JP2010521443A - 炎症の治療において有用なピペリジノン類 - Google Patents

Info

Publication number

JP2010521443A

JP2010521443A JP2009553202A JP2009553202A JP2010521443A JP 2010521443 A JP2010521443 A JP 2010521443A JP 2009553202 A JP2009553202 A JP 2009553202A JP 2009553202 A JP2009553202 A JP 2009553202A JP 2010521443 A JP2010521443 A JP 2010521443A

Authority

JP

Japan

Prior art keywords

optionally substituted

groups

alkyl

compound

hydrogen

Prior art date

2007-03-12

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.)

Pending

Links

• Espacenet
• Global Dossier
• Discuss

• 238000011282 treatment Methods 0.000 title claims abstract description 45
• 206010061218 Inflammation Diseases 0.000 title claims abstract description 25
• 230000004054 inflammatory process Effects 0.000 title claims abstract description 25
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical class O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 title description 35
• 150000001875 compounds Chemical class 0.000 claims abstract description 478
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 45
• 201000010099 disease Diseases 0.000 claims abstract description 44
• -1 1,3-dihydroindol-2-one-yl Chemical group 0.000 claims description 261
• 125000000217 alkyl group Chemical group 0.000 claims description 227
• 125000001424 substituent group Chemical group 0.000 claims description 224
• 239000001257 hydrogen Substances 0.000 claims description 184
• 229910052739 hydrogen Inorganic materials 0.000 claims description 184
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 157
• 229910052736 halogen Inorganic materials 0.000 claims description 111
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 104
• 150000002367 halogens Chemical class 0.000 claims description 104
• 125000003342 alkenyl group Chemical group 0.000 claims description 101
• 238000000034 method Methods 0.000 claims description 83
• 125000002947 alkylene group Chemical group 0.000 claims description 79
• 150000002431 hydrogen Chemical class 0.000 claims description 79
• 125000000304 alkynyl group Chemical group 0.000 claims description 76
• 125000001072 heteroaryl group Chemical group 0.000 claims description 75
• 125000000623 heterocyclic group Chemical group 0.000 claims description 75
• 125000003118 aryl group Chemical group 0.000 claims description 64
• 238000002360 preparation method Methods 0.000 claims description 60
• 239000008194 pharmaceutical composition Substances 0.000 claims description 59
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 54
• 239000003814 drug Substances 0.000 claims description 48
• 241000124008 Mammalia Species 0.000 claims description 41
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 38
• 150000003839 salts Chemical class 0.000 claims description 37
• 208000024891 symptom Diseases 0.000 claims description 35
• 229910052757 nitrogen Chemical group 0.000 claims description 34
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
• 125000004450 alkenylene group Chemical group 0.000 claims description 31
• 125000005843 halogen group Chemical group 0.000 claims description 29
• 125000006647 (C3-C15) cycloalkyl group Chemical group 0.000 claims description 27
• 229910052799 carbon Inorganic materials 0.000 claims description 26
• 125000004122 cyclic group Chemical group 0.000 claims description 26
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 25
• 239000003085 diluting agent Substances 0.000 claims description 23
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 23
• 230000007812 deficiency Effects 0.000 claims description 22
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 21
• 239000002671 adjuvant Substances 0.000 claims description 20
• 239000000651 prodrug Substances 0.000 claims description 20
• 229940002612 prodrug Drugs 0.000 claims description 20
• 125000004419 alkynylene group Chemical group 0.000 claims description 19
• 230000002757 inflammatory effect Effects 0.000 claims description 19
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 19
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 18
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 18
• 125000001153 fluoro group Chemical group F* 0.000 claims description 18
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
• 125000005842 heteroatom Chemical group 0.000 claims description 17
• 229940124597 therapeutic agent Drugs 0.000 claims description 17
• 210000003169 central nervous system Anatomy 0.000 claims description 16
• 230000008569 process Effects 0.000 claims description 16
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 13
• 239000001301 oxygen Substances 0.000 claims description 13
• 229910052760 oxygen Inorganic materials 0.000 claims description 13
• 125000003367 polycyclic group Chemical group 0.000 claims description 13
• 102000004190 Enzymes Human genes 0.000 claims description 12
• 108090000790 Enzymes Proteins 0.000 claims description 12
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
• UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 claims description 11
• 208000006673 asthma Diseases 0.000 claims description 10
• 125000002950 monocyclic group Chemical group 0.000 claims description 10
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 10
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
• 229910052794 bromium Inorganic materials 0.000 claims description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
• 238000004519 manufacturing process Methods 0.000 claims description 9
• 230000001575 pathological effect Effects 0.000 claims description 9
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 9
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 8
• 201000004624 Dermatitis Diseases 0.000 claims description 8
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 8
• 206010028980 Neoplasm Diseases 0.000 claims description 8
• 230000003834 intracellular effect Effects 0.000 claims description 8
• 125000004076 pyridyl group Chemical group 0.000 claims description 8
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 7
• 201000004681 Psoriasis Diseases 0.000 claims description 7
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 7
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 7
• 239000002131 composite material Substances 0.000 claims description 7
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
• 125000002883 imidazolyl group Chemical group 0.000 claims description 7
• 239000012453 solvate Substances 0.000 claims description 7
• 125000001544 thienyl group Chemical group 0.000 claims description 7
• 206010052779 Transplant rejections Diseases 0.000 claims description 6
• 229950006790 adenosine phosphate Drugs 0.000 claims description 6
• 206010003246 arthritis Diseases 0.000 claims description 6
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 6
• 201000011510 cancer Diseases 0.000 claims description 6
• 125000002541 furyl group Chemical group 0.000 claims description 6
• 206010025135 lupus erythematosus Diseases 0.000 claims description 6
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 6
• 125000001425 triazolyl group Chemical group 0.000 claims description 6
• UDMBCSSLTHHNCD-UHFFFAOYSA-N Coenzym Q(11) Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1O UDMBCSSLTHHNCD-UHFFFAOYSA-N 0.000 claims description 5
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
• 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 4
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 4
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 4
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
• 208000011231 Crohn disease Diseases 0.000 claims description 4
• 206010014561 Emphysema Diseases 0.000 claims description 4
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
• 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 4
• 239000000969 carrier Substances 0.000 claims description 4
• 230000003920 cognitive function Effects 0.000 claims description 4
• 125000001041 indolyl group Chemical group 0.000 claims description 4
• 201000006417 multiple sclerosis Diseases 0.000 claims description 4
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 4
• 210000000056 organ Anatomy 0.000 claims description 4
• 201000008482 osteoarthritis Diseases 0.000 claims description 4
• 125000004585 polycyclic heterocycle group Chemical group 0.000 claims description 4
• 201000003651 pulmonary sarcoidosis Diseases 0.000 claims description 4
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 3
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 3
• 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
• 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 3
• 206010006458 Bronchitis chronic Diseases 0.000 claims description 3
• 230000000903 blocking effect Effects 0.000 claims description 3
• 206010006451 bronchitis Diseases 0.000 claims description 3
• 208000007451 chronic bronchitis Diseases 0.000 claims description 3
• 125000005945 imidazopyridyl group Chemical group 0.000 claims description 3
• 230000000302 ischemic effect Effects 0.000 claims description 3
• 230000013016 learning Effects 0.000 claims description 3
• 208000032839 leukemia Diseases 0.000 claims description 3
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 3
• 230000002062 proliferating effect Effects 0.000 claims description 3
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 2
• 208000024827 Alzheimer disease Diseases 0.000 claims description 2
• 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 2
• 206010010741 Conjunctivitis Diseases 0.000 claims description 2
• 206010012438 Dermatitis atopic Diseases 0.000 claims description 2
• 208000001640 Fibromyalgia Diseases 0.000 claims description 2
• 201000005569 Gout Diseases 0.000 claims description 2
• 208000011200 Kawasaki disease Diseases 0.000 claims description 2
• 208000018737 Parkinson disease Diseases 0.000 claims description 2
• 208000029082 Pelvic Inflammatory Disease Diseases 0.000 claims description 2
• 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 2
• 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 2
• 206010063837 Reperfusion injury Diseases 0.000 claims description 2
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 2
• 206010039085 Rhinitis allergic Diseases 0.000 claims description 2
• 206010039710 Scleroderma Diseases 0.000 claims description 2
• 208000024780 Urticaria Diseases 0.000 claims description 2
• 201000010105 allergic rhinitis Diseases 0.000 claims description 2
• 201000008937 atopic dermatitis Diseases 0.000 claims description 2
• 208000010668 atopic eczema Diseases 0.000 claims description 2
• 208000025698 brain inflammatory disease Diseases 0.000 claims description 2
• 230000004663 cell proliferation Effects 0.000 claims description 2
• 208000026106 cerebrovascular disease Diseases 0.000 claims description 2
• 206010012601 diabetes mellitus Diseases 0.000 claims description 2
• 206010014599 encephalitis Diseases 0.000 claims description 2
• 201000001564 eosinophilic gastroenteritis Diseases 0.000 claims description 2
• 238000006735 epoxidation reaction Methods 0.000 claims description 2
• 208000002551 irritable bowel syndrome Diseases 0.000 claims description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
• 230000000366 juvenile effect Effects 0.000 claims description 2
• 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 claims description 2
• 201000008383 nephritis Diseases 0.000 claims description 2
• 239000007800 oxidant agent Substances 0.000 claims description 2
• 206010039083 rhinitis Diseases 0.000 claims description 2
• 201000000980 schizophrenia Diseases 0.000 claims description 2
• 201000005671 spondyloarthropathy Diseases 0.000 claims description 2
• 208000019553 vascular disease Diseases 0.000 claims description 2
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 2
• FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 claims 1
• 208000006045 Spondylarthropathies Diseases 0.000 claims 1
• 206010027175 memory impairment Diseases 0.000 claims 1
• 238000002054 transplantation Methods 0.000 claims 1
• 239000000203 mixture Substances 0.000 description 113
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 73
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
• 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 62
• 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 61
• 210000004027 cell Anatomy 0.000 description 55
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 45
• 239000000243 solution Substances 0.000 description 43
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
• 238000003556 assay Methods 0.000 description 39
• IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 38
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 34
• 238000006243 chemical reaction Methods 0.000 description 34
• 230000000694 effects Effects 0.000 description 34
• 230000005764 inhibitory process Effects 0.000 description 33
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
• 239000007787 solid Substances 0.000 description 31
• 239000002904 solvent Substances 0.000 description 30
• 208000027866 inflammatory disease Diseases 0.000 description 29
• 238000012360 testing method Methods 0.000 description 29
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
• 125000004432 carbon atom Chemical group C* 0.000 description 28
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 26
• 239000002585 base Substances 0.000 description 25
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
• 150000001350 alkyl halides Chemical class 0.000 description 23
• 239000012267 brine Substances 0.000 description 23
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
• 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 21
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
• 229940079593 drug Drugs 0.000 description 20
• 210000001519 tissue Anatomy 0.000 description 19
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 18
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 18
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
• 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 16
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
• 241000699670 Mus sp. Species 0.000 description 15
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 15
• 239000000460 chlorine Substances 0.000 description 15
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 15
• 239000000706 filtrate Substances 0.000 description 15
• 206010030113 Oedema Diseases 0.000 description 14
• 125000004429 atom Chemical group 0.000 description 14
• 229920006395 saturated elastomer Polymers 0.000 description 14
• 238000009472 formulation Methods 0.000 description 13
• 239000000543 intermediate Substances 0.000 description 13
• 239000007788 liquid Substances 0.000 description 13
• 239000007858 starting material Substances 0.000 description 13
• 239000002253 acid Substances 0.000 description 12
• 125000002619 bicyclic group Chemical group 0.000 description 12
• 235000019441 ethanol Nutrition 0.000 description 12
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 12
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 12
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 11
• 230000003110 anti-inflammatory effect Effects 0.000 description 11
• 239000002158 endotoxin Substances 0.000 description 11
• 229940088598 enzyme Drugs 0.000 description 11
• 230000002401 inhibitory effect Effects 0.000 description 11
• 229920006008 lipopolysaccharide Polymers 0.000 description 11
• 239000000047 product Substances 0.000 description 11
• 239000011541 reaction mixture Substances 0.000 description 11
• 230000001225 therapeutic effect Effects 0.000 description 11
• ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 10
• 102000004127 Cytokines Human genes 0.000 description 10
• 108090000695 Cytokines Proteins 0.000 description 10
• 101100135868 Dictyostelium discoideum pde3 gene Proteins 0.000 description 10
• 208000009386 Experimental Arthritis Diseases 0.000 description 10
• 241000282412 Homo Species 0.000 description 10
• 241001465754 Metazoa Species 0.000 description 10
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
• 239000004480 active ingredient Substances 0.000 description 10
• 239000003921 oil Substances 0.000 description 10
• 235000019198 oils Nutrition 0.000 description 10
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 10
• 125000006239 protecting group Chemical group 0.000 description 10
• 150000003254 radicals Chemical class 0.000 description 10
• VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 10
• 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 9
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
• 239000012043 crude product Substances 0.000 description 9
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• 238000012384 transportation and delivery Methods 0.000 description 9
• MSYGAHOHLUJIKV-UHFFFAOYSA-N 3,5-dimethyl-1-(3-nitrophenyl)-1h-pyrazole-4-carboxylic acid ethyl ester Chemical compound CC1=C(C(=O)OCC)C(C)=NN1C1=CC=CC([N+]([O-])=O)=C1 MSYGAHOHLUJIKV-UHFFFAOYSA-N 0.000 description 8
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical group CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 8
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 8
• 239000005089 Luciferase Substances 0.000 description 8
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
• 239000000443 aerosol Substances 0.000 description 8
• 230000015572 biosynthetic process Effects 0.000 description 8
• 150000001721 carbon Chemical group 0.000 description 8
• 229910052731 fluorine Inorganic materials 0.000 description 8
• 239000011737 fluorine Substances 0.000 description 8
• 230000007062 hydrolysis Effects 0.000 description 8
• 238000006460 hydrolysis reaction Methods 0.000 description 8
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 8
• 238000001727 in vivo Methods 0.000 description 8
• 239000007924 injection Substances 0.000 description 8
• 238000002347 injection Methods 0.000 description 8
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 8
• 229920000728 polyester Polymers 0.000 description 8
• 108090000623 proteins and genes Proteins 0.000 description 8
• 239000003642 reactive oxygen metabolite Substances 0.000 description 8
• 238000002390 rotary evaporation Methods 0.000 description 8
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 8
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
• 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 7
• 108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 7
• 239000003153 chemical reaction reagent Substances 0.000 description 7
• 125000001309 chloro group Chemical group Cl* 0.000 description 7
• 125000001183 hydrocarbyl group Chemical group 0.000 description 7
• 238000000338 in vitro Methods 0.000 description 7
• 230000028709 inflammatory response Effects 0.000 description 7
• 239000003112 inhibitor Substances 0.000 description 7
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 7
• 239000012074 organic phase Substances 0.000 description 7
• 239000012071 phase Substances 0.000 description 7
• 230000009467 reduction Effects 0.000 description 7
• 238000006722 reduction reaction Methods 0.000 description 7
• 230000001105 regulatory effect Effects 0.000 description 7
• 238000006467 substitution reaction Methods 0.000 description 7
• 239000000758 substrate Substances 0.000 description 7
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 7
• 239000003981 vehicle Substances 0.000 description 7
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
• OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 6
• 108060001084 Luciferase Proteins 0.000 description 6
• 241000699666 Mus <mouse, genus> Species 0.000 description 6
• 241000700159 Rattus Species 0.000 description 6
• 239000000654 additive Substances 0.000 description 6
• 229910052801 chlorine Inorganic materials 0.000 description 6
• DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 6
• 239000000284 extract Substances 0.000 description 6
• 125000000524 functional group Chemical group 0.000 description 6
• 230000014509 gene expression Effects 0.000 description 6
• 239000002609 medium Substances 0.000 description 6
• 238000012544 monitoring process Methods 0.000 description 6
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 6
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 6
• HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 6
• 229950005741 rolipram Drugs 0.000 description 6
• 238000010561 standard procedure Methods 0.000 description 6
• 238000003756 stirring Methods 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 6
• XLWLWCBWMVYSDN-ARLHGKGLSA-N 2-[(5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxopiperidin-3-yl]acetic acid Chemical compound COC1=CC=C([C@@H]2CC(CC(O)=O)C(=O)NC2)C=C1OC1CCCC1 XLWLWCBWMVYSDN-ARLHGKGLSA-N 0.000 description 5
• AEOBEOJCBAYXBA-UHFFFAOYSA-N A2P5P Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1OP(O)(O)=O AEOBEOJCBAYXBA-UHFFFAOYSA-N 0.000 description 5
• 101001098806 Dictyostelium discoideum cGMP-specific 3',5'-cGMP phosphodiesterase 3 Proteins 0.000 description 5
• 238000002965 ELISA Methods 0.000 description 5
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
• 102000030621 adenylate cyclase Human genes 0.000 description 5
• 108060000200 adenylate cyclase Proteins 0.000 description 5
• 239000000427 antigen Substances 0.000 description 5
• 108091007433 antigens Proteins 0.000 description 5
• 102000036639 antigens Human genes 0.000 description 5
• 239000012298 atmosphere Substances 0.000 description 5
• 210000004369 blood Anatomy 0.000 description 5
• 239000008280 blood Substances 0.000 description 5
• 239000003054 catalyst Substances 0.000 description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 5
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 5
• 229940043279 diisopropylamine Drugs 0.000 description 5
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 210000001616 monocyte Anatomy 0.000 description 5
• 150000007530 organic bases Chemical class 0.000 description 5
• 125000003386 piperidinyl group Chemical group 0.000 description 5
• 230000000770 proinflammatory effect Effects 0.000 description 5
• 235000018102 proteins Nutrition 0.000 description 5
• 102000004169 proteins and genes Human genes 0.000 description 5
• 239000011780 sodium chloride Substances 0.000 description 5
• 239000004317 sodium nitrate Substances 0.000 description 5
• 235000010344 sodium nitrate Nutrition 0.000 description 5
• 241000894007 species Species 0.000 description 5
• 239000006228 supernatant Substances 0.000 description 5
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 5
• 230000000699 topical effect Effects 0.000 description 5
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
• SJHPCNCNNSSLPL-CSKARUKUSA-N (4e)-4-(ethoxymethylidene)-2-phenyl-1,3-oxazol-5-one Chemical compound O1C(=O)C(=C/OCC)\N=C1C1=CC=CC=C1 SJHPCNCNNSSLPL-CSKARUKUSA-N 0.000 description 4
• VJJVDLPITCYXNZ-ZYMOGRSISA-N (5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[2-(1,2,4-triazol-4-ylamino)ethyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(CCNN3C=NN=C3)C(=O)NC2)C=C1OC1CCCC1 VJJVDLPITCYXNZ-ZYMOGRSISA-N 0.000 description 4
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 4
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
• 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 4
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
• 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 4
• 102000000589 Interleukin-1 Human genes 0.000 description 4
• 108010002352 Interleukin-1 Proteins 0.000 description 4
• 108010029485 Protein Isoforms Proteins 0.000 description 4
• 102000001708 Protein Isoforms Human genes 0.000 description 4
• 108091027981 Response element Proteins 0.000 description 4
• 239000007983 Tris buffer Substances 0.000 description 4
• IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 4
• 230000004913 activation Effects 0.000 description 4
• 208000026935 allergic disease Diseases 0.000 description 4
• 150000001412 amines Chemical class 0.000 description 4
• 238000010171 animal model Methods 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 4
• RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 125000002843 carboxylic acid group Chemical group 0.000 description 4
• 230000001684 chronic effect Effects 0.000 description 4
• 229940095074 cyclic amp Drugs 0.000 description 4
• GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 4
• 230000032050 esterification Effects 0.000 description 4
• 238000005886 esterification reaction Methods 0.000 description 4
• 150000002148 esters Chemical class 0.000 description 4
• 239000012091 fetal bovine serum Substances 0.000 description 4
• MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 4
• 239000012458 free base Substances 0.000 description 4
• 238000004128 high performance liquid chromatography Methods 0.000 description 4
• 239000005457 ice water Substances 0.000 description 4
• PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 4
• 239000012139 lysis buffer Substances 0.000 description 4
• 210000002540 macrophage Anatomy 0.000 description 4
• 230000001404 mediated effect Effects 0.000 description 4
• 125000002757 morpholinyl group Chemical group 0.000 description 4
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
• 210000000440 neutrophil Anatomy 0.000 description 4
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 4
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 4
• 229910052763 palladium Inorganic materials 0.000 description 4
• PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 4
• 125000004193 piperazinyl group Chemical group 0.000 description 4
• 229920001223 polyethylene glycol Polymers 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• 239000000843 powder Substances 0.000 description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 4
• 210000002966 serum Anatomy 0.000 description 4
• 239000011734 sodium Substances 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 4
• 229910052717 sulfur Inorganic materials 0.000 description 4
• 239000004094 surface-active agent Substances 0.000 description 4
• 239000003826 tablet Substances 0.000 description 4
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
• ZBYFZNUSUAWAJU-NNVROAHOSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(3-methylphenyl)methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=C(C)C=CC=2)C=C1OC1CCCC1 ZBYFZNUSUAWAJU-NNVROAHOSA-N 0.000 description 3
• PIHFCZGFIZHAIF-XSRYCBBQSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-(oxolan-3-ylmethyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC3COCC3)C(=O)NC2)C=C1OC1CCCC1 PIHFCZGFIZHAIF-XSRYCBBQSA-N 0.000 description 3
• UGNYCQQXLIVWRM-WOJBJXKFSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(5-methoxy-1-benzofuran-2-yl)methyl]piperidin-2-one Chemical compound C=1C([C@@H]2C[C@@H](C(NC2)=O)CC=2OC3=CC=C(C=C3C=2)OC)=CC=C(OC)C=1OC1CCCC1 UGNYCQQXLIVWRM-WOJBJXKFSA-N 0.000 description 3
• MMWJHRKOEGAFLT-IAGOWNOFSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(5-nitro-1,3-benzoxazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3OC4=CC=C(C=C4N=3)[N+]([O-])=O)C(=O)NC2)C=C1OC1CCCC1 MMWJHRKOEGAFLT-IAGOWNOFSA-N 0.000 description 3
• ZQMCYRDMYZYFPT-RTBURBONSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-(pyridin-3-ylmethyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3C=NC=CC=3)C(=O)NC2)C=C1OC1CCCC1 ZQMCYRDMYZYFPT-RTBURBONSA-N 0.000 description 3
• ODBQLLBQYWFRFJ-LJQANCHMSA-N (5s)-1-benzoyl-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@H]2CN(C(=O)CC2)C(=O)C=2C=CC=CC=2)C=C1OC1CCCC1 ODBQLLBQYWFRFJ-LJQANCHMSA-N 0.000 description 3
• OKNONDJDOBRYGV-HXUWFJFHSA-N (5s)-1-benzyl-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@H]2CN(CC=3C=CC=CC=3)C(=O)CC2)C=C1OC1CCCC1 OKNONDJDOBRYGV-HXUWFJFHSA-N 0.000 description 3
• RWZBWCJJKXLMJA-GFOWMXPYSA-N (5s)-3-(2-anilinoethyl)-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(CCNC=3C=CC=CC=3)C(=O)NC2)C=C1OC1CCCC1 RWZBWCJJKXLMJA-GFOWMXPYSA-N 0.000 description 3
• UGBIHQKLJQPIDI-HWOWSKLDSA-N (5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-(2,3-dihydroxypropyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(CC(O)CO)C(=O)NC2)C=C1OC1CCCC1 UGBIHQKLJQPIDI-HWOWSKLDSA-N 0.000 description 3
• RBHYYIWXRVYZOD-OAHLLOKOSA-N (5s)-5-(4-methoxy-3-phenylphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@H]2CNC(=O)CC2)C=C1C1=CC=CC=C1 RBHYYIWXRVYZOD-OAHLLOKOSA-N 0.000 description 3
• 125000004400 (C1-C12) alkyl group Chemical group 0.000 description 3
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 3
• ABADUMLIAZCWJD-UHFFFAOYSA-N 1,3-dioxole Chemical compound C1OC=CO1 ABADUMLIAZCWJD-UHFFFAOYSA-N 0.000 description 3
• GPWIKPHJUQMGFW-MUMRKEEXSA-N 2-[(5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxopiperidin-3-yl]-n-phenylacetamide Chemical compound COC1=CC=C([C@@H]2CC(CC(=O)NC=3C=CC=CC=3)C(=O)NC2)C=C1OC1CCCC1 GPWIKPHJUQMGFW-MUMRKEEXSA-N 0.000 description 3
• QOZLOYKAFDTQNU-UHFFFAOYSA-N 2-amino-3-fluorophenol Chemical compound NC1=C(O)C=CC=C1F QOZLOYKAFDTQNU-UHFFFAOYSA-N 0.000 description 3
• 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 3
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 3
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-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
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• PHEDXBVPIONUQT-UHFFFAOYSA-N Cocarcinogen A1 Natural products CCCCCCCCCCCCCC(=O)OC1C(C)C2(O)C3C=C(C)C(=O)C3(O)CC(CO)=CC2C2C1(OC(C)=O)C2(C)C PHEDXBVPIONUQT-UHFFFAOYSA-N 0.000 description 3
• SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 3
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 3
• 239000005977 Ethylene Substances 0.000 description 3
• 241000282326 Felis catus Species 0.000 description 3
• 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 3
• 101000988424 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4B Proteins 0.000 description 3
• 206010020751 Hypersensitivity Diseases 0.000 description 3
• 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 3
• 229910010082 LiAlH Inorganic materials 0.000 description 3
• 101000909851 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) cAMP/cGMP dual specificity phosphodiesterase Rv0805 Proteins 0.000 description 3
• UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 239000002202 Polyethylene glycol Substances 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 206010070834 Sensitisation Diseases 0.000 description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
• 108091008874 T cell receptors Proteins 0.000 description 3
• 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 3
• 210000001744 T-lymphocyte Anatomy 0.000 description 3
• 210000001015 abdomen Anatomy 0.000 description 3
• 230000001154 acute effect Effects 0.000 description 3
• 208000038016 acute inflammation Diseases 0.000 description 3
• 230000006022 acute inflammation Effects 0.000 description 3
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 3
• 125000003545 alkoxy group Chemical group 0.000 description 3
• 230000007815 allergy Effects 0.000 description 3
• 125000003277 amino group Chemical group 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 239000008346 aqueous phase Substances 0.000 description 3
• 239000012300 argon atmosphere Substances 0.000 description 3
• 239000011324 bead Substances 0.000 description 3
• 230000033228 biological regulation Effects 0.000 description 3
• 102100029168 cAMP-specific 3',5'-cyclic phosphodiesterase 4B Human genes 0.000 description 3
• 229910002091 carbon monoxide Inorganic materials 0.000 description 3
• 230000010261 cell growth Effects 0.000 description 3
• 230000001413 cellular effect Effects 0.000 description 3
• 125000003636 chemical group Chemical group 0.000 description 3
• 239000003795 chemical substances by application Substances 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• 208000037976 chronic inflammation Diseases 0.000 description 3
• 230000006020 chronic inflammation Effects 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 239000011248 coating agent Substances 0.000 description 3
• 238000000576 coating method Methods 0.000 description 3
• OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 3
• 206010009887 colitis Diseases 0.000 description 3
• 239000003086 colorant Substances 0.000 description 3
• 125000002993 cycloalkylene group Chemical group 0.000 description 3
• 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 description 3
• 229960002380 dibutyl phthalate Drugs 0.000 description 3
• 239000002552 dosage form Substances 0.000 description 3
• 239000003937 drug carrier Substances 0.000 description 3
• 238000012377 drug delivery Methods 0.000 description 3
• 230000004064 dysfunction Effects 0.000 description 3
• BGWMHFKCAUBYJJ-UHFFFAOYSA-N ethyl 2-chloroethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)CCl BGWMHFKCAUBYJJ-UHFFFAOYSA-N 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthene Chemical compound C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 description 3
• 235000003599 food sweetener Nutrition 0.000 description 3
• XPFVYQJUAUNWIW-UHFFFAOYSA-N furfuryl alcohol Chemical compound OCC1=CC=CO1 XPFVYQJUAUNWIW-UHFFFAOYSA-N 0.000 description 3
• 239000000499 gel Substances 0.000 description 3
• 102000057041 human TNF Human genes 0.000 description 3
• 230000006872 improvement Effects 0.000 description 3
• 230000006698 induction Effects 0.000 description 3
• 210000004969 inflammatory cell Anatomy 0.000 description 3
• 230000004968 inflammatory condition Effects 0.000 description 3
• 150000007529 inorganic bases Chemical class 0.000 description 3
• 229910052740 iodine Inorganic materials 0.000 description 3
• 210000000265 leukocyte Anatomy 0.000 description 3
• 238000012417 linear regression Methods 0.000 description 3
• 210000004072 lung Anatomy 0.000 description 3
• 239000006166 lysate Substances 0.000 description 3
• 230000002503 metabolic effect Effects 0.000 description 3
• 210000005087 mononuclear cell Anatomy 0.000 description 3
• 238000010172 mouse model Methods 0.000 description 3
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
• 239000002674 ointment Substances 0.000 description 3
• 125000003566 oxetanyl group Chemical group 0.000 description 3
• 239000002953 phosphate buffered saline Substances 0.000 description 3
• 229920000642 polymer Polymers 0.000 description 3
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
• 239000002244 precipitate Substances 0.000 description 3
• 239000003755 preservative agent Substances 0.000 description 3
• 125000000168 pyrrolyl group Chemical group 0.000 description 3
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 3
• 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 239000000523 sample Substances 0.000 description 3
• 230000008313 sensitization Effects 0.000 description 3
• 229910052708 sodium Inorganic materials 0.000 description 3
• 229910000104 sodium hydride Inorganic materials 0.000 description 3
• 239000003381 stabilizer Substances 0.000 description 3
• 239000011593 sulfur Substances 0.000 description 3
• 230000000153 supplemental effect Effects 0.000 description 3
• 239000003765 sweetening agent Substances 0.000 description 3
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 3
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
• 125000003396 thiol group Chemical group [H]S* 0.000 description 3
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 3
• 230000000451 tissue damage Effects 0.000 description 3
• 231100000827 tissue damage Toxicity 0.000 description 3
• 239000002699 waste material Substances 0.000 description 3
• KJJCSWCQNCLXRL-WAGPWIPHSA-N (3e,5s)-3-(1,3-benzodioxol-4-ylmethylidene)-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=3OCOC=3C=CC=2)C=C1OC1CCCC1 KJJCSWCQNCLXRL-WAGPWIPHSA-N 0.000 description 2
• XLNGTBLKLAOMEK-SZVPOVDMSA-N (3e,5s)-3-(1,3-benzodioxol-5-ylmethylidene)-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=C3OCOC3=CC=2)C=C1OC1CCCC1 XLNGTBLKLAOMEK-SZVPOVDMSA-N 0.000 description 2
• MDXPMENZBCCFFQ-TVNWYLLRSA-N (3e,5s)-3-[(2-chlorophenyl)methylidene]-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C(=CC=CC=2)Cl)C=C1OC1CCCC1 MDXPMENZBCCFFQ-TVNWYLLRSA-N 0.000 description 2
• NPMVAOSEYBPCGL-WAGPWIPHSA-N (3e,5s)-3-[(3-chlorophenyl)methylidene]-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=C(Cl)C=CC=2)C=C1OC1CCCC1 NPMVAOSEYBPCGL-WAGPWIPHSA-N 0.000 description 2
• XIKFLZKYZDTFHR-PLJYQOKSSA-N (3e,5s)-3-[(4-butoxyphenyl)methylidene]-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound C1=CC(OCCCC)=CC=C1\C=C/1C(=O)NC[C@H](C=2C=C(OC3CCCC3)C(OC)=CC=2)C\1 XIKFLZKYZDTFHR-PLJYQOKSSA-N 0.000 description 2
• SNBCNHDZQAPMBS-TVNWYLLRSA-N (3e,5s)-3-[(4-chlorophenyl)methylidene]-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=CC(Cl)=CC=2)C=C1OC1CCCC1 SNBCNHDZQAPMBS-TVNWYLLRSA-N 0.000 description 2
• CMGKTLFSRQBEMY-WAFWZSCLSA-N (3e,5s)-3-[[2-chloro-5-(trifluoromethyl)phenyl]methylidene]-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C(=CC=C(C=2)C(F)(F)F)Cl)C=C1OC1CCCC1 CMGKTLFSRQBEMY-WAFWZSCLSA-N 0.000 description 2
• URFQOPPNMVSYII-SMHZUEHJSA-N (3e,5s)-3-[[3,5-bis(trifluoromethyl)phenyl]methylidene]-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C=C1OC1CCCC1 URFQOPPNMVSYII-SMHZUEHJSA-N 0.000 description 2
• SIYZBKMCDLVUEG-VKIDYWOHSA-N (3e,5s)-3-[[3-(4-chlorophenoxy)phenyl]methylidene]-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=C(OC=3C=CC(Cl)=CC=3)C=CC=2)C=C1OC1CCCC1 SIYZBKMCDLVUEG-VKIDYWOHSA-N 0.000 description 2
• FCIVRRINLFMTEA-UMSHPIDHSA-N (3e,5s)-3-benzylidene-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=CC=CC=2)C=C1OC1CCCC1 FCIVRRINLFMTEA-UMSHPIDHSA-N 0.000 description 2
• IFECTEKZCMGWLE-WAFWZSCLSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-(furan-3-ylmethylidene)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C2=COC=C2)C=C1OC1CCCC1 IFECTEKZCMGWLE-WAFWZSCLSA-N 0.000 description 2
• QWFYMZGRAVSLOB-VJSYINPZSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-(pyridin-2-ylmethylidene)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2N=CC=CC=2)C=C1OC1CCCC1 QWFYMZGRAVSLOB-VJSYINPZSA-N 0.000 description 2
• WQPYMKHXAKFJGX-WAGPWIPHSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-(pyridin-3-ylmethylidene)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=NC=CC=2)C=C1OC1CCCC1 WQPYMKHXAKFJGX-WAGPWIPHSA-N 0.000 description 2
• AXNKJQIPYSTSCG-TVNWYLLRSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-(pyridin-4-ylmethylidene)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=CN=CC=2)C=C1OC1CCCC1 AXNKJQIPYSTSCG-TVNWYLLRSA-N 0.000 description 2
• IDCNUQBPYZCTSF-ZKTNYTPDSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(2,3-difluorophenyl)methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C(=C(F)C=CC=2)F)C=C1OC1CCCC1 IDCNUQBPYZCTSF-ZKTNYTPDSA-N 0.000 description 2
• NWPVWMBWULMSGS-WAFWZSCLSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(2,4-difluorophenyl)methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C(=CC(F)=CC=2)F)C=C1OC1CCCC1 NWPVWMBWULMSGS-WAFWZSCLSA-N 0.000 description 2
• DDQQSICFLFADHB-WAFWZSCLSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(2,5-difluorophenyl)methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C(=CC=C(F)C=2)F)C=C1OC1CCCC1 DDQQSICFLFADHB-WAFWZSCLSA-N 0.000 description 2
• ODLGIBSFNBBNEE-YWXUCKCNSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(2,6-dimethoxyphenyl)methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C(=CC=CC=2OC)OC)C=C1OC1CCCC1 ODLGIBSFNBBNEE-YWXUCKCNSA-N 0.000 description 2
• ODCAPJZFZCJPCK-TVNWYLLRSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(2-fluorophenyl)methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C(=CC=CC=2)F)C=C1OC1CCCC1 ODCAPJZFZCJPCK-TVNWYLLRSA-N 0.000 description 2
• FXEIQJQTEDOLCU-UMSHPIDHSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(2-methoxyphenyl)methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C(=CC=CC=2)OC)C=C1OC1CCCC1 FXEIQJQTEDOLCU-UMSHPIDHSA-N 0.000 description 2
• QCZBDEIZDORLEJ-NNVROAHOSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(2-methylphenyl)methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C(=CC=CC=2)C)C=C1OC1CCCC1 QCZBDEIZDORLEJ-NNVROAHOSA-N 0.000 description 2
• PDHFXMBIUPVDNF-TVNWYLLRSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(2-nitrophenyl)methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C(=CC=CC=2)[N+]([O-])=O)C=C1OC1CCCC1 PDHFXMBIUPVDNF-TVNWYLLRSA-N 0.000 description 2
• UZILOXKYDWQNPY-PYIVIEQSSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(3,4,5-trimethoxyphenyl)methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=C(OC)C(OC)=C(OC)C=2)C=C1OC1CCCC1 UZILOXKYDWQNPY-PYIVIEQSSA-N 0.000 description 2
• OCNORCZFTGXRTO-QDDTUJKSSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(3,4-dimethoxyphenyl)methylidene]piperidin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1\C=C/1C(=O)NC[C@H](C=2C=C(OC3CCCC3)C(OC)=CC=2)C\1 OCNORCZFTGXRTO-QDDTUJKSSA-N 0.000 description 2
• RQCCLHNZQZDQPE-WAGPWIPHSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(3-fluoro-4-methoxyphenyl)methylidene]piperidin-2-one Chemical compound C1=C(F)C(OC)=CC=C1\C=C/1C(=O)NC[C@H](C=2C=C(OC3CCCC3)C(OC)=CC=2)C\1 RQCCLHNZQZDQPE-WAGPWIPHSA-N 0.000 description 2
• QPMFZLVHGHEXMV-WAGPWIPHSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(3-fluorophenyl)methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=C(F)C=CC=2)C=C1OC1CCCC1 QPMFZLVHGHEXMV-WAGPWIPHSA-N 0.000 description 2
• TVYKSNCKTIQAOT-QDDTUJKSSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(3-methoxyphenyl)methylidene]piperidin-2-one Chemical compound COC1=CC=CC(\C=C/2C(NC[C@@H](C\2)C=2C=C(OC3CCCC3)C(OC)=CC=2)=O)=C1 TVYKSNCKTIQAOT-QDDTUJKSSA-N 0.000 description 2
• HKIWKKMMEHUMSJ-VOGGAGISSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(3-phenoxyphenyl)methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=C(OC=3C=CC=CC=3)C=CC=2)C=C1OC1CCCC1 HKIWKKMMEHUMSJ-VOGGAGISSA-N 0.000 description 2
• DYAGKYDJHIUPGH-TVNWYLLRSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(4-fluorophenyl)methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=CC(F)=CC=2)C=C1OC1CCCC1 DYAGKYDJHIUPGH-TVNWYLLRSA-N 0.000 description 2
• INLADQWTKLXZFI-QJUACMODSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(4-imidazol-1-ylphenyl)methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=CC(=CC=2)N2C=NC=C2)C=C1OC1CCCC1 INLADQWTKLXZFI-QJUACMODSA-N 0.000 description 2
• LQKHPFOMKQKUFC-YVJFHRMNSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(4-phenoxyphenyl)methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=CC(OC=3C=CC=CC=3)=CC=2)C=C1OC1CCCC1 LQKHPFOMKQKUFC-YVJFHRMNSA-N 0.000 description 2
• SYHJFZLFUOWTQZ-CLMUKVTESA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(4-propan-2-ylphenyl)methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=CC(=CC=2)C(C)C)C=C1OC1CCCC1 SYHJFZLFUOWTQZ-CLMUKVTESA-N 0.000 description 2
• XYSRAWIIOUHLCH-HJDVLLJCSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(6-methylpyridin-2-yl)methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2N=C(C)C=CC=2)C=C1OC1CCCC1 XYSRAWIIOUHLCH-HJDVLLJCSA-N 0.000 description 2
• FNVXKMQZASLAIU-WAGPWIPHSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[[3-(trifluoromethoxy)phenyl]methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=C(OC(F)(F)F)C=CC=2)C=C1OC1CCCC1 FNVXKMQZASLAIU-WAGPWIPHSA-N 0.000 description 2
• CTKVCXOCIIDHBV-WAGPWIPHSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[[3-(trifluoromethyl)phenyl]methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=C(C=CC=2)C(F)(F)F)C=C1OC1CCCC1 CTKVCXOCIIDHBV-WAGPWIPHSA-N 0.000 description 2
• VEXSPVQROLUGPM-VOGGAGISSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[[4-(diethoxymethyl)phenyl]methylidene]piperidin-2-one Chemical compound C1=CC(C(OCC)OCC)=CC=C1\C=C/1C(=O)NC[C@H](C=2C=C(OC3CCCC3)C(OC)=CC=2)C\1 VEXSPVQROLUGPM-VOGGAGISSA-N 0.000 description 2
• VPSJWBASZSHDPQ-PLJYQOKSSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[[4-(diethylamino)phenyl]methylidene]piperidin-2-one Chemical compound C1=CC(N(CC)CC)=CC=C1\C=C/1C(=O)NC[C@H](C=2C=C(OC3CCCC3)C(OC)=CC=2)C\1 VPSJWBASZSHDPQ-PLJYQOKSSA-N 0.000 description 2
• MRSFOEIHYGXVKV-TVNWYLLRSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[[4-(trifluoromethoxy)phenyl]methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=CC(OC(F)(F)F)=CC=2)C=C1OC1CCCC1 MRSFOEIHYGXVKV-TVNWYLLRSA-N 0.000 description 2
• MKKOUUMDSLEIAU-YVJFHRMNSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[[4-[3-(dimethylamino)propoxy]phenyl]methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=CC(OCCCN(C)C)=CC=2)C=C1OC1CCCC1 MKKOUUMDSLEIAU-YVJFHRMNSA-N 0.000 description 2
• LEBOJPXLECDYDJ-QZTJIDSGSA-N (3r,5s)-3-(1,3-benzothiazol-2-ylmethyl)-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3SC4=CC=CC=C4N=3)C(=O)NC2)C=C1OC1CCCC1 LEBOJPXLECDYDJ-QZTJIDSGSA-N 0.000 description 2
• NDAUQSOZNOECBO-QZTJIDSGSA-N (3r,5s)-3-(1,3-benzoxazol-2-ylmethyl)-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3OC4=CC=CC=C4N=3)C(=O)NC2)C=C1OC1CCCC1 NDAUQSOZNOECBO-QZTJIDSGSA-N 0.000 description 2
• XMQFBVSTAIPSQV-WOJBJXKFSA-N (3r,5s)-3-(1-benzofuran-2-ylmethyl)-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3OC4=CC=CC=C4C=3)C(=O)NC2)C=C1OC1CCCC1 XMQFBVSTAIPSQV-WOJBJXKFSA-N 0.000 description 2
• YJYQDOJPAMCUTR-RTBURBONSA-N (3r,5s)-3-(1-benzothiophen-3-ylmethyl)-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3C4=CC=CC=C4SC=3)C(=O)NC2)C=C1OC1CCCC1 YJYQDOJPAMCUTR-RTBURBONSA-N 0.000 description 2
• CGYHJAFMSYJZEC-QZTJIDSGSA-N (3r,5s)-3-(1h-benzimidazol-2-ylmethyl)-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3NC4=CC=CC=C4N=3)C(=O)NC2)C=C1OC1CCCC1 CGYHJAFMSYJZEC-QZTJIDSGSA-N 0.000 description 2
• RWZBWCJJKXLMJA-VQTJNVASSA-N (3r,5s)-3-(2-anilinoethyl)-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CCNC=3C=CC=CC=3)C(=O)NC2)C=C1OC1CCCC1 RWZBWCJJKXLMJA-VQTJNVASSA-N 0.000 description 2
• CTPMVYVTLMVCHD-ZWKOTPCHSA-N (3r,5s)-3-(2h-benzotriazol-4-ylmethyl)-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3C4=NNN=C4C=CC=3)C(=O)NC2)C=C1OC1CCCC1 CTPMVYVTLMVCHD-ZWKOTPCHSA-N 0.000 description 2
• CBQWBWCLDSOZPS-IAGOWNOFSA-N (3r,5s)-3-[(6-chloro-1,3-benzoxazol-2-yl)methyl]-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3OC4=CC(Cl)=CC=C4N=3)C(=O)NC2)C=C1OC1CCCC1 CBQWBWCLDSOZPS-IAGOWNOFSA-N 0.000 description 2
• WHRAWTCKIIDTJJ-IAGOWNOFSA-N (3r,5s)-3-[(7-chloro-1,3-benzoxazol-2-yl)methyl]-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3OC4=C(Cl)C=CC=C4N=3)C(=O)NC2)C=C1OC1CCCC1 WHRAWTCKIIDTJJ-IAGOWNOFSA-N 0.000 description 2
• BXBCZBHPAUVQSU-IAGOWNOFSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-(furan-2-ylmethyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3OC=CC=3)C(=O)NC2)C=C1OC1CCCC1 BXBCZBHPAUVQSU-IAGOWNOFSA-N 0.000 description 2
• OPKOAUYDQZGLKQ-QZTJIDSGSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-(pyridin-2-ylmethyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3N=CC=CC=3)C(=O)NC2)C=C1OC1CCCC1 OPKOAUYDQZGLKQ-QZTJIDSGSA-N 0.000 description 2
• IOWHZSMPPBBVPQ-RBUKOAKNSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-(pyridin-4-ylmethyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3C=CN=CC=3)C(=O)NC2)C=C1OC1CCCC1 IOWHZSMPPBBVPQ-RBUKOAKNSA-N 0.000 description 2
• CRXQWGRSZGIBSP-IAGOWNOFSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-(thiophen-2-ylmethyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3SC=CC=3)C(=O)NC2)C=C1OC1CCCC1 CRXQWGRSZGIBSP-IAGOWNOFSA-N 0.000 description 2
• FJSXVBNYCXVIRT-RTBURBONSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(1-methylbenzimidazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3N(C4=CC=CC=C4N=3)C)C(=O)NC2)C=C1OC1CCCC1 FJSXVBNYCXVIRT-RTBURBONSA-N 0.000 description 2
• DKQDEJQYOLGEKS-IAGOWNOFSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(4-fluoro-1,3-benzoxazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3OC4=CC=CC(F)=C4N=3)C(=O)NC2)C=C1OC1CCCC1 DKQDEJQYOLGEKS-IAGOWNOFSA-N 0.000 description 2
• BCYWOYQZFDYFIS-QZTJIDSGSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(4-methoxy-1,3-benzoxazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3OC4=CC=CC(OC)=C4N=3)C(=O)NC2)C=C1OC1CCCC1 BCYWOYQZFDYFIS-QZTJIDSGSA-N 0.000 description 2
• FXDBARFSUWDUCS-RTBURBONSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(4-methyl-1,3-benzoxazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3OC4=CC=CC(C)=C4N=3)C(=O)NC2)C=C1OC1CCCC1 FXDBARFSUWDUCS-RTBURBONSA-N 0.000 description 2
• NCTQRLZPMYAPEM-HZPDHXFCSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(5,6-dichloro-1h-benzimidazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3NC4=CC(Cl)=C(Cl)C=C4N=3)C(=O)NC2)C=C1OC1CCCC1 NCTQRLZPMYAPEM-HZPDHXFCSA-N 0.000 description 2
• LMMOUDNKSQXIKZ-WOJBJXKFSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(5,6-dimethyl-1h-benzimidazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3NC4=CC(C)=C(C)C=C4N=3)C(=O)NC2)C=C1OC1CCCC1 LMMOUDNKSQXIKZ-WOJBJXKFSA-N 0.000 description 2
• KCEQOSVNLKVSPO-IAGOWNOFSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(5-fluoro-1,3-benzoxazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3OC4=CC=C(F)C=C4N=3)C(=O)NC2)C=C1OC1CCCC1 KCEQOSVNLKVSPO-IAGOWNOFSA-N 0.000 description 2
• HDQURSYBHMHOGD-QZTJIDSGSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(5-methoxy-1,3-benzoxazol-2-yl)methyl]piperidin-2-one Chemical compound C=1C([C@@H]2C[C@@H](C(NC2)=O)CC=2OC3=CC=C(C=C3N=2)OC)=CC=C(OC)C=1OC1CCCC1 HDQURSYBHMHOGD-QZTJIDSGSA-N 0.000 description 2
• VDICCPPRMBAZBQ-RTBURBONSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(5-methyl-1,3-benzoxazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3OC4=CC=C(C)C=C4N=3)C(=O)NC2)C=C1OC1CCCC1 VDICCPPRMBAZBQ-RTBURBONSA-N 0.000 description 2
• JGRJBYNMEPUBIS-RTBURBONSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(6-methyl-1,3-benzoxazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3OC4=CC(C)=CC=C4N=3)C(=O)NC2)C=C1OC1CCCC1 JGRJBYNMEPUBIS-RTBURBONSA-N 0.000 description 2
• ZPRDHQBABHOCOM-RTBURBONSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(6-methylpyridin-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3N=C(C)C=CC=3)C(=O)NC2)C=C1OC1CCCC1 ZPRDHQBABHOCOM-RTBURBONSA-N 0.000 description 2
• JYWYAWOBVVBZJH-IAGOWNOFSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(7-fluoro-1,3-benzoxazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3OC4=C(F)C=CC=C4N=3)C(=O)NC2)C=C1OC1CCCC1 JYWYAWOBVVBZJH-IAGOWNOFSA-N 0.000 description 2
• ZVNRSYGAHDBQDJ-RTBURBONSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(7-fluoro-1-benzofuran-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3OC4=C(F)C=CC=C4C=3)C(=O)NC2)C=C1OC1CCCC1 ZVNRSYGAHDBQDJ-RTBURBONSA-N 0.000 description 2
• DCSYPZAUWXTYNF-WOJBJXKFSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(7-methoxy-1-benzofuran-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3OC4=C(OC)C=CC=C4C=3)C(=O)NC2)C=C1OC1CCCC1 DCSYPZAUWXTYNF-WOJBJXKFSA-N 0.000 description 2
• IELNIJCELQZAKS-RTBURBONSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(7-methyl-1,3-benzoxazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3OC4=C(C)C=CC=C4N=3)C(=O)NC2)C=C1OC1CCCC1 IELNIJCELQZAKS-RTBURBONSA-N 0.000 description 2
• QGYLCGPKLHQXJL-RBUKOAKNSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[2-(4-fluoroanilino)ethyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CCNC=3C=CC(F)=CC=3)C(=O)NC2)C=C1OC1CCCC1 QGYLCGPKLHQXJL-RBUKOAKNSA-N 0.000 description 2
• LRLCYVNNYQGRQW-IAGOWNOFSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[[4-(trifluoromethyl)-1,3-benzoxazol-2-yl]methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3OC4=CC=CC(=C4N=3)C(F)(F)F)C(=O)NC2)C=C1OC1CCCC1 LRLCYVNNYQGRQW-IAGOWNOFSA-N 0.000 description 2
• OYPHTRSDXIKTTE-IAGOWNOFSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[[5-(trifluoromethyl)-1,3-benzoxazol-2-yl]methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3OC4=CC=C(C=C4N=3)C(F)(F)F)C(=O)NC2)C=C1OC1CCCC1 OYPHTRSDXIKTTE-IAGOWNOFSA-N 0.000 description 2
• XWFYCDHFVFDJEZ-RTBURBONSA-N (3s,5s)-3-(1,3-benzodioxol-5-ylmethyl)-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3C=C4OCOC4=CC=3)C(=O)NC2)C=C1OC1CCCC1 XWFYCDHFVFDJEZ-RTBURBONSA-N 0.000 description 2
• LEBOJPXLECDYDJ-ZWKOTPCHSA-N (3s,5s)-3-(1,3-benzothiazol-2-ylmethyl)-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3SC4=CC=CC=C4N=3)C(=O)NC2)C=C1OC1CCCC1 LEBOJPXLECDYDJ-ZWKOTPCHSA-N 0.000 description 2
• NDAUQSOZNOECBO-ZWKOTPCHSA-N (3s,5s)-3-(1,3-benzoxazol-2-ylmethyl)-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC4=CC=CC=C4N=3)C(=O)NC2)C=C1OC1CCCC1 NDAUQSOZNOECBO-ZWKOTPCHSA-N 0.000 description 2
• XMQFBVSTAIPSQV-VQTJNVASSA-N (3s,5s)-3-(1-benzofuran-2-ylmethyl)-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC4=CC=CC=C4C=3)C(=O)NC2)C=C1OC1CCCC1 XMQFBVSTAIPSQV-VQTJNVASSA-N 0.000 description 2
• YJYQDOJPAMCUTR-RBUKOAKNSA-N (3s,5s)-3-(1-benzothiophen-3-ylmethyl)-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3C4=CC=CC=C4SC=3)C(=O)NC2)C=C1OC1CCCC1 YJYQDOJPAMCUTR-RBUKOAKNSA-N 0.000 description 2
• CGYHJAFMSYJZEC-ZWKOTPCHSA-N (3s,5s)-3-(1h-benzimidazol-2-ylmethyl)-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3NC4=CC=CC=C4N=3)C(=O)NC2)C=C1OC1CCCC1 CGYHJAFMSYJZEC-ZWKOTPCHSA-N 0.000 description 2
• CRRGZIAFGVKVQI-MOPGFXCFSA-N (3s,5s)-3-(anilinomethyl)-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CNC=3C=CC=CC=3)C(=O)NC2)C=C1OC1CCCC1 CRRGZIAFGVKVQI-MOPGFXCFSA-N 0.000 description 2
• OGAIFDKWRDZRMV-MSOLQXFVSA-N (3s,5s)-3-[(1,3-benzodioxol-5-ylamino)methyl]-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CNC=3C=C4OCOC4=CC=3)C(=O)NC2)C=C1OC1CCCC1 OGAIFDKWRDZRMV-MSOLQXFVSA-N 0.000 description 2
• QXRSQYYEPHVSSV-MSOLQXFVSA-N (3s,5s)-3-[(4-chloroanilino)methyl]-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CNC=3C=CC(Cl)=CC=3)C(=O)NC2)C=C1OC1CCCC1 QXRSQYYEPHVSSV-MSOLQXFVSA-N 0.000 description 2
• PUGHGURKYVRGCL-RTWAWAEBSA-N (3s,5s)-3-[(4-tert-butylanilino)methyl]-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CNC=3C=CC(=CC=3)C(C)(C)C)C(=O)NC2)C=C1OC1CCCC1 PUGHGURKYVRGCL-RTWAWAEBSA-N 0.000 description 2
• CBQWBWCLDSOZPS-DLBZAZTESA-N (3s,5s)-3-[(6-chloro-1,3-benzoxazol-2-yl)methyl]-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC4=CC(Cl)=CC=C4N=3)C(=O)NC2)C=C1OC1CCCC1 CBQWBWCLDSOZPS-DLBZAZTESA-N 0.000 description 2
• WHRAWTCKIIDTJJ-DLBZAZTESA-N (3s,5s)-3-[(7-chloro-1,3-benzoxazol-2-yl)methyl]-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC4=C(Cl)C=CC=C4N=3)C(=O)NC2)C=C1OC1CCCC1 WHRAWTCKIIDTJJ-DLBZAZTESA-N 0.000 description 2
• QWWMZYLXWJMMTH-FTJBHMTQSA-N (3s,5s)-3-[(n-benzylanilino)methyl]-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CN(CC=3C=CC=CC=3)C=3C=CC=CC=3)C(=O)NC2)C=C1OC1CCCC1 QWWMZYLXWJMMTH-FTJBHMTQSA-N 0.000 description 2
• DJRGOXXGLYGIOB-RBUKOAKNSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-(1h-indol-3-ylmethyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3C4=CC=CC=C4NC=3)C(=O)NC2)C=C1OC1CCCC1 DJRGOXXGLYGIOB-RBUKOAKNSA-N 0.000 description 2
• BXBCZBHPAUVQSU-DLBZAZTESA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-(furan-2-ylmethyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC=CC=3)C(=O)NC2)C=C1OC1CCCC1 BXBCZBHPAUVQSU-DLBZAZTESA-N 0.000 description 2
• OPKOAUYDQZGLKQ-ZWKOTPCHSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-(pyridin-2-ylmethyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3N=CC=CC=3)C(=O)NC2)C=C1OC1CCCC1 OPKOAUYDQZGLKQ-ZWKOTPCHSA-N 0.000 description 2
• IOWHZSMPPBBVPQ-RTBURBONSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-(pyridin-4-ylmethyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3C=CN=CC=3)C(=O)NC2)C=C1OC1CCCC1 IOWHZSMPPBBVPQ-RTBURBONSA-N 0.000 description 2
• CRXQWGRSZGIBSP-DLBZAZTESA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-(thiophen-2-ylmethyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3SC=CC=3)C(=O)NC2)C=C1OC1CCCC1 CRXQWGRSZGIBSP-DLBZAZTESA-N 0.000 description 2
• FJSXVBNYCXVIRT-RBUKOAKNSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(1-methylbenzimidazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3N(C4=CC=CC=C4N=3)C)C(=O)NC2)C=C1OC1CCCC1 FJSXVBNYCXVIRT-RBUKOAKNSA-N 0.000 description 2
• KQYJMAHAAMVEGX-RTWAWAEBSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(2,6-dimethylanilino)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CNC=3C(=CC=CC=3C)C)C(=O)NC2)C=C1OC1CCCC1 KQYJMAHAAMVEGX-RTWAWAEBSA-N 0.000 description 2
• JPPBPLVIIAKHSS-MSOLQXFVSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(2-fluoroanilino)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CNC=3C(=CC=CC=3)F)C(=O)NC2)C=C1OC1CCCC1 JPPBPLVIIAKHSS-MSOLQXFVSA-N 0.000 description 2
• BXECANFKJMUFIU-UXHICEINSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(2-methylanilino)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CNC=3C(=CC=CC=3)C)C(=O)NC2)C=C1OC1CCCC1 BXECANFKJMUFIU-UXHICEINSA-N 0.000 description 2
• BAIJPECAFREWEJ-SJORKVTESA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(3,4-difluoroanilino)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CNC=3C=C(F)C(F)=CC=3)C(=O)NC2)C=C1OC1CCCC1 BAIJPECAFREWEJ-SJORKVTESA-N 0.000 description 2
• QARQPVOWPCGKAX-MOPGFXCFSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(3,4-dimethoxyanilino)methyl]piperidin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1NC[C@H]1C(=O)NC[C@H](C=2C=C(OC3CCCC3)C(OC)=CC=2)C1 QARQPVOWPCGKAX-MOPGFXCFSA-N 0.000 description 2
• DDLOZUIVUTWTHJ-SJORKVTESA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(3,5-dichloroanilino)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CNC=3C=C(Cl)C=C(Cl)C=3)C(=O)NC2)C=C1OC1CCCC1 DDLOZUIVUTWTHJ-SJORKVTESA-N 0.000 description 2
• WDSMDWXLIQWQIM-MOPGFXCFSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(3,5-dimethoxyanilino)methyl]piperidin-2-one Chemical compound COC1=CC(OC)=CC(NC[C@H]2C(NC[C@@H](C2)C=2C=C(OC3CCCC3)C(OC)=CC=2)=O)=C1 WDSMDWXLIQWQIM-MOPGFXCFSA-N 0.000 description 2
• ORSCMIBQYRUYDO-UXHICEINSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(3-ethoxyanilino)methyl]piperidin-2-one Chemical compound CCOC1=CC=CC(NC[C@H]2C(NC[C@@H](C2)C=2C=C(OC3CCCC3)C(OC)=CC=2)=O)=C1 ORSCMIBQYRUYDO-UXHICEINSA-N 0.000 description 2
• NEODOGPCYSCNOS-MSOLQXFVSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(3-fluoroanilino)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CNC=3C=C(F)C=CC=3)C(=O)NC2)C=C1OC1CCCC1 NEODOGPCYSCNOS-MSOLQXFVSA-N 0.000 description 2
• TWJSKMKFMNGBPU-UXHICEINSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(3-methylanilino)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CNC=3C=C(C)C=CC=3)C(=O)NC2)C=C1OC1CCCC1 TWJSKMKFMNGBPU-UXHICEINSA-N 0.000 description 2
• VEOHBZVZVALVPZ-MSOLQXFVSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(3-nitroanilino)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CNC=3C=C(C=CC=3)[N+]([O-])=O)C(=O)NC2)C=C1OC1CCCC1 VEOHBZVZVALVPZ-MSOLQXFVSA-N 0.000 description 2
• AFQHLLRJGABZAU-PKTZIBPZSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(3-phenoxyanilino)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CNC=3C=C(OC=4C=CC=CC=4)C=CC=3)C(=O)NC2)C=C1OC1CCCC1 AFQHLLRJGABZAU-PKTZIBPZSA-N 0.000 description 2
• ZRAAPDYGKSDPEM-UXHICEINSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(4-ethoxyanilino)methyl]piperidin-2-one Chemical compound C1=CC(OCC)=CC=C1NC[C@H]1C(=O)NC[C@H](C=2C=C(OC3CCCC3)C(OC)=CC=2)C1 ZRAAPDYGKSDPEM-UXHICEINSA-N 0.000 description 2
• DKQDEJQYOLGEKS-DLBZAZTESA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(4-fluoro-1,3-benzoxazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC4=CC=CC(F)=C4N=3)C(=O)NC2)C=C1OC1CCCC1 DKQDEJQYOLGEKS-DLBZAZTESA-N 0.000 description 2
• JIHZIZPVUZDAPT-MSOLQXFVSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(4-fluoroanilino)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CNC=3C=CC(F)=CC=3)C(=O)NC2)C=C1OC1CCCC1 JIHZIZPVUZDAPT-MSOLQXFVSA-N 0.000 description 2
• BCYWOYQZFDYFIS-ZWKOTPCHSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(4-methoxy-1,3-benzoxazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC4=CC=CC(OC)=C4N=3)C(=O)NC2)C=C1OC1CCCC1 BCYWOYQZFDYFIS-ZWKOTPCHSA-N 0.000 description 2
• KPDQUVHYBWCLSQ-MOPGFXCFSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(4-methoxyanilino)methyl]piperidin-2-one Chemical compound C1=CC(OC)=CC=C1NC[C@H]1C(=O)NC[C@H](C=2C=C(OC3CCCC3)C(OC)=CC=2)C1 KPDQUVHYBWCLSQ-MOPGFXCFSA-N 0.000 description 2
• FXDBARFSUWDUCS-RBUKOAKNSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(4-methyl-1,3-benzoxazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC4=CC=CC(C)=C4N=3)C(=O)NC2)C=C1OC1CCCC1 FXDBARFSUWDUCS-RBUKOAKNSA-N 0.000 description 2
• WCVCXKTZHGQOHX-UXHICEINSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(4-methylanilino)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CNC=3C=CC(C)=CC=3)C(=O)NC2)C=C1OC1CCCC1 WCVCXKTZHGQOHX-UXHICEINSA-N 0.000 description 2
• NWXGLEXBUZKARS-YADHBBJMSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(4-propan-2-ylanilino)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CNC=3C=CC(=CC=3)C(C)C)C(=O)NC2)C=C1OC1CCCC1 NWXGLEXBUZKARS-YADHBBJMSA-N 0.000 description 2
• NCTQRLZPMYAPEM-JKSUJKDBSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(5,6-dichloro-1h-benzimidazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3NC4=CC(Cl)=C(Cl)C=C4N=3)C(=O)NC2)C=C1OC1CCCC1 NCTQRLZPMYAPEM-JKSUJKDBSA-N 0.000 description 2
• LMMOUDNKSQXIKZ-VQTJNVASSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(5,6-dimethyl-1h-benzimidazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3NC4=CC(C)=C(C)C=C4N=3)C(=O)NC2)C=C1OC1CCCC1 LMMOUDNKSQXIKZ-VQTJNVASSA-N 0.000 description 2
• KCEQOSVNLKVSPO-DLBZAZTESA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(5-fluoro-1,3-benzoxazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC4=CC=C(F)C=C4N=3)C(=O)NC2)C=C1OC1CCCC1 KCEQOSVNLKVSPO-DLBZAZTESA-N 0.000 description 2
• HDQURSYBHMHOGD-ZWKOTPCHSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(5-methoxy-1,3-benzoxazol-2-yl)methyl]piperidin-2-one Chemical compound C=1C([C@@H]2C[C@H](C(NC2)=O)CC=2OC3=CC=C(C=C3N=2)OC)=CC=C(OC)C=1OC1CCCC1 HDQURSYBHMHOGD-ZWKOTPCHSA-N 0.000 description 2
• UGNYCQQXLIVWRM-VQTJNVASSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(5-methoxy-1-benzofuran-2-yl)methyl]piperidin-2-one Chemical compound C=1C([C@@H]2C[C@H](C(NC2)=O)CC=2OC3=CC=C(C=C3C=2)OC)=CC=C(OC)C=1OC1CCCC1 UGNYCQQXLIVWRM-VQTJNVASSA-N 0.000 description 2
• VDICCPPRMBAZBQ-RBUKOAKNSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(5-methyl-1,3-benzoxazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC4=CC=C(C)C=C4N=3)C(=O)NC2)C=C1OC1CCCC1 VDICCPPRMBAZBQ-RBUKOAKNSA-N 0.000 description 2
• MMWJHRKOEGAFLT-DLBZAZTESA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(5-nitro-1,3-benzoxazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC4=CC=C(C=C4N=3)[N+]([O-])=O)C(=O)NC2)C=C1OC1CCCC1 MMWJHRKOEGAFLT-DLBZAZTESA-N 0.000 description 2
• JGRJBYNMEPUBIS-RBUKOAKNSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(6-methyl-1,3-benzoxazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC4=CC(C)=CC=C4N=3)C(=O)NC2)C=C1OC1CCCC1 JGRJBYNMEPUBIS-RBUKOAKNSA-N 0.000 description 2
• ZPRDHQBABHOCOM-RBUKOAKNSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(6-methylpyridin-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3N=C(C)C=CC=3)C(=O)NC2)C=C1OC1CCCC1 ZPRDHQBABHOCOM-RBUKOAKNSA-N 0.000 description 2
• JYWYAWOBVVBZJH-DLBZAZTESA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(7-fluoro-1,3-benzoxazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC4=C(F)C=CC=C4N=3)C(=O)NC2)C=C1OC1CCCC1 JYWYAWOBVVBZJH-DLBZAZTESA-N 0.000 description 2
• ZVNRSYGAHDBQDJ-RBUKOAKNSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(7-fluoro-1-benzofuran-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC4=C(F)C=CC=C4C=3)C(=O)NC2)C=C1OC1CCCC1 ZVNRSYGAHDBQDJ-RBUKOAKNSA-N 0.000 description 2
• DCSYPZAUWXTYNF-VQTJNVASSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(7-methoxy-1-benzofuran-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC4=C(OC)C=CC=C4C=3)C(=O)NC2)C=C1OC1CCCC1 DCSYPZAUWXTYNF-VQTJNVASSA-N 0.000 description 2
• CKVIEBZDEBIPFY-MSOLQXFVSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(pyridin-4-ylamino)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CNC=3C=CN=CC=3)C(=O)NC2)C=C1OC1CCCC1 CKVIEBZDEBIPFY-MSOLQXFVSA-N 0.000 description 2
• QGYLCGPKLHQXJL-RTBURBONSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[2-(4-fluoroanilino)ethyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CCNC=3C=CC(F)=CC=3)C(=O)NC2)C=C1OC1CCCC1 QGYLCGPKLHQXJL-RTBURBONSA-N 0.000 description 2
• LRLCYVNNYQGRQW-DLBZAZTESA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[[4-(trifluoromethyl)-1,3-benzoxazol-2-yl]methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC4=CC=CC(=C4N=3)C(F)(F)F)C(=O)NC2)C=C1OC1CCCC1 LRLCYVNNYQGRQW-DLBZAZTESA-N 0.000 description 2
• OYPHTRSDXIKTTE-DLBZAZTESA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[[5-(trifluoromethyl)-1,3-benzoxazol-2-yl]methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC4=CC=C(C=C4N=3)C(F)(F)F)C(=O)NC2)C=C1OC1CCCC1 OYPHTRSDXIKTTE-DLBZAZTESA-N 0.000 description 2
• RKLXOFXSKVHIHQ-OAHLLOKOSA-N (5s)-1-acetyl-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@H]2CN(C(=O)CC2)C(C)=O)C=C1OC1CCCC1 RKLXOFXSKVHIHQ-OAHLLOKOSA-N 0.000 description 2
• XFPAAVMHUGTZIX-GFCCVEGCSA-N (5s)-5-(3-cyclopentyloxy-4-hydroxyphenyl)piperidin-2-one Chemical compound OC1=CC=C([C@H]2CNC(=O)CC2)C=C1OC1CCCC1 XFPAAVMHUGTZIX-GFCCVEGCSA-N 0.000 description 2
• FXJCDVBVQFGKJK-CQSZACIVSA-N (5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3,3-bis(hydroxymethyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(CO)(CO)C(=O)NC2)C=C1OC1CCCC1 FXJCDVBVQFGKJK-CQSZACIVSA-N 0.000 description 2
• IVMMZCHTKVAJQF-KWCCSABGSA-N (5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-(hydroxymethyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(CO)C(=O)NC2)C=C1OC1CCCC1 IVMMZCHTKVAJQF-KWCCSABGSA-N 0.000 description 2
• FRYMYQIFJGZPLY-FOIFJWKZSA-N (5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[2-oxo-2-(4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(CC(=O)N3CCC(CC3)N3CCCC3)C(=O)NC2)C=C1OC1CCCC1 FRYMYQIFJGZPLY-FOIFJWKZSA-N 0.000 description 2
• JSXVNIXMUZXYLE-CQSZACIVSA-N (5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-methylidenepiperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(=C)C(=O)NC2)C=C1OC1CCCC1 JSXVNIXMUZXYLE-CQSZACIVSA-N 0.000 description 2
• NVZDWCVDHAGDQI-TYZXPVIJSA-N (5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-methylpiperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(C)C(=O)NC2)C=C1OC1CCCC1 NVZDWCVDHAGDQI-TYZXPVIJSA-N 0.000 description 2
• ACIMFSIORGITGU-OAHLLOKOSA-N (5s)-5-(3-cyclopentyloxy-4-propoxyphenyl)piperidin-2-one Chemical compound CCCOC1=CC=C([C@H]2CNC(=O)CC2)C=C1OC1CCCC1 ACIMFSIORGITGU-OAHLLOKOSA-N 0.000 description 2
• JIGSIYCERZINHY-LLVKDONJSA-N (5s)-5-(3-ethoxy-4-methoxyphenyl)piperidin-2-one Chemical compound C1=C(OC)C(OCC)=CC([C@H]2CNC(=O)CC2)=C1 JIGSIYCERZINHY-LLVKDONJSA-N 0.000 description 2
• QNYQAZYHJZKSHW-MRXNPFEDSA-N (5s)-5-(3-heptoxy-4-methoxyphenyl)piperidin-2-one Chemical compound C1=C(OC)C(OCCCCCCC)=CC([C@H]2CNC(=O)CC2)=C1 QNYQAZYHJZKSHW-MRXNPFEDSA-N 0.000 description 2
• TVZMXQRQUKMDBJ-GFCCVEGCSA-N (5s)-5-(4-methoxy-3-propan-2-yloxyphenyl)piperidin-2-one Chemical compound C1=C(OC(C)C)C(OC)=CC=C1[C@H]1CNC(=O)CC1 TVZMXQRQUKMDBJ-GFCCVEGCSA-N 0.000 description 2
• RTBQOJGUBKFGPS-CQSZACIVSA-N (5s)-5-[3-cyclopentyloxy-4-(2-hydroxyethoxy)phenyl]piperidin-2-one Chemical compound OCCOC1=CC=C([C@H]2CNC(=O)CC2)C=C1OC1CCCC1 RTBQOJGUBKFGPS-CQSZACIVSA-N 0.000 description 2
• MYHDZMBAEQGZLN-OAHLLOKOSA-N (5s)-5-[3-cyclopentyloxy-4-(3-hydroxypropoxy)phenyl]piperidin-2-one Chemical compound OCCCOC1=CC=C([C@H]2CNC(=O)CC2)C=C1OC1CCCC1 MYHDZMBAEQGZLN-OAHLLOKOSA-N 0.000 description 2
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
• GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 2
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 2
• DPZNOMCNRMUKPS-UHFFFAOYSA-N 1,3-Dimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1 DPZNOMCNRMUKPS-UHFFFAOYSA-N 0.000 description 2
• LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 2
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
• HSOMHPHYGAQRTF-UHFFFAOYSA-N 1-benzofuran-2-ylmethanol Chemical compound C1=CC=C2OC(CO)=CC2=C1 HSOMHPHYGAQRTF-UHFFFAOYSA-N 0.000 description 2
• UYGMKSKKGSUAHB-UHFFFAOYSA-N 1-benzothiophen-3-ylmethanol Chemical compound C1=CC=C2C(CO)=CSC2=C1 UYGMKSKKGSUAHB-UHFFFAOYSA-N 0.000 description 2
• KYDXWCHDUCDNGR-UHFFFAOYSA-N 1-chloro-2,3-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC(Cl)=C1[N+]([O-])=O KYDXWCHDUCDNGR-UHFFFAOYSA-N 0.000 description 2
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
• NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 2
• WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 2
• SERUZNHRWBXDOX-UHFFFAOYSA-N 2-(chloromethyl)-1,3-benzothiazole Chemical compound C1=CC=C2SC(CCl)=NC2=C1 SERUZNHRWBXDOX-UHFFFAOYSA-N 0.000 description 2
• ANRDUCQCZKLSGF-UHFFFAOYSA-N 2-(chloromethyl)-1,3-benzoxazole Chemical compound C1=CC=C2OC(CCl)=NC2=C1 ANRDUCQCZKLSGF-UHFFFAOYSA-N 0.000 description 2
• WRGVPFAJPMIYOX-UHFFFAOYSA-N 2-(chloromethyl)-1-methylbenzimidazole Chemical compound C1=CC=C2N(C)C(CCl)=NC2=C1 WRGVPFAJPMIYOX-UHFFFAOYSA-N 0.000 description 2
• SPMLMLQATWNZEE-UHFFFAOYSA-N 2-(chloromethyl)-1h-benzimidazole Chemical compound C1=CC=C2NC(CCl)=NC2=C1 SPMLMLQATWNZEE-UHFFFAOYSA-N 0.000 description 2
• SDZRSDOOZFAEMN-UHFFFAOYSA-N 2-(iodomethyl)-1,3-benzoxazole Chemical compound C1=CC=C2OC(CI)=NC2=C1 SDZRSDOOZFAEMN-UHFFFAOYSA-N 0.000 description 2
• CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical compound NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 description 2
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 2
• AQDKZPFDOWHRDZ-UHFFFAOYSA-N 2-methyl-6-nitrophenol Chemical compound CC1=CC=CC([N+]([O-])=O)=C1O AQDKZPFDOWHRDZ-UHFFFAOYSA-N 0.000 description 2
• KLWSGZHZNIOCPO-UHFFFAOYSA-N 2-nitro-3-(trifluoromethyl)phenol Chemical compound OC1=CC=CC(C(F)(F)F)=C1[N+]([O-])=O KLWSGZHZNIOCPO-UHFFFAOYSA-N 0.000 description 2
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
• 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 2
• FNHPUOJKUXFUKN-UHFFFAOYSA-N 3-(bromomethyl)pyridine;hydron;bromide Chemical compound Br.BrCC1=CC=CN=C1 FNHPUOJKUXFUKN-UHFFFAOYSA-N 0.000 description 2
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 2
• JELNXWUZFOQXGZ-UHFFFAOYSA-N 3-hydroxy-2-nitrobenzonitrile Chemical compound OC1=CC=CC(C#N)=C1[N+]([O-])=O JELNXWUZFOQXGZ-UHFFFAOYSA-N 0.000 description 2
• MVQVNTPHUGQQHK-UHFFFAOYSA-N 3-pyridinemethanol Chemical compound OCC1=CC=CN=C1 MVQVNTPHUGQQHK-UHFFFAOYSA-N 0.000 description 2
• NOGNXHAFAQFSLK-BPGUCPLFSA-N 4-[2-[(5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxopiperidin-3-yl]ethylamino]benzonitrile Chemical compound COC1=CC=C([C@@H]2CC(CCNC=3C=CC(=CC=3)C#N)C(=O)NC2)C=C1OC1CCCC1 NOGNXHAFAQFSLK-BPGUCPLFSA-N 0.000 description 2
• ZIHLHNQQZBPEPS-OAHLLOKOSA-N 4-[2-cyclopentyloxy-4-[(3s)-6-oxopiperidin-3-yl]phenoxy]butanoic acid Chemical compound OC(=O)CCCOC1=CC=C([C@H]2CNC(=O)CC2)C=C1OC1CCCC1 ZIHLHNQQZBPEPS-OAHLLOKOSA-N 0.000 description 2
• QCXJEYYXVJIFCE-UHFFFAOYSA-N 4-acetamidobenzoic acid Chemical compound CC(=O)NC1=CC=C(C(O)=O)C=C1 QCXJEYYXVJIFCE-UHFFFAOYSA-N 0.000 description 2
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
• BTZVLMHATKOSQU-UHFFFAOYSA-N 5-(3-cyclopentyloxy-4-methoxyphenyl)-3-(3-methylbenzoyl)-1h-pyridin-2-one Chemical compound COC1=CC=C(C=2C=C(C(=O)NC=2)C(=O)C=2C=C(C)C=CC=2)C=C1OC1CCCC1 BTZVLMHATKOSQU-UHFFFAOYSA-N 0.000 description 2
• FZHSPPYCNDYIKD-UHFFFAOYSA-N 5-methoxysalicylaldehyde Chemical compound COC1=CC=C(O)C(C=O)=C1 FZHSPPYCNDYIKD-UHFFFAOYSA-N 0.000 description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical class [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
• 208000023275 Autoimmune disease Diseases 0.000 description 2
• 241000283690 Bos taurus Species 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• 241000282472 Canis lupus familiaris Species 0.000 description 2
• 241000283707 Capra Species 0.000 description 2
• 241000282693 Cercopithecidae Species 0.000 description 2
• 102000005636 Cyclic AMP Response Element-Binding Protein Human genes 0.000 description 2
• 108010045171 Cyclic AMP Response Element-Binding Protein Proteins 0.000 description 2
• RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
• 108020004414 DNA Proteins 0.000 description 2
• 208000006313 Delayed Hypersensitivity Diseases 0.000 description 2
• 101001117086 Dictyostelium discoideum cAMP/cGMP-dependent 3',5'-cAMP/cGMP phosphodiesterase A Proteins 0.000 description 2
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 2
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
• LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
• 241000283086 Equidae Species 0.000 description 2
• 206010015150 Erythema Diseases 0.000 description 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
• 108010074328 Interferon-gamma Proteins 0.000 description 2
• 108010063738 Interleukins Proteins 0.000 description 2
• 102000015696 Interleukins Human genes 0.000 description 2
• LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
• 239000004166 Lanolin Substances 0.000 description 2
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
• 239000004472 Lysine Substances 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 102000003896 Myeloperoxidases Human genes 0.000 description 2
• 108090000235 Myeloperoxidases Proteins 0.000 description 2
• KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 2
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 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
• UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 2
• 102000003945 NF-kappa B Human genes 0.000 description 2
• 108010057466 NF-kappa B Proteins 0.000 description 2
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
• 241000283973 Oryctolagus cuniculus Species 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• 241001494479 Pecora Species 0.000 description 2
• 229940099471 Phosphodiesterase inhibitor Drugs 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• 239000012979 RPMI medium Substances 0.000 description 2
• 239000012980 RPMI-1640 medium Substances 0.000 description 2
• 208000002200 Respiratory Hypersensitivity Diseases 0.000 description 2
• 241000283984 Rodentia Species 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• 241000282887 Suidae Species 0.000 description 2
• 210000000662 T-lymphocyte subset Anatomy 0.000 description 2
• MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
• 150000001242 acetic acid derivatives Chemical class 0.000 description 2
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
• 239000012346 acetyl chloride Substances 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 239000012190 activator Substances 0.000 description 2
• 150000001263 acyl chlorides Chemical class 0.000 description 2
• 230000000996 additive effect Effects 0.000 description 2
• WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
• 230000008371 airway function Effects 0.000 description 2
• 230000010085 airway hyperresponsiveness Effects 0.000 description 2
• 235000010443 alginic acid Nutrition 0.000 description 2
• 239000000783 alginic acid Substances 0.000 description 2
• 229920000615 alginic acid Polymers 0.000 description 2
• 229960001126 alginic acid Drugs 0.000 description 2
• 150000004781 alginic acids Chemical class 0.000 description 2
• 229910052783 alkali metal Inorganic materials 0.000 description 2
• 150000001340 alkali metals Chemical class 0.000 description 2
• 230000029936 alkylation Effects 0.000 description 2
• 238000005804 alkylation reaction Methods 0.000 description 2
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
• 238000000540 analysis of variance Methods 0.000 description 2
• MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
• 230000001430 anti-depressive effect Effects 0.000 description 2
• 239000000935 antidepressant agent Substances 0.000 description 2
• 229940005513 antidepressants Drugs 0.000 description 2
• 125000003710 aryl alkyl group Chemical group 0.000 description 2
• 235000010323 ascorbic acid Nutrition 0.000 description 2
• 239000011668 ascorbic acid Substances 0.000 description 2
• 229960005070 ascorbic acid Drugs 0.000 description 2
• CUFNKYGDVFVPHO-UHFFFAOYSA-N azulene Chemical compound C1=CC=CC2=CC=CC2=C1 CUFNKYGDVFVPHO-UHFFFAOYSA-N 0.000 description 2
• 230000003542 behavioural effect Effects 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 125000001246 bromo group Chemical group Br* 0.000 description 2
• 239000006172 buffering agent Substances 0.000 description 2
• WQAQPCDUOCURKW-UHFFFAOYSA-N butanethiol Chemical compound CCCCS WQAQPCDUOCURKW-UHFFFAOYSA-N 0.000 description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 230000011496 cAMP-mediated signaling Effects 0.000 description 2
• 229960001948 caffeine Drugs 0.000 description 2
• VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 244000309466 calf Species 0.000 description 2
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 2
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
• 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 2
• 230000020411 cell activation Effects 0.000 description 2
• 238000000423 cell based assay Methods 0.000 description 2
• 230000003915 cell function Effects 0.000 description 2
• 239000013592 cell lysate Substances 0.000 description 2
• 230000036755 cellular response Effects 0.000 description 2
• 239000003638 chemical reducing agent Substances 0.000 description 2
• FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 2
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
• 229960001231 choline Drugs 0.000 description 2
• WDECIBYCCFPHNR-UHFFFAOYSA-N chrysene Chemical compound C1=CC=CC2=CC=C3C4=CC=CC=C4C=CC3=C21 WDECIBYCCFPHNR-UHFFFAOYSA-N 0.000 description 2
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 2
• 238000002648 combination therapy Methods 0.000 description 2
• 230000003750 conditioning effect Effects 0.000 description 2
• 238000013270 controlled release Methods 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• 239000010949 copper Substances 0.000 description 2
• 239000007799 cork Substances 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 2
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 2
• 230000002354 daily effect Effects 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
• 230000007423 decrease Effects 0.000 description 2
• 238000006297 dehydration reaction Methods 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 2
• JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 2
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
• 230000004069 differentiation Effects 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 239000002270 dispersing agent Substances 0.000 description 2
• 238000009826 distribution Methods 0.000 description 2
• POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
• 239000000975 dye Substances 0.000 description 2
• 210000005069 ears Anatomy 0.000 description 2
• 238000004520 electroporation Methods 0.000 description 2
• 230000008030 elimination Effects 0.000 description 2
• 238000003379 elimination reaction Methods 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 230000002255 enzymatic effect Effects 0.000 description 2
• IJCODAOXFYTGBS-UHFFFAOYSA-N ethyl 5-methoxy-1-benzofuran-2-carboxylate Chemical compound COC1=CC=C2OC(C(=O)OCC)=CC2=C1 IJCODAOXFYTGBS-UHFFFAOYSA-N 0.000 description 2
• 239000002024 ethyl acetate extract Substances 0.000 description 2
• DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
• RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 description 2
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 2
• 235000019264 food flavour enhancer Nutrition 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 210000003714 granulocyte Anatomy 0.000 description 2
• 229940093915 gynecological organic acid Drugs 0.000 description 2
• 125000000262 haloalkenyl group Chemical group 0.000 description 2
• 125000000232 haloalkynyl group Chemical group 0.000 description 2
• 230000036541 health Effects 0.000 description 2
• IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
• 150000004677 hydrates Chemical class 0.000 description 2
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 2
• 125000002632 imidazolidinyl group Chemical group 0.000 description 2
• 125000002636 imidazolinyl group Chemical group 0.000 description 2
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
• OLNJUISKUQQNIM-UHFFFAOYSA-N indole-3-carbaldehyde Chemical compound C1=CC=C2C(C=O)=CNC2=C1 OLNJUISKUQQNIM-UHFFFAOYSA-N 0.000 description 2
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 2
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 239000011630 iodine Substances 0.000 description 2
• 125000002346 iodo group Chemical group I* 0.000 description 2
• 239000002085 irritant Substances 0.000 description 2
• 231100000021 irritant Toxicity 0.000 description 2
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
• KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 2
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
• 125000005956 isoquinolyl group Chemical group 0.000 description 2
• 125000001786 isothiazolyl group Chemical group 0.000 description 2
• 239000007951 isotonicity adjuster Substances 0.000 description 2
• 125000000842 isoxazolyl group Chemical group 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 229940039717 lanolin Drugs 0.000 description 2
• 235000019388 lanolin Nutrition 0.000 description 2
• 125000005647 linker group Chemical group 0.000 description 2
• 229910052744 lithium Inorganic materials 0.000 description 2
• JCIVHYBIFRUGKO-UHFFFAOYSA-N lithium;2,2,6,6-tetramethylpiperidine Chemical compound [Li].CC1(C)CCCC(C)(C)N1 JCIVHYBIFRUGKO-UHFFFAOYSA-N 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 238000003670 luciferase enzyme activity assay Methods 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 239000001630 malic acid Substances 0.000 description 2
• 235000011090 malic acid Nutrition 0.000 description 2
• 239000011159 matrix material Substances 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 230000015654 memory Effects 0.000 description 2
• 239000002207 metabolite Substances 0.000 description 2
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
• LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 230000004899 motility Effects 0.000 description 2
• PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
• WWQLYMAILGXGDX-UHFFFAOYSA-N n-(2-fluoro-6-hydroxyphenyl)acetamide Chemical compound CC(=O)NC1=C(O)C=CC=C1F WWQLYMAILGXGDX-UHFFFAOYSA-N 0.000 description 2
• NPGREARFJMFTDF-UHFFFAOYSA-N n-(3,5-dichloro-1-hydroxypyridin-4-ylidene)-8-methoxy-2-(trifluoromethyl)quinoline-5-carboxamide Chemical compound C12=CC=C(C(F)(F)F)N=C2C(OC)=CC=C1C(=O)N=C1C(Cl)=CN(O)C=C1Cl NPGREARFJMFTDF-UHFFFAOYSA-N 0.000 description 2
• DPHDSIQHVGSITN-UHFFFAOYSA-N n-(3,5-dichloropyridin-4-yl)-2-[1-[(4-fluorophenyl)methyl]-5-hydroxyindol-3-yl]-2-oxoacetamide Chemical compound C1=C(C(=O)C(=O)NC=2C(=CN=CC=2Cl)Cl)C2=CC(O)=CC=C2N1CC1=CC=C(F)C=C1 DPHDSIQHVGSITN-UHFFFAOYSA-N 0.000 description 2
• XTEGVFVZDVNBPF-UHFFFAOYSA-N naphthalene-1,5-disulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1S(O)(=O)=O XTEGVFVZDVNBPF-UHFFFAOYSA-N 0.000 description 2
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 2
• 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 description 2
• 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
• NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 2
• QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 2
• WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
• 239000004006 olive oil Substances 0.000 description 2
• 235000008390 olive oil Nutrition 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 125000001979 organolithium group Chemical group 0.000 description 2
• PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 description 2
• 125000001715 oxadiazolyl group Chemical group 0.000 description 2
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
• 125000002971 oxazolyl group Chemical group 0.000 description 2
• 230000003647 oxidation Effects 0.000 description 2
• 238000007254 oxidation reaction Methods 0.000 description 2
• 125000000466 oxiranyl group Chemical group 0.000 description 2
• 125000004043 oxo group Chemical group O=* 0.000 description 2
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• 230000037361 pathway Effects 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
• 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 2
• 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 2
• 235000021317 phosphate Nutrition 0.000 description 2
• 239000002571 phosphodiesterase inhibitor Substances 0.000 description 2
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• 229910000027 potassium carbonate Inorganic materials 0.000 description 2
• 239000002243 precursor Substances 0.000 description 2
• 230000002335 preservative effect Effects 0.000 description 2
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 2
• 238000000746 purification Methods 0.000 description 2
• 125000003373 pyrazinyl group Chemical group 0.000 description 2
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 2
• BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 description 2
• 125000002098 pyridazinyl group Chemical group 0.000 description 2
• 125000000714 pyrimidinyl group Chemical group 0.000 description 2
• 150000004040 pyrrolidinones Chemical class 0.000 description 2
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
• 230000002285 radioactive effect Effects 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 238000010992 reflux Methods 0.000 description 2
• 239000011347 resin Substances 0.000 description 2
• 229920005989 resin Polymers 0.000 description 2
• 229960002586 roflumilast Drugs 0.000 description 2
• MNDBXUUTURYVHR-UHFFFAOYSA-N roflumilast Chemical compound FC(F)OC1=CC=C(C(=O)NC=2C(=CN=CC=2Cl)Cl)C=C1OCC1CC1 MNDBXUUTURYVHR-UHFFFAOYSA-N 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical compound OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 2
• 230000035945 sensitivity Effects 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 239000008247 solid mixture Substances 0.000 description 2
• 239000012265 solid product Substances 0.000 description 2
• 239000012258 stirred mixture Substances 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 125000003107 substituted aryl group Chemical group 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 125000004434 sulfur atom Chemical group 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 230000008961 swelling Effects 0.000 description 2
• 230000002195 synergetic effect Effects 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• 230000009885 systemic effect Effects 0.000 description 2
• WUIIQKLOOURBML-MRXNPFEDSA-N tert-butyl (5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxopiperidine-1-carboxylate Chemical compound COC1=CC=C([C@H]2CN(C(=O)CC2)C(=O)OC(C)(C)C)C=C1OC1CCCC1 WUIIQKLOOURBML-MRXNPFEDSA-N 0.000 description 2
• YNZUHDHIWWRGOR-UHFFFAOYSA-N tert-butyl 2-(chloromethyl)benzimidazole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)C(CCl)=NC2=C1 YNZUHDHIWWRGOR-UHFFFAOYSA-N 0.000 description 2
• BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 2
• YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
• 238000002560 therapeutic procedure Methods 0.000 description 2
• 125000001113 thiadiazolyl group Chemical group 0.000 description 2
• 125000000335 thiazolyl group Chemical group 0.000 description 2
• ZMZDMBWJUHKJPS-UHFFFAOYSA-N thiocyanic acid Chemical compound SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 2
• 125000000464 thioxo group Chemical group S=* 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 125000004306 triazinyl group Chemical group 0.000 description 2
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 125000005455 trithianyl group Chemical group 0.000 description 2
• 230000006433 tumor necrosis factor production Effects 0.000 description 2
• 230000003827 upregulation Effects 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• 239000000080 wetting agent Substances 0.000 description 2
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 1
• ZXZICFBXYVRDKD-SMHZUEHJSA-N (3e,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(3,5-dichlorophenyl)methylidene]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2CC(/C(=O)NC2)=C\C=2C=C(Cl)C=C(Cl)C=2)C=C1OC1CCCC1 ZXZICFBXYVRDKD-SMHZUEHJSA-N 0.000 description 1
• XWFYCDHFVFDJEZ-RBUKOAKNSA-N (3r,5s)-3-(1,3-benzodioxol-5-ylmethyl)-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3C=C4OCOC4=CC=3)C(=O)NC2)C=C1OC1CCCC1 XWFYCDHFVFDJEZ-RBUKOAKNSA-N 0.000 description 1
• VXDXICUVCGSGPR-AVUCRCDLSA-N (3r,5s)-3-[amino-(4-methyl-1h-benzimidazol-2-yl)methyl]-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](C(=O)NC2)C(N)C=2NC3=CC=CC(C)=C3N=2)C=C1OC1CCCC1 VXDXICUVCGSGPR-AVUCRCDLSA-N 0.000 description 1
• ZQMCYRDMYZYFPT-RBUKOAKNSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-(pyridin-3-ylmethyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3C=NC=CC=3)C(=O)NC2)C=C1OC1CCCC1 ZQMCYRDMYZYFPT-RBUKOAKNSA-N 0.000 description 1
• WJPULJCTPZXZQH-STYNFMPRSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(6-methylpyridin-2-yl)methyl]piperidin-2-one;hydrochloride Chemical compound Cl.COC1=CC=C([C@@H]2C[C@H](CC=3N=C(C)C=CC=3)C(=O)NC2)C=C1OC1CCCC1 WJPULJCTPZXZQH-STYNFMPRSA-N 0.000 description 1
• NQBWCGRQJDZWHJ-RTBURBONSA-N (3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[[(4-methyl-1h-benzimidazol-2-yl)amino]methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](CNC=3NC4=C(C)C=CC=C4N=3)C(=O)NC2)C=C1OC1CCCC1 NQBWCGRQJDZWHJ-RTBURBONSA-N 0.000 description 1
• CTPMVYVTLMVCHD-QZTJIDSGSA-N (3s,5s)-3-(2h-benzotriazol-4-ylmethyl)-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3C4=NNN=C4C=CC=3)C(=O)NC2)C=C1OC1CCCC1 CTPMVYVTLMVCHD-QZTJIDSGSA-N 0.000 description 1
• VXDXICUVCGSGPR-OECOBVRJSA-N (3s,5s)-3-[amino-(4-methyl-1h-benzimidazol-2-yl)methyl]-5-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@H](C(=O)NC2)C(N)C=2NC3=CC=CC(C)=C3N=2)C=C1OC1CCCC1 VXDXICUVCGSGPR-OECOBVRJSA-N 0.000 description 1
• IELNIJCELQZAKS-RBUKOAKNSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[(7-methyl-1,3-benzoxazol-2-yl)methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC4=C(C)C=CC=C4N=3)C(=O)NC2)C=C1OC1CCCC1 IELNIJCELQZAKS-RBUKOAKNSA-N 0.000 description 1
• NQBWCGRQJDZWHJ-MOPGFXCFSA-N (3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[[(4-methyl-1h-benzimidazol-2-yl)amino]methyl]piperidin-2-one Chemical compound COC1=CC=C([C@@H]2C[C@@H](CNC=3NC4=C(C)C=CC=C4N=3)C(=O)NC2)C=C1OC1CCCC1 NQBWCGRQJDZWHJ-MOPGFXCFSA-N 0.000 description 1
• ZTGZJYZILIDGMD-UHFFFAOYSA-N (5-methoxy-1-benzofuran-2-yl)methanol Chemical compound COC1=CC=C2OC(CO)=CC2=C1 ZTGZJYZILIDGMD-UHFFFAOYSA-N 0.000 description 1
• 125000004641 (C1-C12) haloalkyl group Chemical group 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 1
• 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 description 1
• 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 description 1
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• 125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 description 1
• 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• 125000005943 1,2,3,6-tetrahydropyridyl group Chemical group 0.000 description 1
• 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
• 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
• 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
• 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
• 125000001401 1,2,4-triazol-4-yl group Chemical group N=1N=C([H])N([*])C=1[H] 0.000 description 1
• QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 description 1
• GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
• 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
• 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
• 125000005871 1,3-benzodioxolyl group Chemical group 0.000 description 1
• IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 description 1
• FLOJNXXFMHCMMR-UHFFFAOYSA-N 1,3-dithiolanyl Chemical group [CH]1SCCS1 FLOJNXXFMHCMMR-UHFFFAOYSA-N 0.000 description 1
• 125000005877 1,4-benzodioxanyl group Chemical group 0.000 description 1
• 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
• HKDFRDIIELOLTJ-UHFFFAOYSA-N 1,4-dithianyl Chemical group [CH]1CSCCS1 HKDFRDIIELOLTJ-UHFFFAOYSA-N 0.000 description 1
• VSEROABGEVRIRY-UHFFFAOYSA-N 1-(chloromethyl)benzotriazole Chemical compound C1=CC=C2N(CCl)N=NC2=C1 VSEROABGEVRIRY-UHFFFAOYSA-N 0.000 description 1
• HRNDLWUCMRVFDF-UHFFFAOYSA-N 1-(iodomethyl)benzotriazole Chemical compound C1=CC=C2N(CI)N=NC2=C1 HRNDLWUCMRVFDF-UHFFFAOYSA-N 0.000 description 1
• VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
• YOBOIKMFTLTNTR-UHFFFAOYSA-N 1-azido-2-fluorobenzene Chemical compound FC1=CC=CC=C1N=[N+]=[N-] YOBOIKMFTLTNTR-UHFFFAOYSA-N 0.000 description 1
• WDJLPQCBTBZTRH-UHFFFAOYSA-N 1-benzothiophene-3-carbaldehyde Chemical compound C1=CC=C2C(C=O)=CSC2=C1 WDJLPQCBTBZTRH-UHFFFAOYSA-N 0.000 description 1
• MLEGMEBCXGDFQT-UHFFFAOYSA-N 1-benzylpiperidin-2-one Chemical compound O=C1CCCCN1CC1=CC=CC=C1 MLEGMEBCXGDFQT-UHFFFAOYSA-N 0.000 description 1
• MICMHFIQSAMEJG-UHFFFAOYSA-N 1-bromopyrrolidine-2,5-dione Chemical compound BrN1C(=O)CCC1=O.BrN1C(=O)CCC1=O MICMHFIQSAMEJG-UHFFFAOYSA-N 0.000 description 1
• 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
• 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
• JFLSOKIMYBSASW-UHFFFAOYSA-N 1-chloro-2-[chloro(diphenyl)methyl]benzene Chemical compound ClC1=CC=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 JFLSOKIMYBSASW-UHFFFAOYSA-N 0.000 description 1
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
• SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 1
• PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
• KKVYYGGCHJGEFJ-UHFFFAOYSA-N 1-n-(4-chlorophenyl)-6-methyl-5-n-[3-(7h-purin-6-yl)pyridin-2-yl]isoquinoline-1,5-diamine Chemical compound N=1C=CC2=C(NC=3C(=CC=CN=3)C=3C=4N=CNC=4N=CN=3)C(C)=CC=C2C=1NC1=CC=C(Cl)C=C1 KKVYYGGCHJGEFJ-UHFFFAOYSA-N 0.000 description 1
• 125000005987 1-oxo-thiomorpholinyl group Chemical group 0.000 description 1
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• FRPZMMHWLSIFAZ-UHFFFAOYSA-N 10-undecenoic acid Chemical compound OC(=O)CCCCCCCCC=C FRPZMMHWLSIFAZ-UHFFFAOYSA-N 0.000 description 1
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 1
• KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 description 1
• ARJOJUQBOMFBDN-UHFFFAOYSA-N 2-(bromomethyl)-1-benzofuran Chemical compound C1=CC=C2OC(CBr)=CC2=C1 ARJOJUQBOMFBDN-UHFFFAOYSA-N 0.000 description 1
• LLLYVNQGWVLUTN-UHFFFAOYSA-N 2-(bromomethyl)-5-(trifluoromethoxy)-1-benzofuran Chemical compound FC(F)(F)OC1=CC=C2OC(CBr)=CC2=C1 LLLYVNQGWVLUTN-UHFFFAOYSA-N 0.000 description 1
• JIHRXWUDSQPLRJ-UHFFFAOYSA-N 2-(bromomethyl)-5-methoxy-1-benzofuran Chemical compound COC1=CC=C2OC(CBr)=CC2=C1 JIHRXWUDSQPLRJ-UHFFFAOYSA-N 0.000 description 1
• WJFDCFHWFHCLIW-UHFFFAOYSA-N 2-(bromomethyl)-6-methylpyridine Chemical compound CC1=CC=CC(CBr)=N1 WJFDCFHWFHCLIW-UHFFFAOYSA-N 0.000 description 1
• IEGOEJOGPYVECQ-UHFFFAOYSA-N 2-(bromomethyl)-7-fluoro-1-benzofuran Chemical compound FC1=CC=CC2=C1OC(CBr)=C2 IEGOEJOGPYVECQ-UHFFFAOYSA-N 0.000 description 1
• HVEHRXXFJVCBAR-UHFFFAOYSA-N 2-(bromomethyl)-7-methoxy-1-benzofuran Chemical compound COC1=CC=CC2=C1OC(CBr)=C2 HVEHRXXFJVCBAR-UHFFFAOYSA-N 0.000 description 1
• CEFVCNWQCJCMHZ-UHFFFAOYSA-N 2-(bromomethyl)furan Chemical compound BrCC1=CC=CO1 CEFVCNWQCJCMHZ-UHFFFAOYSA-N 0.000 description 1
• QZOBOLDDGXPTBP-UHFFFAOYSA-N 2-(bromomethyl)thiophene Chemical compound BrCC1=CC=CS1 QZOBOLDDGXPTBP-UHFFFAOYSA-N 0.000 description 1
• OHETUSKHOVDKQD-UHFFFAOYSA-N 2-(chloromethyl)-1,3-benzoxazol-4-ol Chemical compound OC1=CC=CC2=C1N=C(CCl)O2 OHETUSKHOVDKQD-UHFFFAOYSA-N 0.000 description 1
• NHRGDWQDYAFABZ-UHFFFAOYSA-N 2-(chloromethyl)-4-methoxy-1,3-benzoxazole Chemical compound COC1=CC=CC2=C1N=C(CCl)O2 NHRGDWQDYAFABZ-UHFFFAOYSA-N 0.000 description 1
• JXBONNIKLRSNGF-UHFFFAOYSA-N 2-(iodomethyl)-1,3-benzothiazole Chemical compound C1=CC=C2SC(CI)=NC2=C1 JXBONNIKLRSNGF-UHFFFAOYSA-N 0.000 description 1
• BPNQEOZVDNKFQN-UHFFFAOYSA-N 2-(iodomethyl)-1,3-benzoxazole-4-carbonitrile Chemical compound C1=CC=C2OC(CI)=NC2=C1C#N BPNQEOZVDNKFQN-UHFFFAOYSA-N 0.000 description 1
• SBKNVPMULYNUBQ-UHFFFAOYSA-N 2-(iodomethyl)-1,3-benzoxazole-5-carbonitrile Chemical compound N#CC1=CC=C2OC(CI)=NC2=C1 SBKNVPMULYNUBQ-UHFFFAOYSA-N 0.000 description 1
• BJCVFPVPCKHOBA-UHFFFAOYSA-N 2-(iodomethyl)-1-methylbenzimidazole Chemical compound C1=CC=C2N(C)C(CI)=NC2=C1 BJCVFPVPCKHOBA-UHFFFAOYSA-N 0.000 description 1
• DPQFQWQXSCYVIH-UHFFFAOYSA-N 2-(iodomethyl)-1h-benzimidazole Chemical compound C1=CC=C2NC(CI)=NC2=C1 DPQFQWQXSCYVIH-UHFFFAOYSA-N 0.000 description 1
• YABQKHUYDKQGKQ-UHFFFAOYSA-N 2-(iodomethyl)-4-(trifluoromethyl)-1,3-benzoxazole Chemical compound FC(F)(F)C1=CC=CC2=C1N=C(CI)O2 YABQKHUYDKQGKQ-UHFFFAOYSA-N 0.000 description 1
• SZFXKYQJQYXBPO-UHFFFAOYSA-N 2-(iodomethyl)-4-methoxy-1,3-benzoxazole Chemical compound COC1=CC=CC2=C1N=C(CI)O2 SZFXKYQJQYXBPO-UHFFFAOYSA-N 0.000 description 1
• PHQWSCKTLZOEPO-UHFFFAOYSA-N 2-(iodomethyl)-5,6-dimethyl-1h-benzimidazole Chemical compound C1=C(C)C(C)=CC2=C1NC(CI)=N2 PHQWSCKTLZOEPO-UHFFFAOYSA-N 0.000 description 1
• QZSYJFZFXOVYHD-UHFFFAOYSA-N 2-(iodomethyl)-5-(trifluoromethyl)-1,3-benzoxazole Chemical compound FC(F)(F)C1=CC=C2OC(CI)=NC2=C1 QZSYJFZFXOVYHD-UHFFFAOYSA-N 0.000 description 1
• QGYMIUDURVPLOZ-UHFFFAOYSA-N 2-(iodomethyl)-5-methoxy-1,3-benzoxazole Chemical compound COC1=CC=C2OC(CI)=NC2=C1 QGYMIUDURVPLOZ-UHFFFAOYSA-N 0.000 description 1
• RBSBOHQZFZUKNZ-UHFFFAOYSA-N 2-(iodomethyl)-7-methyl-1,3-benzoxazole Chemical compound CC1=CC=CC2=C1OC(CI)=N2 RBSBOHQZFZUKNZ-UHFFFAOYSA-N 0.000 description 1
• WWMHQSJXUJKWPZ-UHFFFAOYSA-N 2-(iodomethyl)benzimidazole-1-carboxylic acid Chemical compound C1=CC=C2N(C(=O)O)C(CI)=NC2=C1 WWMHQSJXUJKWPZ-UHFFFAOYSA-N 0.000 description 1
• ADDZHRRCUWNSCS-UHFFFAOYSA-N 2-Benzofurancarboxaldehyde Chemical compound C1=CC=C2OC(C=O)=CC2=C1 ADDZHRRCUWNSCS-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
• ZLRMHBYXTDHVQS-IDVLALEDSA-N 2-[(3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxopiperidin-3-yl]-n-(1h-imidazol-2-yl)acetamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.COC1=CC=C([C@@H]2C[C@@H](CC(=O)NC=3NC=CN=3)C(=O)NC2)C=C1OC1CCCC1 ZLRMHBYXTDHVQS-IDVLALEDSA-N 0.000 description 1
• GPWIKPHJUQMGFW-GGYWPGCISA-N 2-[(5r)-5-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxopiperidin-3-yl]-n-phenylacetamide Chemical compound COC1=CC=C([C@H]2CC(CC(=O)NC=3C=CC=CC=3)C(=O)NC2)C=C1OC1CCCC1 GPWIKPHJUQMGFW-GGYWPGCISA-N 0.000 description 1
• AWPHUUTVJPTYON-OEMAIJDKSA-N 2-[(5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxopiperidin-3-yl]-n-(1h-imidazol-2-yl)acetamide Chemical compound COC1=CC=C([C@@H]2CC(CC(=O)NC=3NC=CN=3)C(=O)NC2)C=C1OC1CCCC1 AWPHUUTVJPTYON-OEMAIJDKSA-N 0.000 description 1
• PIZJYOTWHFNLST-YSSOQSIOSA-N 2-[(5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxopiperidin-3-yl]acetaldehyde Chemical compound COC1=CC=C([C@@H]2CC(CC=O)C(=O)NC2)C=C1OC1CCCC1 PIZJYOTWHFNLST-YSSOQSIOSA-N 0.000 description 1
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
• SNWFVQLZAICZIL-RTBURBONSA-N 2-[[(3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxopiperidin-3-yl]methyl]-1,3-benzoxazole-4-carbonitrile Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3OC4=CC=CC(=C4N=3)C#N)C(=O)NC2)C=C1OC1CCCC1 SNWFVQLZAICZIL-RTBURBONSA-N 0.000 description 1
• RYVYBTGUUVQZNO-RTBURBONSA-N 2-[[(3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxopiperidin-3-yl]methyl]-1,3-benzoxazole-5-carbonitrile Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3OC4=CC=C(C=C4N=3)C#N)C(=O)NC2)C=C1OC1CCCC1 RYVYBTGUUVQZNO-RTBURBONSA-N 0.000 description 1
• GWKLVUUVYMJFOK-QZTJIDSGSA-N 2-[[(3r,5s)-5-[3-cyclopentyloxy-4-(difluoromethoxy)phenyl]-2-oxopiperidin-3-yl]methyl]-1,3-benzoxazole-4-carbonitrile Chemical compound FC(F)OC1=CC=C([C@@H]2C[C@H](CC=3OC4=CC=CC(=C4N=3)C#N)C(=O)NC2)C=C1OC1CCCC1 GWKLVUUVYMJFOK-QZTJIDSGSA-N 0.000 description 1
• KLZHKAARTPNEBC-QZTJIDSGSA-N 2-[[(3r,5s)-5-[3-cyclopentyloxy-4-(trifluoromethoxy)phenyl]-2-oxopiperidin-3-yl]methyl]-1,3-benzoxazole-4-carbonitrile Chemical compound FC(F)(F)OC1=CC=C([C@@H]2C[C@H](CC=3OC4=CC=CC(=C4N=3)C#N)C(=O)NC2)C=C1OC1CCCC1 KLZHKAARTPNEBC-QZTJIDSGSA-N 0.000 description 1
• AIHRRUMPKQECFA-KURKYZTESA-N 2-[[(3r,5s)-5-[4-(difluoromethoxy)-3-[(3s)-oxolan-3-yl]oxyphenyl]-2-oxopiperidin-3-yl]methyl]-1,3-benzoxazole-4-carbonitrile Chemical compound FC(F)OC1=CC=C([C@@H]2C[C@H](CC=3OC4=CC=CC(=C4N=3)C#N)C(=O)NC2)C=C1O[C@H]1CCOC1 AIHRRUMPKQECFA-KURKYZTESA-N 0.000 description 1
• HOZVXOPEMQZMIX-RCCFBDPRSA-N 2-[[(3s,5s)-2-oxo-5-[3-[(3r)-oxolan-3-yl]oxy-4-(trifluoromethoxy)phenyl]piperidin-3-yl]methyl]-1,3-benzoxazole-4-carbonitrile Chemical compound FC(F)(F)OC1=CC=C([C@@H]2C[C@@H](CC=3OC4=CC=CC(=C4N=3)C#N)C(=O)NC2)C=C1O[C@@H]1CCOC1 HOZVXOPEMQZMIX-RCCFBDPRSA-N 0.000 description 1
• SNWFVQLZAICZIL-RBUKOAKNSA-N 2-[[(3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxopiperidin-3-yl]methyl]-1,3-benzoxazole-4-carbonitrile Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC4=CC=CC(=C4N=3)C#N)C(=O)NC2)C=C1OC1CCCC1 SNWFVQLZAICZIL-RBUKOAKNSA-N 0.000 description 1
• RYVYBTGUUVQZNO-RBUKOAKNSA-N 2-[[(3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxopiperidin-3-yl]methyl]-1,3-benzoxazole-5-carbonitrile Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC4=CC=C(C=C4N=3)C#N)C(=O)NC2)C=C1OC1CCCC1 RYVYBTGUUVQZNO-RBUKOAKNSA-N 0.000 description 1
• GWKLVUUVYMJFOK-ZWKOTPCHSA-N 2-[[(3s,5s)-5-[3-cyclopentyloxy-4-(difluoromethoxy)phenyl]-2-oxopiperidin-3-yl]methyl]-1,3-benzoxazole-4-carbonitrile Chemical compound FC(F)OC1=CC=C([C@@H]2C[C@@H](CC=3OC4=CC=CC(=C4N=3)C#N)C(=O)NC2)C=C1OC1CCCC1 GWKLVUUVYMJFOK-ZWKOTPCHSA-N 0.000 description 1
• KLZHKAARTPNEBC-ZWKOTPCHSA-N 2-[[(3s,5s)-5-[3-cyclopentyloxy-4-(trifluoromethoxy)phenyl]-2-oxopiperidin-3-yl]methyl]-1,3-benzoxazole-4-carbonitrile Chemical compound FC(F)(F)OC1=CC=C([C@@H]2C[C@@H](CC=3OC4=CC=CC(=C4N=3)C#N)C(=O)NC2)C=C1OC1CCCC1 KLZHKAARTPNEBC-ZWKOTPCHSA-N 0.000 description 1
• AIHRRUMPKQECFA-RCCFBDPRSA-N 2-[[(3s,5s)-5-[4-(difluoromethoxy)-3-[(3r)-oxolan-3-yl]oxyphenyl]-2-oxopiperidin-3-yl]methyl]-1,3-benzoxazole-4-carbonitrile Chemical compound FC(F)OC1=CC=C([C@@H]2C[C@@H](CC=3OC4=CC=CC(=C4N=3)C#N)C(=O)NC2)C=C1O[C@@H]1CCOC1 AIHRRUMPKQECFA-RCCFBDPRSA-N 0.000 description 1
• AIHRRUMPKQECFA-KSZLIROESA-N 2-[[(3s,5s)-5-[4-(difluoromethoxy)-3-[(3s)-oxolan-3-yl]oxyphenyl]-2-oxopiperidin-3-yl]methyl]-1,3-benzoxazole-4-carbonitrile Chemical compound FC(F)OC1=CC=C([C@@H]2C[C@@H](CC=3OC4=CC=CC(=C4N=3)C#N)C(=O)NC2)C=C1O[C@H]1CCOC1 AIHRRUMPKQECFA-KSZLIROESA-N 0.000 description 1
• MIXYYVLILVGURS-IPMKNSEASA-N 2-[[(3s,5s)-5-[4-methoxy-3-[(3r)-oxolan-3-yl]oxyphenyl]-2-oxopiperidin-3-yl]methyl]-1,3-benzoxazole-4-carbonitrile Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3OC4=CC=CC(=C4N=3)C#N)C(=O)NC2)C=C1O[C@@H]1CCOC1 MIXYYVLILVGURS-IPMKNSEASA-N 0.000 description 1
• MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
• ATJGAHFTSOPTCH-UHFFFAOYSA-N 2-amino-3-(trifluoromethyl)phenol Chemical compound NC1=C(O)C=CC=C1C(F)(F)F ATJGAHFTSOPTCH-UHFFFAOYSA-N 0.000 description 1
• JJWWVLVYSOCRPL-UHFFFAOYSA-N 2-amino-3-hydroxybenzonitrile Chemical compound NC1=C(O)C=CC=C1C#N JJWWVLVYSOCRPL-UHFFFAOYSA-N 0.000 description 1
• ALQKEYVDQYGZDN-UHFFFAOYSA-N 2-amino-6-methylphenol Chemical compound CC1=CC=CC(N)=C1O ALQKEYVDQYGZDN-UHFFFAOYSA-N 0.000 description 1
• JEPCLNGRAIMPQV-UHFFFAOYSA-N 2-aminobenzene-1,3-diol Chemical compound NC1=C(O)C=CC=C1O JEPCLNGRAIMPQV-UHFFFAOYSA-N 0.000 description 1
• VRVRGVPWCUEOGV-UHFFFAOYSA-N 2-aminothiophenol Chemical compound NC1=CC=CC=C1S VRVRGVPWCUEOGV-UHFFFAOYSA-N 0.000 description 1
• VIRWKAJWTKAIMA-UHFFFAOYSA-N 2-chloroethyl acetate Chemical compound CC(=O)OCCCl VIRWKAJWTKAIMA-UHFFFAOYSA-N 0.000 description 1
• BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
• 229940013085 2-diethylaminoethanol Drugs 0.000 description 1
• FTZQXOJYPFINKJ-UHFFFAOYSA-N 2-fluoroaniline Chemical compound NC1=CC=CC=C1F FTZQXOJYPFINKJ-UHFFFAOYSA-N 0.000 description 1
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
• IWTFOFMTUOBLHG-UHFFFAOYSA-N 2-methoxypyridine Chemical compound COC1=CC=CC=N1 IWTFOFMTUOBLHG-UHFFFAOYSA-N 0.000 description 1
• RPKCLSMBVQLWIN-UHFFFAOYSA-N 2-n-methylbenzene-1,2-diamine Chemical compound CNC1=CC=CC=C1N RPKCLSMBVQLWIN-UHFFFAOYSA-N 0.000 description 1
• VLRSADZEDXVUPG-UHFFFAOYSA-N 2-naphthalen-1-ylpyridine Chemical class N1=CC=CC=C1C1=CC=CC2=CC=CC=C12 VLRSADZEDXVUPG-UHFFFAOYSA-N 0.000 description 1
• ZLCPKMIJYMHZMJ-UHFFFAOYSA-N 2-nitrobenzene-1,3-diol Chemical compound OC1=CC=CC(O)=C1[N+]([O-])=O ZLCPKMIJYMHZMJ-UHFFFAOYSA-N 0.000 description 1
• 125000006088 2-oxoazepinyl group Chemical group 0.000 description 1
• KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 1
• 125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
• 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
• AZYTZQYCOBXDGY-UHFFFAOYSA-N 2-pyrrolidin-1-ylpyridine Chemical compound C1CCCN1C1=CC=CC=N1 AZYTZQYCOBXDGY-UHFFFAOYSA-N 0.000 description 1
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
• 102000001707 3',5'-Cyclic-AMP Phosphodiesterases Human genes 0.000 description 1
• 108010054479 3',5'-Cyclic-AMP Phosphodiesterases Proteins 0.000 description 1
• 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
• WYKHJZSILIVQKU-UHFFFAOYSA-N 3-(bromomethyl)-1-benzothiophene Chemical compound C1=CC=C2C(CBr)=CSC2=C1 WYKHJZSILIVQKU-UHFFFAOYSA-N 0.000 description 1
• UGEJOEBBMPOJMT-UHFFFAOYSA-N 3-(trifluoromethyl)phenol Chemical compound OC1=CC=CC(C(F)(F)F)=C1 UGEJOEBBMPOJMT-UHFFFAOYSA-N 0.000 description 1
• NKFHABDRVJVORB-UHFFFAOYSA-N 3-benzyl-5-phenylpiperidin-2-one Chemical class O=C1NCC(C=2C=CC=CC=2)CC1CC1=CC=CC=C1 NKFHABDRVJVORB-UHFFFAOYSA-N 0.000 description 1
• UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• SGHBRHKBCLLVCI-UHFFFAOYSA-N 3-hydroxybenzonitrile Chemical compound OC1=CC=CC(C#N)=C1 SGHBRHKBCLLVCI-UHFFFAOYSA-N 0.000 description 1
• DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical compound OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 description 1
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
• 125000003469 3-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
• VAJUUDUWDNCECT-UHFFFAOYSA-N 4-(bromomethyl)pyridine;hydron;bromide Chemical compound Br.BrCC1=CC=NC=C1 VAJUUDUWDNCECT-UHFFFAOYSA-N 0.000 description 1
• YRNWIFYIFSBPAU-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(N(C)C)C=C1 YRNWIFYIFSBPAU-UHFFFAOYSA-N 0.000 description 1
• WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
• 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
• BBOHPZFCFFXABP-UHFFFAOYSA-N 4-fluoro-2-(iodomethyl)-1,3-benzoxazole Chemical compound FC1=CC=CC2=C1N=C(CI)O2 BBOHPZFCFFXABP-UHFFFAOYSA-N 0.000 description 1
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
• 125000005986 4-piperidonyl group Chemical group 0.000 description 1
• 102100022464 5'-nucleotidase Human genes 0.000 description 1
• 125000004606 5,6,7,8-tetrahydroisoquinolinyl group Chemical group C1(=NC=CC=2CCCCC12)* 0.000 description 1
• DRMBVWKDGWBKIV-UHFFFAOYSA-N 5,6-dichloro-2-(iodomethyl)-1h-benzimidazole Chemical compound C1=C(Cl)C(Cl)=CC2=C1NC(CI)=N2 DRMBVWKDGWBKIV-UHFFFAOYSA-N 0.000 description 1
• PVSNOTMQRGNNHL-UHFFFAOYSA-N 5-fluoro-2-(iodomethyl)-1,3-benzoxazole Chemical compound FC1=CC=C2OC(CI)=NC2=C1 PVSNOTMQRGNNHL-UHFFFAOYSA-N 0.000 description 1
• RXGJTUSBYWCRBK-UHFFFAOYSA-M 5-methylphenazinium methyl sulfate Chemical compound COS([O-])(=O)=O.C1=CC=C2[N+](C)=C(C=CC=C3)C3=NC2=C1 RXGJTUSBYWCRBK-UHFFFAOYSA-M 0.000 description 1
• ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
• JLVBSBMJQUMAMW-UHFFFAOYSA-N 6-methyl-2-pyridinemethanol Chemical compound CC1=CC=CC(CO)=N1 JLVBSBMJQUMAMW-UHFFFAOYSA-N 0.000 description 1
• UOIPUKBRINTHBH-UHFFFAOYSA-N 7-fluoro-2-(iodomethyl)-1,3-benzoxazole Chemical compound FC1=CC=CC2=C1OC(CI)=N2 UOIPUKBRINTHBH-UHFFFAOYSA-N 0.000 description 1
• AMKGKYQBASDDJB-UHFFFAOYSA-N 9$l^{2}-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1[B]2 AMKGKYQBASDDJB-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 1
• 208000030507 AIDS Diseases 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 241000271566 Aves Species 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• 208000014644 Brain disease Diseases 0.000 description 1
• DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
• LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
• 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
• 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
• OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 241001466804 Carnivora Species 0.000 description 1
• 241000700199 Cavia porcellus Species 0.000 description 1
• 206010057854 Cerebral Toxoplasmosis Diseases 0.000 description 1
• 108010012236 Chemokines Proteins 0.000 description 1
• 102000019034 Chemokines Human genes 0.000 description 1
• 241000819038 Chichester Species 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• 239000004821 Contact adhesive Substances 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
• 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
• 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
• 241000699800 Cricetinae Species 0.000 description 1
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
• AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
• 206010012289 Dementia Diseases 0.000 description 1
• 102000007260 Deoxyribonuclease I Human genes 0.000 description 1
• 108010008532 Deoxyribonuclease I Proteins 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• 239000004375 Dextrin Substances 0.000 description 1
• 229920001353 Dextrin Polymers 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 101100407335 Dictyostelium discoideum pde7 gene Proteins 0.000 description 1
• 101100135859 Dictyostelium discoideum regA gene Proteins 0.000 description 1
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
• 238000012286 ELISA Assay Methods 0.000 description 1
• 208000032274 Encephalopathy Diseases 0.000 description 1
• 102000002045 Endothelin Human genes 0.000 description 1
• 108050009340 Endothelin Proteins 0.000 description 1
• 241000588724 Escherichia coli Species 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• DSLZVSRJTYRBFB-UHFFFAOYSA-N Galactaric acid Natural products OC(=O)C(O)C(O)C(O)C(O)C(O)=O DSLZVSRJTYRBFB-UHFFFAOYSA-N 0.000 description 1
• IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
• 241000287828 Gallus gallus Species 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 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 1
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
• 208000009329 Graft vs Host Disease Diseases 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 208000000903 Herpes simplex encephalitis Diseases 0.000 description 1
• 241000238631 Hexapoda Species 0.000 description 1
• 241001272567 Hominoidea Species 0.000 description 1
• 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
• 101001098805 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4A Proteins 0.000 description 1
• 101000988423 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4C Proteins 0.000 description 1
• 101000988419 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4D Proteins 0.000 description 1
• 102100037850 Interferon gamma Human genes 0.000 description 1
• 108010002350 Interleukin-2 Proteins 0.000 description 1
• 108010002616 Interleukin-5 Proteins 0.000 description 1
• 108090001007 Interleukin-8 Proteins 0.000 description 1
• 108010044467 Isoenzymes Proteins 0.000 description 1
• 208000003456 Juvenile Arthritis Diseases 0.000 description 1
• 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
• 229930182816 L-glutamine Natural products 0.000 description 1
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 239000005639 Lauric acid Substances 0.000 description 1
• GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
• 206010062049 Lymphocytic infiltration Diseases 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
• 244000246386 Mentha pulegium Species 0.000 description 1
• 235000016257 Mentha pulegium Nutrition 0.000 description 1
• 235000004357 Mentha x piperita Nutrition 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
• 241001529936 Murinae Species 0.000 description 1
• 101100381978 Mus musculus Braf gene Proteins 0.000 description 1
• 240000001307 Myosotis scorpioides Species 0.000 description 1
• KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 1
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
• RPHYDHHCPVWNGB-RTBURBONSA-N N-[2-[[(3R,5S)-5-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxopiperidin-3-yl]methyl]-1,3-benzoxazol-4-yl]acetamide Chemical compound C(C)(=O)NC1=CC=CC2=C1N=C(O2)C[C@@H]2C(NC[C@@H](C2)C2=CC(=C(C=C2)OC)OC2CCCC2)=O RPHYDHHCPVWNGB-RTBURBONSA-N 0.000 description 1
• MVACQQUPDPXDKL-RTBURBONSA-N N-[2-[[(3R,5S)-5-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxopiperidin-3-yl]methyl]-1,3-benzoxazol-7-yl]acetamide Chemical compound C(C)(=O)NC1=CC=CC=2N=C(OC21)C[C@@H]2C(NC[C@@H](C2)C2=CC(=C(C=C2)OC)OC2CCCC2)=O MVACQQUPDPXDKL-RTBURBONSA-N 0.000 description 1
• RPHYDHHCPVWNGB-RBUKOAKNSA-N N-[2-[[(3S,5S)-5-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxopiperidin-3-yl]methyl]-1,3-benzoxazol-4-yl]acetamide Chemical compound C(C)(=O)NC1=CC=CC2=C1N=C(O2)C[C@H]2C(NC[C@@H](C2)C2=CC(=C(C=C2)OC)OC2CCCC2)=O RPHYDHHCPVWNGB-RBUKOAKNSA-N 0.000 description 1
• MVACQQUPDPXDKL-RBUKOAKNSA-N N-[2-[[(3S,5S)-5-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxopiperidin-3-yl]methyl]-1,3-benzoxazol-7-yl]acetamide Chemical compound C(C)(=O)NC1=CC=CC=2N=C(OC21)C[C@H]2C(NC[C@@H](C2)C2=CC(=C(C=C2)OC)OC2CCCC2)=O MVACQQUPDPXDKL-RBUKOAKNSA-N 0.000 description 1
• HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
• 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 1
• FIWILGQIZHDAQG-UHFFFAOYSA-N NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F Chemical compound NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F FIWILGQIZHDAQG-UHFFFAOYSA-N 0.000 description 1
• 244000061176 Nicotiana tabacum Species 0.000 description 1
• 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
• 208000002193 Pain Diseases 0.000 description 1
• 235000021314 Palmitic acid Nutrition 0.000 description 1
• 101150003085 Pdcl gene Proteins 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• 102000003992 Peroxidases Human genes 0.000 description 1
• 239000004264 Petrolatum Substances 0.000 description 1
• 241000286209 Phasianidae Species 0.000 description 1
• 229940123263 Phosphodiesterase 3 inhibitor Drugs 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 101100082606 Plasmodium falciparum (isolate 3D7) PDEbeta gene Proteins 0.000 description 1
• 229920001213 Polysorbate 20 Polymers 0.000 description 1
• 239000004793 Polystyrene Substances 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
• 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
• 239000004365 Protease Substances 0.000 description 1
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
• 206010037660 Pyrexia Diseases 0.000 description 1
• ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 108700008625 Reporter Genes Proteins 0.000 description 1
• LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 1
• QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 1
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
• 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
• 206010039281 Rubinstein-Taybi syndrome Diseases 0.000 description 1
• 241000282849 Ruminantia Species 0.000 description 1
• 101100135860 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PDE2 gene Proteins 0.000 description 1
• 229940124639 Selective inhibitor Drugs 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 230000024932 T cell mediated immunity Effects 0.000 description 1
• 230000005867 T cell response Effects 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 210000004241 Th2 cell Anatomy 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
• SLGBZMMZGDRARJ-UHFFFAOYSA-N Triphenylene Natural products C1=CC=C2C3=CC=CC=C3C3=CC=CC=C3C2=C1 SLGBZMMZGDRARJ-UHFFFAOYSA-N 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
• 208000025865 Ulcer Diseases 0.000 description 1
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
• 239000003875 Wang resin Substances 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• BLGXFZZNTVWLAY-CCZXDCJGSA-N Yohimbine Natural products C1=CC=C2C(CCN3C[C@@H]4CC[C@@H](O)[C@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-CCZXDCJGSA-N 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 description 1
• KACBNBQMSXQASC-UHFFFAOYSA-J [O-]C(F)=O.[O-]C(F)=O.[O-]C(F)=O.[O-]C(F)=O.C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1.C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1.C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1.C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 Chemical compound [O-]C(F)=O.[O-]C(F)=O.[O-]C(F)=O.[O-]C(F)=O.C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1.C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1.C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1.C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 KACBNBQMSXQASC-UHFFFAOYSA-J 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• 238000009825 accumulation Methods 0.000 description 1
• JDPAVWAQGBGGHD-UHFFFAOYSA-N aceanthrylene Chemical group C1=CC=C2C(C=CC3=CC=C4)=C3C4=CC2=C1 JDPAVWAQGBGGHD-UHFFFAOYSA-N 0.000 description 1
• 125000004054 acenaphthylenyl group Chemical group C1(=CC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
• SQFPKRNUGBRTAR-UHFFFAOYSA-N acephenanthrylene Chemical group C1=CC(C=C2)=C3C2=CC2=CC=CC=C2C3=C1 SQFPKRNUGBRTAR-UHFFFAOYSA-N 0.000 description 1
• IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
• AZPAHSPONLKXPA-UHFFFAOYSA-N acetic acid 2-bromo-2-methylpropane Chemical compound C(C)(=O)O.C(C)(C)(C)Br AZPAHSPONLKXPA-UHFFFAOYSA-N 0.000 description 1
• HXGDTGSAIMULJN-UHFFFAOYSA-N acetnaphthylene Natural products C1=CC(C=C2)=C3C2=CC=CC3=C1 HXGDTGSAIMULJN-UHFFFAOYSA-N 0.000 description 1
• ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 239000008186 active pharmaceutical agent Substances 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• 235000011037 adipic acid Nutrition 0.000 description 1
• 239000001361 adipic acid Substances 0.000 description 1
• 229960000250 adipic acid Drugs 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 239000013566 allergen Substances 0.000 description 1
• 230000000172 allergic effect Effects 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
• AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 230000009435 amidation Effects 0.000 description 1
• 238000007112 amidation reaction Methods 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 229940024606 amino acid Drugs 0.000 description 1
• 235000001014 amino acid Nutrition 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 229960004909 aminosalicylic acid Drugs 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
• 239000003957 anion exchange resin Substances 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 239000000924 antiasthmatic agent Substances 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 239000003435 antirheumatic agent Substances 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000000010 aprotic solvent Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• KNNXFYIMEYKHBZ-UHFFFAOYSA-N as-indacene Chemical compound C1=CC2=CC=CC2=C2C=CC=C21 KNNXFYIMEYKHBZ-UHFFFAOYSA-N 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• 229960005261 aspartic acid Drugs 0.000 description 1
• 239000000305 astragalus gummifer gum Substances 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• 125000002785 azepinyl group Chemical group 0.000 description 1
• 125000002393 azetidinyl group Chemical group 0.000 description 1
• 125000004069 aziridinyl group Chemical group 0.000 description 1
• OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 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
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• 125000005870 benzindolyl group Chemical group 0.000 description 1
• 125000005605 benzo group Chemical group 0.000 description 1
• 125000005875 benzo[b][1,4]dioxepinyl group Chemical group 0.000 description 1
• BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 1
• BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 1
• 125000000928 benzodioxinyl group Chemical group O1C(=COC2=C1C=CC=C2)* 0.000 description 1
• 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 229960004365 benzoic acid Drugs 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• 125000005878 benzonaphthofuranyl group Chemical group 0.000 description 1
• 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
• 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
• RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
• 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• BLGXFZZNTVWLAY-UHFFFAOYSA-N beta-Yohimbin Natural products C1=CC=C2C(CCN3CC4CCC(O)C(C4CC33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-UHFFFAOYSA-N 0.000 description 1
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
• WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
• 229960003237 betaine Drugs 0.000 description 1
• 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000003851 biochemical process Effects 0.000 description 1
• 230000031018 biological processes and functions Effects 0.000 description 1
• 239000012472 biological sample Substances 0.000 description 1
• 238000001574 biopsy Methods 0.000 description 1
• PFYXSUNOLOJMDX-UHFFFAOYSA-N bis(2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)ON1C(=O)CCC1=O PFYXSUNOLOJMDX-UHFFFAOYSA-N 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• 210000001185 bone marrow Anatomy 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 238000005893 bromination reaction Methods 0.000 description 1
• 230000003182 bronchodilatating effect Effects 0.000 description 1
• 230000003523 bronchorelaxing effect Effects 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 102100037092 cAMP-specific 3',5'-cyclic phosphodiesterase 4A Human genes 0.000 description 1
• 102100029169 cAMP-specific 3',5'-cyclic phosphodiesterase 4C Human genes 0.000 description 1
• 102100029170 cAMP-specific 3',5'-cyclic phosphodiesterase 4D Human genes 0.000 description 1
• LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
• KHAVLLBUVKBTBG-UHFFFAOYSA-N caproleic acid Natural products OC(=O)CCCCCCCC=C KHAVLLBUVKBTBG-UHFFFAOYSA-N 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 229940105329 carboxymethylcellulose Drugs 0.000 description 1
• 210000000845 cartilage Anatomy 0.000 description 1
• 230000008355 cartilage degradation Effects 0.000 description 1
• 108020001778 catalytic domains Proteins 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
• 230000001364 causal effect Effects 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 230000022131 cell cycle Effects 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 230000003833 cell viability Effects 0.000 description 1
• 230000033077 cellular process Effects 0.000 description 1
• 208000015114 central nervous system disease Diseases 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 239000002738 chelating agent Substances 0.000 description 1
• CFBUZOUXXHZCFB-OYOVHJISSA-N chembl511115 Chemical compound COC1=CC=C([C@@]2(CC[C@H](CC2)C(O)=O)C#N)C=C1OC1CCCC1 CFBUZOUXXHZCFB-OYOVHJISSA-N 0.000 description 1
• 210000000038 chest Anatomy 0.000 description 1
• 229940112822 chewing gum Drugs 0.000 description 1
• 235000015218 chewing gum Nutrition 0.000 description 1
• 235000013330 chicken meat Nutrition 0.000 description 1
• 239000012069 chiral reagent Substances 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
• 208000019069 chronic childhood arthritis Diseases 0.000 description 1
• 230000037326 chronic stress Effects 0.000 description 1
• 229950001653 cilomilast Drugs 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 150000001860 citric acid derivatives Chemical class 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 230000019771 cognition Effects 0.000 description 1
• 230000037410 cognitive enhancement Effects 0.000 description 1
• 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 239000007891 compressed tablet Substances 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 235000008504 concentrate Nutrition 0.000 description 1
• 239000012084 conversion product Substances 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 239000012228 culture supernatant Substances 0.000 description 1
• 239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 description 1
• 229940126513 cyclase activator Drugs 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
• 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 1
• HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• KFGVRWGDTLZAAO-UHFFFAOYSA-N cyclopenta-1,3-diene dicyclohexyl(cyclopenta-1,3-dien-1-yl)phosphane iron(2+) Chemical compound [Fe++].c1cc[cH-]c1.C1CCC(CC1)P(C1CCCCC1)c1ccc[cH-]1 KFGVRWGDTLZAAO-UHFFFAOYSA-N 0.000 description 1
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
• 230000009089 cytolysis Effects 0.000 description 1
• 210000004395 cytoplasmic granule Anatomy 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 229960002887 deanol Drugs 0.000 description 1
• 125000005507 decahydroisoquinolyl group Chemical group 0.000 description 1
• 125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 230000018044 dehydration Effects 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 230000023077 detection of light stimulus Effects 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 229960000633 dextran sulfate Drugs 0.000 description 1
• 235000019425 dextrin Nutrition 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 229940039227 diagnostic agent Drugs 0.000 description 1
• 239000000032 diagnostic agent Substances 0.000 description 1
• 239000012954 diazonium Substances 0.000 description 1
• 150000001989 diazonium salts Chemical class 0.000 description 1
• 125000005509 dibenzothiophenyl group Chemical group 0.000 description 1
• 235000020805 dietary restrictions Nutrition 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
• 150000004683 dihydrates Chemical class 0.000 description 1
• 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
• 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
• 125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 description 1
• JMRYOSQOYJBDOI-UHFFFAOYSA-N dilithium;di(propan-2-yl)azanide Chemical compound [Li+].CC(C)[N-]C(C)C.CC(C)N([Li])C(C)C JMRYOSQOYJBDOI-UHFFFAOYSA-N 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• 125000000532 dioxanyl group Chemical group 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• 230000006806 disease prevention Effects 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 239000012153 distilled water Substances 0.000 description 1
• LMAJREOZDVKQCZ-UHFFFAOYSA-N ditert-butyl-[2-(2-ditert-butylphosphanylphenyl)phenyl]phosphane Chemical group CC(C)(C)P(C(C)(C)C)C1=CC=CC=C1C1=CC=CC=C1P(C(C)(C)C)C(C)(C)C LMAJREOZDVKQCZ-UHFFFAOYSA-N 0.000 description 1
• 125000005883 dithianyl group Chemical group 0.000 description 1
• 150000004662 dithiols Chemical class 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
• 230000003828 downregulation Effects 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 230000008482 dysregulation Effects 0.000 description 1
• 230000002500 effect on skin Effects 0.000 description 1
• 239000012636 effector Substances 0.000 description 1
• 239000012039 electrophile Substances 0.000 description 1
• ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 238000007824 enzymatic assay Methods 0.000 description 1
• 230000007515 enzymatic degradation Effects 0.000 description 1
• 238000001952 enzyme assay Methods 0.000 description 1
• YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
• 210000003979 eosinophil Anatomy 0.000 description 1
• 150000002118 epoxides Chemical class 0.000 description 1
• 231100000321 erythema Toxicity 0.000 description 1
• 125000004185 ester group Chemical group 0.000 description 1
• AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
• 239000012259 ether extract Substances 0.000 description 1
• 238000006266 etherification reaction Methods 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• 229960004667 ethyl cellulose Drugs 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
• 230000003203 everyday effect Effects 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 230000001605 fetal effect Effects 0.000 description 1
• 230000027950 fever generation Effects 0.000 description 1
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• 150000004675 formic acid derivatives Chemical class 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 239000012634 fragment Substances 0.000 description 1
• 125000003844 furanonyl group Chemical group 0.000 description 1
• DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 1
• 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 229960005219 gentisic acid Drugs 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 239000000174 gluconic acid Substances 0.000 description 1
• 235000012208 gluconic acid Nutrition 0.000 description 1
• 229960002442 glucosamine Drugs 0.000 description 1
• 229940097043 glucuronic acid Drugs 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• 208000024908 graft versus host disease Diseases 0.000 description 1
• 235000013928 guanylic acid Nutrition 0.000 description 1
• 125000001188 haloalkyl group Chemical group 0.000 description 1
• 230000026030 halogenation Effects 0.000 description 1
• 238000005658 halogenation reaction Methods 0.000 description 1
• BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 1
• 229960003132 halothane Drugs 0.000 description 1
• 230000035876 healing Effects 0.000 description 1
• 150000002391 heterocyclic compounds Chemical class 0.000 description 1
• 239000008241 heterogeneous mixture Substances 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 229960001340 histamine Drugs 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 239000012456 homogeneous solution Substances 0.000 description 1
• 235000001050 hortel pimenta Nutrition 0.000 description 1
• 210000005260 human cell Anatomy 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
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 150000002430 hydrocarbons Chemical class 0.000 description 1
• LEUJVEZIEALICS-UHFFFAOYSA-N hydrogen sulfate;1h-imidazol-2-ylazanium Chemical compound OS(O)(=O)=O.NC1=NC=CN1 LEUJVEZIEALICS-UHFFFAOYSA-N 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 230000002631 hypothermal effect Effects 0.000 description 1
• 125000005946 imidazo[1,2-a]pyridyl group Chemical group 0.000 description 1
• 125000001841 imino group Chemical group [H]N=* 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 239000003547 immunosorbent Substances 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 238000010874 in vitro model Methods 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 230000008595 infiltration Effects 0.000 description 1
• 238000001764 infiltration Methods 0.000 description 1
• 230000004941 influx Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 230000031261 interleukin-10 production Effects 0.000 description 1
• 230000017307 interleukin-4 production Effects 0.000 description 1
• 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 230000009545 invasion Effects 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 230000002427 irreversible effect Effects 0.000 description 1
• 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
• 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
• 150000002540 isothiocyanates Chemical class 0.000 description 1
• 238000001948 isotopic labelling Methods 0.000 description 1
• 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
• 201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 1
• 230000003907 kidney function Effects 0.000 description 1
• 238000011813 knockout mouse model Methods 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 229940099563 lactobionic acid Drugs 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 231100001231 less toxic Toxicity 0.000 description 1
• 231100000518 lethal Toxicity 0.000 description 1
• 230000001665 lethal effect Effects 0.000 description 1
• 230000011268 leukocyte chemotaxis Effects 0.000 description 1
• VNYSSYRCGWBHLG-AMOLWHMGSA-N leukotriene B4 Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O VNYSSYRCGWBHLG-AMOLWHMGSA-N 0.000 description 1
• GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
• 108010052968 leupeptin Proteins 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
• WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
• 230000003908 liver function Effects 0.000 description 1
• 244000144972 livestock Species 0.000 description 1
• 230000007787 long-term memory Effects 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 230000004199 lung function Effects 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• 230000002101 lytic effect Effects 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 235000019359 magnesium stearate Nutrition 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
• 239000011976 maleic acid Substances 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 229910052748 manganese Inorganic materials 0.000 description 1
• 239000011572 manganese Substances 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 239000000155 melt Substances 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 229960001047 methyl salicylate Drugs 0.000 description 1
• JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
• 229960002216 methylparaben Drugs 0.000 description 1
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
• 230000000813 microbial effect Effects 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 230000003278 mimic effect Effects 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 230000000116 mitigating effect Effects 0.000 description 1
• 239000003226 mitogen Substances 0.000 description 1
• 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 150000004682 monohydrates Chemical class 0.000 description 1
• 239000012452 mother liquor Substances 0.000 description 1
• VGGNVBNNVSIGKG-UHFFFAOYSA-N n,n,2-trimethylaziridine-1-carboxamide Chemical compound CC1CN1C(=O)N(C)C VGGNVBNNVSIGKG-UHFFFAOYSA-N 0.000 description 1
• PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
• WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 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
• 229940097496 nasal spray Drugs 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 230000007302 negative regulation of cytokine production Effects 0.000 description 1
• 239000002858 neurotransmitter agent Substances 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 230000011242 neutrophil chemotaxis Effects 0.000 description 1
• 229960003512 nicotinic acid Drugs 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 238000006396 nitration reaction Methods 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 125000002560 nitrile group Chemical group 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 229910000510 noble metal Inorganic materials 0.000 description 1
• 125000006574 non-aromatic ring group Chemical group 0.000 description 1
• 231100000344 non-irritating Toxicity 0.000 description 1
• 239000000346 nonvolatile oil Substances 0.000 description 1
• 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
• 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
• 239000002777 nucleoside Substances 0.000 description 1
• 108010028584 nucleotidase Proteins 0.000 description 1
• 239000002773 nucleotide Substances 0.000 description 1
• 125000003729 nucleotide group Chemical group 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 125000005060 octahydroindolyl group Chemical group N1(CCC2CCCCC12)* 0.000 description 1
• 125000005061 octahydroisoindolyl group Chemical group C1(NCC2CCCCC12)* 0.000 description 1
• 229960002446 octanoic acid Drugs 0.000 description 1
• 239000003883 ointment base Substances 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 229960002969 oleic acid Drugs 0.000 description 1
• 239000003401 opiate antagonist Substances 0.000 description 1
• 239000008203 oral pharmaceutical composition Substances 0.000 description 1
• 239000007968 orange flavor Substances 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 125000002524 organometallic group Chemical group 0.000 description 1
• 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
• 229960005010 orotic acid Drugs 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 229940116315 oxalic acid Drugs 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
• 230000036407 pain Effects 0.000 description 1
• 229940098695 palmitic acid Drugs 0.000 description 1
• WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 235000019371 penicillin G benzathine Nutrition 0.000 description 1
• 229950000964 pepstatin Drugs 0.000 description 1
• 108010091212 pepstatin Proteins 0.000 description 1
• FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 108040007629 peroxidase activity proteins Proteins 0.000 description 1
• 229940066842 petrolatum Drugs 0.000 description 1
• 235000019271 petrolatum Nutrition 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 238000011458 pharmacological treatment Methods 0.000 description 1
• NQFOGDIWKQWFMN-UHFFFAOYSA-N phenalene Chemical compound C1=CC([CH]C=C2)=C3C2=CC=CC3=C1 NQFOGDIWKQWFMN-UHFFFAOYSA-N 0.000 description 1
• 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 239000002570 phosphodiesterase III inhibitor Substances 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 239000002504 physiological saline solution Substances 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 150000004885 piperazines Chemical class 0.000 description 1
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 1
• 150000003053 piperidines Chemical class 0.000 description 1
• 239000013612 plasmid Substances 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 229920003023 plastic Polymers 0.000 description 1
• 239000003880 polar aprotic solvent Substances 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 230000010287 polarization Effects 0.000 description 1
• 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
• 229920000768 polyamine Polymers 0.000 description 1
• 239000002952 polymeric resin Substances 0.000 description 1
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
• 229920002223 polystyrene Polymers 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
• WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 238000011533 pre-incubation Methods 0.000 description 1
• 238000012746 preparative thin layer chromatography Methods 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 230000007112 pro inflammatory response Effects 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
• 230000035755 proliferation Effects 0.000 description 1
• 125000006410 propenylene group Chemical group 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 238000011321 prophylaxis Methods 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
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
• 150000003180 prostaglandins Chemical class 0.000 description 1
• 108010043671 prostatic acid phosphatase Proteins 0.000 description 1
• 235000019419 proteases Nutrition 0.000 description 1
• 230000000541 pulsatile effect Effects 0.000 description 1
• 150000003212 purines Chemical class 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
• WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 1
• 125000001422 pyrrolinyl group Chemical group 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• 238000010791 quenching Methods 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
• 239000006215 rectal suppository Substances 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 238000002694 regional anesthesia Methods 0.000 description 1
• 230000008439 repair process Effects 0.000 description 1
• 230000010410 reperfusion Effects 0.000 description 1
• BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
• 229960003147 reserpine Drugs 0.000 description 1
• 230000000241 respiratory effect Effects 0.000 description 1
• 230000029058 respiratory gaseous exchange Effects 0.000 description 1
• 230000004043 responsiveness Effects 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 238000007363 ring formation reaction Methods 0.000 description 1
• MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
• WEMQMWWWCBYPOV-UHFFFAOYSA-N s-indacene Chemical compound C=1C2=CC=CC2=CC2=CC=CC2=1 WEMQMWWWCBYPOV-UHFFFAOYSA-N 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 201000000306 sarcoidosis Diseases 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 238000007423 screening assay Methods 0.000 description 1
• 229940116353 sebacic acid Drugs 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 239000004208 shellac Substances 0.000 description 1
• 229940113147 shellac Drugs 0.000 description 1
• ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
• 235000013874 shellac Nutrition 0.000 description 1
• 229910000077 silane Inorganic materials 0.000 description 1
• 230000000391 smoking effect Effects 0.000 description 1
• AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
• 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
• 238000003797 solvolysis reaction Methods 0.000 description 1
• SLRCCWJSBJZJBV-AJNGGQMLSA-N sparteine Chemical compound C1N2CCCC[C@H]2[C@@H]2CN3CCCC[C@H]3[C@H]1C2 SLRCCWJSBJZJBV-AJNGGQMLSA-N 0.000 description 1
• 229960001945 sparteine Drugs 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 229960004274 stearic acid Drugs 0.000 description 1
• 239000008174 sterile solution Substances 0.000 description 1
• 239000012089 stop solution Substances 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 238000005556 structure-activity relationship Methods 0.000 description 1
• 230000004960 subcellular localization Effects 0.000 description 1
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 230000009182 swimming Effects 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 210000001258 synovial membrane Anatomy 0.000 description 1
• 229920003002 synthetic resin Polymers 0.000 description 1
• 238000012385 systemic delivery Methods 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 229960001367 tartaric acid Drugs 0.000 description 1
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
• ZPRUWGJSBSHAEW-FOIFJWKZSA-N tert-butyl (5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxo-3-(pyridin-3-ylmethyl)piperidine-1-carboxylate Chemical compound COC1=CC=C([C@H]2CN(C(=O)C(CC=3C=NC=CC=3)C2)C(=O)OC(C)(C)C)C=C1OC1CCCC1 ZPRUWGJSBSHAEW-FOIFJWKZSA-N 0.000 description 1
• GDOYJSAHAYONOD-GFOWMXPYSA-N tert-butyl (5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-2-oxopiperidine-1-carboxylate Chemical compound COC1=CC=C([C@H]2CN(C(=O)C(CC(=O)OC(C)(C)C)C2)C(=O)OC(C)(C)C)C=C1OC1CCCC1 GDOYJSAHAYONOD-GFOWMXPYSA-N 0.000 description 1
• VNAAVSUMNSPCJO-UHFFFAOYSA-N tert-butyl 2-(iodomethyl)-5,6-dimethylbenzimidazole-1-carboxylate Chemical compound C1=C(C)C(C)=CC2=C1N(C(=O)OC(C)(C)C)C(CI)=N2 VNAAVSUMNSPCJO-UHFFFAOYSA-N 0.000 description 1
• UISWQXGHOHEKNG-DHIUTWEWSA-N tert-butyl 2-[[(3r,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxopiperidin-3-yl]methyl]-5,6-dimethylbenzimidazole-1-carboxylate Chemical compound COC1=CC=C([C@@H]2C[C@H](CC=3N(C4=CC(C)=C(C)C=C4N=3)C(=O)OC(C)(C)C)C(=O)NC2)C=C1OC1CCCC1 UISWQXGHOHEKNG-DHIUTWEWSA-N 0.000 description 1
• UISWQXGHOHEKNG-XZOQPEGZSA-N tert-butyl 2-[[(3s,5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxopiperidin-3-yl]methyl]-5,6-dimethylbenzimidazole-1-carboxylate Chemical compound COC1=CC=C([C@@H]2C[C@@H](CC=3N(C4=CC(C)=C(C)C=C4N=3)C(=O)OC(C)(C)C)C(=O)NC2)C=C1OC1CCCC1 UISWQXGHOHEKNG-XZOQPEGZSA-N 0.000 description 1
• AEQHHOBTWZZNLM-FXDYGKIASA-N tert-butyl 2-[[(5s)-5-(3-cyclopentyloxy-4-methoxyphenyl)-1-[(2-methylpropan-2-yl)oxycarbonyl]-2-oxopiperidin-3-yl]methyl]-5,6-dimethylbenzimidazole-1-carboxylate Chemical compound COC1=CC=C([C@H]2CN(C(=O)C(CC=3N(C4=CC(C)=C(C)C=C4N=3)C(=O)OC(C)(C)C)C2)C(=O)OC(C)(C)C)C=C1OC1CCCC1 AEQHHOBTWZZNLM-FXDYGKIASA-N 0.000 description 1
• NRFDZZBPGMUOQD-UHFFFAOYSA-N tert-butyl 3-(bromomethyl)indole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)C=C(CBr)C2=C1 NRFDZZBPGMUOQD-UHFFFAOYSA-N 0.000 description 1
• OOVPQKQFSDFRFA-UHFFFAOYSA-N tert-butyl 3-(hydroxymethyl)indole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)C=C(CO)C2=C1 OOVPQKQFSDFRFA-UHFFFAOYSA-N 0.000 description 1
• ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
• 229960003604 testosterone Drugs 0.000 description 1
• 150000004685 tetrahydrates Chemical class 0.000 description 1
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• 125000005942 tetrahydropyridyl group Chemical group 0.000 description 1
• 229960004559 theobromine Drugs 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 125000005985 thienyl[1,3]dithianyl group Chemical group 0.000 description 1
• 125000002053 thietanyl group Chemical group 0.000 description 1
• 125000001166 thiolanyl group Chemical group 0.000 description 1
• 238000003325 tomography Methods 0.000 description 1
• 239000012049 topical pharmaceutical composition Substances 0.000 description 1
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
• 230000002103 transcriptional effect Effects 0.000 description 1
• 230000037317 transdermal delivery Effects 0.000 description 1
• 238000001890 transfection Methods 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 230000001052 transient effect Effects 0.000 description 1
• 238000013519 translation Methods 0.000 description 1
• 230000014616 translation Effects 0.000 description 1
• 125000004665 trialkylsilyl group Chemical group 0.000 description 1
• IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
• 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
• 150000004684 trihydrates Chemical class 0.000 description 1
• 125000005580 triphenylene group Chemical group 0.000 description 1
• YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 229960004418 trolamine Drugs 0.000 description 1
• 229960000281 trometamol Drugs 0.000 description 1
• 230000005951 type IV hypersensitivity Effects 0.000 description 1
• 208000027930 type IV hypersensitivity disease Diseases 0.000 description 1
• 229960002703 undecylenic acid Drugs 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1
• 210000002700 urine Anatomy 0.000 description 1
• 238000003828 vacuum filtration Methods 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 239000008215 water for injection Substances 0.000 description 1
• 238000010626 work up procedure Methods 0.000 description 1
• BLGXFZZNTVWLAY-SCYLSFHTSA-N yohimbine Chemical compound C1=CC=C2C(CCN3C[C@@H]4CC[C@H](O)[C@@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-SCYLSFHTSA-N 0.000 description 1
• 229960000317 yohimbine Drugs 0.000 description 1
• AADVZSXPNRLYLV-UHFFFAOYSA-N yohimbine carboxylic acid Natural products C1=CC=C2C(CCN3CC4CCC(C(C4CC33)C(O)=O)O)=C3NC2=C1 AADVZSXPNRLYLV-UHFFFAOYSA-N 0.000 description 1
• 229910052727 yttrium Inorganic materials 0.000 description 1
• VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
• 229960001763 zinc sulfate Drugs 0.000 description 1
• 229910000368 zinc sulfate Inorganic materials 0.000 description 1