AU2011305667A1 - Oxadiazole inhibitors of leukotriene production - Google Patents
Oxadiazole inhibitors of leukotriene production Download PDFInfo
- Publication number
- AU2011305667A1 AU2011305667A1 AU2011305667A AU2011305667A AU2011305667A1 AU 2011305667 A1 AU2011305667 A1 AU 2011305667A1 AU 2011305667 A AU2011305667 A AU 2011305667A AU 2011305667 A AU2011305667 A AU 2011305667A AU 2011305667 A1 AU2011305667 A1 AU 2011305667A1
- Authority
- AU
- Australia
- Prior art keywords
- alkyl
- pct
- cyclobutyl
- pyridin
- oxadiazol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000002617 leukotrienes Chemical class 0.000 title claims description 23
- 239000003112 inhibitor Substances 0.000 title description 12
- 238000004519 manufacturing process Methods 0.000 title description 6
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 167
- 150000003839 salts Chemical class 0.000 claims abstract description 56
- -1 pyrrolopyridinyl Chemical group 0.000 claims description 144
- 125000000217 alkyl group Chemical group 0.000 claims description 135
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 129
- 238000000034 method Methods 0.000 claims description 103
- 125000000623 heterocyclic group Chemical group 0.000 claims description 63
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 62
- 229910052736 halogen Inorganic materials 0.000 claims description 49
- 125000003545 alkoxy group Chemical group 0.000 claims description 47
- 150000002367 halogens Chemical class 0.000 claims description 41
- 229910052799 carbon Inorganic materials 0.000 claims description 32
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 29
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 25
- 125000003386 piperidinyl group Chemical group 0.000 claims description 25
- 125000004076 pyridyl group Chemical group 0.000 claims description 25
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- 125000004193 piperazinyl group Chemical group 0.000 claims description 23
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 23
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
- 125000002883 imidazolyl group Chemical group 0.000 claims description 21
- 125000002757 morpholinyl group Chemical group 0.000 claims description 21
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 21
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 19
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 125000005189 alkyl hydroxy group Chemical group 0.000 claims description 15
- 125000002393 azetidinyl group Chemical group 0.000 claims description 15
- 125000000335 thiazolyl group Chemical group 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 125000002541 furyl group Chemical group 0.000 claims description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 13
- 125000002971 oxazolyl group Chemical group 0.000 claims description 13
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 13
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 13
- 125000001425 triazolyl group Chemical group 0.000 claims description 13
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 12
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 12
- 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 11
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 229910052717 sulfur Chemical group 0.000 claims description 11
- 125000001544 thienyl group Chemical group 0.000 claims description 11
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 10
- 125000003277 amino group Chemical group 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 claims description 9
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 9
- 230000001404 mediated effect Effects 0.000 claims description 9
- 125000003566 oxetanyl group Chemical group 0.000 claims description 9
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 9
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 150000002825 nitriles Chemical class 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 239000001301 oxygen Chemical group 0.000 claims description 8
- 125000005958 tetrahydrothienyl group Chemical group 0.000 claims description 8
- 201000001320 Atherosclerosis Diseases 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 125000001041 indolyl group Chemical group 0.000 claims description 7
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 7
- 239000011593 sulfur Chemical group 0.000 claims description 7
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 230000000172 allergic effect Effects 0.000 claims description 6
- 208000010668 atopic eczema Diseases 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000002837 carbocyclic group Chemical group 0.000 claims description 6
- 230000003176 fibrotic effect Effects 0.000 claims description 6
- 230000002757 inflammatory effect Effects 0.000 claims description 6
- 230000002685 pulmonary effect Effects 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
- 208000017169 kidney disease Diseases 0.000 claims description 5
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 3
- 206010038389 Renal cancer Diseases 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 3
- 201000010982 kidney cancer Diseases 0.000 claims description 3
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 2
- ARUKYTASOALXFG-UHFFFAOYSA-N cycloheptylcycloheptane Chemical group C1CCCCCC1C1CCCCCC1 ARUKYTASOALXFG-UHFFFAOYSA-N 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 119
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 114
- 230000015572 biosynthetic process Effects 0.000 description 93
- 238000003786 synthesis reaction Methods 0.000 description 92
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 89
- 239000000543 intermediate Substances 0.000 description 64
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 64
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
- 238000006243 chemical reaction Methods 0.000 description 56
- 239000002904 solvent Substances 0.000 description 56
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 52
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 40
- 235000019439 ethyl acetate Nutrition 0.000 description 40
- 239000012071 phase Substances 0.000 description 32
- 239000011734 sodium Substances 0.000 description 32
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 30
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 28
- 239000000460 chlorine Substances 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- 238000003818 flash chromatography Methods 0.000 description 24
- 239000012074 organic phase Substances 0.000 description 24
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 23
- 101000755875 Homo sapiens Arachidonate 5-lipoxygenase-activating protein Proteins 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 102100022278 Arachidonate 5-lipoxygenase-activating protein Human genes 0.000 description 20
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 20
- 229920006395 saturated elastomer Polymers 0.000 description 20
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000012267 brine Substances 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- 239000003153 chemical reaction reagent Substances 0.000 description 17
- 229910004298 SiO 2 Inorganic materials 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 150000001721 carbon Chemical group 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- 238000001914 filtration Methods 0.000 description 12
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 12
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 description 11
- 238000004007 reversed phase HPLC Methods 0.000 description 11
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 10
- XBJFCYDKBDVADW-UHFFFAOYSA-N acetonitrile;formic acid Chemical group CC#N.OC=O XBJFCYDKBDVADW-UHFFFAOYSA-N 0.000 description 10
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 10
- 235000019253 formic acid Nutrition 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000013543 active substance Substances 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 description 8
- 108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- 239000007821 HATU Substances 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 6
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 6
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 6
- 208000006673 asthma Diseases 0.000 description 6
- 125000002619 bicyclic group Chemical group 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 6
- 238000002953 preparative HPLC Methods 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 125000001766 1,2,4-oxadiazol-3-yl group Chemical group [H]C1=NC(*)=NO1 0.000 description 5
- 208000024172 Cardiovascular disease Diseases 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 229940113088 dimethylacetamide Drugs 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- 102000004023 5-Lipoxygenase-Activating Proteins Human genes 0.000 description 4
- 108090000411 5-Lipoxygenase-Activating Proteins Proteins 0.000 description 4
- VIBVAXDIZBKQDW-UHFFFAOYSA-N 5-[5-[1-[5-[1-(oxetan-3-yl)pyrazol-4-yl]-1,2,4-oxadiazol-3-yl]cyclobutyl]pyridin-2-yl]pyridin-2-amine Chemical compound C1=NC(N)=CC=C1C1=CC=C(C2(CCC2)C=2N=C(ON=2)C2=CN(N=C2)C2COC2)C=N1 VIBVAXDIZBKQDW-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 208000037765 diseases and disorders Diseases 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 208000010125 myocardial infarction Diseases 0.000 description 4
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 4
- 229910052701 rubidium Inorganic materials 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- HUJLNVZUZCIXBT-UHFFFAOYSA-N 1-[6-(5-aminopyrazin-2-yl)pyridin-3-yl]-n'-hydroxycyclobutane-1-carboximidamide Chemical compound C1=NC(N)=CN=C1C1=CC=C(C2(CCC2)C(=N)NO)C=N1 HUJLNVZUZCIXBT-UHFFFAOYSA-N 0.000 description 3
- NYUWVBNZXPTPHE-UHFFFAOYSA-N 1-[6-(5-aminopyrazin-2-yl)pyridin-3-yl]cyclobutane-1-carbonitrile Chemical compound C1=NC(N)=CN=C1C1=CC=C(C2(CCC2)C#N)C=N1 NYUWVBNZXPTPHE-UHFFFAOYSA-N 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- 206010018364 Glomerulonephritis Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 3
- 102100022118 Leukotriene A-4 hydrolase Human genes 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 3
- 208000026935 allergic disease Diseases 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 229940114079 arachidonic acid Drugs 0.000 description 3
- 235000021342 arachidonic acid Nutrition 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 230000003143 atherosclerotic effect Effects 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Substances CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 3
- FJFVGPGORQGBDX-UHFFFAOYSA-N methyl 5-(2-methoxyethylamino)pyrazine-2-carboxylate Chemical compound COCCNC1=CN=C(C(=O)OC)C=N1 FJFVGPGORQGBDX-UHFFFAOYSA-N 0.000 description 3
- CVVMLRFXZPKILB-UHFFFAOYSA-N methyl 5-chloropyrazine-2-carboxylate Chemical compound COC(=O)C1=CN=C(Cl)C=N1 CVVMLRFXZPKILB-UHFFFAOYSA-N 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 238000000159 protein binding assay Methods 0.000 description 3
- 229910052705 radium Inorganic materials 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000002821 scintillation proximity assay Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- DSRBZOOCXAMQMK-UHFFFAOYSA-N 1-[3-[1-(6-chloropyridin-3-yl)cyclobutyl]-1,2,4-oxadiazol-5-yl]piperidin-4-ol Chemical compound C1CC(O)CCN1C1=NC(C2(CCC2)C=2C=NC(Cl)=CC=2)=NO1 DSRBZOOCXAMQMK-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- MDZZLIVEAJHMGH-UHFFFAOYSA-N 2-[4-[3-[1-[6-(2-aminopyrimidin-5-yl)pyridin-3-yl]cyclobutyl]-1,2,4-oxadiazol-5-yl]pyrazol-1-yl]-2-methylpropanoic acid Chemical compound C1=NN(C(C)(C(O)=O)C)C=C1C1=NC(C2(CCC2)C=2C=NC(=CC=2)C=2C=NC(N)=NC=2)=NO1 MDZZLIVEAJHMGH-UHFFFAOYSA-N 0.000 description 2
- GWHXYTKINTWEDS-UHFFFAOYSA-N 2-[4-[3-[1-[6-(2-aminopyrimidin-5-yl)pyridin-3-yl]cyclobutyl]-1,2,4-oxadiazol-5-yl]pyrazol-1-yl]acetic acid Chemical compound C1=NC(N)=NC=C1C1=CC=C(C2(CCC2)C=2N=C(ON=2)C2=CN(CC(O)=O)N=C2)C=N1 GWHXYTKINTWEDS-UHFFFAOYSA-N 0.000 description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 2
- QFYGRJJJLJJYPZ-UHFFFAOYSA-N 3-[4-[3-[1-[6-(2-aminopyrimidin-5-yl)pyridin-3-yl]cyclobutyl]-1,2,4-oxadiazol-5-yl]pyrazol-1-yl]-2,2-dimethylpropanoic acid Chemical compound C1=NN(CC(C)(C)C(O)=O)C=C1C1=NC(C2(CCC2)C=2C=NC(=CC=2)C=2C=NC(N)=NC=2)=NO1 QFYGRJJJLJJYPZ-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- FEDAGQSFDTWQEP-UHFFFAOYSA-N 5-(2-methoxyethylamino)pyrazine-2-carboxylic acid Chemical compound COCCNC1=CN=C(C(O)=O)C=N1 FEDAGQSFDTWQEP-UHFFFAOYSA-N 0.000 description 2
- YRXBCVCCLKNRHG-UHFFFAOYSA-N 5-[5-[1-[5-(1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl]cyclobutyl]pyridin-2-yl]pyrazin-2-amine Chemical compound C1=NC(N)=CN=C1C1=CC=C(C2(CCC2)C=2N=C(ON=2)C2=CNN=C2)C=N1 YRXBCVCCLKNRHG-UHFFFAOYSA-N 0.000 description 2
- IRXIKKOGYMPZEC-UHFFFAOYSA-N 5-chloro-3-[1-(6-chloropyridin-3-yl)cyclobutyl]-1,2,4-oxadiazole Chemical compound O1C(Cl)=NC(C2(CCC2)C=2C=NC(Cl)=CC=2)=N1 IRXIKKOGYMPZEC-UHFFFAOYSA-N 0.000 description 2
- KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- 101150037123 APOE gene Proteins 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 101100216294 Danio rerio apoeb gene Proteins 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 206010065390 Inflammatory pain Diseases 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 150000007942 carboxylates Chemical class 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000007876 drug discovery Methods 0.000 description 2
- ZVOJEVLYZWDTKM-UHFFFAOYSA-N ethyl 3-[4-[3-[1-[6-(2-aminopyrimidin-5-yl)pyridin-3-yl]cyclobutyl]-1,2,4-oxadiazol-5-yl]pyrazol-1-yl]-2,2-dimethylpropanoate Chemical compound C1=NN(CC(C)(C)C(=O)OCC)C=C1C1=NC(C2(CCC2)C=2C=NC(=CC=2)C=2C=NC(N)=NC=2)=NO1 ZVOJEVLYZWDTKM-UHFFFAOYSA-N 0.000 description 2
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 2
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 2
- DFQGDHBGRSTTHX-UHFFFAOYSA-N fiboflapon Chemical compound C1=NC(OCC)=CC=C1C(C=C1)=CC=C1CN1C2=CC=C(OCC=3N=CC(C)=CC=3)C=C2C(SC(C)(C)C)=C1CC(C)(C)C(O)=O DFQGDHBGRSTTHX-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 125000002346 iodo group Chemical group I* 0.000 description 2
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 2
- 108010072713 leukotriene A4 hydrolase Proteins 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 2
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- YPFDHNVEDLHUCE-UHFFFAOYSA-N propane-1,3-diol Chemical compound OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 201000001474 proteinuria Diseases 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
- 238000013389 whole blood assay Methods 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 1
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- AEBWATHAIVJLTA-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydropentalene Chemical compound C1CCC2CCCC21 AEBWATHAIVJLTA-UHFFFAOYSA-N 0.000 description 1
- 125000004505 1,2,4-oxadiazol-5-yl group Chemical group O1N=CN=C1* 0.000 description 1
- LXWAHEQTYXIWOL-UHFFFAOYSA-N 1-(5-bromopyridin-2-yl)cyclobutane-1-carbonitrile Chemical compound N1=CC(Br)=CC=C1C1(C#N)CCC1 LXWAHEQTYXIWOL-UHFFFAOYSA-N 0.000 description 1
- LGOCJYPKNBNQPL-UHFFFAOYSA-N 1-(6-chloropyridin-3-yl)-n'-hydroxycyclobutane-1-carboximidamide Chemical compound C=1C=C(Cl)N=CC=1C1(C(=N)NO)CCC1 LGOCJYPKNBNQPL-UHFFFAOYSA-N 0.000 description 1
- ISMOOOHNYQPYDE-UHFFFAOYSA-N 1-(6-chloropyridin-3-yl)cyclobutane-1-carbonitrile Chemical compound C1=NC(Cl)=CC=C1C1(C#N)CCC1 ISMOOOHNYQPYDE-UHFFFAOYSA-N 0.000 description 1
- REJZSDGHMLFPIL-UHFFFAOYSA-N 1-(oxetan-3-yl)pyrazole Chemical compound C1OCC1N1N=CC=C1 REJZSDGHMLFPIL-UHFFFAOYSA-N 0.000 description 1
- URYWLMOXFFOFLE-UHFFFAOYSA-N 1-(trifluoromethyl)-2h-pyridine Chemical compound FC(F)(F)N1CC=CC=C1 URYWLMOXFFOFLE-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- HTELJZKEPOOTIK-UHFFFAOYSA-N 2-[4-[3-[1-[6-(2-aminopyrimidin-5-yl)pyridin-3-yl]cyclobutyl]-1,2,4-oxadiazol-5-yl]pyrazol-1-yl]-n-tert-butyl-n-methylacetamide Chemical compound C1=NN(CC(=O)N(C)C(C)(C)C)C=C1C1=NC(C2(CCC2)C=2C=NC(=CC=2)C=2C=NC(N)=NC=2)=NO1 HTELJZKEPOOTIK-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 1
- DFNJKJJPJAVTNY-UHFFFAOYSA-N 2-methylsulfonyl-1h-pyrrole Chemical compound CS(=O)(=O)C1=CC=CN1 DFNJKJJPJAVTNY-UHFFFAOYSA-N 0.000 description 1
- PCLKVJBRTCQNDU-UHFFFAOYSA-N 2-methylsulfonylpyridine Chemical compound CS(=O)(=O)C1=CC=CC=N1 PCLKVJBRTCQNDU-UHFFFAOYSA-N 0.000 description 1
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
- BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- ANDWAJHNYJXSJC-UHFFFAOYSA-N 5-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]pyrazine-2-carboxylic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CN=C(C(O)=O)C=N1 ANDWAJHNYJXSJC-UHFFFAOYSA-N 0.000 description 1
- RWPBGNDGAWDIJG-UHFFFAOYSA-N 5-[5-[1-[5-(3-nitro-1h-pyrazol-5-yl)-1,2,4-oxadiazol-3-yl]cyclobutyl]pyridin-2-yl]pyrimidin-2-amine Chemical compound C1=NC(N)=NC=C1C1=CC=C(C2(CCC2)C=2N=C(ON=2)C=2NN=C(C=2)[N+]([O-])=O)C=N1 RWPBGNDGAWDIJG-UHFFFAOYSA-N 0.000 description 1
- SZJLALQHZCIFPW-UHFFFAOYSA-N 5-[5-[1-[5-(5-imidazol-1-ylpyrazin-2-yl)-1,2,4-oxadiazol-3-yl]cyclobutyl]pyridin-2-yl]pyrimidin-2-amine Chemical compound C1=NC(N)=NC=C1C1=CC=C(C2(CCC2)C=2N=C(ON=2)C=2N=CC(=NC=2)N2C=NC=C2)C=N1 SZJLALQHZCIFPW-UHFFFAOYSA-N 0.000 description 1
- GOFYEFSGVHDNIZ-UHFFFAOYSA-N 5-[5-[1-[5-[1-(methylsulfanylmethyl)pyrazol-4-yl]-1,2,4-oxadiazol-3-yl]cyclobutyl]pyridin-2-yl]pyrimidin-2-amine Chemical compound C1=NN(CSC)C=C1C1=NC(C2(CCC2)C=2C=NC(=CC=2)C=2C=NC(N)=NC=2)=NO1 GOFYEFSGVHDNIZ-UHFFFAOYSA-N 0.000 description 1
- IZQIQDTXJMZGLT-UHFFFAOYSA-N 5-[5-[1-[5-[1-(methylsulfonylmethyl)pyrazol-4-yl]-1,2,4-oxadiazol-3-yl]cyclobutyl]pyridin-2-yl]pyrimidin-2-amine Chemical compound C1=NN(CS(=O)(=O)C)C=C1C1=NC(C2(CCC2)C=2C=NC(=CC=2)C=2C=NC(N)=NC=2)=NO1 IZQIQDTXJMZGLT-UHFFFAOYSA-N 0.000 description 1
- 239000003406 5-lipoxygenase-activating protein inhibitor Substances 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- 208000036065 Airway Remodeling Diseases 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 102000013918 Apolipoproteins E Human genes 0.000 description 1
- 108010025628 Apolipoproteins E Proteins 0.000 description 1
- 208000033116 Asbestos intoxication Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 206010006448 Bronchiolitis Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- PBZCWVTYHMVGSD-UHFFFAOYSA-N C1(CCCCC1)P(C1=CC=CC=C1)C1CCCCC1.C(C)(=O)O Chemical compound C1(CCCCC1)P(C1=CC=CC=C1)C1CCCCC1.C(C)(=O)O PBZCWVTYHMVGSD-UHFFFAOYSA-N 0.000 description 1
- HIYAVKIYRIFSCZ-CVXKHCKVSA-N Calcimycin Chemical compound CC([C@H]1OC2([C@@H](C[C@H]1C)C)O[C@H]([C@H](CC2)C)CC=1OC2=CC=C(C(=C2N=1)C(O)=O)NC)C(=O)C1=CC=CN1 HIYAVKIYRIFSCZ-CVXKHCKVSA-N 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101100455054 Homo sapiens LTA4H gene Proteins 0.000 description 1
- 101000633429 Homo sapiens Structural maintenance of chromosomes protein 1A Proteins 0.000 description 1
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
- 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 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 208000005615 Interstitial Cystitis Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- UCHDWCPVSPXUMX-TZIWLTJVSA-N Montelukast Chemical compound CC(C)(O)C1=CC=CC=C1CC[C@H](C=1C=C(\C=C\C=2N=C3C=C(Cl)C=CC3=CC=2)C=CC=1)SCC1(CC(O)=O)CC1 UCHDWCPVSPXUMX-TZIWLTJVSA-N 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 1
- 206010051739 Pulmonary sepsis Diseases 0.000 description 1
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 101100075025 Scheffersomyces stipitis (strain ATCC 58785 / CBS 6054 / NBRC 10063 / NRRL Y-11545) LTA4 gene Proteins 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 206010040642 Sickle cell anaemia with crisis Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 102100029538 Structural maintenance of chromosomes protein 1A Human genes 0.000 description 1
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 1
- 108091005735 TGF-beta receptors Proteins 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 102000016715 Transforming Growth Factor beta Receptors Human genes 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 208000002365 Viral Bronchiolitis Diseases 0.000 description 1
- YEEZWCHGZNKEEK-UHFFFAOYSA-N Zafirlukast Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)C)=CC=C1CC(C1=C2)=CN(C)C1=CC=C2NC(=O)OC1CCCC1 YEEZWCHGZNKEEK-UHFFFAOYSA-N 0.000 description 1
- LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 206010051895 acute chest syndrome Diseases 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 208000007474 aortic aneurysm Diseases 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- 206010003441 asbestosis Diseases 0.000 description 1
- 230000036523 atherogenesis Effects 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 125000002785 azepinyl group Chemical group 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 150000008107 benzenesulfonic acids Chemical class 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 239000012148 binding buffer Substances 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000006696 biosynthetic metabolic pathway Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 230000003435 bronchoconstrictive effect Effects 0.000 description 1
- 206010006475 bronchopulmonary dysplasia Diseases 0.000 description 1
- HIYAVKIYRIFSCZ-UHFFFAOYSA-N calcium ionophore A23187 Natural products N=1C2=C(C(O)=O)C(NC)=CC=C2OC=1CC(C(CC1)C)OC1(C(CC1C)C)OC1C(C)C(=O)C1=CC=CN1 HIYAVKIYRIFSCZ-UHFFFAOYSA-N 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000002517 constrictor effect Effects 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- GFBLFDSCAKHHGX-UHFFFAOYSA-N cyclobutanecarbonitrile Chemical compound N#CC1CCC1 GFBLFDSCAKHHGX-UHFFFAOYSA-N 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- WXQFLZZSZCDWCV-UHFFFAOYSA-N cyclopropanol Chemical compound OC1[CH]C1 WXQFLZZSZCDWCV-UHFFFAOYSA-N 0.000 description 1
- 125000006317 cyclopropyl amino group Chemical group 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 125000005508 decahydronaphthalenyl group Chemical group 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 125000005046 dihydronaphthyl group Chemical group 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- AZHSSKPUVBVXLK-UHFFFAOYSA-N ethane-1,1-diol Chemical compound CC(O)O AZHSSKPUVBVXLK-UHFFFAOYSA-N 0.000 description 1
- QIHWDPMLGZEHIS-UHFFFAOYSA-N ethyl 2-[4-[3-[1-[6-(2-aminopyrimidin-5-yl)pyridin-3-yl]cyclobutyl]-1,2,4-oxadiazol-5-yl]pyrazol-1-yl]acetate Chemical compound C1=NN(CC(=O)OCC)C=C1C1=NC(C2(CCC2)C=2C=NC(=CC=2)C=2C=NC(N)=NC=2)=NO1 QIHWDPMLGZEHIS-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- HQVFCQRVQFYGRJ-UHFFFAOYSA-N formic acid;hydrate Chemical compound O.OC=O HQVFCQRVQFYGRJ-UHFFFAOYSA-N 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 1
- 102000043957 human ALOX5AP Human genes 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- BNRNAKTVFSZAFA-UHFFFAOYSA-N hydrindane Chemical compound C1CCCC2CCCC21 BNRNAKTVFSZAFA-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000005298 iminyl group Chemical group 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
- 229940047889 isobutyramide Drugs 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- UFPQIRYSPUYQHK-WAQVJNLQSA-N leukotriene A4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@@H]1O[C@H]1CCCC(O)=O UFPQIRYSPUYQHK-WAQVJNLQSA-N 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- SQBIMRFPOXLQBE-UHFFFAOYSA-N methyl 2-[4-[3-[1-[6-(2-aminopyrimidin-5-yl)pyridin-3-yl]cyclobutyl]-1,2,4-oxadiazol-5-yl]pyrazol-1-yl]-2-methylpropanoate Chemical compound C1=NN(C(C)(C)C(=O)OC)C=C1C1=NC(C2(CCC2)C=2C=NC(=CC=2)C=2C=NC(N)=NC=2)=NO1 SQBIMRFPOXLQBE-UHFFFAOYSA-N 0.000 description 1
- KBGRQUIYGLVTOX-UHFFFAOYSA-N methyl 5-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]pyrazine-2-carboxylate Chemical compound C1=NC(C(=O)OC)=CN=C1N1CCN(C(=O)OC(C)(C)C)CC1 KBGRQUIYGLVTOX-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000001620 monocyclic carbocycle group Chemical group 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 229960005127 montelukast Drugs 0.000 description 1
- SVEUVITYHIHZQE-UHFFFAOYSA-N n-methylpyridin-2-amine Chemical compound CNC1=CC=CC=N1 SVEUVITYHIHZQE-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 208000001797 obstructive sleep apnea Diseases 0.000 description 1
- 125000005060 octahydroindolyl group Chemical group N1(CCC2CCCCC12)* 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 150000004866 oxadiazoles Chemical class 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000009038 pharmacological inhibition Effects 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- SIOXPEMLGUPBBT-UHFFFAOYSA-M picolinate Chemical compound [O-]C(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-M 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 1
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960004583 pranlukast Drugs 0.000 description 1
- UAJUXJSXCLUTNU-UHFFFAOYSA-N pranlukast Chemical compound C=1C=C(OCCCCC=2C=CC=CC=2)C=CC=1C(=O)NC(C=1)=CC=C(C(C=2)=O)C=1OC=2C=1N=NNN=1 UAJUXJSXCLUTNU-UHFFFAOYSA-N 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- NITSAQJPBJYMFL-UHFFFAOYSA-N pyridin-4-ol Chemical compound O=C1C=[C]NC=C1 NITSAQJPBJYMFL-UHFFFAOYSA-N 0.000 description 1
- JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- ZTEOUUSHYMVQTI-UHFFFAOYSA-N tert-butyl 4-[5-[3-[1-[6-(2-aminopyrimidin-5-yl)pyridin-3-yl]cyclobutyl]-1,2,4-oxadiazol-5-yl]pyrazin-2-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CN=C(C=2ON=C(N=2)C2(CCC2)C=2C=NC(=CC=2)C=2C=NC(N)=NC=2)C=N1 ZTEOUUSHYMVQTI-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 125000000464 thioxo group Chemical group S=* 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 229960004764 zafirlukast Drugs 0.000 description 1
- MWLSOWXNZPKENC-SSDOTTSWSA-N zileuton Chemical compound C1=CC=C2SC([C@H](N(O)C(N)=O)C)=CC2=C1 MWLSOWXNZPKENC-SSDOTTSWSA-N 0.000 description 1
- 229960005332 zileuton Drugs 0.000 description 1
Classifications
-
- 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
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61P9/10—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)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38573310P | 2010-09-23 | 2010-09-23 | |
| US61/385,733 | 2010-09-23 | ||
| US201161533349P | 2011-09-12 | 2011-09-12 | |
| US61/533,349 | 2011-09-12 | ||
| PCT/US2011/052254 WO2012040139A1 (en) | 2010-09-23 | 2011-09-20 | Oxadiazole inhibitors of leukotriene production |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2011305667A1 true AU2011305667A1 (en) | 2013-03-21 |
Family
ID=44720163
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2011305667A Abandoned AU2011305667A1 (en) | 2010-09-23 | 2011-09-20 | Oxadiazole inhibitors of leukotriene production |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US8575201B2 (enExample) |
| EP (1) | EP2619197B1 (enExample) |
| JP (1) | JP5713511B2 (enExample) |
| KR (1) | KR20130109122A (enExample) |
| CN (1) | CN103261193A (enExample) |
| AU (1) | AU2011305667A1 (enExample) |
| BR (1) | BR112013008638A2 (enExample) |
| CA (1) | CA2812449A1 (enExample) |
| CL (1) | CL2013000788A1 (enExample) |
| CO (1) | CO6710902A2 (enExample) |
| EA (1) | EA201300389A1 (enExample) |
| EC (1) | ECSP13012548A (enExample) |
| IN (1) | IN2013DN02555A (enExample) |
| MX (1) | MX2013003202A (enExample) |
| PE (1) | PE20131398A1 (enExample) |
| PH (1) | PH12013500545A1 (enExample) |
| SG (1) | SG188604A1 (enExample) |
| WO (1) | WO2012040139A1 (enExample) |
| ZA (1) | ZA201301747B (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3150164B2 (ja) | 1991-05-01 | 2001-03-26 | 電気化学工業株式会社 | セメント混和材及びセメント組成物 |
| WO2012027322A1 (en) * | 2010-08-26 | 2012-03-01 | Boehringer Ingelheim International Gmbh | Oxadiazole inhibitors of leukotriene production |
| EP2619196B1 (en) * | 2010-09-23 | 2015-09-16 | Boehringer Ingelheim International GmbH | Oxadiazole inhibitors of leukotriene production |
| EA201300389A1 (ru) | 2010-09-23 | 2013-09-30 | Бёрингер Ингельхайм Интернациональ Гмбх | Оксадиазольные ингибиторы продуцирования лейкотриена |
| AR089853A1 (es) | 2012-02-01 | 2014-09-24 | Boehringer Ingelheim Int | Inhibidores de oxadiazol de la produccion de leucotrienos para terapia de combinacion, composicion farmaceutica, uso |
| EP3495359A1 (en) * | 2013-02-04 | 2019-06-12 | Janssen Pharmaceutica NV | Flap modulators |
| EP2875736B1 (en) | 2013-11-26 | 2016-07-27 | Citrage | N-Carbamoylputrescine to enhance muscle protein synthesis |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2260031T3 (es) | 1999-08-06 | 2006-11-01 | Janssen Pharmaceutica N.V. | Derivados de 6-azauracilo que inhiben la interleucina-5. |
| JP2007502300A (ja) * | 2003-08-13 | 2007-02-08 | カイロン コーポレイション | Ｇｓｋ−３インヒビターおよびその使用 |
| US7319108B2 (en) | 2004-01-25 | 2008-01-15 | Sanofi-Aventis Deutschland Gmbh | Aryl-substituted heterocycles, process for their preparation and their use as medicaments |
| AU2005295646B2 (en) | 2004-10-18 | 2008-11-20 | Merck Sharp & Dohme Corp. | Diphenyl substituted alkanes as flap inhibitors |
| US7977359B2 (en) * | 2005-11-04 | 2011-07-12 | Amira Pharmaceuticals, Inc. | 5-lipdxygenase-activating protein (FLAP) inhibitors |
| US8399666B2 (en) * | 2005-11-04 | 2013-03-19 | Panmira Pharmaceuticals, Llc | 5-lipoxygenase-activating protein (FLAP) inhibitors |
| GB2431927B (en) | 2005-11-04 | 2010-03-17 | Amira Pharmaceuticals Inc | 5-Lipoxygenase-activating protein (FLAP) inhibitors |
| AU2007238878A1 (en) | 2006-04-11 | 2007-10-25 | Merck Sharp & Dohme Corp. | Diaryl substituted alkanes |
| CA2787343C (en) | 2006-06-26 | 2016-08-02 | Amgen Inc. | Compositions comprising modified lcat and uses thereof |
| ATE543810T1 (de) | 2006-09-01 | 2012-02-15 | Merck Sharp & Dohme | Hemmer des 5-lipoxygenase aktivierenden proteins (flap) |
| AU2008241313A1 (en) | 2007-04-20 | 2008-10-30 | Merck Frosst Canada Ltd. | Novel heteroaromatic compounds as inhibitors of stearoyl-coenzyme a delta-9 desaturase |
| CA2707360A1 (en) | 2007-06-20 | 2008-12-24 | Merck Sharp & Dohme Corp. | Diphenyl substituted alkanes |
| WO2009048547A1 (en) | 2007-10-10 | 2009-04-16 | Merck & Co., Inc. | Diphenyl substituted cycloalkanes |
| DE102008037790A1 (de) * | 2008-08-14 | 2010-02-18 | Merck Patent Gmbh | Bicyclische Triazolderivate |
| CA2741666C (en) * | 2008-10-31 | 2017-04-11 | Merck Sharp & Dohme Corp. | P2x3, receptor antagonists for treatment of pain |
| CA2749893A1 (en) | 2009-02-04 | 2010-08-12 | Pfizer Inc. | 4-amino-7,8-dihydropyrido[4,3-d]pyrimidin-5(6h)-one derivatives |
| EP2568809A4 (en) | 2010-05-12 | 2013-11-06 | Univ Vanderbilt | HETEROCYCLIC ALLOSTERE SULFON MGLUR4 POTENTIATORS, COMPOSITIONS AND METHODS OF TREATING NEUROLOGICAL DYSFUNCTIONS |
| PH12013500301A1 (en) * | 2010-08-16 | 2013-03-25 | Boehringer Ingelheim Int | Oxadiazole inhibitors of leukotriene production |
| WO2012027322A1 (en) * | 2010-08-26 | 2012-03-01 | Boehringer Ingelheim International Gmbh | Oxadiazole inhibitors of leukotriene production |
| EA201300389A1 (ru) | 2010-09-23 | 2013-09-30 | Бёрингер Ингельхайм Интернациональ Гмбх | Оксадиазольные ингибиторы продуцирования лейкотриена |
| EP2619196B1 (en) * | 2010-09-23 | 2015-09-16 | Boehringer Ingelheim International GmbH | Oxadiazole inhibitors of leukotriene production |
-
2011
- 2011-09-20 EA EA201300389A patent/EA201300389A1/ru unknown
- 2011-09-20 PH PH1/2013/500545A patent/PH12013500545A1/en unknown
- 2011-09-20 BR BR112013008638A patent/BR112013008638A2/pt not_active IP Right Cessation
- 2011-09-20 CA CA2812449A patent/CA2812449A1/en not_active Abandoned
- 2011-09-20 US US13/237,112 patent/US8575201B2/en active Active
- 2011-09-20 AU AU2011305667A patent/AU2011305667A1/en not_active Abandoned
- 2011-09-20 WO PCT/US2011/052254 patent/WO2012040139A1/en not_active Ceased
- 2011-09-20 SG SG2013020300A patent/SG188604A1/en unknown
- 2011-09-20 CN CN2011800565586A patent/CN103261193A/zh active Pending
- 2011-09-20 MX MX2013003202A patent/MX2013003202A/es active IP Right Grant
- 2011-09-20 JP JP2013530221A patent/JP5713511B2/ja active Active
- 2011-09-20 IN IN2555DEN2013 patent/IN2013DN02555A/en unknown
- 2011-09-20 EP EP11761775.3A patent/EP2619197B1/en active Active
- 2011-09-20 PE PE2013000629A patent/PE20131398A1/es not_active Application Discontinuation
- 2011-09-20 KR KR1020137007287A patent/KR20130109122A/ko not_active Withdrawn
-
2013
- 2013-03-07 ZA ZA2013/01747A patent/ZA201301747B/en unknown
- 2013-03-21 CL CL2013000788A patent/CL2013000788A1/es unknown
- 2013-03-22 CO CO13057875A patent/CO6710902A2/es not_active Application Discontinuation
- 2013-04-11 EC ECSP13012548 patent/ECSP13012548A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2012040139A1 (en) | 2012-03-29 |
| ECSP13012548A (es) | 2013-06-28 |
| KR20130109122A (ko) | 2013-10-07 |
| EA201300389A1 (ru) | 2013-09-30 |
| CA2812449A1 (en) | 2012-03-29 |
| EP2619197B1 (en) | 2015-08-05 |
| US8575201B2 (en) | 2013-11-05 |
| ZA201301747B (en) | 2014-08-27 |
| CO6710902A2 (es) | 2013-07-15 |
| MX2013003202A (es) | 2013-04-24 |
| JP2013537909A (ja) | 2013-10-07 |
| IN2013DN02555A (enExample) | 2015-08-07 |
| EP2619197A1 (en) | 2013-07-31 |
| JP5713511B2 (ja) | 2015-05-07 |
| PH12013500545A1 (en) | 2013-05-06 |
| CN103261193A (zh) | 2013-08-21 |
| BR112013008638A2 (pt) | 2016-06-21 |
| SG188604A1 (en) | 2013-04-30 |
| PE20131398A1 (es) | 2013-12-19 |
| CL2013000788A1 (es) | 2013-06-28 |
| US20120295896A1 (en) | 2012-11-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5862669B2 (ja) | ロイコトリエン産生のオキサジアゾール阻害剤 | |
| RU2610840C2 (ru) | Тиазолопиримидины | |
| JP6759514B2 (ja) | ブロモドメインに対して活性な化合物 | |
| CN105339368B (zh) | 3‑芳基‑取代的咪唑并[1,2‑a]吡啶及其用途 | |
| US9187464B2 (en) | TRPV4 antagonists | |
| AU2011292285A1 (en) | Oxadiazole inhibitors of leukotriene production | |
| CA2919783C (en) | Heterobicycloaryl rorc2 inhibitors and methods of use thereof | |
| CN110156770A (zh) | 作为tam族激酶抑制剂的氨基吡啶衍生物 | |
| WO2017210545A1 (en) | Potassium channel modulators | |
| US8575201B2 (en) | Oxadiazole inhibitors of leukotriene production | |
| CA3183676A1 (en) | Piperazine cyclic ureas | |
| US8580825B2 (en) | Oxadiazole inhibitors of leukotriene production | |
| CN120225521A (zh) | Akt1调节剂 | |
| WO2006109817A1 (ja) | １，４－置換ピペラジン誘導体 | |
| JP7823226B2 (ja) | Ｄｄｒ１キナーゼ阻害剤としての化合物および医薬 | |
| OA16344A (en) | Oxadiazole inhibitors of leukotriene production. | |
| HK40087839A (en) | Piperazine cyclic ureas | |
| HK1183300A (en) | Oxadiazole inhibitors of leukotriene production |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1 | Application lapsed section 142(2)(a) - no request for examination in relevant period |