JP5685580B2 - Ｃｃｒ２の４−アゼチジニル−１−ヘテロアリール−シクロヘキサンアンタゴニスト - Google Patents
Ｃｃｒ２の４−アゼチジニル−１−ヘテロアリール−シクロヘキサンアンタゴニスト Download PDFInfo
- Publication number
- JP5685580B2 JP5685580B2 JP2012506216A JP2012506216A JP5685580B2 JP 5685580 B2 JP5685580 B2 JP 5685580B2 JP 2012506216 A JP2012506216 A JP 2012506216A JP 2012506216 A JP2012506216 A JP 2012506216A JP 5685580 B2 JP5685580 B2 JP 5685580B2
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- substituted
- pyridin
- group
- compound
- 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.)
- Expired - Fee Related
Links
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 title claims 2
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 title claims 2
- 239000005557 antagonist Substances 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims description 239
- -1 pyridyl-N-oxide Chemical group 0.000 claims description 126
- 238000000034 method Methods 0.000 claims description 118
- 125000000217 alkyl group Chemical group 0.000 claims description 90
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 53
- 125000004432 carbon atom Chemical group C* 0.000 claims description 47
- 229910052799 carbon Inorganic materials 0.000 claims description 39
- 150000003839 salts Chemical class 0.000 claims description 33
- 125000000335 thiazolyl group Chemical group 0.000 claims description 32
- 101710155857 C-C motif chemokine 2 Proteins 0.000 claims description 31
- 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
- 208000035475 disorder Diseases 0.000 claims description 27
- 201000010099 disease Diseases 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 208000011580 syndromic disease Diseases 0.000 claims description 23
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 21
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 20
- 230000008569 process Effects 0.000 claims description 20
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 18
- 208000006673 asthma Diseases 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 11
- 208000008589 Obesity Diseases 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000001041 indolyl group Chemical group 0.000 claims description 10
- 235000020824 obesity Nutrition 0.000 claims description 10
- 206010046851 Uveitis Diseases 0.000 claims description 9
- 230000014509 gene expression Effects 0.000 claims description 9
- 230000001404 mediated effect Effects 0.000 claims description 9
- 125000001544 thienyl group Chemical group 0.000 claims description 9
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 9
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 8
- 206010061218 Inflammation 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
- 230000004054 inflammatory process Effects 0.000 claims description 8
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 7
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 7
- 201000009961 allergic asthma Diseases 0.000 claims description 7
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 7
- 206010012601 diabetes mellitus Diseases 0.000 claims description 7
- 125000002883 imidazolyl group Chemical group 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
- 238000002360 preparation method Methods 0.000 claims description 7
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 6
- 201000010105 allergic rhinitis Diseases 0.000 claims description 6
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 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
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
- 201000001320 Atherosclerosis Diseases 0.000 claims description 5
- 208000007342 Diabetic Nephropathies 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
- 208000033679 diabetic kidney 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
- 206010005003 Bladder cancer Diseases 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 206010007558 Cardiac failure chronic Diseases 0.000 claims description 4
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 206010056370 Congestive cardiomyopathy Diseases 0.000 claims description 4
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 4
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 4
- 208000002249 Diabetes Complications Diseases 0.000 claims description 4
- 206010012655 Diabetic complications Diseases 0.000 claims description 4
- 206010054044 Diabetic microangiopathy Diseases 0.000 claims description 4
- 201000010046 Dilated cardiomyopathy 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
- 206010058467 Lung neoplasm malignant 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
- 206010060862 Prostate cancer Diseases 0.000 claims description 4
- 208000000236 Prostatic Neoplasms 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
- 206010063837 Reperfusion injury Diseases 0.000 claims description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 4
- 206010052779 Transplant rejections Diseases 0.000 claims description 4
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 4
- 206010052568 Urticaria chronic Diseases 0.000 claims description 4
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 4
- 206010057469 Vascular stenosis 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
- 201000011510 cancer Diseases 0.000 claims description 4
- 201000010881 cervical cancer Diseases 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 4
- 208000024376 chronic urticaria Diseases 0.000 claims description 4
- 201000009101 diabetic angiopathy Diseases 0.000 claims description 4
- 208000030533 eye disease Diseases 0.000 claims description 4
- 206010017758 gastric cancer Diseases 0.000 claims description 4
- 208000024693 gingival disease Diseases 0.000 claims description 4
- 208000007565 gingivitis Diseases 0.000 claims description 4
- 201000006370 kidney failure Diseases 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- 230000003211 malignant effect Effects 0.000 claims description 4
- 238000004519 manufacturing process 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
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 208000028169 periodontal disease Diseases 0.000 claims description 4
- 201000001245 periodontitis Diseases 0.000 claims description 4
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 4
- 208000037803 restenosis Diseases 0.000 claims description 4
- 201000011549 stomach cancer Diseases 0.000 claims description 4
- 238000001356 surgical procedure Methods 0.000 claims description 4
- 201000008827 tuberculosis Diseases 0.000 claims description 4
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 4
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 3
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
- 206010022489 Insulin Resistance Diseases 0.000 claims description 3
- 206010036346 Posterior capsule opacification Diseases 0.000 claims description 3
- 206010041925 Staphylococcal infections Diseases 0.000 claims description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 claims description 3
- 208000029742 colonic neoplasm 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
- 238000002156 mixing Methods 0.000 claims description 3
- 208000010125 myocardial infarction Diseases 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 206010033307 Overweight Diseases 0.000 claims description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
- 235000020825 overweight Nutrition 0.000 claims description 2
- 102100021943 C-C motif chemokine 2 Human genes 0.000 claims 4
- 239000004480 active ingredient Substances 0.000 claims 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- 206010062198 microangiopathy Diseases 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 174
- 239000007787 solid Substances 0.000 description 127
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 100
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 85
- 235000019439 ethyl acetate Nutrition 0.000 description 63
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 50
- 238000006243 chemical reaction Methods 0.000 description 49
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 48
- 239000000243 solution Substances 0.000 description 36
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 34
- 239000000203 mixture Substances 0.000 description 33
- 239000000741 silica gel Substances 0.000 description 33
- 229910002027 silica gel Inorganic materials 0.000 description 33
- 239000011734 sodium Substances 0.000 description 32
- 102000000018 Chemokine CCL2 Human genes 0.000 description 27
- 239000003960 organic solvent Substances 0.000 description 27
- 241001465754 Metazoa Species 0.000 description 26
- 239000012044 organic layer Substances 0.000 description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 239000012267 brine Substances 0.000 description 21
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
- 238000011282 treatment Methods 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 230000002829 reductive effect Effects 0.000 description 18
- 150000002576 ketones Chemical class 0.000 description 17
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 16
- 229940002612 prodrug Drugs 0.000 description 16
- 239000000651 prodrug Substances 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 15
- 238000006268 reductive amination reaction Methods 0.000 description 14
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
- 150000004677 hydrates Chemical class 0.000 description 13
- 239000010410 layer Substances 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 239000003981 vehicle Substances 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 238000001704 evaporation Methods 0.000 description 12
- 230000008020 evaporation Effects 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 238000005984 hydrogenation reaction Methods 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 0.000 description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 10
- 239000002604 chemokine receptor CCR2 antagonist Substances 0.000 description 10
- 238000010511 deprotection reaction Methods 0.000 description 10
- 210000001616 monocyte Anatomy 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 8
- 150000001336 alkenes Chemical class 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 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
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 150000003254 radicals Chemical class 0.000 description 6
- 102000019034 Chemokines Human genes 0.000 description 5
- 108010012236 Chemokines Proteins 0.000 description 5
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 5
- 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 5
- 150000001408 amides Chemical class 0.000 description 5
- YSHOWEKUVWPFNR-UHFFFAOYSA-N burgess reagent Chemical compound CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC YSHOWEKUVWPFNR-UHFFFAOYSA-N 0.000 description 5
- 235000018417 cysteine Nutrition 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 238000004237 preparative chromatography Methods 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 238000010992 reflux Methods 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
- 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 4
- 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 4
- ZDJUNNCVIDKJAN-UHFFFAOYSA-N 5-iodo-1h-pyridin-2-one Chemical compound OC1=CC=C(I)C=N1 ZDJUNNCVIDKJAN-UHFFFAOYSA-N 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-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
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 208000011231 Crohn disease Diseases 0.000 description 4
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- 101150003085 Pdcl gene Proteins 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 150000003840 hydrochlorides Chemical class 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 238000010791 quenching Methods 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 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 3
- HKDVVTLISGIPFE-UHFFFAOYSA-N 2-bromopyridin-3-amine Chemical compound NC1=CC=CN=C1Br HKDVVTLISGIPFE-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
- 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 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
- 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 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
- XTHKRYHULUJQHN-UHFFFAOYSA-N 6-bromopyridin-3-amine Chemical compound NC1=CC=C(Br)N=C1 XTHKRYHULUJQHN-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
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 238000002738 Giemsa staining Methods 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
- 229910004298 SiO 2 Inorganic materials 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
- PZAGQUOSOTUKEC-UHFFFAOYSA-N acetic acid;sulfuric acid Chemical compound CC(O)=O.OS(O)(=O)=O PZAGQUOSOTUKEC-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-FIBGUPNXSA-N acetonitrile-d3 Chemical compound [2H]C([2H])([2H])C#N WEVYAHXRMPXWCK-FIBGUPNXSA-N 0.000 description 3
- 150000001335 aliphatic alkanes Chemical class 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 230000012292 cell migration Effects 0.000 description 3
- 239000007822 coupling agent Substances 0.000 description 3
- PQZTVWVYCLIIJY-UHFFFAOYSA-N diethyl(propyl)amine Chemical compound CCCN(CC)CC PQZTVWVYCLIIJY-UHFFFAOYSA-N 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 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 3
- CLAQZTUBEOSXPX-UHFFFAOYSA-N n-[2-oxo-2-[[1-[4-[5-[(2,2,2-trifluoroacetyl)amino]pyridin-2-yl]cyclohexyl]azetidin-3-yl]amino]ethyl]-3-(trifluoromethyl)benzamide Chemical compound N1=CC(NC(=O)C(F)(F)F)=CC=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 CLAQZTUBEOSXPX-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 150000007530 organic bases Chemical class 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
- 125000006239 protecting group Chemical group 0.000 description 3
- 229940124530 sulfonamide Drugs 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 229940071127 thioglycolate Drugs 0.000 description 3
- CWERGRDVMFNCDR-UHFFFAOYSA-M thioglycolate(1-) Chemical compound [O-]C(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-M 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 230000004393 visual impairment Effects 0.000 description 3
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 2
- 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 2
- WZWQNWWFCHNJON-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decane-8-carbonitrile Chemical compound C1CC(C#N)CCC21OCCO2 WZWQNWWFCHNJON-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 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 2
- 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 2
- 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 2
- NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-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
- 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 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
- 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
- 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 2
- 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 2
- 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 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
- 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 2
- 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 2
- 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 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
- 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 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
- 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 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
- 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
- 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 2
- 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 2
- 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 2
- 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 2
- 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 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
- 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 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
- 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
- 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
- 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 2
- 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 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
- 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 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
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 201000004569 Blindness Diseases 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
- 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
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 108010061486 HLA-B27 Antigen Proteins 0.000 description 2
- 102000012153 HLA-B27 Antigen Human genes 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-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
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 108700018351 Major Histocompatibility Complex Proteins 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
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-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
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000002152 alkylating effect Effects 0.000 description 2
- 239000013566 allergen Substances 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 229910021529 ammonia Inorganic materials 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
- 229910052786 argon Inorganic materials 0.000 description 2
- 150000001543 aryl boronic acids Chemical class 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
- 230000027455 binding 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
- 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
- 238000004113 cell culture Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction 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
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Substances CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000002612 dispersion medium Substances 0.000 description 2
- 210000003979 eosinophil Anatomy 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- VDDXQSUSMHZCLS-UHFFFAOYSA-N ethenyl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC=C VDDXQSUSMHZCLS-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 235000009200 high fat diet Nutrition 0.000 description 2
- 229960001340 histamine Drugs 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 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
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 210000000713 mesentery Anatomy 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 2
- 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 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
- 239000002808 molecular sieve Substances 0.000 description 2
- 125000002950 monocyclic group Chemical group 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
- PAMCRRDMORMCSM-UHFFFAOYSA-N n-(trifluoromethyl)benzamide Chemical compound FC(F)(F)NC(=O)C1=CC=CC=C1 PAMCRRDMORMCSM-UHFFFAOYSA-N 0.000 description 2
- 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 2
- NBTIPXWOPCPOQA-UHFFFAOYSA-N n-[2-[[1-[4-(1,5-dimethyl-6-oxopyridin-3-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CN1C(=O)C(C)=CC(C2CCC(CC2)N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)=C1 NBTIPXWOPCPOQA-UHFFFAOYSA-N 0.000 description 2
- AMFHQGULEXFQER-UHFFFAOYSA-N n-[2-[[1-[4-(1-ethyl-6-oxopyridin-3-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=CC(=O)N(CC)C=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 AMFHQGULEXFQER-UHFFFAOYSA-N 0.000 description 2
- DGFZUMFCPVCFSD-UHFFFAOYSA-N n-[2-[[1-[4-(1-methyl-2,4-dioxopyrimidin-5-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound O=C1NC(=O)N(C)C=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 DGFZUMFCPVCFSD-UHFFFAOYSA-N 0.000 description 2
- 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 2
- DYOTUXQFPIWGNY-UHFFFAOYSA-N n-[2-[[1-[4-(3-acetamidopyridin-2-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC(=O)NC1=CC=CN=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 DYOTUXQFPIWGNY-UHFFFAOYSA-N 0.000 description 2
- WTXGXHROIBXUJC-UHFFFAOYSA-N n-[2-[[1-[4-(3-aminopyridin-2-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound NC1=CC=CN=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 WTXGXHROIBXUJC-UHFFFAOYSA-N 0.000 description 2
- 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 2
- UOPRHVPDLPNSEU-UHFFFAOYSA-N n-[2-[[1-[4-(5-aminopyridin-2-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N1=CC(N)=CC=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 UOPRHVPDLPNSEU-UHFFFAOYSA-N 0.000 description 2
- ZXLRVOHADIRDTA-UHFFFAOYSA-N n-[2-[[1-[4-(5-hydroxypyridin-2-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N1=CC(O)=CC=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 ZXLRVOHADIRDTA-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
- OGIYGBLZTMNGCI-UHFFFAOYSA-N n-[2-[[1-[4-[3-(methanesulfonamido)pyridin-2-yl]cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CS(=O)(=O)NC1=CC=CN=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 OGIYGBLZTMNGCI-UHFFFAOYSA-N 0.000 description 2
- NBAVBXONUWCJSN-UHFFFAOYSA-N n-[2-oxo-2-[[1-[4-(2-oxo-1h-pyridin-3-yl)cyclohexyl]azetidin-3-yl]amino]ethyl]-3-(trifluoromethyl)benzamide Chemical compound OC1=NC=CC=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 NBAVBXONUWCJSN-UHFFFAOYSA-N 0.000 description 2
- GLLKSZDEZBGCJV-UHFFFAOYSA-N n-[2-oxo-2-[[1-[4-(5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-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)C2=NN3CCCCC3=N2)=C1 GLLKSZDEZBGCJV-UHFFFAOYSA-N 0.000 description 2
- IJVTYMAAOCKLGZ-UHFFFAOYSA-N n-[2-oxo-2-[[1-[4-(5-oxo-2h-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=2NC(=O)ON=2)=C1 IJVTYMAAOCKLGZ-UHFFFAOYSA-N 0.000 description 2
- KHQNBVVASIIVHY-UHFFFAOYSA-N n-[2-oxo-2-[[1-[4-(6-oxo-1-propan-2-ylpyridin-3-yl)cyclohexyl]azetidin-3-yl]amino]ethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=CC(=O)N(C(C)C)C=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 KHQNBVVASIIVHY-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
- 125000002524 organometallic group Chemical group 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 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 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000012746 preparative thin layer chromatography Methods 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 229910000029 sodium carbonate 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
- 150000003456 sulfonamides Chemical class 0.000 description 2
- 229910052717 sulfur Inorganic materials 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
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-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
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 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
- 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
- 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
- GLUCVWFGSMGWDI-ODZAUARKSA-N (z)-but-2-enedioic acid;2-hydroxypropanoic acid Chemical compound CC(O)C(O)=O.OC(=O)\C=C/C(O)=O GLUCVWFGSMGWDI-ODZAUARKSA-N 0.000 description 1
- 0 *c1cccc(C(CC2)CCC2N(C2)CC2NC(CNC(c2cc(C(F)(F)F)ccc2)=O)=O)n1 Chemical compound *c1cccc(C(CC2)CCC2N(C2)CC2NC(CNC(c2cc(C(F)(F)F)ccc2)=O)=O)n1 0.000 description 1
- NAOLWIGVYRIGTP-UHFFFAOYSA-N 1,3,5-trihydroxyanthracene-9,10-dione Chemical compound C1=CC(O)=C2C(=O)C3=CC(O)=CC(O)=C3C(=O)C2=C1 NAOLWIGVYRIGTP-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
- WLXGQMVCYPUOLM-UHFFFAOYSA-N 1-hydroxyethanesulfonic acid Chemical compound CC(O)S(O)(=O)=O WLXGQMVCYPUOLM-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
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 1
- 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 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
- 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 1
- 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 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
- 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
- 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 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
- 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 1
- 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 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
- WEMPEMXDSUATEK-UHFFFAOYSA-N 2-bromo-6-phenylmethoxypyridine Chemical compound BrC1=CC=CC(OCC=2C=CC=CC=2)=N1 WEMPEMXDSUATEK-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
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 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
- 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
- TXDFHVCFOQGIMV-UHFFFAOYSA-N 3-(4-oxocyclohexyl)-1h-pyridin-2-one Chemical compound OC1=NC=CC=C1C1CCC(=O)CC1 TXDFHVCFOQGIMV-UHFFFAOYSA-N 0.000 description 1
- RPONRSSXDCJHAN-UHFFFAOYSA-N 3-(4-oxocyclohexyl)-1h-pyridin-4-one Chemical compound OC1=CC=NC=C1C1CCC(=O)CC1 RPONRSSXDCJHAN-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
- 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
- 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
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- WRFYIYOXJWKONR-UHFFFAOYSA-N 4-bromo-2-methoxyaniline Chemical compound COC1=CC(Br)=CC=C1N WRFYIYOXJWKONR-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
- WFJIVOKAWHGMBH-UHFFFAOYSA-N 4-hexylbenzene-1,3-diol Chemical compound CCCCCCC1=CC=C(O)C=C1O WFJIVOKAWHGMBH-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
- 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
- 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
- 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
- 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
- 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 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
- 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
- YSTBQNLGXDQAAF-UHFFFAOYSA-N 5-chloro-3-(1,4-dioxaspiro[4.5]decan-8-yl)-1,2,4-thiadiazole Chemical compound S1C(Cl)=NC(C2CCC3(CC2)OCCO3)=N1 YSTBQNLGXDQAAF-UHFFFAOYSA-N 0.000 description 1
- 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 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
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 239000004475 Arginine Substances 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
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 102000001902 CC Chemokines Human genes 0.000 description 1
- 108010040471 CC Chemokines Proteins 0.000 description 1
- ZGVJJZROSLVDRX-UHFFFAOYSA-N CC(C)(CC1CNC1)OC(=O)O Chemical compound CC(C)(CC1CNC1)OC(=O)O ZGVJJZROSLVDRX-UHFFFAOYSA-N 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
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000002177 Cataract Diseases 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
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 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
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 208000030814 Eating disease Diseases 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 208000019454 Feeding and Eating disease Diseases 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
- 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
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 101000668058 Infectious salmon anemia virus (isolate Atlantic salmon/Norway/810/9/99) RNA-directed RNA polymerase catalytic subunit Proteins 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
- FEWJPZIEWOKRBE-JCYAYHJZSA-M L-tartrate(1-) Chemical compound OC(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-M 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 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
- 241000124008 Mammalia Species 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108010006035 Metalloproteases 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
- 241000699666 Mus <mouse, genus> 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
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- BQXNXOXMDCRLRA-UHFFFAOYSA-N O=C(CC1)CCC1c1n[o]c(N2CCCC2)n1 Chemical compound O=C(CC1)CCC1c1n[o]c(N2CCCC2)n1 BQXNXOXMDCRLRA-UHFFFAOYSA-N 0.000 description 1
- PSKCMKAZXPYOOQ-UHFFFAOYSA-N O=C(CNC(c1cc(C(F)(F)F)ccc1)=O)NC1CNC1 Chemical compound O=C(CNC(c1cc(C(F)(F)F)ccc1)=O)NC1CNC1 PSKCMKAZXPYOOQ-UHFFFAOYSA-N 0.000 description 1
- BFUQZCUOKFIPAB-UHFFFAOYSA-N Oc1c(C(CC2)CCC2N(C2)CC2NC(CNC(c2cc(C(F)(F)F)ccc2)=O)=O)nccc1 Chemical compound Oc1c(C(CC2)CCC2N(C2)CC2NC(CNC(c2cc(C(F)(F)F)ccc2)=O)=O)nccc1 BFUQZCUOKFIPAB-UHFFFAOYSA-N 0.000 description 1
- JDSBDWHONWCKEU-UHFFFAOYSA-N Oc1ccnc(C(CC2)CCC2N(C2)CC2NC(CNC(c2cc(C(F)(F)F)ccc2)=O)=O)c1 Chemical compound Oc1ccnc(C(CC2)CCC2N(C2)CC2NC(CNC(c2cc(C(F)(F)F)ccc2)=O)=O)c1 JDSBDWHONWCKEU-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920002230 Pectic acid Chemical class 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
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 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
- 239000007983 Tris buffer Substances 0.000 description 1
- 206010047571 Visual impairment 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
- 210000000577 adipose tissue Anatomy 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
- 150000001447 alkali salts Chemical class 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
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000003444 anaesthetic effect Effects 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
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 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
- HEWRTOMNMWSWOD-UHFFFAOYSA-N azetidin-3-yl hydrogen carbonate Chemical compound OC(=O)OC1CNC1 HEWRTOMNMWSWOD-UHFFFAOYSA-N 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
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 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
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 239000000969 carrier Substances 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
- 239000002975 chemoattractant 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
- 239000011248 coating agent Substances 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
- 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
- VNLZLLDMKRKVEX-UHFFFAOYSA-N cyclohex-3-enone Chemical compound O=C1CCC=CC1 VNLZLLDMKRKVEX-UHFFFAOYSA-N 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 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
- 150000001945 cysteines Chemical class 0.000 description 1
- 125000005508 decahydronaphthalenyl group Chemical group 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
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 239000008121 dextrose Substances 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
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical class [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 235000014632 disordered eating Nutrition 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
- 229940079593 drug 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
- 238000005265 energy consumption Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000006203 ethylation Effects 0.000 description 1
- 238000006200 ethylation reaction Methods 0.000 description 1
- 235000019197 fats Nutrition 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
- 239000012530 fluid Substances 0.000 description 1
- 239000012025 fluorinating agent Substances 0.000 description 1
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 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
- 238000009472 formulation Methods 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
- 229940050410 gluconate Drugs 0.000 description 1
- 238000007446 glucose tolerance test Methods 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 230000012010 growth Effects 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
- 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
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 229940071870 hydroiodic acid Drugs 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
- 230000007574 infarction 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
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 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
- 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
- 238000011813 knockout mouse model Methods 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
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000003819 low-pressure liquid chromatography Methods 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
- UGVPKMAWLOMPRS-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].CC[CH2-] UGVPKMAWLOMPRS-UHFFFAOYSA-M 0.000 description 1
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 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
- 239000011159 matrix 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
- 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
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 1
- NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 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
- 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 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
- RHUGJMIZMHMWOL-UHFFFAOYSA-N methyl n-[5-[4-[3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]azetidin-1-yl]cyclohexyl]-1,3-thiazol-2-yl]carbamate Chemical compound S1C(NC(=O)OC)=NC=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 RHUGJMIZMHMWOL-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
- 230000000813 microbial effect Effects 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
- 238000012544 monitoring process Methods 0.000 description 1
- 210000005087 mononuclear cell Anatomy 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
- 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
- MPKGUHCWHYKJBD-UHFFFAOYSA-N n-[2-[[1-(4-cyanocyclohexyl)azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)NC2CN(C2)C2CCC(CC2)C#N)=C1 MPKGUHCWHYKJBD-UHFFFAOYSA-N 0.000 description 1
- UGMMDBWAUPTALK-UHFFFAOYSA-N n-[2-[[1-[4-(1-methyl-2-oxopyridin-3-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound O=C1N(C)C=CC=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 UGMMDBWAUPTALK-UHFFFAOYSA-N 0.000 description 1
- MEMRXUCNUKAUBV-UHFFFAOYSA-N n-[2-[[1-[4-(1-methyl-2-oxopyridin-4-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound O=C1N(C)C=CC(C2CCC(CC2)N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)=C1 MEMRXUCNUKAUBV-UHFFFAOYSA-N 0.000 description 1
- FJNWTDVVZNEGPW-UHFFFAOYSA-N n-[2-[[1-[4-(1h-indol-3-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)NC2CN(C2)C2CCC(CC2)C=2C3=CC=CC=C3NC=2)=C1 FJNWTDVVZNEGPW-UHFFFAOYSA-N 0.000 description 1
- RIFJKQILKBALKJ-UHFFFAOYSA-N n-[2-[[1-[4-(1h-indol-3-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]benzamide Chemical compound C1N(C2CCC(CC2)C=2C3=CC=CC=C3NC=2)CC1NC(=O)CNC(=O)C1=CC=CC=C1 RIFJKQILKBALKJ-UHFFFAOYSA-N 0.000 description 1
- WGEOQJXLKFYXBI-UHFFFAOYSA-N n-[2-[[1-[4-(2-aminopyridin-3-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound NC1=NC=CC=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 WGEOQJXLKFYXBI-UHFFFAOYSA-N 0.000 description 1
- BIHPTOAFJFSPHQ-UHFFFAOYSA-N n-[2-[[1-[4-(2-methoxypyridin-3-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound COC1=NC=CC=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 BIHPTOAFJFSPHQ-UHFFFAOYSA-N 0.000 description 1
- KTQOBGHRYHVWCO-UHFFFAOYSA-N n-[2-[[1-[4-(2-methoxypyridin-4-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=NC(OC)=CC(C2CCC(CC2)N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)=C1 KTQOBGHRYHVWCO-UHFFFAOYSA-N 0.000 description 1
- DYHXIFIYWDLXGM-UHFFFAOYSA-N n-[2-[[1-[4-(3-amino-5-methylsulfonylpyridin-2-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound NC1=CC(S(=O)(=O)C)=CN=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 DYHXIFIYWDLXGM-UHFFFAOYSA-N 0.000 description 1
- ZKEPOUHFWZULPQ-UHFFFAOYSA-N n-[2-[[1-[4-(3-hydroxy-6-methylpyridin-2-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC=C(O)C(C2CCC(CC2)N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)=N1 ZKEPOUHFWZULPQ-UHFFFAOYSA-N 0.000 description 1
- OWGBFYYPIAIMDH-UHFFFAOYSA-N n-[2-[[1-[4-(3-hydroxypyridin-4-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound OC1=CN=CC=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 OWGBFYYPIAIMDH-UHFFFAOYSA-N 0.000 description 1
- YDRJGUAHTREIDU-UHFFFAOYSA-N n-[2-[[1-[4-(4-aminopyridin-2-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound NC1=CC=NC(C2CCC(CC2)N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)=C1 YDRJGUAHTREIDU-UHFFFAOYSA-N 0.000 description 1
- JCURBPMBHQQMKE-UHFFFAOYSA-N n-[2-[[1-[4-(4-aminopyridin-3-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound NC1=CC=NC=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 JCURBPMBHQQMKE-UHFFFAOYSA-N 0.000 description 1
- BDKFMHDWLXELLQ-UHFFFAOYSA-N n-[2-[[1-[4-(5-acetamidopyridin-2-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N1=CC(NC(=O)C)=CC=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 BDKFMHDWLXELLQ-UHFFFAOYSA-N 0.000 description 1
- XMNQMINIHKOUGR-UHFFFAOYSA-N n-[2-[[1-[4-(5-aminopyridin-3-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound NC1=CN=CC(C2CCC(CC2)N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)=C1 XMNQMINIHKOUGR-UHFFFAOYSA-N 0.000 description 1
- DXTBIZSFVOZEMC-UHFFFAOYSA-N n-[2-[[1-[4-(5-chloro-1,2,4-thiadiazol-3-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)NC2CN(C2)C2CCC(CC2)C=2N=C(Cl)SN=2)=C1 DXTBIZSFVOZEMC-UHFFFAOYSA-N 0.000 description 1
- YLKAZLGHGXXYRZ-UHFFFAOYSA-N n-[2-[[1-[4-(5-hydroxypyridin-3-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound OC1=CN=CC(C2CCC(CC2)N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)=C1 YLKAZLGHGXXYRZ-UHFFFAOYSA-N 0.000 description 1
- ULOSWLILLQCEMR-UHFFFAOYSA-N n-[2-[[1-[4-(6-aminopyridin-2-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-fluoro-5-(trifluoromethyl)benzamide Chemical compound NC1=CC=CC(C2CCC(CC2)N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=C(F)C=2)C(F)(F)F)=N1 ULOSWLILLQCEMR-UHFFFAOYSA-N 0.000 description 1
- VTZNXRJHMFWHLJ-UHFFFAOYSA-N n-[2-[[1-[4-(6-aminopyridin-2-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-4-fluoro-3-(trifluoromethyl)benzamide Chemical compound NC1=CC=CC(C2CCC(CC2)N2CC(C2)NC(=O)CNC(=O)C=2C=C(C(F)=CC=2)C(F)(F)F)=N1 VTZNXRJHMFWHLJ-UHFFFAOYSA-N 0.000 description 1
- MRWPODGPQYFBDR-UHFFFAOYSA-N n-[2-[[1-[4-(6-aminopyridin-3-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=NC(N)=CC=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 MRWPODGPQYFBDR-UHFFFAOYSA-N 0.000 description 1
- PWZJJDJNMPHXPO-UHFFFAOYSA-N n-[2-[[1-[4-(6-methoxypyridin-3-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=NC(OC)=CC=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 PWZJJDJNMPHXPO-UHFFFAOYSA-N 0.000 description 1
- HMQQZEJILDGGRN-UHFFFAOYSA-N n-[2-[[1-[4-(6-methyl-4-oxo-1h-pyrimidin-2-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(=O)NC(C2CCC(CC2)N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)=N1 HMQQZEJILDGGRN-UHFFFAOYSA-N 0.000 description 1
- UBFVILDSRHKATO-UHFFFAOYSA-N n-[2-[[1-[4-(n'-hydroxycarbamimidoyl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1CC(C(=N)NO)CCC1N1CC(NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)C1 UBFVILDSRHKATO-UHFFFAOYSA-N 0.000 description 1
- AIHPWYJJMWSZAU-UHFFFAOYSA-N n-[2-[[1-[4-[1-(2-hydroxyethyl)-6-oxopyridin-3-yl]cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=CC(=O)N(CCO)C=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 AIHPWYJJMWSZAU-UHFFFAOYSA-N 0.000 description 1
- AIKPWQXONBBAND-UHFFFAOYSA-N n-[2-[[1-[4-[1-(cyanomethyl)-6-oxopyridin-3-yl]cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)NC2CN(C2)C2CCC(CC2)C2=CN(CC#N)C(=O)C=C2)=C1 AIKPWQXONBBAND-UHFFFAOYSA-N 0.000 description 1
- JDTBCALLGFLGKK-UHFFFAOYSA-N n-[2-[[1-[4-[4-(dimethylamino)pyridin-3-yl]cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CN(C)C1=CC=NC=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 JDTBCALLGFLGKK-UHFFFAOYSA-N 0.000 description 1
- ZGIWEIBHRAITLC-UHFFFAOYSA-N n-[2-[[1-[4-[4-(methylamino)pyridin-3-yl]cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CNC1=CC=NC=C1C1CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 ZGIWEIBHRAITLC-UHFFFAOYSA-N 0.000 description 1
- UWXAQDMWMWAWRS-UHFFFAOYSA-N n-[2-[[1-[4-[6-(cyanoamino)pyridin-2-yl]cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)NC2CN(C2)C2CCC(CC2)C=2N=C(NC#N)C=CC=2)=C1 UWXAQDMWMWAWRS-UHFFFAOYSA-N 0.000 description 1
- MNVHTPQFLWEYFC-UHFFFAOYSA-N n-[2-[[1-[4-[6-(methanesulfonamido)pyridin-2-yl]cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CS(=O)(=O)NC1=CC=CC(C2CCC(CC2)N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)=N1 MNVHTPQFLWEYFC-UHFFFAOYSA-N 0.000 description 1
- KJPDQGXTTPNKFG-UHFFFAOYSA-N n-[2-[[1-[4-fluoro-4-(6-methoxypyridin-3-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=NC(OC)=CC=C1C1(F)CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 KJPDQGXTTPNKFG-UHFFFAOYSA-N 0.000 description 1
- FVPWVSLYNHVZAW-UHFFFAOYSA-N n-[2-[[1-[4-hydroxy-4-(6-methoxypyridin-3-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=NC(OC)=CC=C1C1(O)CCC(N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 FVPWVSLYNHVZAW-UHFFFAOYSA-N 0.000 description 1
- YCFZQCRYKACGKE-UHFFFAOYSA-N n-[2-oxo-2-[[1-(4-pyrazin-2-ylcyclohexyl)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=CC=NC=2)=C1 YCFZQCRYKACGKE-UHFFFAOYSA-N 0.000 description 1
- ITQNXQXQMVINMG-UHFFFAOYSA-N n-[2-oxo-2-[[1-[4-(2-oxo-3h-1,3-thiazol-5-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=2SC(=O)NC=2)=C1 ITQNXQXQMVINMG-UHFFFAOYSA-N 0.000 description 1
- ZWLQJDSPPOUXBQ-UHFFFAOYSA-N n-[2-oxo-2-[[1-[4-(4-oxo-5,6,7,8-tetrahydro-1h-quinazolin-2-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=2NC(=O)C=3CCCCC=3N=2)=C1 ZWLQJDSPPOUXBQ-UHFFFAOYSA-N 0.000 description 1
- YGALFKXWBYAMQL-UHFFFAOYSA-N n-[2-oxo-2-[[1-[4-(5-pyrrolidin-1-yl-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)N2CCCC2)=C1 YGALFKXWBYAMQL-UHFFFAOYSA-N 0.000 description 1
- YQYPVLSRAKQNJF-UHFFFAOYSA-N n-[2-oxo-2-[[1-[4-(6-oxo-1h-pyridin-2-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=2NC(=O)C=CC=2)=C1 YQYPVLSRAKQNJF-UHFFFAOYSA-N 0.000 description 1
- ADKNLTBZNHRXLH-UHFFFAOYSA-N n-[2-oxo-2-[[1-[4-(6-oxo-1h-pyridin-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)C2=CNC(=O)C=C2)=C1 ADKNLTBZNHRXLH-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
- ZYEKGZWYJNQRGK-UHFFFAOYSA-N n-[2-oxo-2-[[1-[4-[6-[(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=CC(C2CCC(CC2)N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)=N1 ZYEKGZWYJNQRGK-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
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000010807 negative regulation of binding Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- LFLZOWIFJOBEPN-UHFFFAOYSA-N nitrate, nitrate Chemical compound O[N+]([O-])=O.O[N+]([O-])=O LFLZOWIFJOBEPN-UHFFFAOYSA-N 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
- 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
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000001301 oxygen Substances 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
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000008188 pellet Substances 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
- 210000003200 peritoneal cavity Anatomy 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
- 235000021317 phosphate Nutrition 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
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000010318 polygalacturonic acid Chemical class 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 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
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 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
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 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
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 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
- 238000001525 receptor binding assay Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000000306 recurrent effect Effects 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
- 210000002345 respiratory system Anatomy 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 206010039083 rhinitis Diseases 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
- 239000002002 slurry Substances 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 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
- 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
- 125000001010 sulfinic acid amide group Chemical group 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
- 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 1
- 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 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
- SDPLODHJSZGBKU-UHFFFAOYSA-N tert-butyl n-[1-(4-cyanocyclohexyl)azetidin-3-yl]carbamate Chemical compound C1C(NC(=O)OC(C)(C)C)CN1C1CCC(C#N)CC1 SDPLODHJSZGBKU-UHFFFAOYSA-N 0.000 description 1
- SAHNINCRMUZRDP-UHFFFAOYSA-N tert-butyl n-[1-[4-(n'-hydroxycarbamimidoyl)cyclohexyl]azetidin-3-yl]carbamate Chemical compound C1C(NC(=O)OC(C)(C)C)CN1C1CCC(C(=N)NO)CC1 SAHNINCRMUZRDP-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
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 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
- 210000004291 uterus Anatomy 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 208000029257 vision disease Diseases 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 238000010626 work up procedure Methods 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 (3)
| Publication Number | Publication Date |
|---|---|
| JP2012524107A JP2012524107A (ja) | 2012-10-11 |
| JP2012524107A5 JP2012524107A5 (enExample) | 2013-05-30 |
| JP5685580B2 true JP5685580B2 (ja) | 2015-03-18 |
Family
ID=42154522
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012506216A Expired - Fee Related JP5685580B2 (ja) | 2009-04-16 | 2010-04-15 | Ｃｃｒ２の４−アゼチジニル−１−ヘテロアリール−シクロヘキサンアンタゴニスト |
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 |
| 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 |
| CA2758918A1 (en) | 2010-10-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5685580B2 (ja) | Ｃｃｒ２の４−アゼチジニル−１−ヘテロアリール−シクロヘキサンアンタゴニスト | |
| JP5675773B2 (ja) | Ｃｃｒ２の４−アゼチジニル−１−フェニル−シクロヘキサンアンタゴニスト | |
| JP5782381B2 (ja) | Ｃｃｒ２の４−アゼチジニル−１−ヘテロアリール−シクロヘキサノールアンタゴニスト | |
| JP5685581B2 (ja) | Ｃｃｒ２の４−アゼチジニル−１−ヘテロ原子結合シクロヘキサンアンタゴニスト | |
| JP5937580B2 (ja) | Ｃｃｒ２のシクロヘキシル−アゼチジニルアンタゴニスト | |
| KR20130121891A (ko) | Ｃｃｒ２의 4-치환된-사이클로헥실아미노-4-피페리디닐-아세트아미드길항제 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130404 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130404 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140423 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20140424 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140723 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20141224 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150119 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5685580 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |