UA78297C2 - 1- or 3-thiabenzonaphlhoazulene as inhibitors of tumour necrosis factor production and intermediates for synthesis thereof - Google Patents

1- or 3-thiabenzonaphlhoazulene as inhibitors of tumour necrosis factor production and intermediates for synthesis thereof Download PDF

Info

Publication number: UA78297C2
Authority: UA; Ukraine
Prior art keywords: oxa; compounds; formula; thiabenzo; alkyl
Prior art date: 2002-04-10

Application number

UA20041008543A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Pliva Istrazivacki Inst D O O

Priority date (The priority date 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 date listed.)

2002-04-10

Filing date

2003-09-04

Publication date

2007-03-15

2003-09-04 Application filed by Pliva Istrazivacki Inst D O O filed Critical Pliva Istrazivacki Inst D O O

2007-03-15 Publication of UA78297C2 publication Critical patent/UA78297C2/uk

Links

238000004519 manufacturing process Methods 0.000 title claims abstract description 19
239000003112 inhibitor Substances 0.000 title claims description 9
239000000543 intermediate Substances 0.000 title abstract description 5
230000015572 biosynthetic process Effects 0.000 title description 4
238000003786 synthesis reaction Methods 0.000 title description 2
102000018594 Tumour necrosis factor Human genes 0.000 title 1
108050007852 Tumour necrosis factor Proteins 0.000 title 1
238000000034 method Methods 0.000 claims abstract description 37
150000003839 salts Chemical class 0.000 claims abstract description 14
230000003110 anti-inflammatory effect Effects 0.000 claims abstract description 6
239000012453 solvate Substances 0.000 claims abstract description 6
150000001875 compounds Chemical class 0.000 claims description 135
238000006243 chemical reaction Methods 0.000 claims description 51
-1 substituted Chemical class 0.000 claims description 50
125000000217 alkyl group Chemical group 0.000 claims description 30
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
125000003118 aryl group Chemical group 0.000 claims description 23
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
125000001424 substituent group Chemical group 0.000 claims description 21
125000000623 heterocyclic group Chemical group 0.000 claims description 18
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 16
125000003545 alkoxy group Chemical group 0.000 claims description 15
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 15
125000001072 heteroaryl group Chemical group 0.000 claims description 15
150000003573 thiols Chemical class 0.000 claims description 15
150000001412 amines Chemical class 0.000 claims description 14
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 14
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 14
125000003342 alkenyl group Chemical group 0.000 claims description 12
229910052799 carbon Inorganic materials 0.000 claims description 12
125000004432 carbon atom Chemical group C* 0.000 claims description 12
239000001257 hydrogen Substances 0.000 claims description 12
229910052739 hydrogen Inorganic materials 0.000 claims description 12
125000001589 carboacyl group Chemical group 0.000 claims description 11
229910052736 halogen Inorganic materials 0.000 claims description 11
150000002367 halogens Chemical class 0.000 claims description 11
125000005842 heteroatom Chemical group 0.000 claims description 11
150000001298 alcohols Chemical class 0.000 claims description 10
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
125000000304 alkynyl group Chemical group 0.000 claims description 10
125000005843 halogen group Chemical group 0.000 claims description 10
125000004414 alkyl thio group Chemical group 0.000 claims description 9
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
125000003112 azulen-2-yl group Chemical group [H]C1=C2C([H])=C([H])C([H])=C([H])C([H])=C2C([H])=C1* 0.000 claims description 8
201000010099 disease Diseases 0.000 claims description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
229910052757 nitrogen Inorganic materials 0.000 claims description 8
125000002947 alkylene group Chemical group 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
125000006239 protecting group Chemical group 0.000 claims description 7
229910052717 sulfur Inorganic materials 0.000 claims description 7
102000004127 Cytokines Human genes 0.000 claims description 6
108090000695 Cytokines Proteins 0.000 claims description 6
206010061218 Inflammation Diseases 0.000 claims description 6
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
125000003282 alkyl amino group Chemical group 0.000 claims description 6
239000003814 drug Substances 0.000 claims description 6
230000004054 inflammatory process Effects 0.000 claims description 6
230000001575 pathological effect Effects 0.000 claims description 6
239000011593 sulfur Substances 0.000 claims description 6
UDEQOVGVLPGNGN-UHFFFAOYSA-N C12=CC=CC2=CC=CC2=C1C=CC1=CC=C(C=CC=C3)C3=C21 Chemical class C12=CC=CC2=CC=CC2=C1C=CC1=CC=C(C=CC=C3)C3=C21 UDEQOVGVLPGNGN-UHFFFAOYSA-N 0.000 claims description 5
150000002148 esters Chemical class 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 4
125000004429 atom Chemical group 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
125000004093 cyano group Chemical group *C#N 0.000 claims description 4
125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 claims description 4
125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 4
238000007363 ring formation reaction Methods 0.000 claims description 4
229920006395 saturated elastomer Polymers 0.000 claims description 4
125000003107 substituted aryl group Chemical group 0.000 claims description 4
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
125000002619 bicyclic group Chemical group 0.000 claims description 3
BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 claims description 3
125000001841 imino group Chemical group [H]N=* 0.000 claims description 3
125000002950 monocyclic group Chemical group 0.000 claims description 3
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
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 claims description 3
230000002265 prevention Effects 0.000 claims description 3
125000000547 substituted alkyl group Chemical group 0.000 claims description 3
231100000252 nontoxic Toxicity 0.000 claims description 2
230000003000 nontoxic effect Effects 0.000 claims description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims 8
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 8
150000002431 hydrogen Chemical class 0.000 claims 6
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims 4
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 3
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 2
CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 claims 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
230000005764 inhibitory process Effects 0.000 abstract description 13
238000002360 preparation method Methods 0.000 abstract description 8
102000000589 Interleukin-1 Human genes 0.000 abstract description 7
108010002352 Interleukin-1 Proteins 0.000 abstract description 7
230000000202 analgesic effect Effects 0.000 abstract description 6
102000009270 Tumour necrosis factor alpha Human genes 0.000 abstract 2
108050000101 Tumour necrosis factor alpha Proteins 0.000 abstract 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
108060008682 Tumor Necrosis Factor Proteins 0.000 description 29
239000000243 solution Substances 0.000 description 29
102000003390 tumor necrosis factor Human genes 0.000 description 29
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
239000000047 product Substances 0.000 description 26
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
229910001868 water Inorganic materials 0.000 description 21
239000011541 reaction mixture Substances 0.000 description 20
230000028327 secretion Effects 0.000 description 17
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
238000004440 column chromatography Methods 0.000 description 16
238000012360 testing method Methods 0.000 description 15
239000000203 mixture Substances 0.000 description 14
238000010992 reflux Methods 0.000 description 14
239000010410 layer Substances 0.000 description 13
210000004027 cell Anatomy 0.000 description 12
241001465754 Metazoa Species 0.000 description 11
230000002829 reductive effect Effects 0.000 description 11
206010039073 rheumatoid arthritis Diseases 0.000 description 11
239000000126 substance Substances 0.000 description 10
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
241000699666 Mus <mouse, genus> Species 0.000 description 8
241000699670 Mus sp. Species 0.000 description 8
HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 8
239000012043 crude product Substances 0.000 description 8
239000002904 solvent Substances 0.000 description 8
238000000746 purification Methods 0.000 description 7
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
LJQNMDZRCXJETK-UHFFFAOYSA-N 3-chloro-n,n-dimethylpropan-1-amine;hydron;chloride Chemical compound Cl.CN(C)CCCCl LJQNMDZRCXJETK-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
125000004122 cyclic group Chemical group 0.000 description 6
229910052740 iodine Inorganic materials 0.000 description 6
238000001953 recrystallisation Methods 0.000 description 6
LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 5
230000002378 acidificating effect Effects 0.000 description 5
125000003435 aroyl group Chemical group 0.000 description 5
229940079593 drug Drugs 0.000 description 5
230000000694 effects Effects 0.000 description 5
125000004356 hydroxy functional group Chemical group O* 0.000 description 5
239000007788 liquid Substances 0.000 description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
230000003647 oxidation Effects 0.000 description 5
238000007254 oxidation reaction Methods 0.000 description 5
239000007787 solid Substances 0.000 description 5
239000007858 starting material Substances 0.000 description 5
CJNZAXGUTKBIHP-UHFFFAOYSA-N 2-iodobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1I CJNZAXGUTKBIHP-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
125000002252 acyl group Chemical group 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
150000001721 carbon Chemical group 0.000 description 4
230000003197 catalytic effect Effects 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
239000013078 crystal Substances 0.000 description 4
239000002158 endotoxin Substances 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
125000000524 functional group Chemical group 0.000 description 4
230000007062 hydrolysis Effects 0.000 description 4
238000006460 hydrolysis reaction Methods 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
108020003175 receptors Proteins 0.000 description 4
238000006722 reduction reaction Methods 0.000 description 4
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 4
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
206010010904 Convulsion Diseases 0.000 description 3
208000011231 Crohn disease Diseases 0.000 description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
208000007101 Muscle Cramp Diseases 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
208000005392 Spasm Diseases 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
230000009471 action Effects 0.000 description 3
125000005103 alkyl silyl group Chemical group 0.000 description 3
125000005101 aryl methoxy carbonyl group Chemical group 0.000 description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
230000004071 biological effect Effects 0.000 description 3
239000000969 carrier Substances 0.000 description 3
125000004185 ester group Chemical group 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
229910052731 fluorine Inorganic materials 0.000 description 3
239000011737 fluorine Substances 0.000 description 3
230000026030 halogenation Effects 0.000 description 3
238000005658 halogenation reaction Methods 0.000 description 3
125000004435 hydrogen atom Chemical class [H]* 0.000 description 3
230000002757 inflammatory effect Effects 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
239000011630 iodine Substances 0.000 description 3
150000002576 ketones Chemical class 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
239000013642 negative control Substances 0.000 description 3
238000010534 nucleophilic substitution reaction Methods 0.000 description 3
210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
210000003024 peritoneal macrophage Anatomy 0.000 description 3
239000008194 pharmaceutical composition Substances 0.000 description 3
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
239000013641 positive control Substances 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
230000009467 reduction Effects 0.000 description 3
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
150000003577 thiophenes Chemical class 0.000 description 3
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 2
IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
JWAZRIHNYRIHIV-UHFFFAOYSA-N 2-naphthol Chemical compound C1=CC=CC2=CC(O)=CC=C21 JWAZRIHNYRIHIV-UHFFFAOYSA-N 0.000 description 2
IHPRVZKJZGXTBQ-UHFFFAOYSA-N 3-chloropropan-1-amine;hydron;chloride Chemical compound Cl.NCCCCl IHPRVZKJZGXTBQ-UHFFFAOYSA-N 0.000 description 2
GXMSLNZIHPZWAI-UHFFFAOYSA-N 5-thiatetracyclo[12.4.0.02,6.08,13]octadeca-1(18),2,6,8,10,12,14,16-octaene Chemical class S1CC=C2C3=C(C4=C(C=C12)C=CC=C4)C=CC=C3 GXMSLNZIHPZWAI-UHFFFAOYSA-N 0.000 description 2
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
239000004342 Benzoyl peroxide Substances 0.000 description 2
OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
239000004215 Carbon black (E152) Substances 0.000 description 2
206010009900 Colitis ulcerative Diseases 0.000 description 2
108010008165 Etanercept Proteins 0.000 description 2
235000010469 Glycine max Nutrition 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
229930182555 Penicillin Natural products 0.000 description 2
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 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
201000004681 Psoriasis Diseases 0.000 description 2
206010040070 Septic Shock Diseases 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
210000001744 T-lymphocyte Anatomy 0.000 description 2
XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
201000006704 Ulcerative Colitis Diseases 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
210000000683 abdominal cavity Anatomy 0.000 description 2
229960001138 acetylsalicylic acid Drugs 0.000 description 2
125000003172 aldehyde group Chemical group 0.000 description 2
150000001350 alkyl halides Chemical class 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
239000005557 antagonist Substances 0.000 description 2
238000007080 aromatic substitution reaction Methods 0.000 description 2
230000002917 arthritic effect Effects 0.000 description 2
208000006673 asthma Diseases 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
235000019400 benzoyl peroxide Nutrition 0.000 description 2
238000009835 boiling Methods 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
238000004113 cell culture Methods 0.000 description 2
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
238000006482 condensation reaction Methods 0.000 description 2
229960000403 etanercept Drugs 0.000 description 2
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
125000006125 ethylsulfonyl group Chemical group 0.000 description 2
125000004705 ethylthio group Chemical group C(C)S* 0.000 description 2
239000012091 fetal bovine serum Substances 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
125000001188 haloalkyl group Chemical group 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
125000002883 imidazolyl group Chemical group 0.000 description 2
229960000598 infliximab Drugs 0.000 description 2
PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
229920006008 lipopolysaccharide Polymers 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
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 2
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
150000002825 nitriles Chemical class 0.000 description 2
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
239000003921 oil Substances 0.000 description 2
235000019198 oils Nutrition 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
201000008482 osteoarthritis Diseases 0.000 description 2
230000004963 pathophysiological condition Effects 0.000 description 2
229940049954 penicillin Drugs 0.000 description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
229920000137 polyphosphoric acid Polymers 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
239000000843 powder Substances 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
125000003373 pyrazinyl group Chemical group 0.000 description 2
230000035945 sensitivity Effects 0.000 description 2
230000035939 shock Effects 0.000 description 2
230000008054 signal transmission Effects 0.000 description 2
230000011664 signaling Effects 0.000 description 2
235000017281 sodium acetate Nutrition 0.000 description 2
238000003756 stirring Methods 0.000 description 2
229960005322 streptomycin Drugs 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
230000004083 survival effect Effects 0.000 description 2
239000000725 suspension Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
239000006188 syrup Substances 0.000 description 2
MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 2
238000004448 titration Methods 0.000 description 2
229960002415 trichloroethylene Drugs 0.000 description 2
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
XVJVDXVBVSCWOF-UHFFFAOYSA-N 1-chloro-n,n-dimethylpropan-2-amine;hydrochloride Chemical compound Cl.ClCC(C)N(C)C XVJVDXVBVSCWOF-UHFFFAOYSA-N 0.000 description 1
VKFNROSEPYJGGI-UHFFFAOYSA-N 2-(2-naphthalen-1-yloxyphenyl)acetonitrile Chemical compound N#CCC1=CC=CC=C1OC1=CC=CC2=CC=CC=C12 VKFNROSEPYJGGI-UHFFFAOYSA-N 0.000 description 1
MFZFLPLECMXFPQ-UHFFFAOYSA-N 2-(2-naphthalen-2-yloxyphenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1OC1=CC=C(C=CC=C2)C2=C1 MFZFLPLECMXFPQ-UHFFFAOYSA-N 0.000 description 1
XCHBLJCDPWRGOB-UHFFFAOYSA-N 2-(2-naphthalen-2-ylsulfanylphenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1SC1=CC=C(C=CC=C2)C2=C1 XCHBLJCDPWRGOB-UHFFFAOYSA-N 0.000 description 1
BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 1
BRXSPPTZUSTKKI-UHFFFAOYSA-N 2-(5,6,7,8-tetrahydronaphthalen-2-yloxy)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OC1=CC=C(CCCC2)C2=C1 BRXSPPTZUSTKKI-UHFFFAOYSA-N 0.000 description 1
XXKCDKIJGBTTEW-UHFFFAOYSA-N 2-(7-methoxynaphthalen-2-yl)oxybenzoic acid Chemical compound C=1C2=CC(OC)=CC=C2C=CC=1OC1=CC=CC=C1C(O)=O XXKCDKIJGBTTEW-UHFFFAOYSA-N 0.000 description 1
RFCQDOVPMUSZMN-UHFFFAOYSA-N 2-Naphthalenethiol Chemical compound C1=CC=CC2=CC(S)=CC=C21 RFCQDOVPMUSZMN-UHFFFAOYSA-N 0.000 description 1
BPLMIWRJNAFXHY-UHFFFAOYSA-N 2-[2-(5,6,7,8-tetrahydronaphthalen-1-yloxy)phenyl]acetonitrile Chemical compound N#CCC1=CC=CC=C1OC1=CC=CC2=C1CCCC2 BPLMIWRJNAFXHY-UHFFFAOYSA-N 0.000 description 1
MPHCIYJOJLTCQJ-UHFFFAOYSA-N 2-[2-(bromomethyl)phenyl]sulfanylnaphthalene Chemical compound BrCC1=CC=CC=C1SC1=CC=C(C=CC=C2)C2=C1 MPHCIYJOJLTCQJ-UHFFFAOYSA-N 0.000 description 1
OCWGRWAYARCRTQ-UHFFFAOYSA-N 2-chloro-n,n-dimethylpropan-1-amine;hydron;chloride Chemical compound Cl.CC(Cl)CN(C)C OCWGRWAYARCRTQ-UHFFFAOYSA-N 0.000 description 1
UHYMCGZSUOMOPR-UHFFFAOYSA-N 2-naphthalen-1-yloxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1OC1=CC=CC2=CC=CC=C12 UHYMCGZSUOMOPR-UHFFFAOYSA-N 0.000 description 1
NWIXWWXCNJCGKM-UHFFFAOYSA-N 2-naphthalen-1-ylsulfanylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 NWIXWWXCNJCGKM-UHFFFAOYSA-N 0.000 description 1
ARFSVQLPOGEABB-UHFFFAOYSA-N 2-naphthalen-2-ylsulfanylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1SC1=CC=C(C=CC=C2)C2=C1 ARFSVQLPOGEABB-UHFFFAOYSA-N 0.000 description 1
NKTGZAKMRRHEKM-UHFFFAOYSA-N 3,5-diazatetracyclo[12.4.0.02,6.08,13]octadeca-1(18),2,4,6,8,10,12,14,16-nonaene Chemical class N1=CN=C2C3=C(C4=C(C=C12)C=CC=C4)C=CC=C3 NKTGZAKMRRHEKM-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
NBJHDLKSWUDGJG-UHFFFAOYSA-N 4-(2-chloroethyl)morpholin-4-ium;chloride Chemical compound Cl.ClCCN1CCOCC1 NBJHDLKSWUDGJG-UHFFFAOYSA-N 0.000 description 1
SCWNNOCLLOHZIG-UHFFFAOYSA-N 5,6,7,8-tetrahydro-1-naphthol Chemical compound C1CCCC2=C1C=CC=C2O SCWNNOCLLOHZIG-UHFFFAOYSA-N 0.000 description 1
UMKXSOXZAXIOPJ-UHFFFAOYSA-N 5,6,7,8-tetrahydro-2-naphthol Chemical compound C1CCCC2=CC(O)=CC=C21 UMKXSOXZAXIOPJ-UHFFFAOYSA-N 0.000 description 1
COBFKLACTXXGOF-UHFFFAOYSA-N 5-[2-(bromomethyl)phenoxy]-1,2,3,4-tetrahydronaphthalene Chemical compound BrCC1=CC=CC=C1OC1=CC=CC2=C1CCCC2 COBFKLACTXXGOF-UHFFFAOYSA-N 0.000 description 1
CMYJSGFSQMNOLH-UHFFFAOYSA-N 6-[2-(bromomethyl)phenoxy]-1,2,3,4-tetrahydronaphthalene Chemical compound BrCC1=CC=CC=C1OC1=CC=C(CCCC2)C2=C1 CMYJSGFSQMNOLH-UHFFFAOYSA-N 0.000 description 1
UNFNRIIETORURP-UHFFFAOYSA-N 7-methoxynaphthalen-2-ol Chemical compound C1=CC(O)=CC2=CC(OC)=CC=C21 UNFNRIIETORURP-UHFFFAOYSA-N 0.000 description 1
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 1
208000030507 AIDS Diseases 0.000 description 1
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
206010006895 Cachexia Diseases 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
RZGJWVFLDKZTTI-UHFFFAOYSA-L Cl[Cr](=O)(=O)OC1=CC=CC=N1 Chemical compound Cl[Cr](=O)(=O)OC1=CC=CC=N1 RZGJWVFLDKZTTI-UHFFFAOYSA-L 0.000 description 1
102000029816 Collagenase Human genes 0.000 description 1
108060005980 Collagenase Proteins 0.000 description 1
PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
108010036949 Cyclosporine Proteins 0.000 description 1
201000004624 Dermatitis Diseases 0.000 description 1
206010012438 Dermatitis atopic Diseases 0.000 description 1
206010012442 Dermatitis contact Diseases 0.000 description 1
RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
239000005977 Ethylene Substances 0.000 description 1
208000009386 Experimental Arthritis Diseases 0.000 description 1
238000005727 Friedel-Crafts reaction Methods 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
206010018364 Glomerulonephritis Diseases 0.000 description 1
201000005569 Gout Diseases 0.000 description 1
208000010496 Heart Arrest Diseases 0.000 description 1
206010022489 Insulin Resistance Diseases 0.000 description 1
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-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
239000002841 Lewis acid Substances 0.000 description 1
101100112373 Mus musculus Ctsm gene Proteins 0.000 description 1
206010028347 Muscle twitching Diseases 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
RHHSGLPWDHEVIR-UHFFFAOYSA-L O[Cr](O[Cr](OC1=CC=CC=N1)(=O)=O)(=O)=O Chemical compound O[Cr](O[Cr](OC1=CC=CC=N1)(=O)=O)(=O)=O RHHSGLPWDHEVIR-UHFFFAOYSA-L 0.000 description 1
208000037273 Pathologic Processes Diseases 0.000 description 1
206010036030 Polyarthritis Diseases 0.000 description 1
FCLZCOCSZQNREK-UHFFFAOYSA-N Pyrrolidine, hydrochloride Chemical compound Cl.C1CCNC1 FCLZCOCSZQNREK-UHFFFAOYSA-N 0.000 description 1
206010039710 Scleroderma Diseases 0.000 description 1
206010040047 Sepsis Diseases 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
201000002661 Spondylitis Diseases 0.000 description 1
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 1
229930006000 Sucrose Natural products 0.000 description 1
235000019486 Sunflower oil Nutrition 0.000 description 1
239000005844 Thymol Substances 0.000 description 1
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
206010044248 Toxic shock syndrome Diseases 0.000 description 1
231100000650 Toxic shock syndrome Toxicity 0.000 description 1
206010054094 Tumour necrosis Diseases 0.000 description 1
208000036142 Viral infection Diseases 0.000 description 1
229920000392 Zymosan Polymers 0.000 description 1
SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
150000001266 acyl halides Chemical class 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
125000003158 alcohol group Chemical group 0.000 description 1
150000001335 aliphatic alkanes Chemical class 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
238000010171 animal model Methods 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
238000013459 approach Methods 0.000 description 1
125000003710 aryl alkyl group Chemical group 0.000 description 1
125000005161 aryl oxy carbonyl group Chemical group 0.000 description 1
238000003556 assay Methods 0.000 description 1
201000008937 atopic dermatitis Diseases 0.000 description 1
208000010668 atopic eczema Diseases 0.000 description 1
230000001363 autoimmune Effects 0.000 description 1
USGSIOLMWXWKQP-UHFFFAOYSA-N azulene-2-carboxylic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CC2=C1 USGSIOLMWXWKQP-UHFFFAOYSA-N 0.000 description 1
150000001545 azulenes Chemical class 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
CHQVQXZFZHACQQ-UHFFFAOYSA-M benzyl(triethyl)azanium;bromide Chemical compound [Br-].CC[N+](CC)(CC)CC1=CC=CC=C1 CHQVQXZFZHACQQ-UHFFFAOYSA-M 0.000 description 1
229950011260 betanaphthol Drugs 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
238000004159 blood analysis Methods 0.000 description 1
230000031709 bromination Effects 0.000 description 1
238000005893 bromination reaction Methods 0.000 description 1
125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
239000002775 capsule Substances 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
230000009134 cell regulation Effects 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
230000035605 chemotaxis Effects 0.000 description 1
238000005660 chlorination reaction Methods 0.000 description 1
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
ZCDOYSPFYFSLEW-UHFFFAOYSA-N chromate(2-) Chemical compound [O-][Cr]([O-])(=O)=O ZCDOYSPFYFSLEW-UHFFFAOYSA-N 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
208000037976 chronic inflammation Diseases 0.000 description 1
208000037893 chronic inflammatory disorder Diseases 0.000 description 1
229960001265 ciclosporin Drugs 0.000 description 1
229960002424 collagenase Drugs 0.000 description 1
229940126540 compound 41 Drugs 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
238000012790 confirmation Methods 0.000 description 1
208000010247 contact dermatitis Diseases 0.000 description 1
230000036461 convulsion Effects 0.000 description 1
238000010411 cooking Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 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
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
229930182912 cyclosporin Natural products 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
238000006193 diazotization reaction Methods 0.000 description 1
125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
229940088598 enzyme Drugs 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
PVBRSNZAOAJRKO-UHFFFAOYSA-N ethyl 2-sulfanylacetate Chemical compound CCOC(=O)CS PVBRSNZAOAJRKO-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
UAYKGOMDUQLCJS-UHFFFAOYSA-N ethylsulfanyl acetate Chemical compound CCSOC(C)=O UAYKGOMDUQLCJS-UHFFFAOYSA-N 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
208000030533 eye disease Diseases 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
238000009472 formulation Methods 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
108020001507 fusion proteins Proteins 0.000 description 1
102000037865 fusion proteins Human genes 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
239000011521 glass Substances 0.000 description 1
229940074045 glyceryl distearate Drugs 0.000 description 1
229940075507 glyceryl monostearate Drugs 0.000 description 1
239000008187 granular material Substances 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
210000003630 histaminocyte Anatomy 0.000 description 1
230000013632 homeostatic process Effects 0.000 description 1
229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
230000033444 hydroxylation Effects 0.000 description 1
238000005805 hydroxylation reaction Methods 0.000 description 1
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
230000007365 immunoregulation Effects 0.000 description 1
239000003547 immunosorbent Substances 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
230000006872 improvement Effects 0.000 description 1
230000006698 induction Effects 0.000 description 1
230000004968 inflammatory condition Effects 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
230000003993 interaction Effects 0.000 description 1
230000016507 interphase Effects 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
230000002427 irreversible effect Effects 0.000 description 1
239000002085 irritant Substances 0.000 description 1
231100000021 irritant Toxicity 0.000 description 1
238000002955 isolation Methods 0.000 description 1
239000008101 lactose Substances 0.000 description 1
ACKFDYCQCBEDNU-UHFFFAOYSA-J lead(2+);tetraacetate Chemical compound [Pb+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O ACKFDYCQCBEDNU-UHFFFAOYSA-J 0.000 description 1
VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
229960000681 leflunomide Drugs 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
239000006194 liquid suspension Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 1
206010025135 lupus erythematosus Diseases 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
229910052987 metal hydride Inorganic materials 0.000 description 1
150000004681 metal hydrides Chemical class 0.000 description 1
229960000485 methotrexate Drugs 0.000 description 1
229940102396 methyl bromide Drugs 0.000 description 1
229940050176 methyl chloride Drugs 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
238000002156 mixing Methods 0.000 description 1
210000005087 mononuclear cell Anatomy 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
201000006417 multiple sclerosis Diseases 0.000 description 1
SEXOVMIIVBKGGM-UHFFFAOYSA-N naphthalene-1-thiol Chemical compound C1=CC=C2C(S)=CC=CC2=C1 SEXOVMIIVBKGGM-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
210000000440 neutrophil Anatomy 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
125000002560 nitrile group Chemical group 0.000 description 1
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
125000005489 p-toluenesulfonic acid group Chemical class 0.000 description 1
231100000915 pathological change Toxicity 0.000 description 1
230000036285 pathological change Effects 0.000 description 1
230000009054 pathological process Effects 0.000 description 1
239000001814 pectin Substances 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
210000005259 peripheral blood Anatomy 0.000 description 1
239000011886 peripheral blood Substances 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
IMACFCSSMIZSPP-UHFFFAOYSA-N phenacyl chloride Chemical compound ClCC(=O)C1=CC=CC=C1 IMACFCSSMIZSPP-UHFFFAOYSA-N 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
239000000902 placebo Substances 0.000 description 1
229940068196 placebo Drugs 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000012545 processing Methods 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
150000003180 prostaglandins Chemical class 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
208000005069 pulmonary fibrosis Diseases 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
150000003242 quaternary ammonium salts Chemical class 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
230000005855 radiation Effects 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
230000036303 septic shock Effects 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000011863 silicon-based powder Substances 0.000 description 1
210000003491 skin Anatomy 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
229940087562 sodium acetate trihydrate Drugs 0.000 description 1
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
239000012265 solid product Substances 0.000 description 1
239000003549 soybean oil Substances 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
125000005017 substituted alkenyl group Chemical group 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000002600 sunflower oil Substances 0.000 description 1
230000002195 synergetic effect Effects 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
LXIKEPCNDFVJKC-QXMHVHEDSA-N tenidap Chemical compound C12=CC(Cl)=CC=C2N(C(=O)N)C(=O)\C1=C(/O)C1=CC=CS1 LXIKEPCNDFVJKC-QXMHVHEDSA-N 0.000 description 1
229960003676 tenidap Drugs 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
150000007970 thio esters Chemical class 0.000 description 1
229960000790 thymol Drugs 0.000 description 1
230000009466 transformation Effects 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 description 1
208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
230000009385 viral infection Effects 0.000 description 1
239000008096 xylene Substances 0.000 description 1
CZPRKINNVBONSF-UHFFFAOYSA-M zinc;dioxido(oxo)phosphanium Chemical compound [Zn+2].[O-][P+]([O-])=O CZPRKINNVBONSF-UHFFFAOYSA-M 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/78—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings
- C07D333/80—Seven-membered rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/78—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pulmonology (AREA)
Immunology (AREA)
Oncology (AREA)
Virology (AREA)
Communicable Diseases (AREA)
Rheumatology (AREA)
Pain & Pain Management (AREA)
Physical Education & Sports Medicine (AREA)
Dermatology (AREA)
AIDS & HIV (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Molecular Biology (AREA)
Tropical Medicine & Parasitology (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (AREA)
Cardiology (AREA)
Orthopedic Medicine & Surgery (AREA)
Biomedical Technology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

UA20041008543A 2002-04-10 2003-09-04 1- or 3-thiabenzonaphlhoazulene as inhibitors of tumour necrosis factor production and intermediates for synthesis thereof UA78297C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
HR20020303A HRP20020303A8 (en)	2002-04-10	2002-04-10	Benzonaphthoazulenes as inhibitors of tumour necrosis factor production and intermediates for the preparation thereof
PCT/HR2003/000014 WO2003084961A1 (en)	2002-04-10	2003-04-09	1- or 3-thia-benzonaphthoazulenes as inhibitors of tumour necrosis factor production and intermediates for the preparation thereof

Publications (1)

Publication Number	Publication Date
UA78297C2 true UA78297C2 (en)	2007-03-15

Family

ID=28686901

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA20041008543A UA78297C2 (en)	2002-04-10	2003-09-04	1- or 3-thiabenzonaphlhoazulene as inhibitors of tumour necrosis factor production and intermediates for synthesis thereof

Country Status (24)

Country	Link
US (2)	US20050137249A1 (no)
EP (1)	EP1492795B1 (no)
JP (1)	JP2005526827A (no)
KR (1)	KR20050014806A (no)
CN (1)	CN1649876A (no)
AT (1)	ATE310005T1 (no)
AU (1)	AU2003259958A1 (no)
BR (1)	BR0309097A (no)
CA (1)	CA2481850A1 (no)
DE (1)	DE60302344T2 (no)
ES (1)	ES2253694T3 (no)
HR (1)	HRP20020303A8 (no)
IL (1)	IL164395A0 (no)
IS (1)	IS7472A (no)
MX (1)	MXPA04009872A (no)
NO (1)	NO20044508L (no)
NZ (1)	NZ535622A (no)
PL (1)	PL374005A1 (no)
RU (1)	RU2318827C2 (no)
SI (1)	SI1492795T1 (no)
UA (1)	UA78297C2 (no)
WO (1)	WO2003084961A1 (no)
YU (1)	YU88104A (no)
ZA (1)	ZA200408059B (no)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
HRP20020304B1 (en) *	2002-04-10	2008-04-30	GlaxoSmithKline istra�iva�ki centar Zagreb d.o.o.	1-oxa-3-aza-dibenzoazulenes as inhibitors of tumor necrosis factor production and intermediates for the production thereof
HRP20030160A2 (en) *	2003-03-06	2005-04-30	Pliva-Istra�iva�ki institut d.o.o.	1-thiadibenzoazulene derivatives and biological action thereof
HRP20030955A2 (en) *	2003-11-21	2005-08-31	Pliva-Istra�iva�ki institut d.o.o.	USE OF 1-OXADIBENZO[e,h]AZULENES FOR THE MANUFACTURE OF PHARMACEUTICAL FORMULATIONS FOR THE TREATMENT AND PREVENTION OF CENTRAL NERVOUS SYSTEM DISEASES AND DISORDERS
HRP20030954A2 (en) *	2003-11-21	2005-08-31	Pliva D.D.	USE OF 1-AZA-DIBENZO[e,h]AZULENES FOR THE MANUFACTURENT AND PREVENTION OF CENTRAL NERVOUS SYSTEM DISEASES AND DISORDERS
HRP20040104A2 (en) *	2004-01-30	2005-10-31	Pliva-Istra�iva�ki institut d.o.o.	Use of benzonaphthoazulenes for the manufacture of pharmaceutical formulations for the treatment and prevention of central nervous system diseases and disorders
JP5606440B2 (ja) *	2009-07-28	2014-10-15	日本臓器製薬株式会社	チアベンゾアズレンプロピオン酸誘導体の製造法
CN109248310B (zh) *	2011-06-02	2022-07-01	加利福尼亚大学董事会	利用θ-防御素的炎性蛋白酶的阻断
CN104163811A (zh) *	2013-05-16	2014-11-26	重庆圣华曦药业股份有限公司	一种制备度洛西汀盐酸盐的新方法

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3711489A (en) *	1971-03-31	1973-01-16	Pfizer	Certain 8,9-dihydro(3,4,7,8)cycloocta(1,2-d)imidazoles
CA967573A (en)	1972-12-22	1975-05-13	Joseph G. Lombardino	Tetracyclic anti-inflammatory agents
US4198421A (en) *	1978-11-30	1980-04-15	E. I. Du Pont De Nemours And Company	Antiinflammatory 2-substituted-dibenzo[2,3:6,7]oxepino[4,5-d]imidazoles
HRP20000310A2 (en) *	2000-05-17	2002-02-28	Pliva Farmaceutska Ind Dioniko	New dibenzoazulene compounds as tumor necrosis factor inhibitors

2002
- 2002-04-10 HR HR20020303A patent/HRP20020303A8/xx not_active IP Right Cessation
2003
- 2003-04-09 CA CA002481850A patent/CA2481850A1/en not_active Abandoned
- 2003-04-09 YU YU88104A patent/YU88104A/sh unknown
- 2003-04-09 ES ES03745847T patent/ES2253694T3/es not_active Expired - Lifetime
- 2003-04-09 NZ NZ535622A patent/NZ535622A/xx unknown
- 2003-04-09 DE DE60302344T patent/DE60302344T2/de not_active Expired - Fee Related
- 2003-04-09 WO PCT/HR2003/000014 patent/WO2003084961A1/en active IP Right Grant
- 2003-04-09 US US10/510,867 patent/US20050137249A1/en not_active Abandoned
- 2003-04-09 EP EP03745847A patent/EP1492795B1/en not_active Expired - Lifetime
- 2003-04-09 RU RU2004132866/04A patent/RU2318827C2/ru not_active IP Right Cessation
- 2003-04-09 AU AU2003259958A patent/AU2003259958A1/en not_active Abandoned
- 2003-04-09 MX MXPA04009872A patent/MXPA04009872A/es active IP Right Grant
- 2003-04-09 SI SI200330152T patent/SI1492795T1/sl unknown
- 2003-04-09 KR KR10-2004-7016269A patent/KR20050014806A/ko not_active Application Discontinuation
- 2003-04-09 AT AT03745847T patent/ATE310005T1/de not_active IP Right Cessation
- 2003-04-09 CN CNA038099578A patent/CN1649876A/zh active Pending
- 2003-04-09 BR BR0309097-3A patent/BR0309097A/pt not_active IP Right Cessation
- 2003-04-09 JP JP2003582158A patent/JP2005526827A/ja active Pending
- 2003-04-09 PL PL03374005A patent/PL374005A1/xx not_active Application Discontinuation
- 2003-04-09 IL IL16439503A patent/IL164395A0/xx unknown
- 2003-09-04 UA UA20041008543A patent/UA78297C2/uk unknown
2004
- 2004-09-27 IS IS7472A patent/IS7472A/is unknown
- 2004-10-06 ZA ZA200408059A patent/ZA200408059B/en unknown
- 2004-10-12 US US10/963,979 patent/US7262309B2/en not_active Expired - Fee Related
- 2004-10-21 NO NO20044508A patent/NO20044508L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
MXPA04009872A (es)	2005-08-16
US20050137249A1 (en)	2005-06-23
NZ535622A (en)	2006-03-31
ZA200408059B (en)	2005-10-06
HRP20020303A2 (en)	2003-10-31
HRP20020303B8 (en)	2009-03-31
WO2003084961A1 (en)	2003-10-16
CA2481850A1 (en)	2003-10-16
HRP20020303A8 (en)	2009-03-31
JP2005526827A (ja)	2005-09-08
SI1492795T1 (sl)	2006-04-30
HRP20020303B1 (en)	2007-05-31
BR0309097A (pt)	2005-02-09
ATE310005T1 (de)	2005-12-15
RU2318827C2 (ru)	2008-03-10
IL164395A0 (en)	2005-12-18
EP1492795B1 (en)	2005-11-16
DE60302344D1 (de)	2005-12-22
NO20044508L (no)	2004-11-09
CN1649876A (zh)	2005-08-03
AU2003259958A1 (en)	2003-10-20
DE60302344T2 (de)	2006-07-27
US20050130964A1 (en)	2005-06-16
IS7472A (is)	2004-09-27
US7262309B2 (en)	2007-08-28
YU88104A (sh)	2006-08-17
EP1492795A1 (en)	2005-01-05
PL374005A1 (en)	2005-09-19
KR20050014806A (ko)	2005-02-07
RU2004132866A (ru)	2005-06-10
ES2253694T3 (es)	2006-06-01

Publication	Publication Date	Title
ZA200209180B (en)	2003-11-12	Thienodibenzoazulene compounds as tumor necrosis factor inhibitors.
AU2001256560A1 (en)	2002-02-14	Thienodibenzoazulene compounds as tumor necrosis factor inhibitors
UA78297C2 (en)	2007-03-15	1- or 3-thiabenzonaphlhoazulene as inhibitors of tumour necrosis factor production and intermediates for synthesis thereof
JP2005534637A (ja)	2005-11-17	腫瘍壊死因子産生の阻害剤として１−アザ−ジベンゾアズレン及びその製造用中間体
RU2334749C2 (ru)	2008-09-27	2-тиадибензоазулены в качестве ингибиторов продуцирования фактора некроза опухоли и промежуточные продукты для их получения
JP2005531586A (ja)	2005-10-20	腫瘍壊死因子産生の阻害剤としての１，３−ジアザ−ジベンゾアズレン類及びその製造用中間体
US20060069149A1 (en)	2006-03-30	Thiadibenzoazulene derivatives for the treatment of inflammatory diseases
JP2005532327A (ja)	2005-10-27	腫瘍壊死因子産生の阻害剤として１−オキサ−ジベンゾアズレン及びその製造用中間体
JP2005529157A (ja)	2005-09-29	腫瘍壊死因子産生の阻害剤としての１−チア−３−アザ−ジベンゾアズレン類及びその製造用中間体
RU2323222C2 (ru)	2008-04-27	1-окса-3-азадибензоазулены в качестве ингибиторов продуцирования фактора некроза опухоли и промежуточные продукты для их получения
KR20050016336A (ko)	2005-02-21	종양괴사인자 생성 억제제로서의 2-티아-디벤조아줄렌 및그의 제조를 위한 중간체
US20050131056A1 (en)	2005-06-16	2- thia-dibenzoazulenes as inhibitors of tumor necrosis factor production and intermediates for the preparation thereof
KR20050020774A (ko)	2005-03-04	종양괴사인자 생성의 억제제로서의1-옥사-3-아자-디벤조아줄렌 및 그의 제조를 위한 중간체