CA2758918A1 - 4-azetidinyl-1-heteroaryl-cyclohexane antagonists of ccr2 - Google Patents
4-azetidinyl-1-heteroaryl-cyclohexane antagonists of ccr2 Download PDFInfo
- Publication number
- CA2758918A1 CA2758918A1 CA2758918A CA2758918A CA2758918A1 CA 2758918 A1 CA2758918 A1 CA 2758918A1 CA 2758918 A CA2758918 A CA 2758918A CA 2758918 A CA2758918 A CA 2758918A CA 2758918 A1 CA2758918 A1 CA 2758918A1
- Authority
- CA
- Canada
- Prior art keywords
- pyridin
- alkyl
- group
- optionally substituted
- prepared
- 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
- 239000005557 antagonist Substances 0.000 title description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 286
- 238000000034 method Methods 0.000 claims abstract description 155
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 74
- 208000035475 disorder Diseases 0.000 claims abstract description 41
- 201000010099 disease Diseases 0.000 claims abstract description 33
- 208000011580 syndromic disease Diseases 0.000 claims abstract description 29
- 208000006673 asthma Diseases 0.000 claims abstract description 17
- 208000008589 Obesity Diseases 0.000 claims abstract description 11
- 235000020824 obesity Nutrition 0.000 claims abstract description 11
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 10
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 claims abstract 3
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 claims abstract 3
- -1 pyridyl-N-oxide Chemical group 0.000 claims description 145
- 125000000217 alkyl group Chemical group 0.000 claims description 84
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 60
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 52
- 125000004432 carbon atom Chemical group C* 0.000 claims description 49
- 150000003839 salts Chemical class 0.000 claims description 41
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 33
- 125000000335 thiazolyl group Chemical group 0.000 claims description 33
- 101710155857 C-C motif chemokine 2 Proteins 0.000 claims description 32
- 125000004076 pyridyl group Chemical group 0.000 claims description 31
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 31
- 239000012453 solvate Substances 0.000 claims description 29
- 229910052799 carbon Inorganic materials 0.000 claims description 28
- 229910052731 fluorine Inorganic materials 0.000 claims description 25
- 229940002612 prodrug Drugs 0.000 claims description 23
- 239000000651 prodrug Substances 0.000 claims description 23
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 150000004677 hydrates Chemical class 0.000 claims description 21
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 21
- 230000008569 process Effects 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 229910052801 chlorine Inorganic materials 0.000 claims description 16
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 15
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 14
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 14
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 14
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 11
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 10
- 206010046851 Uveitis Diseases 0.000 claims description 10
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims description 10
- 125000001041 indolyl group Chemical group 0.000 claims description 10
- 230000001404 mediated effect Effects 0.000 claims description 10
- 230000014509 gene expression Effects 0.000 claims description 9
- 125000002883 imidazolyl group Chemical group 0.000 claims description 9
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 9
- 125000001544 thienyl group Chemical group 0.000 claims description 9
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 8
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 210000004072 lung Anatomy 0.000 claims description 8
- 206010061218 Inflammation Diseases 0.000 claims description 7
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 7
- 201000009961 allergic asthma Diseases 0.000 claims description 7
- 201000010105 allergic rhinitis Diseases 0.000 claims description 7
- 125000002619 bicyclic group Chemical group 0.000 claims description 7
- 230000002757 inflammatory effect Effects 0.000 claims description 7
- 230000004054 inflammatory process Effects 0.000 claims description 7
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 7
- 125000002971 oxazolyl group Chemical group 0.000 claims description 7
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 6
- 229910007161 Si(CH3)3 Inorganic materials 0.000 claims description 6
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 claims description 6
- 125000005872 benzooxazolyl group Chemical group 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 230000002018 overexpression Effects 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
- 201000001320 Atherosclerosis Diseases 0.000 claims description 5
- 208000011231 Crohn disease Diseases 0.000 claims description 5
- 208000002249 Diabetes Complications Diseases 0.000 claims description 5
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 5
- 206010012655 Diabetic complications Diseases 0.000 claims description 5
- 206010054044 Diabetic microangiopathy Diseases 0.000 claims description 5
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- 206010038910 Retinitis Diseases 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 201000009101 diabetic angiopathy Diseases 0.000 claims description 5
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 5
- 208000028169 periodontal disease Diseases 0.000 claims description 5
- 201000000306 sarcoidosis Diseases 0.000 claims description 5
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 4
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 4
- 201000009030 Carcinoma Diseases 0.000 claims description 4
- 206010007558 Cardiac failure chronic Diseases 0.000 claims description 4
- 208000031229 Cardiomyopathies Diseases 0.000 claims description 4
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 4
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 4
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 4
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 4
- 208000017604 Hodgkin disease Diseases 0.000 claims description 4
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 4
- 206010061216 Infarction Diseases 0.000 claims description 4
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 4
- 208000034578 Multiple myelomas Diseases 0.000 claims description 4
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 4
- 208000009525 Myocarditis Diseases 0.000 claims description 4
- 206010036346 Posterior capsule opacification Diseases 0.000 claims description 4
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 4
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 4
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 4
- 206010052568 Urticaria chronic Diseases 0.000 claims description 4
- 208000002205 allergic conjunctivitis Diseases 0.000 claims description 4
- 208000024998 atopic conjunctivitis Diseases 0.000 claims description 4
- 201000008937 atopic dermatitis Diseases 0.000 claims description 4
- 210000000481 breast Anatomy 0.000 claims description 4
- 230000000747 cardiac effect Effects 0.000 claims description 4
- 210000003679 cervix uteri Anatomy 0.000 claims description 4
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 4
- 208000024376 chronic urticaria Diseases 0.000 claims description 4
- 210000001072 colon Anatomy 0.000 claims description 4
- 230000003205 diastolic effect Effects 0.000 claims description 4
- 208000024693 gingival disease Diseases 0.000 claims description 4
- 208000007565 gingivitis Diseases 0.000 claims description 4
- 230000007574 infarction Effects 0.000 claims description 4
- 201000006370 kidney failure Diseases 0.000 claims description 4
- 201000010260 leiomyoma Diseases 0.000 claims description 4
- 230000003211 malignant effect Effects 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 4
- 201000008383 nephritis Diseases 0.000 claims description 4
- 210000000056 organ Anatomy 0.000 claims description 4
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 4
- 210000002307 prostate Anatomy 0.000 claims description 4
- 230000010410 reperfusion Effects 0.000 claims description 4
- 208000037803 restenosis Diseases 0.000 claims description 4
- 210000002784 stomach Anatomy 0.000 claims description 4
- 238000001356 surgical procedure Methods 0.000 claims description 4
- 201000008827 tuberculosis Diseases 0.000 claims description 4
- 210000003932 urinary bladder Anatomy 0.000 claims description 4
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
- 206010022489 Insulin Resistance Diseases 0.000 claims description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 230000004968 inflammatory condition Effects 0.000 claims description 3
- 206010033307 Overweight Diseases 0.000 claims description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 235000020825 overweight Nutrition 0.000 claims description 2
- ZBZJXHCVGLJWFG-UHFFFAOYSA-N trichloromethyl(.) Chemical compound Cl[C](Cl)Cl ZBZJXHCVGLJWFG-UHFFFAOYSA-N 0.000 claims 5
- 102100021943 C-C motif chemokine 2 Human genes 0.000 claims 4
- 230000000694 effects Effects 0.000 abstract description 4
- 241000124008 Mammalia Species 0.000 abstract description 3
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 235000013350 formula milk Nutrition 0.000 abstract 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 205
- 239000007787 solid Substances 0.000 description 158
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 95
- 238000005481 NMR spectroscopy Methods 0.000 description 89
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 87
- 235000019439 ethyl acetate Nutrition 0.000 description 74
- 101150041968 CDC13 gene Proteins 0.000 description 72
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 55
- 238000005160 1H NMR spectroscopy Methods 0.000 description 50
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 47
- 238000006243 chemical reaction Methods 0.000 description 46
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 41
- 239000000741 silica gel Substances 0.000 description 41
- 229910002027 silica gel Inorganic materials 0.000 description 41
- 239000000243 solution Substances 0.000 description 41
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 40
- 229910052740 iodine Inorganic materials 0.000 description 40
- 239000000203 mixture Substances 0.000 description 40
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- 238000006268 reductive amination reaction Methods 0.000 description 36
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 30
- PSKCMKAZXPYOOQ-UHFFFAOYSA-N n-[2-(azetidin-3-ylamino)-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)NC2CNC2)=C1 PSKCMKAZXPYOOQ-UHFFFAOYSA-N 0.000 description 30
- 239000007832 Na2SO4 Substances 0.000 description 29
- 229910052938 sodium sulfate Inorganic materials 0.000 description 29
- 235000011152 sodium sulphate Nutrition 0.000 description 29
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 28
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 28
- 102000000018 Chemokine CCL2 Human genes 0.000 description 28
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 28
- 241001465754 Metazoa Species 0.000 description 28
- 239000012044 organic layer Substances 0.000 description 27
- 239000003960 organic solvent Substances 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- 230000000875 corresponding effect Effects 0.000 description 23
- 238000005984 hydrogenation reaction Methods 0.000 description 23
- 239000012267 brine Substances 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- 241000699670 Mus sp. Species 0.000 description 19
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 150000002576 ketones Chemical class 0.000 description 18
- DKKFUAGGDZFVON-UHFFFAOYSA-N 2-(fluoromethyl)benzamide Chemical compound NC(=O)C1=CC=CC=C1CF DKKFUAGGDZFVON-UHFFFAOYSA-N 0.000 description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 15
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 15
- 238000010511 deprotection reaction Methods 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
- 238000001704 evaporation Methods 0.000 description 14
- 230000008020 evaporation Effects 0.000 description 14
- 239000003981 vehicle Substances 0.000 description 14
- 239000000047 product Substances 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 12
- 239000003814 drug Substances 0.000 description 11
- 210000001616 monocyte Anatomy 0.000 description 11
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 10
- 239000003480 eluent Substances 0.000 description 10
- 238000011282 treatment Methods 0.000 description 10
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 9
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 229910000029 sodium carbonate Inorganic materials 0.000 description 8
- 235000017550 sodium carbonate Nutrition 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 230000008878 coupling Effects 0.000 description 7
- 238000010168 coupling process Methods 0.000 description 7
- 238000005859 coupling reaction Methods 0.000 description 7
- 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 7
- 239000000706 filtrate Substances 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- 238000012746 preparative thin layer chromatography Methods 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 235000011149 sulphuric acid Nutrition 0.000 description 7
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- ZDJUNNCVIDKJAN-UHFFFAOYSA-N 5-iodo-1h-pyridin-2-one Chemical compound OC1=CC=C(I)C=N1 ZDJUNNCVIDKJAN-UHFFFAOYSA-N 0.000 description 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 5
- WEVYAHXRMPXWCK-FIBGUPNXSA-N acetonitrile-d3 Chemical compound [2H]C([2H])([2H])C#N WEVYAHXRMPXWCK-FIBGUPNXSA-N 0.000 description 5
- 150000001335 aliphatic alkanes Chemical class 0.000 description 5
- 150000001336 alkenes Chemical class 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- VKRKCBWIVLSRBJ-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decan-8-one Chemical compound C1CC(=O)CCC21OCCO2 VKRKCBWIVLSRBJ-UHFFFAOYSA-N 0.000 description 4
- PLPYFDYELOJEAS-UHFFFAOYSA-N 4-(6-aminopyridin-2-yl)cyclohexan-1-one Chemical compound NC1=CC=CC(C2CCC(=O)CC2)=N1 PLPYFDYELOJEAS-UHFFFAOYSA-N 0.000 description 4
- XTHKRYHULUJQHN-UHFFFAOYSA-N 6-bromopyridin-3-amine Chemical compound NC1=CC=C(Br)N=C1 XTHKRYHULUJQHN-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- 235000011089 carbon dioxide Nutrition 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 230000005012 migration Effects 0.000 description 4
- 238000013508 migration Methods 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 150000007530 organic bases Chemical class 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- MSRREIDXJQTTJQ-UHFFFAOYSA-N 2-(1,4-dioxaspiro[4.5]decan-8-yl)-1,3-thiazole-5-carboxylic acid Chemical compound S1C(C(=O)O)=CN=C1C1CCC2(OCCO2)CC1 MSRREIDXJQTTJQ-UHFFFAOYSA-N 0.000 description 3
- HKDVVTLISGIPFE-UHFFFAOYSA-N 2-bromopyridin-3-amine Chemical compound NC1=CC=CN=C1Br HKDVVTLISGIPFE-UHFFFAOYSA-N 0.000 description 3
- PSZKQMPSKNEZPT-UHFFFAOYSA-N 3-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-2-methoxypyridine Chemical compound COC1=NC=CC=C1C(CC1)=CCC21OCCO2 PSZKQMPSKNEZPT-UHFFFAOYSA-N 0.000 description 3
- PUHILLSSLQKHBD-UHFFFAOYSA-N 3-(1,4-dioxaspiro[4.5]decan-8-yl)-1h-pyridin-2-one Chemical compound OC1=NC=CC=C1C1CCC2(OCCO2)CC1 PUHILLSSLQKHBD-UHFFFAOYSA-N 0.000 description 3
- GCNJSOCCQBURTJ-UHFFFAOYSA-N 4-(2-methoxypyridin-3-yl)cyclohex-3-en-1-one Chemical compound COC1=NC=CC=C1C1=CCC(=O)CC1 GCNJSOCCQBURTJ-UHFFFAOYSA-N 0.000 description 3
- VQZVMRZEBPGSFQ-UHFFFAOYSA-N 4-hydroxy-4-(6-methoxypyridin-3-yl)cyclohexan-1-one Chemical compound C1=NC(OC)=CC=C1C1(O)CCC(=O)CC1 VQZVMRZEBPGSFQ-UHFFFAOYSA-N 0.000 description 3
- IRBOWELCALHZAI-UHFFFAOYSA-N 5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1h-pyridin-2-one Chemical compound N1C(=O)C=CC(C=2CCC3(CC=2)OCCO3)=C1 IRBOWELCALHZAI-UHFFFAOYSA-N 0.000 description 3
- PKAWXPRLRLJKGU-UHFFFAOYSA-N 6-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyridin-2-amine Chemical compound NC1=CC=CC(C=2CCC3(CC=2)OCCO3)=N1 PKAWXPRLRLJKGU-UHFFFAOYSA-N 0.000 description 3
- YULQWWIKHWORAH-UHFFFAOYSA-N 6-(1,4-dioxaspiro[4.5]decan-8-yl)pyridin-3-amine Chemical compound N1=CC(N)=CC=C1C1CCC2(OCCO2)CC1 YULQWWIKHWORAH-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 102000019034 Chemokines Human genes 0.000 description 3
- 108010012236 Chemokines Proteins 0.000 description 3
- 238000002738 Giemsa staining Methods 0.000 description 3
- 108010061486 HLA-B27 Antigen Proteins 0.000 description 3
- 102000012153 HLA-B27 Antigen Human genes 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- NXQGGXCHGDYOHB-UHFFFAOYSA-L [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium (II) Substances [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- 150000001945 cysteines Chemical class 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- PQZTVWVYCLIIJY-UHFFFAOYSA-N diethyl(propyl)amine Chemical compound CCCN(CC)CC PQZTVWVYCLIIJY-UHFFFAOYSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- VDDXQSUSMHZCLS-UHFFFAOYSA-N ethenyl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC=C VDDXQSUSMHZCLS-UHFFFAOYSA-N 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 206010034674 peritonitis Diseases 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 229940124530 sulfonamide Drugs 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- WZWQNWWFCHNJON-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decane-8-carbonitrile Chemical compound C1CC(C#N)CCC21OCCO2 WZWQNWWFCHNJON-UHFFFAOYSA-N 0.000 description 2
- LIXFPFLXMYMGNC-UHFFFAOYSA-N 2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1,3-thiazole Chemical compound O1CCOC11CC=C(C=2SC=CN=2)CC1 LIXFPFLXMYMGNC-UHFFFAOYSA-N 0.000 description 2
- GRJLRFHPKXMRLD-UHFFFAOYSA-N 2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1h-pyridin-4-one Chemical compound OC1=CC=NC(C=2CCC3(CC=2)OCCO3)=C1 GRJLRFHPKXMRLD-UHFFFAOYSA-N 0.000 description 2
- BOJFZIPAQZMBLQ-UHFFFAOYSA-N 2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyrazine Chemical compound O1CCOC11CC=C(C=2N=CC=NC=2)CC1 BOJFZIPAQZMBLQ-UHFFFAOYSA-N 0.000 description 2
- MJHSLKOJQUPDKY-UHFFFAOYSA-N 2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyridin-3-ol Chemical compound OC1=CC=CN=C1C(CC1)=CCC21OCCO2 MJHSLKOJQUPDKY-UHFFFAOYSA-N 0.000 description 2
- GIMWGWNJYAWERO-UHFFFAOYSA-N 2-(1,4-dioxaspiro[4.5]decan-8-yl)-1,3-thiazole Chemical compound O1CCOC11CCC(C=2SC=CN=2)CC1 GIMWGWNJYAWERO-UHFFFAOYSA-N 0.000 description 2
- SFUMTNYVZUAFFC-UHFFFAOYSA-N 2-(1,4-dioxaspiro[4.5]decan-8-yl)-1,3-thiazole-5-carboxamide Chemical compound S1C(C(=O)N)=CN=C1C1CCC2(OCCO2)CC1 SFUMTNYVZUAFFC-UHFFFAOYSA-N 0.000 description 2
- YPXOGQXZASYMFI-UHFFFAOYSA-N 2-(1,4-dioxaspiro[4.5]decan-8-yl)propanedinitrile Chemical compound C1CC(C(C#N)C#N)CCC21OCCO2 YPXOGQXZASYMFI-UHFFFAOYSA-N 0.000 description 2
- ACRKESVOHVYDHW-UHFFFAOYSA-N 2-(1,4-dioxaspiro[4.5]decan-8-yl)pyridin-3-ol Chemical compound OC1=CC=CN=C1C1CCC2(OCCO2)CC1 ACRKESVOHVYDHW-UHFFFAOYSA-N 0.000 description 2
- ISEHHGWITPJNPE-UHFFFAOYSA-N 2-(4-oxocyclohexyl)-1,3-thiazole-5-carboxamide Chemical compound S1C(C(=O)N)=CN=C1C1CCC(=O)CC1 ISEHHGWITPJNPE-UHFFFAOYSA-N 0.000 description 2
- UBXHHSQITIEELF-UHFFFAOYSA-N 2-(4-oxocyclohexyl)-1h-pyridin-4-one Chemical compound OC1=CC=NC(C2CCC(=O)CC2)=C1 UBXHHSQITIEELF-UHFFFAOYSA-N 0.000 description 2
- QGWMZWAFPQPZKF-UHFFFAOYSA-N 2-[2-oxo-5-(4-oxocyclohexyl)pyridin-1-yl]acetonitrile Chemical compound C1CC(=O)CCC1C1=CN(CC#N)C(=O)C=C1 QGWMZWAFPQPZKF-UHFFFAOYSA-N 0.000 description 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
- WEMPEMXDSUATEK-UHFFFAOYSA-N 2-bromo-6-phenylmethoxypyridine Chemical compound BrC1=CC=CC(OCC=2C=CC=CC=2)=N1 WEMPEMXDSUATEK-UHFFFAOYSA-N 0.000 description 2
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- LACDNSNDJJPCJW-UHFFFAOYSA-N 3-(1,4-dioxaspiro[4.5]decan-8-yl)-1h-pyridin-4-one Chemical compound OC1=CC=NC=C1C1CCC2(OCCO2)CC1 LACDNSNDJJPCJW-UHFFFAOYSA-N 0.000 description 2
- MCBAJGFSXNNPCL-UHFFFAOYSA-N 3-(1,4-dioxaspiro[4.5]decan-8-yl)-5-(trichloromethyl)-1,2,4-oxadiazole Chemical compound O1C(C(Cl)(Cl)Cl)=NC(C2CCC3(CC2)OCCO3)=N1 MCBAJGFSXNNPCL-UHFFFAOYSA-N 0.000 description 2
- VHDPVEMFQSUFCT-UHFFFAOYSA-N 3-(1,4-dioxaspiro[4.5]decan-8-yl)pyridin-4-amine Chemical compound NC1=CC=NC=C1C1CCC2(OCCO2)CC1 VHDPVEMFQSUFCT-UHFFFAOYSA-N 0.000 description 2
- TXDFHVCFOQGIMV-UHFFFAOYSA-N 3-(4-oxocyclohexyl)-1h-pyridin-2-one Chemical compound OC1=NC=CC=C1C1CCC(=O)CC1 TXDFHVCFOQGIMV-UHFFFAOYSA-N 0.000 description 2
- RPONRSSXDCJHAN-UHFFFAOYSA-N 3-(4-oxocyclohexyl)-1h-pyridin-4-one Chemical compound OC1=CC=NC=C1C1CCC(=O)CC1 RPONRSSXDCJHAN-UHFFFAOYSA-N 0.000 description 2
- XOKWCSOPFXZXIU-UHFFFAOYSA-N 3-methyl-5-(4-oxocyclohexyl)-1h-pyridin-2-one Chemical compound N1C(=O)C(C)=CC(C2CCC(=O)CC2)=C1 XOKWCSOPFXZXIU-UHFFFAOYSA-N 0.000 description 2
- QEFAYLKOFVVZGR-UHFFFAOYSA-M 4-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1-methylpyridin-1-ium;iodide Chemical compound [I-].C1=C[N+](C)=CC=C1C(CC1)=CCC21OCCO2 QEFAYLKOFVVZGR-UHFFFAOYSA-M 0.000 description 2
- VQWAWWSDRNNUEF-UHFFFAOYSA-N 4-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyridine Chemical compound O1CCOC11CC=C(C=2C=CN=CC=2)CC1 VQWAWWSDRNNUEF-UHFFFAOYSA-N 0.000 description 2
- OBGHRGWYHZRPLX-UHFFFAOYSA-N 4-(1,4-dioxaspiro[4.5]decan-8-yl)-5-imino-4h-1,2-oxazol-3-amine Chemical compound N=C1NOC(=N)C1C1CCC2(OCCO2)CC1 OBGHRGWYHZRPLX-UHFFFAOYSA-N 0.000 description 2
- JDRWSFQUHCLDAE-UHFFFAOYSA-N 4-(1h-indol-3-yl)cyclohexan-1-one Chemical compound C1CC(=O)CCC1C1=CNC2=CC=CC=C12 JDRWSFQUHCLDAE-UHFFFAOYSA-N 0.000 description 2
- BEYWXZHKUQXINL-UHFFFAOYSA-N 4-(3-amino-5-imino-4h-1,2-oxazol-4-yl)cyclohexan-1-one Chemical compound N=C1NOC(=N)C1C1CCC(=O)CC1 BEYWXZHKUQXINL-UHFFFAOYSA-N 0.000 description 2
- RAMHTXDZBJOIIE-UHFFFAOYSA-N 4-(3-hydroxypyridin-2-yl)cyclohexan-1-one Chemical compound OC1=CC=CN=C1C1CCC(=O)CC1 RAMHTXDZBJOIIE-UHFFFAOYSA-N 0.000 description 2
- WHCXCQWDAQWHHW-UHFFFAOYSA-N 4-(4-aminopyridin-3-yl)cyclohexan-1-one Chemical compound NC1=CC=NC=C1C1CCC(=O)CC1 WHCXCQWDAQWHHW-UHFFFAOYSA-N 0.000 description 2
- RHLVHVVCEPDIBW-UHFFFAOYSA-N 4-(5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclohexan-1-one Chemical compound C1CC(=O)CCC1C1=NN2CCCCC2=N1 RHLVHVVCEPDIBW-UHFFFAOYSA-N 0.000 description 2
- XVQMMTUOOWCFJI-UHFFFAOYSA-N 4-(5-chloro-1,2,4-thiadiazol-3-yl)cyclohexan-1-one Chemical compound S1C(Cl)=NC(C2CCC(=O)CC2)=N1 XVQMMTUOOWCFJI-UHFFFAOYSA-N 0.000 description 2
- POTCZKRZTNLCAL-UHFFFAOYSA-N 4-(6-aminopyridin-3-yl)cyclohexan-1-one Chemical compound C1=NC(N)=CC=C1C1CCC(=O)CC1 POTCZKRZTNLCAL-UHFFFAOYSA-N 0.000 description 2
- VCEKBGKNNSAKGE-UHFFFAOYSA-N 4-(6-methoxypyridin-3-yl)cyclohex-3-en-1-one Chemical compound C1=NC(OC)=CC=C1C1=CCC(=O)CC1 VCEKBGKNNSAKGE-UHFFFAOYSA-N 0.000 description 2
- UPUAQYXJZIJKNW-UHFFFAOYSA-N 4-[2-(dimethylamino)pyrimidin-5-yl]cyclohexan-1-one Chemical compound C1=NC(N(C)C)=NC=C1C1CCC(=O)CC1 UPUAQYXJZIJKNW-UHFFFAOYSA-N 0.000 description 2
- IXKOAHDOQFJMIK-UHFFFAOYSA-N 4-[5-(trichloromethyl)-1,2,4-oxadiazol-3-yl]cyclohexan-1-one Chemical compound O1C(C(Cl)(Cl)Cl)=NC(C2CCC(=O)CC2)=N1 IXKOAHDOQFJMIK-UHFFFAOYSA-N 0.000 description 2
- DVCMSRCKPVPEPN-UHFFFAOYSA-N 4-[6-(methylamino)pyridin-2-yl]cyclohexan-1-one Chemical compound CNC1=CC=CC(C2CCC(=O)CC2)=N1 DVCMSRCKPVPEPN-UHFFFAOYSA-N 0.000 description 2
- GCNTZFIIOFTKIY-UHFFFAOYSA-N 4-hydroxypyridine Chemical compound OC1=CC=NC=C1 GCNTZFIIOFTKIY-UHFFFAOYSA-N 0.000 description 2
- QIWQJGMBIABGRX-UHFFFAOYSA-N 4-oxocyclohexane-1-carbonitrile Chemical compound O=C1CCC(C#N)CC1 QIWQJGMBIABGRX-UHFFFAOYSA-N 0.000 description 2
- NZYFNPGQFHMXCL-UHFFFAOYSA-N 4-pyrazin-2-ylcyclohexan-1-one Chemical compound C1CC(=O)CCC1C1=CN=CC=N1 NZYFNPGQFHMXCL-UHFFFAOYSA-N 0.000 description 2
- UITRXELURYBMAS-UHFFFAOYSA-N 5-(1,4-dioxaspiro[4.5]decan-8-yl)pyridin-2-amine Chemical compound C1=NC(N)=CC=C1C1CCC2(OCCO2)CC1 UITRXELURYBMAS-UHFFFAOYSA-N 0.000 description 2
- SLQWDCVQEQIAEU-UHFFFAOYSA-N 5-(4-oxocyclohexen-1-yl)-3h-1,3-thiazol-2-one Chemical compound C1C(=O)CCC(C=2SC(=O)NC=2)=C1 SLQWDCVQEQIAEU-UHFFFAOYSA-N 0.000 description 2
- QJJUZPFOBSCMPH-UHFFFAOYSA-N 5-(4-oxocyclohexyl)-1,3-thiazole-2-carboxylic acid Chemical compound S1C(C(=O)O)=NC=C1C1CCC(=O)CC1 QJJUZPFOBSCMPH-UHFFFAOYSA-N 0.000 description 2
- QBEVWQJFHZHMJC-UHFFFAOYSA-N 5-(4-oxocyclohexyl)-1-(2,2,2-trifluoroethyl)pyridin-2-one Chemical compound C1=CC(=O)N(CC(F)(F)F)C=C1C1CCC(=O)CC1 QBEVWQJFHZHMJC-UHFFFAOYSA-N 0.000 description 2
- KSKQEWQBWGHXOJ-UHFFFAOYSA-N 5-(4-oxocyclohexyl)-3h-1,3-thiazol-2-one Chemical compound C1CC(=O)CCC1C1=CNC(=O)S1 KSKQEWQBWGHXOJ-UHFFFAOYSA-N 0.000 description 2
- VNYBIBSZZDAEOK-UHFFFAOYSA-N 5-bromopyridin-3-ol Chemical compound OC1=CN=CC(Br)=C1 VNYBIBSZZDAEOK-UHFFFAOYSA-N 0.000 description 2
- UKUXTWJAKMVBMW-UHFFFAOYSA-N 5-iodo-1-(2,2,2-trifluoroethyl)pyridin-2-one Chemical compound FC(F)(F)CN1C=C(I)C=CC1=O UKUXTWJAKMVBMW-UHFFFAOYSA-N 0.000 description 2
- ZYCAFBXFACOJCS-UHFFFAOYSA-N 5-iodo-1-propan-2-ylpyridin-2-one Chemical compound CC(C)N1C=C(I)C=CC1=O ZYCAFBXFACOJCS-UHFFFAOYSA-N 0.000 description 2
- AUBILMVWHCJLMQ-UHFFFAOYSA-N 5-iodo-2-(2,2,2-trifluoroethoxy)pyridine Chemical compound FC(F)(F)COC1=CC=C(I)C=N1 AUBILMVWHCJLMQ-UHFFFAOYSA-N 0.000 description 2
- ILSMTBLMXJOTOQ-UHFFFAOYSA-N 5-iodo-2-propan-2-yloxypyridine Chemical compound CC(C)OC1=CC=C(I)C=N1 ILSMTBLMXJOTOQ-UHFFFAOYSA-N 0.000 description 2
- SHBORRYEDSHTJF-UHFFFAOYSA-N 6-(1,4-dioxaspiro[4.5]decan-8-yl)pyridin-2-amine Chemical compound NC1=CC=CC(C2CCC3(CC2)OCCO3)=N1 SHBORRYEDSHTJF-UHFFFAOYSA-N 0.000 description 2
- TYJFPKOOBVRRBM-UHFFFAOYSA-N 8-(2-methoxy-1,3-thiazol-5-yl)-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound S1C(OC)=NC=C1C1(O)CCC2(OCCO2)CC1 TYJFPKOOBVRRBM-UHFFFAOYSA-N 0.000 description 2
- ROGWOKOMFSPRMV-UHFFFAOYSA-N 8-(6-methoxypyridin-3-yl)-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound C1=NC(OC)=CC=C1C1(O)CCC2(OCCO2)CC1 ROGWOKOMFSPRMV-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- 201000004569 Blindness Diseases 0.000 description 2
- 238000011740 C57BL/6 mouse Methods 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 102000009410 Chemokine receptor Human genes 0.000 description 2
- 108050000299 Chemokine receptor Proteins 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 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
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- 229910021120 PdC12 Inorganic materials 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102100040247 Tumor necrosis factor Human genes 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000013566 allergen Substances 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 125000000129 anionic group Chemical group 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- HEWRTOMNMWSWOD-UHFFFAOYSA-N azetidin-3-yl hydrogen carbonate Chemical compound OC(=O)OC1CNC1 HEWRTOMNMWSWOD-UHFFFAOYSA-N 0.000 description 2
- 229940077388 benzenesulfonate Drugs 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- YSHOWEKUVWPFNR-UHFFFAOYSA-N burgess reagent Chemical compound CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC YSHOWEKUVWPFNR-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 229960005069 calcium Drugs 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000002975 chemoattractant Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 210000003979 eosinophil Anatomy 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 235000009200 high fat diet Nutrition 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- ZDGGJQMSELMHLK-UHFFFAOYSA-N m-Trifluoromethylhippuric acid Chemical compound OC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 ZDGGJQMSELMHLK-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- MXCYSXQBTPIAJC-UHFFFAOYSA-N methyl n-[5-(4-oxocyclohexyl)-1,3-thiazol-2-yl]carbamate Chemical compound S1C(NC(=O)OC)=NC=C1C1CCC(=O)CC1 MXCYSXQBTPIAJC-UHFFFAOYSA-N 0.000 description 2
- 230000011987 methylation Effects 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- ONIGMBFFLWOJBC-UHFFFAOYSA-N n-(1,4-dioxaspiro[4.5]decan-8-ylidene)-2-methylpropane-2-sulfinamide Chemical compound C1CC(=NS(=O)C(C)(C)C)CCC21OCCO2 ONIGMBFFLWOJBC-UHFFFAOYSA-N 0.000 description 2
- ONCNILWAYKHTSJ-UHFFFAOYSA-N n-[2-[[1-[4-(6-aminopyridin-2-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound NC1=CC=CC(C2CCC(CC2)N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)=N1 ONCNILWAYKHTSJ-UHFFFAOYSA-N 0.000 description 2
- DTHDGCVFVJQLLR-UHFFFAOYSA-N n-[6-(1,4-dioxaspiro[4.5]decan-8-yl)pyridin-3-yl]methanesulfonamide Chemical compound N1=CC(NS(=O)(=O)C)=CC=C1C1CCC2(OCCO2)CC1 DTHDGCVFVJQLLR-UHFFFAOYSA-N 0.000 description 2
- 210000002850 nasal mucosa Anatomy 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000007115 recruitment Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 2
- 201000005671 spondyloarthropathy Diseases 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- YSJICHRHPMNYNP-UHFFFAOYSA-N tert-butyl 3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]azetidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC1NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 YSJICHRHPMNYNP-UHFFFAOYSA-N 0.000 description 2
- WPGLRFGDZJSQGI-UHFFFAOYSA-N tert-butyl 3-aminoazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(N)C1 WPGLRFGDZJSQGI-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- CWERGRDVMFNCDR-UHFFFAOYSA-M thioglycolate(1-) Chemical compound [O-]C(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-M 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- MEFKFJOEVLUFAY-UHFFFAOYSA-N (2,2,2-trichloroacetyl) 2,2,2-trichloroacetate Chemical compound ClC(Cl)(Cl)C(=O)OC(=O)C(Cl)(Cl)Cl MEFKFJOEVLUFAY-UHFFFAOYSA-N 0.000 description 1
- NVOLYUXUHWBCRJ-UHFFFAOYSA-N (2-methoxypyridin-3-yl)boronic acid Chemical compound COC1=NC=CC=C1B(O)O NVOLYUXUHWBCRJ-UHFFFAOYSA-N 0.000 description 1
- CMIBUZBMZCBCAT-HZPDHXFCSA-N (2r,3r)-2,3-bis[(4-methylbenzoyl)oxy]butanedioic acid Chemical compound C1=CC(C)=CC=C1C(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(=O)C1=CC=C(C)C=C1 CMIBUZBMZCBCAT-HZPDHXFCSA-N 0.000 description 1
- SPFMQWBKVUQXJV-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;hydrate Chemical compound O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O SPFMQWBKVUQXJV-BTVCFUMJSA-N 0.000 description 1
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
- RKOUFQLNMRAACI-UHFFFAOYSA-N 1,1,1-trifluoro-2-iodoethane Chemical compound FC(F)(F)CI RKOUFQLNMRAACI-UHFFFAOYSA-N 0.000 description 1
- IDPDEOZBANAEGG-UHFFFAOYSA-N 1,3-dimethyl-5-(4-oxocyclohexyl)pyridin-2-one Chemical compound CN1C(=O)C(C)=CC(C2CCC(=O)CC2)=C1 IDPDEOZBANAEGG-UHFFFAOYSA-N 0.000 description 1
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
- 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
- NOLMGELTBIIGOL-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]dec-7-en-8-yl trifluoromethanesulfonate Chemical compound C1CC(OS(=O)(=O)C(F)(F)F)=CCC21OCCO2 NOLMGELTBIIGOL-UHFFFAOYSA-N 0.000 description 1
- HKDFRDIIELOLTJ-UHFFFAOYSA-N 1,4-dithianyl Chemical group [CH]1CSCCS1 HKDFRDIIELOLTJ-UHFFFAOYSA-N 0.000 description 1
- IDIPYAQEJIEKQF-UHFFFAOYSA-N 1-(2-hydroxyethyl)-5-(4-oxocyclohexyl)pyridin-2-one Chemical compound C1=CC(=O)N(CCO)C=C1C1CCC(=O)CC1 IDIPYAQEJIEKQF-UHFFFAOYSA-N 0.000 description 1
- ZZAYACKRRRXJOJ-UHFFFAOYSA-N 1-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyridin-2-one Chemical compound C1=CC(=O)N(CCO[Si](C)(C)C(C)(C)C)C=C1C(CC1)=CCC21OCCO2 ZZAYACKRRRXJOJ-UHFFFAOYSA-N 0.000 description 1
- LNDMMSCJVVKYPI-UHFFFAOYSA-N 1-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-5-iodopyridin-2-one Chemical compound CC(C)(C)[Si](C)(C)OCCN1C=C(I)C=CC1=O LNDMMSCJVVKYPI-UHFFFAOYSA-N 0.000 description 1
- QDPGWZNOWZNLSV-UHFFFAOYSA-N 1-[4-[5-(trichloromethyl)-1,2,4-oxadiazol-3-yl]cyclohexyl]azetidin-3-amine Chemical compound C1C(N)CN1C1CCC(C=2N=C(ON=2)C(Cl)(Cl)Cl)CC1 QDPGWZNOWZNLSV-UHFFFAOYSA-N 0.000 description 1
- UFWQMECLUSMLOH-UHFFFAOYSA-N 1-ethyl-5-(4-oxocyclohexyl)pyridin-2-one Chemical compound C1=CC(=O)N(CC)C=C1C1CCC(=O)CC1 UFWQMECLUSMLOH-UHFFFAOYSA-N 0.000 description 1
- PMYXTKSJCQWJGS-UHFFFAOYSA-N 1-methyl-3-(4-oxocyclohexyl)pyridin-2-one Chemical compound O=C1N(C)C=CC=C1C1CCC(=O)CC1 PMYXTKSJCQWJGS-UHFFFAOYSA-N 0.000 description 1
- LVWNMLICGKNFPF-UHFFFAOYSA-N 1-methyl-4-(4-oxocyclohexyl)pyridin-2-one Chemical compound O=C1N(C)C=CC(C2CCC(=O)CC2)=C1 LVWNMLICGKNFPF-UHFFFAOYSA-N 0.000 description 1
- WMQNJZRYWNYOEE-UHFFFAOYSA-N 1-methyl-5-(4-oxocyclohexyl)pyridin-2-one Chemical compound C1=CC(=O)N(C)C=C1C1CCC(=O)CC1 WMQNJZRYWNYOEE-UHFFFAOYSA-N 0.000 description 1
- JCHWHOHZZYWUMP-UHFFFAOYSA-N 2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C(CC1)=CCC21OCCO2 JCHWHOHZZYWUMP-UHFFFAOYSA-N 0.000 description 1
- SLGUOFWLTCGYPR-UHFFFAOYSA-N 2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-6-phenylmethoxypyridine Chemical compound C=1C=CC=CC=1COC(N=1)=CC=CC=1C(CC1)=CCC21OCCO2 SLGUOFWLTCGYPR-UHFFFAOYSA-N 0.000 description 1
- VYYLIDOSROROCY-UHFFFAOYSA-N 2-(1,4-dioxaspiro[4.5]decan-8-yl)-1-methylpyridin-4-one Chemical compound CN1C=CC(=O)C=C1C1CCC2(OCCO2)CC1 VYYLIDOSROROCY-UHFFFAOYSA-N 0.000 description 1
- ZKAQMNGHKHTZJU-UHFFFAOYSA-N 2-(1,4-dioxaspiro[4.5]decan-8-yl)-1h-pyridin-4-one Chemical compound OC1=CC=NC(C2CCC3(CC2)OCCO3)=C1 ZKAQMNGHKHTZJU-UHFFFAOYSA-N 0.000 description 1
- GSDFHZVPTBOJBB-UHFFFAOYSA-N 2-(1,4-dioxaspiro[4.5]decan-8-yl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridine Chemical compound O1CCOC11CCC(C2=NN3CCCCC3=N2)CC1 GSDFHZVPTBOJBB-UHFFFAOYSA-N 0.000 description 1
- LIAQBVLGJCPUBA-UHFFFAOYSA-N 2-(1,4-dioxaspiro[4.5]decan-8-yl)pyrazine Chemical compound O1CCOC11CCC(C=2N=CC=NC=2)CC1 LIAQBVLGJCPUBA-UHFFFAOYSA-N 0.000 description 1
- JNOQCIMSBVNTOM-UHFFFAOYSA-N 2-(1,4-dioxaspiro[4.5]decan-8-yl)pyridin-3-amine Chemical compound NC1=CC=CN=C1C1CCC2(OCCO2)CC1 JNOQCIMSBVNTOM-UHFFFAOYSA-N 0.000 description 1
- BXJCGZLOVAWWEL-UHFFFAOYSA-N 2-(5-iodo-2-oxopyridin-1-yl)acetonitrile Chemical compound IC=1C=CC(=O)N(CC#N)C=1 BXJCGZLOVAWWEL-UHFFFAOYSA-N 0.000 description 1
- JSFYHRSFIIRNRM-UHFFFAOYSA-N 2-[5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-2-oxopyridin-1-yl]acetonitrile Chemical compound N#CCN1C(=O)C=CC(C=2CCC3(CC=2)OCCO3)=C1 JSFYHRSFIIRNRM-UHFFFAOYSA-N 0.000 description 1
- RXNZFHIEDZEUQM-UHFFFAOYSA-N 2-bromo-1,3-thiazole Chemical compound BrC1=NC=CS1 RXNZFHIEDZEUQM-UHFFFAOYSA-N 0.000 description 1
- GGXSDQDNOMWAFV-UHFFFAOYSA-N 2-bromo-1h-pyridin-4-one Chemical compound BrC1=CC(=O)C=CN1 GGXSDQDNOMWAFV-UHFFFAOYSA-N 0.000 description 1
- JBKINHFZTVLNEM-UHFFFAOYSA-N 2-bromoethoxy-tert-butyl-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCBr JBKINHFZTVLNEM-UHFFFAOYSA-N 0.000 description 1
- GNTGEMWEXKBWBX-UHFFFAOYSA-N 2-bromopyridin-4-amine Chemical compound NC1=CC=NC(Br)=C1 GNTGEMWEXKBWBX-UHFFFAOYSA-N 0.000 description 1
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 1
- OYWPFIUVDKHHGQ-UHFFFAOYSA-N 2-iodopyrazine Chemical compound IC1=CN=CC=N1 OYWPFIUVDKHHGQ-UHFFFAOYSA-N 0.000 description 1
- HJBGMPCMSWJZNH-UHFFFAOYSA-N 2-iodopyridin-3-ol Chemical compound OC1=CC=CN=C1I HJBGMPCMSWJZNH-UHFFFAOYSA-N 0.000 description 1
- MJJRDTKNLLMJDJ-UHFFFAOYSA-N 2-methoxy-1,3-thiazole Chemical compound COC1=NC=CS1 MJJRDTKNLLMJDJ-UHFFFAOYSA-N 0.000 description 1
- LGCYVLDNGBSOOW-UHFFFAOYSA-N 2H-benzotriazol-4-ol 1-hydroxybenzotriazole Chemical compound OC1=CC=CC2=C1N=NN2.C1=CC=C2N(O)N=NC2=C1 LGCYVLDNGBSOOW-UHFFFAOYSA-N 0.000 description 1
- OIWNUJHMFVKWNM-UHFFFAOYSA-N 3-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1h-pyridin-4-one Chemical compound OC1=CC=NC=C1C(CC1)=CCC21OCCO2 OIWNUJHMFVKWNM-UHFFFAOYSA-N 0.000 description 1
- SJQHNSLZMVOQDQ-UHFFFAOYSA-N 3-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-2-phenylmethoxypyridine Chemical compound C=1C=CC=CC=1COC1=NC=CC=C1C(CC1)=CCC21OCCO2 SJQHNSLZMVOQDQ-UHFFFAOYSA-N 0.000 description 1
- RVALVKSOTZQTRC-UHFFFAOYSA-N 3-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyridin-4-amine Chemical compound NC1=CC=NC=C1C(CC1)=CCC21OCCO2 RVALVKSOTZQTRC-UHFFFAOYSA-N 0.000 description 1
- PPVARHQEDBRMIF-UHFFFAOYSA-N 3-(1,4-dioxaspiro[4.5]decan-8-yl)-1-methylpyridin-2-one Chemical compound O=C1N(C)C=CC=C1C1CCC2(OCCO2)CC1 PPVARHQEDBRMIF-UHFFFAOYSA-N 0.000 description 1
- GTJITUBGWPUXQY-UHFFFAOYSA-N 3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]azetidine-1-carboxylic acid Chemical compound C1N(C(=O)O)CC1NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 GTJITUBGWPUXQY-UHFFFAOYSA-N 0.000 description 1
- JWHZKNRXTDYNJO-UHFFFAOYSA-N 3-bromo-1h-pyridin-4-one Chemical compound OC1=CC=NC=C1Br JWHZKNRXTDYNJO-UHFFFAOYSA-N 0.000 description 1
- RPBPHGSYVPJXKT-UHFFFAOYSA-N 3-bromo-2-phenylmethoxypyridine Chemical compound BrC1=CC=CN=C1OCC1=CC=CC=C1 RPBPHGSYVPJXKT-UHFFFAOYSA-N 0.000 description 1
- RBCARPJOEUEZLS-UHFFFAOYSA-N 3-bromopyridin-2-amine Chemical compound NC1=NC=CC=C1Br RBCARPJOEUEZLS-UHFFFAOYSA-N 0.000 description 1
- DDQYSZWFFXOXER-UHFFFAOYSA-N 3-bromopyridin-4-amine Chemical compound NC1=CC=NC=C1Br DDQYSZWFFXOXER-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
- ITUNMVTUGPNWLL-UHFFFAOYSA-N 3-methyl-5-(4-oxocyclohexen-1-yl)-1h-pyridin-2-one Chemical compound N1C(=O)C(C)=CC(C=2CCC(=O)CC=2)=C1 ITUNMVTUGPNWLL-UHFFFAOYSA-N 0.000 description 1
- 125000004364 3-pyrrolinyl group Chemical group [H]C1=C([H])C([H])([H])N(*)C1([H])[H] 0.000 description 1
- SAWRSAOFADLYOA-UHFFFAOYSA-N 4-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1-methylpyridin-2-one Chemical compound O=C1N(C)C=CC(C=2CCC3(CC=2)OCCO3)=C1 SAWRSAOFADLYOA-UHFFFAOYSA-N 0.000 description 1
- JNJLZJNAPGDFHI-UHFFFAOYSA-N 4-(1,4-dioxaspiro[4.5]decan-8-yl)-1-methylpyridin-2-one Chemical compound O=C1N(C)C=CC(C2CCC3(CC2)OCCO3)=C1 JNJLZJNAPGDFHI-UHFFFAOYSA-N 0.000 description 1
- BQXNXOXMDCRLRA-UHFFFAOYSA-N 4-(5-pyrrolidin-1-yl-1,2,4-oxadiazol-3-yl)cyclohexan-1-one Chemical compound C1CC(=O)CCC1C1=NOC(N2CCCC2)=N1 BQXNXOXMDCRLRA-UHFFFAOYSA-N 0.000 description 1
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 1
- RLJLJPJHDXLJFY-UHFFFAOYSA-N 4-bromo-3-methoxypyridine Chemical compound COC1=CN=CC=C1Br RLJLJPJHDXLJFY-UHFFFAOYSA-N 0.000 description 1
- BSDGZUDFPKIYQG-UHFFFAOYSA-N 4-bromopyridine Chemical compound BrC1=CC=NC=C1 BSDGZUDFPKIYQG-UHFFFAOYSA-N 0.000 description 1
- JWIBTPMTSDSVQR-UHFFFAOYSA-N 4-iodo-2-methoxypyridine Chemical compound COC1=CC(I)=CC=N1 JWIBTPMTSDSVQR-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- DMYOLOARCFIOJC-UHFFFAOYSA-N 5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1-(2,2,2-trifluoroethyl)pyridin-2-one Chemical compound C1=CC(=O)N(CC(F)(F)F)C=C1C(CC1)=CCC21OCCO2 DMYOLOARCFIOJC-UHFFFAOYSA-N 0.000 description 1
- MQVDSKUQPWRQCY-UHFFFAOYSA-N 5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1-propan-2-ylpyridin-2-one Chemical compound C1=CC(=O)N(C(C)C)C=C1C(CC1)=CCC21OCCO2 MQVDSKUQPWRQCY-UHFFFAOYSA-N 0.000 description 1
- SNVUVZJJCRGESL-UHFFFAOYSA-N 5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-3-methyl-1h-pyridin-2-one Chemical compound N1C(=O)C(C)=CC(C=2CCC3(CC=2)OCCO3)=C1 SNVUVZJJCRGESL-UHFFFAOYSA-N 0.000 description 1
- NHHMLSQELHJMGP-UHFFFAOYSA-N 5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-n,n-dimethylpyrimidin-2-amine Chemical compound C1=NC(N(C)C)=NC=C1C(CC1)=CCC21OCCO2 NHHMLSQELHJMGP-UHFFFAOYSA-N 0.000 description 1
- IXGUVHKOLMEMCS-UHFFFAOYSA-N 5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyridin-2-amine Chemical compound C1=NC(N)=CC=C1C(CC1)=CCC21OCCO2 IXGUVHKOLMEMCS-UHFFFAOYSA-N 0.000 description 1
- FYSMEEKNZBUGJM-UHFFFAOYSA-N 5-(1,4-dioxaspiro[4.5]decan-8-yl)-1-(2,2,2-trifluoroethyl)pyridin-2-one Chemical compound C1=CC(=O)N(CC(F)(F)F)C=C1C1CCC2(OCCO2)CC1 FYSMEEKNZBUGJM-UHFFFAOYSA-N 0.000 description 1
- OEABVLBRCQGPEE-UHFFFAOYSA-N 5-(1,4-dioxaspiro[4.5]decan-8-yl)-1-ethylpyridin-2-one Chemical compound C1=CC(=O)N(CC)C=C1C1CCC2(OCCO2)CC1 OEABVLBRCQGPEE-UHFFFAOYSA-N 0.000 description 1
- WNXJNZUMRNOKNX-UHFFFAOYSA-N 5-(1,4-dioxaspiro[4.5]decan-8-yl)-1-methylpyridin-2-one Chemical compound C1=CC(=O)N(C)C=C1C1CCC2(OCCO2)CC1 WNXJNZUMRNOKNX-UHFFFAOYSA-N 0.000 description 1
- HGTLKVRWWDOAMY-UHFFFAOYSA-N 5-(1,4-dioxaspiro[4.5]decan-8-yl)-1h-pyridin-2-one Chemical compound N1C(=O)C=CC(C2CCC3(CC2)OCCO3)=C1 HGTLKVRWWDOAMY-UHFFFAOYSA-N 0.000 description 1
- NQYUIGANXUHILK-UHFFFAOYSA-N 5-(1,4-dioxaspiro[4.5]decan-8-yl)-2-methoxypyridine Chemical compound C1=NC(OC)=CC=C1C1CCC2(OCCO2)CC1 NQYUIGANXUHILK-UHFFFAOYSA-N 0.000 description 1
- SCZORUZPHBSQIP-UHFFFAOYSA-N 5-(1,4-dioxaspiro[4.5]decan-8-yl)-n,n-dimethylpyrimidin-2-amine Chemical compound C1=NC(N(C)C)=NC=C1C1CCC2(OCCO2)CC1 SCZORUZPHBSQIP-UHFFFAOYSA-N 0.000 description 1
- DUJTZIYSIWBOAZ-UHFFFAOYSA-N 5-(4-oxocyclohexen-1-yl)-1h-pyridin-2-one Chemical compound C1C(=O)CCC(C2=CNC(=O)C=C2)=C1 DUJTZIYSIWBOAZ-UHFFFAOYSA-N 0.000 description 1
- LXINUCJKJBWWPB-UHFFFAOYSA-N 5-(4-oxocyclohexyl)-1-propan-2-ylpyridin-2-one Chemical compound C1=CC(=O)N(C(C)C)C=C1C1CCC(=O)CC1 LXINUCJKJBWWPB-UHFFFAOYSA-N 0.000 description 1
- KRHYQOWEQGOVOM-UHFFFAOYSA-N 5-(4-oxocyclohexyl)-1h-pyridin-2-one Chemical compound C1CC(=O)CCC1C1=CNC(=O)C=C1 KRHYQOWEQGOVOM-UHFFFAOYSA-N 0.000 description 1
- RMIDGJYAVWPZHC-UHFFFAOYSA-N 5-[4-[3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]azetidin-1-yl]cyclohexyl]-1,3-thiazole-2-carboxamide Chemical compound S1C(C(=O)N)=NC=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 RMIDGJYAVWPZHC-UHFFFAOYSA-N 0.000 description 1
- YUDARCLWNGNYRG-UHFFFAOYSA-N 5-[4-[3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]azetidin-1-yl]cyclohexyl]-1,3-thiazole-2-carboxylic acid Chemical compound S1C(C(=O)O)=NC=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 YUDARCLWNGNYRG-UHFFFAOYSA-N 0.000 description 1
- PIVKLKRNXWUHSD-UHFFFAOYSA-N 5-bromo-1-methylpyrimidine-2,4-dione Chemical compound CN1C=C(Br)C(=O)NC1=O PIVKLKRNXWUHSD-UHFFFAOYSA-N 0.000 description 1
- XADICJHFELMBGX-UHFFFAOYSA-N 5-bromo-2-methoxypyridine Chemical compound COC1=CC=C(Br)C=N1 XADICJHFELMBGX-UHFFFAOYSA-N 0.000 description 1
- HXPMRPRBABWPKL-UHFFFAOYSA-N 5-bromo-3-methyl-1h-pyridin-2-one Chemical compound CC1=CC(Br)=CN=C1O HXPMRPRBABWPKL-UHFFFAOYSA-N 0.000 description 1
- NYMYGNLCILQUMT-UHFFFAOYSA-N 5-bromo-n,n-dimethylpyrimidin-2-amine Chemical compound CN(C)C1=NC=C(Br)C=N1 NYMYGNLCILQUMT-UHFFFAOYSA-N 0.000 description 1
- WGOLHUGPTDEKCF-UHFFFAOYSA-N 5-bromopyridin-2-amine Chemical compound NC1=CC=C(Br)C=N1 WGOLHUGPTDEKCF-UHFFFAOYSA-N 0.000 description 1
- MDQXGHBCDCOOSM-UHFFFAOYSA-N 5-bromopyridin-3-amine Chemical compound NC1=CN=CC(Br)=C1 MDQXGHBCDCOOSM-UHFFFAOYSA-N 0.000 description 1
- VLBJHNJOAACCMB-UHFFFAOYSA-N 6-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-n-methylpyridin-2-amine Chemical compound CNC1=CC=CC(C=2CCC3(CC=2)OCCO3)=N1 VLBJHNJOAACCMB-UHFFFAOYSA-N 0.000 description 1
- UPDLIVUSQSROBS-UHFFFAOYSA-N 6-(1,4-dioxaspiro[4.5]decan-8-yl)-1h-pyridin-2-one Chemical compound N1C(=O)C=CC=C1C1CCC2(OCCO2)CC1 UPDLIVUSQSROBS-UHFFFAOYSA-N 0.000 description 1
- JXZFNSAICOUNFX-UHFFFAOYSA-N 6-(1,4-dioxaspiro[4.5]decan-8-yl)-n-methylpyridin-2-amine Chemical compound CNC1=CC=CC(C2CCC3(CC2)OCCO3)=N1 JXZFNSAICOUNFX-UHFFFAOYSA-N 0.000 description 1
- LQQRBECXGGNVJN-UHFFFAOYSA-N 6-(4-oxocyclohexyl)-1h-pyridin-2-one Chemical compound C1CC(=O)CCC1C1=CC=CC(=O)N1 LQQRBECXGGNVJN-UHFFFAOYSA-N 0.000 description 1
- BKLJUYPLUWUEOQ-UHFFFAOYSA-N 6-bromopyridin-2-amine Chemical compound NC1=CC=CC(Br)=N1 BKLJUYPLUWUEOQ-UHFFFAOYSA-N 0.000 description 1
- PTEFNEALEPSHLC-UHFFFAOYSA-N 6-bromopyridin-3-ol Chemical compound OC1=CC=C(Br)N=C1 PTEFNEALEPSHLC-UHFFFAOYSA-N 0.000 description 1
- 206010027654 Allergic conditions Diseases 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 241001674044 Blattodea Species 0.000 description 1
- 206010005186 Blindness unilateral Diseases 0.000 description 1
- 208000031648 Body Weight Changes Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- GUDPJHONHNSJBI-PMMFOGROSA-N C([ClH]([2H])([2H])([2H])([2H])[2H])(Cl)(Cl)[2H] Chemical compound C([ClH]([2H])([2H])([2H])([2H])[2H])(Cl)(Cl)[2H] GUDPJHONHNSJBI-PMMFOGROSA-N 0.000 description 1
- 102000001902 CC Chemokines Human genes 0.000 description 1
- 108010040471 CC Chemokines Proteins 0.000 description 1
- 108010017312 CCR2 Receptors Proteins 0.000 description 1
- 102000004497 CCR2 Receptors Human genes 0.000 description 1
- 108050006947 CXC Chemokine Proteins 0.000 description 1
- 102000019388 CXC chemokine Human genes 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 235000019743 Choline chloride Nutrition 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 102000020897 Formins Human genes 0.000 description 1
- 108091022623 Formins Proteins 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 101000609762 Gallus gallus Ovalbumin Proteins 0.000 description 1
- 102100028976 HLA class I histocompatibility antigen, B alpha chain Human genes 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 101000777599 Homo sapiens C-C chemokine receptor type 2 Proteins 0.000 description 1
- 101000897480 Homo sapiens C-C motif chemokine 2 Proteins 0.000 description 1
- 101000986087 Homo sapiens HLA class I histocompatibility antigen, B alpha chain Proteins 0.000 description 1
- 101000976075 Homo sapiens Insulin Proteins 0.000 description 1
- 101001013648 Homo sapiens Methionine synthase Proteins 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-O Htris Chemical compound OCC([NH3+])(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-O 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 206010022941 Iridocyclitis Diseases 0.000 description 1
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 229940123313 MCP-1 antagonist Drugs 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
- 229920003091 Methocel™ Polymers 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
- 241001529936 Murinae Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101000777597 Mus musculus C-C chemokine receptor type 2 Proteins 0.000 description 1
- 102000003896 Myeloperoxidases Human genes 0.000 description 1
- 108090000235 Myeloperoxidases Proteins 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 1
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 1
- 102000015439 Phospholipases Human genes 0.000 description 1
- 108010064785 Phospholipases Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 235000006040 Prunus persica var persica Nutrition 0.000 description 1
- 240000006413 Prunus persica var. persica Species 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 208000006045 Spondylarthropathies Diseases 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- 201000005485 Toxoplasmosis Diseases 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 206010054094 Tumour necrosis Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000011256 aggressive treatment Methods 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 201000004612 anterior uveitis Diseases 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical class CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000003725 azepanyl group Chemical group 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000004579 body weight change Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000004227 calcium gluconate Substances 0.000 description 1
- 235000013927 calcium gluconate Nutrition 0.000 description 1
- 229960004494 calcium gluconate Drugs 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 229940095643 calcium hydroxide Drugs 0.000 description 1
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
- 239000002604 chemokine receptor CCR2 antagonist Substances 0.000 description 1
- 239000005482 chemotactic factor Substances 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 1
- 229960003178 choline chloride Drugs 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 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 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 125000005508 decahydronaphthalenyl group Chemical group 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- ZHXTWWCDMUWMDI-UHFFFAOYSA-N dihydroxyboron Chemical compound O[B]O ZHXTWWCDMUWMDI-UHFFFAOYSA-N 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
- 229960002986 dinoprostone Drugs 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 229940009662 edetate Drugs 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 229950000206 estolate Drugs 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- FGSGHBPKHFDJOP-UHFFFAOYSA-N ethyl 2-oxocyclohexane-1-carboxylate Chemical compound CCOC(=O)C1CCCCC1=O FGSGHBPKHFDJOP-UHFFFAOYSA-N 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 230000006203 ethylation Effects 0.000 description 1
- 238000006200 ethylation reaction Methods 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012025 fluorinating agent Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 238000007446 glucose tolerance test Methods 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 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 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 102000046768 human CCL2 Human genes 0.000 description 1
- 102000043994 human CCR2 Human genes 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- DQKGOGJIOHUEGK-UHFFFAOYSA-M hydron;2-hydroxyethyl(trimethyl)azanium;carbonate Chemical compound OC([O-])=O.C[N+](C)(C)CCO DQKGOGJIOHUEGK-UHFFFAOYSA-M 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 238000002350 laparotomy Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- VNYSSYRCGWBHLG-AMOLWHMGSA-N leukotriene B4 Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O VNYSSYRCGWBHLG-AMOLWHMGSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 210000003071 memory t lymphocyte Anatomy 0.000 description 1
- 210000003584 mesangial cell Anatomy 0.000 description 1
- 210000000713 mesentery Anatomy 0.000 description 1
- 238000003328 mesylation reaction Methods 0.000 description 1
- NZWOPGCLSHLLPA-UHFFFAOYSA-N methacholine Chemical compound C[N+](C)(C)CC(C)OC(C)=O NZWOPGCLSHLLPA-UHFFFAOYSA-N 0.000 description 1
- 229960002329 methacholine Drugs 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- NAFBIYLNNXZOFN-UHFFFAOYSA-N methyl n-(1,3-thiazol-2-yl)carbamate Chemical compound COC(=O)NC1=NC=CS1 NAFBIYLNNXZOFN-UHFFFAOYSA-N 0.000 description 1
- RGHMJFIVWSOQTH-UHFFFAOYSA-N methyl n-[5-(1,4-dioxaspiro[4.5]decan-8-yl)-1,3-thiazol-2-yl]carbamate Chemical compound S1C(NC(=O)OC)=NC=C1C1CCC2(OCCO2)CC1 RGHMJFIVWSOQTH-UHFFFAOYSA-N 0.000 description 1
- GATYSAHRFHMPJQ-UHFFFAOYSA-N methyl n-[5-(8-hydroxy-1,4-dioxaspiro[4.5]decan-8-yl)-1,3-thiazol-2-yl]carbamate Chemical compound S1C(NC(=O)OC)=NC=C1C1(O)CCC2(OCCO2)CC1 GATYSAHRFHMPJQ-UHFFFAOYSA-N 0.000 description 1
- LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 238000010232 migration assay Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 229960005127 montelukast Drugs 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- JECANBWJGUJWSY-UHFFFAOYSA-N n'-hydroxy-1,4-dioxaspiro[4.5]decane-8-carboximidamide Chemical compound C1CC(C(=N)NO)CCC21OCCO2 JECANBWJGUJWSY-UHFFFAOYSA-N 0.000 description 1
- BUHXVHHIXWZBCX-UHFFFAOYSA-N n-[2-(1,4-dioxaspiro[4.5]decan-8-yl)pyridin-3-yl]-2,2,2-trifluoroacetamide Chemical compound FC(F)(F)C(=O)NC1=CC=CN=C1C1CCC2(OCCO2)CC1 BUHXVHHIXWZBCX-UHFFFAOYSA-N 0.000 description 1
- BGHXJRZSWFHOFA-UHFFFAOYSA-N n-[2-(1,4-dioxaspiro[4.5]decan-8-yl)pyridin-3-yl]acetamide Chemical compound CC(=O)NC1=CC=CN=C1C1CCC2(OCCO2)CC1 BGHXJRZSWFHOFA-UHFFFAOYSA-N 0.000 description 1
- UDLODMIVTNIERH-UHFFFAOYSA-N n-[2-(1,4-dioxaspiro[4.5]decan-8-yl)pyridin-3-yl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CN=C1C1CCC2(OCCO2)CC1 UDLODMIVTNIERH-UHFFFAOYSA-N 0.000 description 1
- VYMRYMKCHVPBDU-UHFFFAOYSA-N n-[2-(azetidin-3-ylamino)-2-oxoethyl]-3-fluoro-5-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC(F)=CC(C(=O)NCC(=O)NC2CNC2)=C1 VYMRYMKCHVPBDU-UHFFFAOYSA-N 0.000 description 1
- LIDGWINURFOALA-UHFFFAOYSA-N n-[2-(azetidin-3-ylamino)-2-oxoethyl]-4-fluoro-3-(trifluoromethyl)benzamide Chemical compound C1=C(C(F)(F)F)C(F)=CC=C1C(=O)NCC(=O)NC1CNC1 LIDGWINURFOALA-UHFFFAOYSA-N 0.000 description 1
- FXAYUMDJIGJARA-UHFFFAOYSA-N n-[2-[[1-[4-(2-methoxypyridin-3-yl)cyclohex-3-en-1-yl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound COC1=NC=CC=C1C1=CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 FXAYUMDJIGJARA-UHFFFAOYSA-N 0.000 description 1
- JBYSLYJGZMRBFN-UHFFFAOYSA-N n-[2-[[1-[4-(3-methoxypyridin-4-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound COC1=CN=CC=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 JBYSLYJGZMRBFN-UHFFFAOYSA-N 0.000 description 1
- YXSHHTFKZDJGIA-UHFFFAOYSA-N n-[2-oxo-2-[[1-[4-[3-[(2,2,2-trifluoroacetyl)amino]pyridin-2-yl]cyclohexyl]azetidin-3-yl]amino]ethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C(=O)NC1=CC=CN=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 YXSHHTFKZDJGIA-UHFFFAOYSA-N 0.000 description 1
- DJOVSLDCZONKKT-UHFFFAOYSA-N n-[2-oxo-2-[[1-[4-[5-(trichloromethyl)-1,2,4-oxadiazol-3-yl]cyclohexyl]azetidin-3-yl]amino]ethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)NC2CN(C2)C2CCC(CC2)C=2N=C(ON=2)C(Cl)(Cl)Cl)=C1 DJOVSLDCZONKKT-UHFFFAOYSA-N 0.000 description 1
- NFSRHKFSNGAFHD-UHFFFAOYSA-N n-[6-(1,4-dioxaspiro[4.5]decan-8-yl)pyridin-3-yl]-2,2,2-trifluoroacetamide Chemical compound N1=CC(NC(=O)C(F)(F)F)=CC=C1C1CCC2(OCCO2)CC1 NFSRHKFSNGAFHD-UHFFFAOYSA-N 0.000 description 1
- XYDRAEAHFSCKIB-UHFFFAOYSA-N n-[6-(1,4-dioxaspiro[4.5]decan-8-yl)pyridin-3-yl]acetamide Chemical compound N1=CC(NC(=O)C)=CC=C1C1CCC2(OCCO2)CC1 XYDRAEAHFSCKIB-UHFFFAOYSA-N 0.000 description 1
- JCCGSOVTBIJRGP-UHFFFAOYSA-N n-piperidin-1-ylprop-2-enamide Chemical class C=CC(=O)NN1CCCCC1 JCCGSOVTBIJRGP-UHFFFAOYSA-N 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000010807 negative regulation of binding Effects 0.000 description 1
- 230000013152 negative regulation of cell migration Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 201000007407 panuveitis Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 235000021401 pellet diet Nutrition 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- RYFZYYUIAZYQLC-UHFFFAOYSA-N perchloromethyl mercaptan Chemical compound ClSC(Cl)(Cl)Cl RYFZYYUIAZYQLC-UHFFFAOYSA-N 0.000 description 1
- 239000003330 peritoneal dialysis fluid Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000001932 seasonal effect Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 229940001593 sodium carbonate Drugs 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 125000001010 sulfinic acid amide group Chemical group 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229950002757 teoclate Drugs 0.000 description 1
- CESUXLKAADQNTB-UHFFFAOYSA-N tert-butanesulfinamide Chemical compound CC(C)(C)S(N)=O CESUXLKAADQNTB-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
- CNOMGANPPUUQTH-UHFFFAOYSA-N tert-butyl n-[1-(4-carbamimidoylcyclohexyl)azetidin-3-yl]carbamate Chemical compound C1C(NC(=O)OC(C)(C)C)CN1C1CCC(C(N)=N)CC1 CNOMGANPPUUQTH-UHFFFAOYSA-N 0.000 description 1
- GZZRLYNLQHTPHF-UHFFFAOYSA-N tert-butyl n-[1-[4-(4-oxo-5,6,7,8-tetrahydro-1h-quinazolin-2-yl)cyclohexyl]azetidin-3-yl]carbamate Chemical compound C1C(NC(=O)OC(C)(C)C)CN1C1CCC(C=2NC(=O)C=3CCCCC=3N=2)CC1 GZZRLYNLQHTPHF-UHFFFAOYSA-N 0.000 description 1
- MUYKGYGYLUQAFJ-UHFFFAOYSA-N tert-butyl n-[1-[4-(6-methyl-4-oxo-1h-pyrimidin-2-yl)cyclohexyl]azetidin-3-yl]carbamate Chemical compound CC1=CC(=O)NC(C2CCC(CC2)N2CC(C2)NC(=O)OC(C)(C)C)=N1 MUYKGYGYLUQAFJ-UHFFFAOYSA-N 0.000 description 1
- TYGAKAIAXZQCOE-UHFFFAOYSA-N tert-butyl n-[1-[4-[5-(trichloromethyl)-1,2,4-oxadiazol-3-yl]cyclohexyl]azetidin-3-yl]carbamate Chemical compound C1C(NC(=O)OC(C)(C)C)CN1C1CCC(C=2N=C(ON=2)C(Cl)(Cl)Cl)CC1 TYGAKAIAXZQCOE-UHFFFAOYSA-N 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 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
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 238000005583 trifluoroacetylation reaction Methods 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/08—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing alicyclic 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
- A61P11/06—Antiasthmatics
-
- 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/08—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing alicyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/08—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing alicyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/08—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing alicyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Obesity (AREA)
- Oncology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Vascular Medicine (AREA)
- Dermatology (AREA)
- Ophthalmology & Optometry (AREA)
- Child & Adolescent Psychology (AREA)
- Communicable Diseases (AREA)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Otolaryngology (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16987609P | 2009-04-16 | 2009-04-16 | |
| US61/169,876 | 2009-04-16 | ||
| PCT/US2010/031212 WO2010121011A1 (en) | 2009-04-16 | 2010-04-15 | 4-azetidinyl-1-heteroaryl-cyclohexane antagonists of ccr2 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2758918A1 true CA2758918A1 (en) | 2010-10-21 |
Family
ID=42154522
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2758918A Abandoned CA2758918A1 (en) | 2009-04-16 | 2010-04-15 | 4-azetidinyl-1-heteroaryl-cyclohexane antagonists of ccr2 |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US8269015B2 (enExample) |
| EP (1) | EP2419417B1 (enExample) |
| JP (1) | JP5685580B2 (enExample) |
| KR (1) | KR20120061060A (enExample) |
| CN (1) | CN102459225B (enExample) |
| AR (1) | AR076310A1 (enExample) |
| AU (1) | AU2010236393B2 (enExample) |
| BR (1) | BRPI1016207A2 (enExample) |
| CA (1) | CA2758918A1 (enExample) |
| ES (1) | ES2539161T3 (enExample) |
| MX (1) | MX2011010919A (enExample) |
| NZ (1) | NZ595431A (enExample) |
| TW (1) | TW201105649A (enExample) |
| WO (1) | WO2010121011A1 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2376475B1 (en) * | 2008-12-10 | 2015-09-02 | Janssen Pharmaceutica NV | 4-azetidinyl-1-heteroaryl-cyclohexanol antagonists of ccr2 |
| WO2010121036A1 (en) * | 2009-04-17 | 2010-10-21 | Janssen Pharmaceutica Nv | 4-azetidinyl-1-heteroatom linked-cyclohexane antagonists of ccr2 |
| NZ595432A (en) * | 2009-04-17 | 2013-12-20 | Janssen Pharmaceutica Nv | 4-azetidinyl-1-phenyl-cyclohexane antagonists of ccr2 |
| TW201211027A (en) * | 2010-06-09 | 2012-03-16 | Janssen Pharmaceutica Nv | Cyclohexyl-azetidinyl antagonists of CCR2 |
| KR101743280B1 (ko) | 2010-06-17 | 2017-06-02 | 얀센 파마슈티카 엔.브이. | Ccr2의 사이클로헥실-아제티디닐 길항제 |
| US20140329809A1 (en) | 2011-10-28 | 2014-11-06 | Galderma Research & Development | New leukocyte infiltrate markers for rosacea and uses thereof |
| KR102622891B1 (ko) | 2015-05-21 | 2024-01-08 | 케모센트릭스, 인크. | Ccr2 조절제 |
| KR102677442B1 (ko) | 2017-09-25 | 2024-06-20 | 케모센트릭스, 인크. | 케모카인 수용체 2(ccr2) 길항제 및 pd-1/pd-l1 억제제를 사용하는 병용 요법 |
| US20190269664A1 (en) | 2018-01-08 | 2019-09-05 | Chemocentryx, Inc. | Methods of treating solid tumors with ccr2 antagonists |
| ES2991280T3 (es) | 2018-01-08 | 2024-12-03 | Chemocentryx Inc | Antagonistas de CCR2 para el tratamiento del linfoma cutáneo de linfocitos T |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6037354A (en) * | 1997-06-18 | 2000-03-14 | Merck & Co., Inc. | Alpha 1a adrenergic receptor antagonists |
| EP1201239A4 (en) | 1999-08-04 | 2004-12-08 | Teijin Ltd | CCR3 CYCLIC AMINE ANTAGONISTS |
| US6245799B1 (en) * | 1999-11-08 | 2001-06-12 | American Home Products Corp | [(Indol-3-yl)-cycloalkyl]-3-substituted azetidines for the treatment of central nervous system disorders |
| AR035773A1 (es) * | 2000-12-20 | 2004-07-14 | Bristol Myers Squibb Pharma Co | Compuestos diamino ciclico, composicion farmaceutica y su uso en la fabricacion de un medicamento util para modular la actividad de una quimioquina |
| ATE555087T1 (de) | 2002-11-27 | 2012-05-15 | Incyte Corp | 3-aminopyrrolidinderivate als modulatoren von chemokinrezeptoren |
| UA87449C2 (ru) * | 2002-11-27 | 2009-07-27 | Инсайт Корпорейшн | Производные 3-аминопиролидина как модуляторы рецепторов хемокина |
| GB0417801D0 (en) * | 2004-08-10 | 2004-09-15 | Novartis Ag | Organic compounds |
| JP2008514700A (ja) * | 2004-09-28 | 2008-05-08 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 置換されたジピペリジンccr2アンタゴニスト |
| UY29219A1 (es) | 2004-11-22 | 2006-04-28 | Incyte Corp | Sales de la n-(2- (((3r)-1-(trans-4-hidroxi-4-(6-metoxipiridin-3-il)-cilohexil) pirrolidin-3-il)amino)-2-oxoetil)-3- (trifluorometil) benzamida |
| WO2007053498A1 (en) | 2005-11-01 | 2007-05-10 | Millennium Pharmaceuticals, Inc. | Compounds useful as antagonists of ccr2 |
| US20070197590A1 (en) | 2006-01-31 | 2007-08-23 | Demong Duane E | Substituted dipiperidine ccr2 antagonists |
| CA2708364A1 (en) * | 2007-12-11 | 2009-06-18 | Efrat Ben-Zeev | Carboxamide compounds and their use as chemokine receptor agonists |
| EP2376475B1 (en) * | 2008-12-10 | 2015-09-02 | Janssen Pharmaceutica NV | 4-azetidinyl-1-heteroaryl-cyclohexanol antagonists of ccr2 |
| WO2010121036A1 (en) * | 2009-04-17 | 2010-10-21 | Janssen Pharmaceutica Nv | 4-azetidinyl-1-heteroatom linked-cyclohexane antagonists of ccr2 |
| NZ595432A (en) * | 2009-04-17 | 2013-12-20 | Janssen Pharmaceutica Nv | 4-azetidinyl-1-phenyl-cyclohexane antagonists of ccr2 |
-
2010
- 2010-04-15 EP EP10714148.3A patent/EP2419417B1/en active Active
- 2010-04-15 CA CA2758918A patent/CA2758918A1/en not_active Abandoned
- 2010-04-15 NZ NZ595431A patent/NZ595431A/en not_active IP Right Cessation
- 2010-04-15 WO PCT/US2010/031212 patent/WO2010121011A1/en not_active Ceased
- 2010-04-15 TW TW099111730A patent/TW201105649A/zh unknown
- 2010-04-15 AU AU2010236393A patent/AU2010236393B2/en not_active Ceased
- 2010-04-15 AR ARP100101263A patent/AR076310A1/es unknown
- 2010-04-15 ES ES10714148.3T patent/ES2539161T3/es active Active
- 2010-04-15 CN CN201080027215.2A patent/CN102459225B/zh not_active Expired - Fee Related
- 2010-04-15 BR BRPI1016207A patent/BRPI1016207A2/pt not_active Application Discontinuation
- 2010-04-15 US US12/760,832 patent/US8269015B2/en not_active Expired - Fee Related
- 2010-04-15 KR KR1020117026815A patent/KR20120061060A/ko not_active Withdrawn
- 2010-04-15 JP JP2012506216A patent/JP5685580B2/ja not_active Expired - Fee Related
- 2010-04-15 MX MX2011010919A patent/MX2011010919A/es active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| US20100267688A1 (en) | 2010-10-21 |
| WO2010121011A1 (en) | 2010-10-21 |
| BRPI1016207A2 (pt) | 2016-04-26 |
| NZ595431A (en) | 2013-12-20 |
| KR20120061060A (ko) | 2012-06-12 |
| JP5685580B2 (ja) | 2015-03-18 |
| EP2419417A1 (en) | 2012-02-22 |
| TW201105649A (en) | 2011-02-16 |
| CN102459225B (zh) | 2014-08-20 |
| MX2011010919A (es) | 2011-11-02 |
| AU2010236393B2 (en) | 2014-11-13 |
| CN102459225A (zh) | 2012-05-16 |
| ES2539161T3 (es) | 2015-06-26 |
| AR076310A1 (es) | 2011-06-01 |
| JP2012524107A (ja) | 2012-10-11 |
| US8269015B2 (en) | 2012-09-18 |
| AU2010236393A1 (en) | 2011-11-03 |
| EP2419417B1 (en) | 2015-03-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2419417B1 (en) | 4-azetidinyl-1-heteroaryl-cyclohexane antagonists of ccr2 | |
| JP6800325B2 (ja) | オートタキシン阻害剤としての新規化合物及びそれらを含む医薬組成物 | |
| CA2745969C (en) | 4-azetidinyl-1-heteroaryl-cyclohexanol antagonists of ccr2 | |
| AU2011268375B2 (en) | Cyclohexyl-azetidinyl antagonists of CCR2 | |
| US9062033B2 (en) | Chemical compounds | |
| EP2419418B1 (en) | 4-azetidinyl-1-heteroatom linked-cyclohexane antagonists of ccr2 | |
| JP2013526537A (ja) | Pde10阻害剤としてのヘテロアリールオキシカルボシクリル化合物 | |
| EP2580208B1 (en) | Cyclohexyl-azetidinyl antagonists of ccr2 | |
| JP2013540792A (ja) | オレキシン受容体アンタゴニストとして有用なジアザ−スピロ[5.5]ウンデカン類 | |
| CA2819508A1 (en) | 4-substituted-cyclohexylamino-4-piperidinyl-acetamide antagonists of ccr2 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20160415 |