CN104402833B - Pyrazine compounds containing cyclobutane substituent and combinations thereof thing and purposes - Google Patents
Pyrazine compounds containing cyclobutane substituent and combinations thereof thing and purposes Download PDFInfo
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- CN104402833B CN104402833B CN201410667916.2A CN201410667916A CN104402833B CN 104402833 B CN104402833 B CN 104402833B CN 201410667916 A CN201410667916 A CN 201410667916A CN 104402833 B CN104402833 B CN 104402833B
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- compound
- methyl
- amino
- alkyl
- present
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- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 title abstract description 31
- 150000003216 pyrazines Chemical class 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 195
- -1 hydrate Substances 0.000 claims abstract description 127
- 239000003814 drug Substances 0.000 claims abstract description 45
- 150000003839 salts Chemical class 0.000 claims abstract description 41
- 241000712461 unidentified influenza virus Species 0.000 claims abstract description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 55
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
- 239000008194 pharmaceutical composition Substances 0.000 claims description 27
- 239000003795 chemical substances by application Substances 0.000 claims description 23
- 238000002360 preparation method Methods 0.000 claims description 23
- 206010022000 influenza Diseases 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 241000700605 Viruses Species 0.000 claims description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 239000003085 diluting agent Substances 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- KZIMLUFVKJLCCH-UHFFFAOYSA-N 5-[2-(1h-imidazol-5-yl)ethylamino]-5-oxopentanoic acid Chemical compound OC(=O)CCCC(=O)NCCC1=CNC=N1 KZIMLUFVKJLCCH-UHFFFAOYSA-N 0.000 claims description 8
- 229910021529 ammonia Inorganic materials 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 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
- VSZGPKBBMSAYNT-RRFJBIMHSA-N oseltamivir Chemical compound CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 VSZGPKBBMSAYNT-RRFJBIMHSA-N 0.000 claims description 6
- 229960003752 oseltamivir Drugs 0.000 claims description 6
- UBCHPRBFMUDMNC-UHFFFAOYSA-N 1-(1-adamantyl)ethanamine Chemical compound C1C(C2)CC3CC2CC1(C(N)C)C3 UBCHPRBFMUDMNC-UHFFFAOYSA-N 0.000 claims description 5
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 229960000888 rimantadine Drugs 0.000 claims description 5
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 4
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 4
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims description 4
- 229960003805 amantadine Drugs 0.000 claims description 4
- 229960000329 ribavirin Drugs 0.000 claims description 4
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 4
- KCFYEAOKVJSACF-UHFFFAOYSA-N umifenovir Chemical compound CN1C2=CC(Br)=C(O)C(CN(C)C)=C2C(C(=O)OCC)=C1CSC1=CC=CC=C1 KCFYEAOKVJSACF-UHFFFAOYSA-N 0.000 claims description 4
- 229960004626 umifenovir Drugs 0.000 claims description 4
- ARAIBEBZBOPLMB-UFGQHTETSA-N zanamivir Chemical compound CC(=O)N[C@@H]1[C@@H](N=C(N)N)C=C(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO ARAIBEBZBOPLMB-UFGQHTETSA-N 0.000 claims description 4
- 229960001028 zanamivir Drugs 0.000 claims description 4
- ZCGNOVWYSGBHAU-UHFFFAOYSA-N favipiravir Chemical compound NC(=O)C1=NC(F)=CNC1=O ZCGNOVWYSGBHAU-UHFFFAOYSA-N 0.000 claims description 3
- 229950008454 favipiravir Drugs 0.000 claims description 3
- XRQDFNLINLXZLB-CKIKVBCHSA-N peramivir Chemical compound CCC(CC)[C@H](NC(C)=O)[C@@H]1[C@H](O)[C@@H](C(O)=O)C[C@H]1NC(N)=N XRQDFNLINLXZLB-CKIKVBCHSA-N 0.000 claims description 3
- 229960001084 peramivir Drugs 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 abstract description 27
- 239000000651 prodrug Substances 0.000 abstract description 16
- 229940002612 prodrug Drugs 0.000 abstract description 15
- 239000002207 metabolite Substances 0.000 abstract description 12
- 239000012453 solvate Substances 0.000 abstract description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 114
- 239000000203 mixture Substances 0.000 description 87
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 62
- 239000002585 base Substances 0.000 description 46
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluenecarboxylic acid Natural products CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 description 45
- 239000000243 solution Substances 0.000 description 45
- 239000000376 reactant Substances 0.000 description 44
- 235000002639 sodium chloride Nutrition 0.000 description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 37
- 230000015572 biosynthetic process Effects 0.000 description 37
- 238000006243 chemical reaction Methods 0.000 description 36
- 238000003786 synthesis reaction Methods 0.000 description 36
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 35
- 239000007787 solid Substances 0.000 description 34
- 238000000034 method Methods 0.000 description 32
- 235000019439 ethyl acetate Nutrition 0.000 description 30
- 238000010898 silica gel chromatography Methods 0.000 description 30
- 239000003480 eluent Substances 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 150000002500 ions Chemical class 0.000 description 27
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N DMSO-d6 Substances [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 24
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 238000005160 1H NMR spectroscopy Methods 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 229910001868 water Inorganic materials 0.000 description 21
- 239000004698 Polyethylene Substances 0.000 description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- 239000000126 substance Substances 0.000 description 17
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
- 125000000217 alkyl group Chemical group 0.000 description 15
- 239000007864 aqueous solution Substances 0.000 description 15
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 14
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 14
- 229910052805 deuterium Inorganic materials 0.000 description 14
- 229910052799 carbon Inorganic materials 0.000 description 13
- 239000000463 material Substances 0.000 description 13
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- 239000000825 pharmaceutical preparation Substances 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 11
- 230000008859 change Effects 0.000 description 11
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 150000001721 carbon Chemical group 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 238000011282 treatment Methods 0.000 description 10
- 239000007788 liquid Substances 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- IPEHBUMCGVEMRF-UHFFFAOYSA-N pyrazinecarboxamide Chemical compound NC(=O)C1=CN=CC=N1 IPEHBUMCGVEMRF-UHFFFAOYSA-N 0.000 description 9
- 238000010189 synthetic method Methods 0.000 description 9
- 239000012230 colorless oil Substances 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 8
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 7
- 125000003545 alkoxy group Chemical group 0.000 description 7
- 125000003282 alkyl amino group Chemical group 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
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- 0 *CC1CC(*)(CN(*)c2ncc(*)nc2C#N)C1 Chemical compound *CC1CC(*)(CN(*)c2ncc(*)nc2C#N)C1 0.000 description 6
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
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- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
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- 239000001301 oxygen Substances 0.000 description 6
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- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl chloride Substances ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
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- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000002594 sorbent Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000001562 sternum Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229960005137 succinic acid Drugs 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000033912 thigmotaxis Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229950004288 tosilate Drugs 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-M undecanoate Chemical compound CCCCCCCCCCC([O-])=O ZDPHROOEEOARMN-UHFFFAOYSA-M 0.000 description 1
- 239000002691 unilamellar liposome Substances 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
- C07D241/28—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms
Abstract
Description
Time (min) | A(CH3CN, 0.1%HCOOH) | B(H2O, 0.1%HCOOH) |
0-3 | 5-100 | 95-0 |
3-6 | 100 | 0 |
6-6.1 | 100-5 | 0-95 |
6.1-8 | 5 | 95 |
Claims (7)
Priority Applications (1)
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CN201410667916.2A CN104402833B (en) | 2014-11-20 | 2014-11-20 | Pyrazine compounds containing cyclobutane substituent and combinations thereof thing and purposes |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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CN201410667916.2A CN104402833B (en) | 2014-11-20 | 2014-11-20 | Pyrazine compounds containing cyclobutane substituent and combinations thereof thing and purposes |
Publications (2)
Publication Number | Publication Date |
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CN104402833A CN104402833A (en) | 2015-03-11 |
CN104402833B true CN104402833B (en) | 2016-08-24 |
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CN201410667916.2A Active CN104402833B (en) | 2014-11-20 | 2014-11-20 | Pyrazine compounds containing cyclobutane substituent and combinations thereof thing and purposes |
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CN (1) | CN104402833B (en) |
Families Citing this family (2)
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CN109953977A (en) * | 2017-12-25 | 2019-07-02 | 深圳市华力康生物医药有限公司 | A kind of nasal inhalation powder formulation and its device |
CN114644597B (en) * | 2022-03-23 | 2023-11-21 | 南京农业大学 | Tetra-substituted pyrazine derivative and preparation method and application thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1942437A (en) * | 2004-02-16 | 2007-04-04 | 埃斯特韦实验室有限公司 | Substituted azetidine compounds as cyclooxygenase-1-cyclooxygenase-2 inhibitors, and their preparation and use as medicaments |
CN101268064A (en) * | 2005-07-29 | 2008-09-17 | 奥米罗实验室有限公司 | Pyrazine derivatives useful as adenosine receptor antagonists |
CN101610772A (en) * | 2007-02-16 | 2009-12-23 | 富山化学工业株式会社 | The method that comprises pharmaceutical composition with the drug combination that uses pyrazines derivatives of pyrazines derivatives |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012082817A1 (en) * | 2010-12-16 | 2012-06-21 | Boehringer Ingelheim International Gmbh | Biarylamide inhibitors of leukotriene production |
-
2014
- 2014-11-20 CN CN201410667916.2A patent/CN104402833B/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1942437A (en) * | 2004-02-16 | 2007-04-04 | 埃斯特韦实验室有限公司 | Substituted azetidine compounds as cyclooxygenase-1-cyclooxygenase-2 inhibitors, and their preparation and use as medicaments |
CN101268064A (en) * | 2005-07-29 | 2008-09-17 | 奥米罗实验室有限公司 | Pyrazine derivatives useful as adenosine receptor antagonists |
CN101610772A (en) * | 2007-02-16 | 2009-12-23 | 富山化学工业株式会社 | The method that comprises pharmaceutical composition with the drug combination that uses pyrazines derivatives of pyrazines derivatives |
Non-Patent Citations (1)
Title |
---|
Discovery of LAS101057: A Potent, Selective, and Orally Efficacious A2B Adenosine Receptor Antagonist;Paul Eastwood,et al.;《ACS Medicinal Chemistry Letters》;20111231(第2期);第213-218页 * |
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CN104402833A (en) | 2015-03-11 |
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Denomination of invention: Pyrazine compound containing diethylene substituent and composition and application thereof Effective date of registration: 20190920 Granted publication date: 20160824 Pledgee: Shenzhen branch of China Import and Export Bank Pledgor: SUNSHINE LAKE PHARMA Co.,Ltd. Registration number: Y2019990000260 |
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Date of cancellation: 20211105 Granted publication date: 20160824 Pledgee: Shenzhen branch of China Import and Export Bank Pledgor: SUNSHINE LAKE PHARMA Co.,Ltd. Registration number: Y2019990000260 |
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Address after: 523808 No.1, Gongye North Road, Songshanhu Park, Dongguan City, Guangdong Province Patentee after: Guangdong Dongyangguang Pharmaceutical Co.,Ltd. Address before: 523808 No. 1 Industrial North Road, Songshan Industrial Park, Songshan, Guangdong, Dongguan, Hubei Patentee before: SUNSHINE LAKE PHARMA Co.,Ltd. |
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Effective date of registration: 20240125 Address after: 300000 Tianjin Binhai New Area Free Trade Pilot Zone (Dongjiang Bonded Port Area), No. 6975 Asia Road, Financial and Trade Center South Zone 1-1-2019 Patentee after: Haitong Hengxin International Finance Leasing (Tianjin) Co.,Ltd. Country or region after: China Address before: 523808 No.1, Gongye North Road, Songshanhu Park, Dongguan City, Guangdong Province Patentee before: Guangdong Dongyangguang Pharmaceutical Co.,Ltd. Country or region before: China |