 99
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 96
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 81
- 239000007787 solid Substances 0.000 description 79
- 230000002441 reversible effect Effects 0.000 description 69
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 65
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 63
- 238000003756 stirring Methods 0.000 description 59
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- 238000005160 1H NMR spectroscopy Methods 0.000 description 51
- 239000007821 HATU Substances 0.000 description 40
- 229920006395 saturated elastomer Polymers 0.000 description 40
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 39
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 35
- 125000004432 carbon atom Chemical group C* 0.000 description 33
- 239000011734 sodium Substances 0.000 description 31
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 29
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 28
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 229910052796 boron Inorganic materials 0.000 description 27
- 206010012812 Diffuse cutaneous mastocytosis Diseases 0.000 description 26
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 26
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 22
- 125000004692 haloalkylcarbonyl group Chemical group 0.000 description 22
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 239000000460 chlorine Substances 0.000 description 17
- 229910052717 sulfur Inorganic materials 0.000 description 17
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- 150000001975 deuterium Chemical group 0.000 description 15
- 229940079593 drug Drugs 0.000 description 15
- 235000019439 ethyl acetate Nutrition 0.000 description 15
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 14
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 14
- 238000001914 filtration Methods 0.000 description 14
- 229910052760 oxygen Inorganic materials 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 13
- 239000012043 crude product Substances 0.000 description 13
- 239000012299 nitrogen atmosphere Substances 0.000 description 13
- 125000006595 (C1-C3) alkylsulfinyl group Chemical group 0.000 description 12
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 12
- YSHOWEKUVWPFNR-UHFFFAOYSA-N burgess reagent Chemical compound CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC YSHOWEKUVWPFNR-UHFFFAOYSA-N 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- 230000036454 renin-angiotensin system Effects 0.000 description 12
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 11
- 125000004992 haloalkylamino group Chemical group 0.000 description 11
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 125000003342 alkenyl group Chemical group 0.000 description 10
- 125000004993 haloalkoxycarbonyl group Chemical group 0.000 description 10
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 10
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- 125000003282 alkyl amino group Chemical group 0.000 description 9
- 239000000651 prodrug Substances 0.000 description 9
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 125000004414 alkyl thio group Chemical group 0.000 description 8
- 125000000304 alkynyl group Chemical group 0.000 description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- 238000002953 preparative HPLC Methods 0.000 description 8
- 125000006594 (C1-C3) alkylsulfony group Chemical group 0.000 description 7
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 7
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- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 7
- 125000003118 aryl group Chemical group 0.000 description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 description 7
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 description 6
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- 125000004741 (C1-C6) haloalkylsulfonyl group Chemical group 0.000 description 6
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 6
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- 125000000262 haloalkenyl group Chemical group 0.000 description 6
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
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- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
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- 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 5
- 241001465754 Metazoa Species 0.000 description 5
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- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 4
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- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 description 4
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- 125000004749 (C1-C6) haloalkylsulfinyl group Chemical group 0.000 description 4
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 4
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- CTZHBPUHGUPFSN-UHFFFAOYSA-N 3-methoxycyclobutan-1-amine Chemical compound COC1CC(N)C1 CTZHBPUHGUPFSN-UHFFFAOYSA-N 0.000 description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 4
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- 230000002588 toxic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 150000003918 triazines Chemical class 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
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical class CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-M valerate Chemical class CCCCC([O-])=O NQPDZGIKBAWPEJ-UHFFFAOYSA-M 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
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- 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
- C07D401/14—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 three or more hetero rings
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P9/12—Antihypertensives
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (19)
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Citations (1)
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AU2011244858A1 (en) * | 2006-09-18 | 2011-11-24 | Vitae Pharmaceuticals, Inc. | Renin inhibitors |
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PL375214A1 (en) * | 2002-06-27 | 2005-11-28 | Actelion Pharmaceuticals Ltd. | Novel tetrahydropyridine derivatives as renin inhibitors |
TW200722424A (en) * | 2005-03-31 | 2007-06-16 | Speedel Experimenta Ag | Substituted piperidines |
CN101365680A (zh) * | 2005-12-30 | 2009-02-11 | 诺瓦提斯公司 | 作为肾素抑制剂的3,5-取代的哌啶化合物 |
US20090105251A1 (en) * | 2007-01-25 | 2009-04-23 | Benjamin Jones | Renin inhibitors |
US20120035214A1 (en) * | 2009-04-03 | 2012-02-09 | Merck Canada Inc. | Renin inhibitors |
US20120115907A1 (en) * | 2009-04-24 | 2012-05-10 | Cadila Healthcare Limited | Novel compounds as inhibitors of renin |
EP3034501A1 (en) * | 2014-12-17 | 2016-06-22 | Gilead Sciences, Inc. | Hydroxy containing FXR (NR1H4) modulating compounds |
WO2019006548A1 (en) * | 2017-07-04 | 2019-01-10 | Trillium Therapeutics Inc. | FLUORINATED 2,4-DIAMINOPYRIMIDINE COMPOUNDS AS INHIBITORS OF TYROSINE KINASE MER (MERTK) AND USES THEREOF |
BR112022000474A2 (pt) * | 2019-07-16 | 2022-05-17 | Myokardia Inc | Formas polimórficas de (r)-4-(1-((3-(difluorometil)-1-metil-1h-pirazol-4-il)sulfonil)-1-fluoroetil)-n-(isoxazol-3-il)piperidina-1-carboxamida |
CN111423411B (zh) * | 2020-04-02 | 2021-04-16 | 南京生命源医药科技有限公司 | 一种新型肾素抑制剂 |
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AU2011244858A1 (en) * | 2006-09-18 | 2011-11-24 | Vitae Pharmaceuticals, Inc. | Renin inhibitors |
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