CN105399731A - 药物化合物 - Google Patents
药物化合物 Download PDFInfo
- Publication number
- CN105399731A CN105399731A CN201510829064.7A CN201510829064A CN105399731A CN 105399731 A CN105399731 A CN 105399731A CN 201510829064 A CN201510829064 A CN 201510829064A CN 105399731 A CN105399731 A CN 105399731A
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- CN
- China
- Prior art keywords
- alkyl
- aryl
- heterocyclyl
- heteroaryl
- substituted
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 217
- 239000000203 mixture Substances 0.000 claims abstract description 53
- 238000000034 method Methods 0.000 claims abstract description 16
- 239000000758 substrate Substances 0.000 claims abstract description 11
- 238000011282 treatment Methods 0.000 claims abstract description 9
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- 208000024891 symptom Diseases 0.000 claims abstract description 8
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 913
- 125000000623 heterocyclic group Chemical group 0.000 claims description 884
- 125000003118 aryl group Chemical group 0.000 claims description 643
- 125000001072 heteroaryl group Chemical group 0.000 claims description 619
- 125000003545 alkoxy group Chemical group 0.000 claims description 402
- -1 COOR1a Chemical group 0.000 claims description 327
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 263
- 229910052736 halogen Inorganic materials 0.000 claims description 213
- 150000002367 halogens Chemical class 0.000 claims description 213
- 125000005842 heteroatom Chemical group 0.000 claims description 187
- 125000004104 aryloxy group Chemical group 0.000 claims description 159
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 150
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 144
- 125000002950 monocyclic group Chemical group 0.000 claims description 119
- 229910004013 NO 2 Inorganic materials 0.000 claims description 105
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 83
- 125000001424 substituent group Chemical group 0.000 claims description 76
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 73
- 229910052799 carbon Inorganic materials 0.000 claims description 71
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 67
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 61
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims description 57
- 125000003386 piperidinyl group Chemical group 0.000 claims description 55
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 52
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- 125000000160 oxazolidinyl group Chemical group 0.000 claims description 38
- 229910052757 nitrogen Inorganic materials 0.000 claims description 35
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- 125000004193 piperazinyl group Chemical group 0.000 claims description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 32
- 229910003204 NH2 Inorganic materials 0.000 claims description 31
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- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 30
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 29
- 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 27
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 25
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 239000001301 oxygen Substances 0.000 claims description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- 229910006069 SO3H Inorganic materials 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 21
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 19
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 19
- 238000006467 substitution reaction Methods 0.000 claims description 18
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical group [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 claims description 14
- 125000000304 alkynyl group Chemical group 0.000 claims description 14
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
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- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 12
- 229910052794 bromium Inorganic materials 0.000 claims description 12
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
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- 125000004663 dialkyl amino group Chemical group 0.000 claims description 11
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- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 11
- 125000003700 epoxy group Chemical group 0.000 claims description 10
- JMNKYLBIVQBMBW-UHFFFAOYSA-N (4-phenylimidazol-1-yl)-[4-(quinolin-2-ylmethyl)piperazin-1-yl]methanone Chemical compound C1CN(CC=2N=C3C=CC=CC3=CC=2)CCN1C(=O)N(C=1)C=NC=1C1=CC=CC=C1 JMNKYLBIVQBMBW-UHFFFAOYSA-N 0.000 claims description 9
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 9
- 229910003827 NRaRb Inorganic materials 0.000 claims description 9
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 9
- 125000004429 atom Chemical group 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 9
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- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 8
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 8
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 208000002193 Pain Diseases 0.000 claims description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 6
- 125000005605 benzo group Chemical group 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 241000689227 Cora <basidiomycete fungus> Species 0.000 claims description 5
- 239000004593 Epoxy Substances 0.000 claims description 5
- 229910017711 NHRa Inorganic materials 0.000 claims description 5
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 5
- 239000008186 active pharmaceutical agent Substances 0.000 claims description 5
- 230000001154 acute effect Effects 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 4
- 230000036407 pain Effects 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 3
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- 230000008673 vomiting Effects 0.000 claims description 3
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 2
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- 208000007848 Alcoholism Diseases 0.000 claims description 2
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- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 2
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 2
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- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 2
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- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 35
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| US9062055B2 (en) | 2010-06-21 | 2015-06-23 | Incyte Corporation | Fused pyrrole derivatives as PI3K inhibitors |
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| US20150197503A1 (en) | 2012-07-27 | 2015-07-16 | Bial-Portela & Cª, S.A. | Process for the synthesis of substituted urea compounds |
| AU2014293731B2 (en) * | 2013-07-24 | 2018-03-08 | Bial - Portela & Ca, S.A. | Imidazolecarboxamides and their use as FAAH inhibitors |
| MX2016001391A (es) | 2013-08-01 | 2016-08-17 | BIAL - PORTELA & Cª S A | Compuestos de urea y su uso como inhibidores de la enzima amida hidrolasa de acido graso (faah). |
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| GB201401198D0 (en) * | 2014-01-24 | 2014-03-12 | Bial Portela & Ca Sa | Process for the syntheis of substituted urea compounds |
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| CN104292172B (zh) * | 2014-09-12 | 2016-08-17 | 浙江理工大学 | 一种苯并三氮唑类衍生物及其制备方法 |
| CN117736209A (zh) | 2015-02-27 | 2024-03-22 | 因赛特控股公司 | Pi3k抑制剂的盐及其制备方法 |
| WO2016183063A1 (en) | 2015-05-11 | 2016-11-17 | Incyte Corporation | Crystalline forms of a pi3k inhibitor |
| US9732097B2 (en) | 2015-05-11 | 2017-08-15 | Incyte Corporation | Process for the synthesis of a phosphoinositide 3-kinase inhibitor |
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| US10323038B2 (en) | 2015-11-20 | 2019-06-18 | Abide Therapeutics, Inc. | Pyrazole compounds and methods of making and using same |
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| DK3548033T3 (da) | 2016-11-28 | 2024-07-15 | Praxis Prec Medicines Inc | Forbindelser og deres fremgangsmåde til anvendelse |
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| CA2747784A1 (en) | 2010-07-01 |
| US20120065191A1 (en) | 2012-03-15 |
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| BR122013027950A2 (pt) | 2019-12-10 |
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| JP2012513990A (ja) | 2012-06-21 |
| TW201028408A (en) | 2010-08-01 |
| BRPI0923819B1 (pt) | 2021-11-09 |
| CN102333568A (zh) | 2012-01-25 |
| MX342128B (es) | 2016-09-14 |
| IL213747A (en) | 2017-01-31 |
| JP2015071622A (ja) | 2015-04-16 |
| JP5657566B2 (ja) | 2015-01-21 |
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| RU2553451C2 (ru) | 2015-06-20 |
| MX2011006643A (es) | 2011-07-29 |
| NZ593418A (en) | 2013-10-25 |
| AR075111A1 (es) | 2011-03-09 |
| CA2747784C (en) | 2018-07-31 |
| US9353082B2 (en) | 2016-05-31 |
| AU2009330821B2 (en) | 2015-06-11 |
| TWI469979B (zh) | 2015-01-21 |
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| SG172301A1 (en) | 2011-07-28 |
| BRPI0923819A2 (pt) | 2019-11-19 |
| WO2010074588A3 (en) | 2011-05-19 |
| EP2382012A2 (en) | 2011-11-02 |
| WO2010074588A2 (en) | 2010-07-01 |
| ZA201104336B (en) | 2016-10-26 |
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