DD270909A5 - Verfahren zur herstellung von 2,1-benzothiazepin-2,2-dioxid-5-carbonsaeurederivaten - Google Patents

Verfahren zur herstellung von 2,1-benzothiazepin-2,2-dioxid-5-carbonsaeurederivaten Download PDF

Info

Publication number: DD270909A5
Authority: DD; German Democratic Republic
Prior art keywords: alkyl; phenyl; formula; halogen; compounds
Prior art date: 1987-01-12

Application number

DD88312142A

Other languages

German (de)

English (en)

Inventor

Jan W F Wasley

Original Assignee

��@��@��k��

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.)

1987-01-12

Filing date

1988-01-08

Publication date

1989-08-16

1988-01-08 Application filed by ��@��@��k�� filed Critical ��@��@��k��

1989-08-16 Publication of DD270909A5 publication Critical patent/DD270909A5/de

Links

238000000034 method Methods 0.000 title claims abstract description 54
238000002360 preparation method Methods 0.000 title claims abstract description 27
150000001875 compounds Chemical class 0.000 claims abstract description 120
239000003814 drug Substances 0.000 claims abstract description 5
150000002576 ketones Chemical class 0.000 claims abstract description 5
-1 heterocyclic aryl radical Chemical class 0.000 claims description 103
125000000217 alkyl group Chemical group 0.000 claims description 63
229910052736 halogen Inorganic materials 0.000 claims description 62
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 62
150000002367 halogens Chemical class 0.000 claims description 61
150000003839 salts Chemical class 0.000 claims description 50
239000001257 hydrogen Substances 0.000 claims description 46
229910052739 hydrogen Inorganic materials 0.000 claims description 46
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 45
150000002431 hydrogen Chemical class 0.000 claims description 37
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 37
150000003254 radicals Chemical class 0.000 claims description 32
125000003545 alkoxy group Chemical group 0.000 claims description 30
239000000243 solution Substances 0.000 claims description 29
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 27
229910052799 carbon Inorganic materials 0.000 claims description 26
239000002253 acid Substances 0.000 claims description 22
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 18
125000004414 alkyl thio group Chemical group 0.000 claims description 17
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 17
229910052757 nitrogen Inorganic materials 0.000 claims description 15
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 14
125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 12
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
125000004432 carbon atom Chemical group C* 0.000 claims description 11
239000001301 oxygen Chemical group 0.000 claims description 11
229910052760 oxygen Inorganic materials 0.000 claims description 11
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical class NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 10
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 10
125000005842 heteroatom Chemical group 0.000 claims description 10
125000000168 pyrrolyl group Chemical group 0.000 claims description 10
239000011593 sulfur Substances 0.000 claims description 10
229910052717 sulfur Inorganic materials 0.000 claims description 10
150000002081 enamines Chemical class 0.000 claims description 9
125000005843 halogen group Chemical group 0.000 claims description 9
125000001041 indolyl group Chemical group 0.000 claims description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
125000004076 pyridyl group Chemical group 0.000 claims description 8
125000000335 thiazolyl group Chemical group 0.000 claims description 8
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
150000001412 amines Chemical class 0.000 claims description 7
150000002148 esters Chemical class 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
NALBLJLOBICXRH-UHFFFAOYSA-N dinitrogen monohydride Chemical compound N=[N] NALBLJLOBICXRH-UHFFFAOYSA-N 0.000 claims description 6
125000003373 pyrazinyl group Chemical group 0.000 claims description 6
125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 5
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
239000012876 carrier material Substances 0.000 claims description 5
125000002541 furyl group Chemical group 0.000 claims description 5
125000000623 heterocyclic group Chemical group 0.000 claims description 5
125000002883 imidazolyl group Chemical group 0.000 claims description 5
125000005956 isoquinolyl group Chemical group 0.000 claims description 5
238000004519 manufacturing process Methods 0.000 claims description 5
125000002971 oxazolyl group Chemical group 0.000 claims description 5
125000005493 quinolyl group Chemical group 0.000 claims description 5
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
230000003110 anti-inflammatory effect Effects 0.000 claims description 4
125000002619 bicyclic group Chemical group 0.000 claims description 4
239000002775 capsule Substances 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
125000003282 alkyl amino group Chemical group 0.000 claims description 3
125000005530 alkylenedioxy group Chemical group 0.000 claims description 3
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
239000011230 binding agent Substances 0.000 claims description 3
125000002837 carbocyclic group Chemical group 0.000 claims description 3
239000000796 flavoring agent Substances 0.000 claims description 3
235000013355 food flavoring agent Nutrition 0.000 claims description 3
238000002347 injection Methods 0.000 claims description 3
239000007924 injection Substances 0.000 claims description 3
125000000842 isoxazolyl group Chemical group 0.000 claims description 3
239000000314 lubricant Substances 0.000 claims description 3
125000001424 substituent group Chemical group 0.000 claims description 3
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 3
239000000829 suppository Substances 0.000 claims description 3
125000001544 thienyl group Chemical group 0.000 claims description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
150000001408 amides Chemical class 0.000 claims description 2
150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
239000011737 fluorine Substances 0.000 claims description 2
229910052731 fluorine Inorganic materials 0.000 claims description 2
239000006187 pill Substances 0.000 claims 2
239000003826 tablet Substances 0.000 claims 2
125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims 1
125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims 1
241001120493 Arene Species 0.000 claims 1
ZBEIGTVYIHPXMK-UHFFFAOYSA-N COClSC Chemical compound COClSC ZBEIGTVYIHPXMK-UHFFFAOYSA-N 0.000 claims 1
150000003973 alkyl amines Chemical class 0.000 claims 1
125000003710 aryl alkyl group Chemical group 0.000 claims 1
238000011282 treatment Methods 0.000 abstract description 17
206010039073 rheumatoid arthritis Diseases 0.000 abstract description 7
229940124597 therapeutic agent Drugs 0.000 abstract description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
239000000203 mixture Substances 0.000 description 35
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
241000124008 Mammalia Species 0.000 description 17
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
239000002585 base Substances 0.000 description 15
239000007858 starting material Substances 0.000 description 15
239000002904 solvent Substances 0.000 description 14
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
230000005764 inhibitory process Effects 0.000 description 11
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
210000000845 cartilage Anatomy 0.000 description 10
210000000440 neutrophil Anatomy 0.000 description 10
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 9
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
125000005907 alkyl ester group Chemical group 0.000 description 8
230000015556 catabolic process Effects 0.000 description 8
238000006731 degradation reaction Methods 0.000 description 8
125000004494 ethyl ester group Chemical group 0.000 description 8
238000010992 reflux Methods 0.000 description 8
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
230000004913 activation Effects 0.000 description 7
238000000338 in vitro Methods 0.000 description 7
239000000543 intermediate Substances 0.000 description 7
238000012360 testing method Methods 0.000 description 7
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
238000009833 condensation Methods 0.000 description 6
230000005494 condensation Effects 0.000 description 6
239000000825 pharmaceutical preparation Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
241000700159 Rattus Species 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
201000010099 disease Diseases 0.000 description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
239000005457 ice water Substances 0.000 description 5
239000003112 inhibitor Substances 0.000 description 5
239000012299 nitrogen atmosphere Substances 0.000 description 5
201000008482 osteoarthritis Diseases 0.000 description 5
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 5
239000002798 polar solvent Substances 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
239000000126 substance Substances 0.000 description 5
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
KGIJOOYOSFUGPC-CABOLEKPSA-N 5-HETE Natural products CCCCC\C=C/C\C=C/C\C=C/C=C/[C@H](O)CCCC(O)=O KGIJOOYOSFUGPC-CABOLEKPSA-N 0.000 description 4
KGIJOOYOSFUGPC-MSFIICATSA-N 5-Hydroxyeicosatetraenoic acid Chemical compound CCCCCC=CCC=CCC=C\C=C\[C@@H](O)CCCC(O)=O KGIJOOYOSFUGPC-MSFIICATSA-N 0.000 description 4
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
108010008211 N-Formylmethionine Leucyl-Phenylalanine Proteins 0.000 description 4
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
239000013543 active substance Substances 0.000 description 4
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 4
230000003399 chemotactic effect Effects 0.000 description 4
PRQROPMIIGLWRP-BZSNNMDCSA-N chemotactic peptide Chemical compound CSCC[C@H](NC=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 PRQROPMIIGLWRP-BZSNNMDCSA-N 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
239000012065 filter cake Substances 0.000 description 4
210000003714 granulocyte Anatomy 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
239000012312 sodium hydride Substances 0.000 description 4
229910000104 sodium hydride Inorganic materials 0.000 description 4
235000019698 starch Nutrition 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
241000283690 Bos taurus Species 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
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 3
102000003820 Lipoxygenases Human genes 0.000 description 3
108090000128 Lipoxygenases Proteins 0.000 description 3
206010030113 Oedema Diseases 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
125000001931 aliphatic group Chemical group 0.000 description 3
150000008064 anhydrides Chemical class 0.000 description 3
210000004369 blood Anatomy 0.000 description 3
239000008280 blood Substances 0.000 description 3
239000012267 brine Substances 0.000 description 3
230000008355 cartilage degradation Effects 0.000 description 3
238000006243 chemical reaction Methods 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
238000001816 cooling Methods 0.000 description 3
239000003937 drug carrier Substances 0.000 description 3
ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 3
239000000284 extract Substances 0.000 description 3
150000004820 halides Chemical class 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
239000012948 isocyanate Substances 0.000 description 3
150000002513 isocyanates Chemical class 0.000 description 3
239000008101 lactose Substances 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
210000002184 nasal cartilage Anatomy 0.000 description 3
230000003448 neutrophilic effect Effects 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
239000000047 product Substances 0.000 description 3
238000000746 purification Methods 0.000 description 3
159000000000 sodium salts Chemical class 0.000 description 3
239000007787 solid Substances 0.000 description 3
239000008107 starch Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
241000282412 Homo Species 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
238000009825 accumulation Methods 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
125000002015 acyclic group Chemical group 0.000 description 2
230000001476 alcoholic effect Effects 0.000 description 2
150000001299 aldehydes Chemical class 0.000 description 2
239000011260 aqueous acid Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
230000002917 arthritic effect Effects 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
208000006673 asthma Diseases 0.000 description 2
230000027455 binding Effects 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
239000000872 buffer Substances 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
235000010418 carrageenan Nutrition 0.000 description 2
229920001525 carrageenan Polymers 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
238000000354 decomposition reaction Methods 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
238000001035 drying Methods 0.000 description 2
DWCZKKQRUBQFIB-UHFFFAOYSA-N ethyl 2-chlorosulfonylacetate Chemical compound CCOC(=O)CS(Cl)(=O)=O DWCZKKQRUBQFIB-UHFFFAOYSA-N 0.000 description 2
125000006125 ethylsulfonyl group Chemical group 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
238000001914 filtration Methods 0.000 description 2
235000019256 formaldehyde Nutrition 0.000 description 2
229960004279 formaldehyde Drugs 0.000 description 2
125000000524 functional group Chemical group 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
238000011534 incubation Methods 0.000 description 2
208000027866 inflammatory disease Diseases 0.000 description 2
230000002757 inflammatory effect Effects 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
239000010410 layer Substances 0.000 description 2
150000002617 leukotrienes Chemical class 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
229910052749 magnesium Inorganic materials 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
BWQBYHGDMBHIIQ-UHFFFAOYSA-N methyl 2-(2-aminophenyl)acetate Chemical compound COC(=O)CC1=CC=CC=C1N BWQBYHGDMBHIIQ-UHFFFAOYSA-N 0.000 description 2
SWMFAAPTSMVULA-UHFFFAOYSA-N methyl 2-(2-nitrophenyl)acetate Chemical compound COC(=O)CC1=CC=CC=C1[N+]([O-])=O SWMFAAPTSMVULA-UHFFFAOYSA-N 0.000 description 2
GGXQFGLHGRJPJI-UHFFFAOYSA-N methyl 2-[2-(methanesulfonamido)phenyl]acetate Chemical compound COC(=O)CC1=CC=CC=C1NS(C)(=O)=O GGXQFGLHGRJPJI-UHFFFAOYSA-N 0.000 description 2
NYVQAXDZWUCOSA-UHFFFAOYSA-N methyl 2-[2-[(4-chlorophenyl)methylamino]phenyl]acetate Chemical compound COC(=O)CC1=CC=CC=C1NCC1=CC=C(Cl)C=C1 NYVQAXDZWUCOSA-UHFFFAOYSA-N 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
230000004048 modification Effects 0.000 description 2
238000012986 modification Methods 0.000 description 2
125000000896 monocarboxylic acid group Chemical group 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
239000008194 pharmaceutical composition Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
229960003424 phenylacetic acid Drugs 0.000 description 2
239000003279 phenylacetic acid Substances 0.000 description 2
238000007363 ring formation reaction Methods 0.000 description 2
150000003335 secondary amines Chemical class 0.000 description 2
238000000926 separation method Methods 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
239000012258 stirred mixture Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
239000012485 toluene extract Substances 0.000 description 2
SOGMTIUFXBAUON-UHFFFAOYSA-N 1-[(4-bromophenyl)methyl]-n-(4-chlorophenyl)-4-hydroxy-2,2-dioxo-3h-2$l^{6},1-benzothiazepine-5-carboxamide Chemical compound C12=CC=CC=C2N(CC=2C=CC(Br)=CC=2)S(=O)(=O)CC(O)=C1C(=O)NC1=CC=C(Cl)C=C1 SOGMTIUFXBAUON-UHFFFAOYSA-N 0.000 description 1
WNVYDHWOZGJRCU-UHFFFAOYSA-N 1-[(4-chlorophenyl)methyl]-2,2-dioxo-5h-2$l^{6},1-benzothiazepin-4-one Chemical compound C1=CC(Cl)=CC=C1CN1S(=O)(=O)CC(=O)CC2=CC=CC=C21 WNVYDHWOZGJRCU-UHFFFAOYSA-N 0.000 description 1
JQZAEUFPPSRDOP-UHFFFAOYSA-N 1-chloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C=C1 JQZAEUFPPSRDOP-UHFFFAOYSA-N 0.000 description 1
ADAKRBAJFHTIEW-UHFFFAOYSA-N 1-chloro-4-isocyanatobenzene Chemical compound ClC1=CC=C(N=C=O)C=C1 ADAKRBAJFHTIEW-UHFFFAOYSA-N 0.000 description 1
WLXGQMVCYPUOLM-UHFFFAOYSA-N 1-hydroxyethanesulfonic acid Chemical compound CC(O)S(O)(=O)=O WLXGQMVCYPUOLM-UHFFFAOYSA-N 0.000 description 1
SRXFXCKTIGELTI-UHFFFAOYSA-N 2-(4-chlorophenyl)ethanamine Chemical compound NCCC1=CC=C(Cl)C=C1 SRXFXCKTIGELTI-UHFFFAOYSA-N 0.000 description 1
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 1
125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 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
PXACTUVBBMDKRW-UHFFFAOYSA-N 4-bromobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-N 0.000 description 1
QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 description 1
AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
ZGKWHQNXVWODHO-UHFFFAOYSA-N 4-hydroxy-1-methyl-2,2-dioxo-n-(1,3-thiazol-2-yl)-3h-2$l^{6},1-benzothiazepine-5-carboxamide Chemical compound OC=1CS(=O)(=O)N(C)C2=CC=CC=C2C=1C(=O)NC1=NC=CS1 ZGKWHQNXVWODHO-UHFFFAOYSA-N 0.000 description 1
125000005274 4-hydroxybenzoic acid group Chemical group 0.000 description 1
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
HIYAVKIYRIFSCZ-CYEMHPAKSA-N 5-(methylamino)-2-[[(2S,3R,5R,6S,8R,9R)-3,5,9-trimethyl-2-[(2S)-1-oxo-1-(1H-pyrrol-2-yl)propan-2-yl]-1,7-dioxaspiro[5.5]undecan-8-yl]methyl]-1,3-benzoxazole-4-carboxylic acid Chemical compound O=C([C@@H](C)[C@H]1O[C@@]2([C@@H](C[C@H]1C)C)O[C@@H]([C@@H](CC2)C)CC=1OC2=CC=C(C(=C2N=1)C(O)=O)NC)C1=CC=CN1 HIYAVKIYRIFSCZ-CYEMHPAKSA-N 0.000 description 1
KWWZIJCMGKNMMG-UHFFFAOYSA-N 5-chloro-2-[[1-[(4-chlorophenyl)methyl]-4-hydroxy-2,2-dioxo-3h-2$l^{6},1-benzothiazepine-5-carbonyl]amino]benzoic acid Chemical compound OC(=O)C1=CC(Cl)=CC=C1NC(=O)C(C1=CC=CC=C11)=C(O)CS(=O)(=O)N1CC1=CC=C(Cl)C=C1 KWWZIJCMGKNMMG-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
206010027654 Allergic conditions Diseases 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
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
241000700198 Cavia Species 0.000 description 1
241000700199 Cavia porcellus Species 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
208000009386 Experimental Arthritis Diseases 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
239000001828 Gelatine Substances 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
239000004471 Glycine Substances 0.000 description 1
229920002683 Glycosaminoglycan Polymers 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
102000003777 Interleukin-1 beta Human genes 0.000 description 1
108090000193 Interleukin-1 beta Proteins 0.000 description 1
239000000867 Lipoxygenase Inhibitor Substances 0.000 description 1
102000055008 Matrilin Proteins Human genes 0.000 description 1
108010072582 Matrilin Proteins Proteins 0.000 description 1
CRZQGDNQQAALAY-UHFFFAOYSA-N Methyl benzeneacetate Chemical compound COC(=O)CC1=CC=CC=C1 CRZQGDNQQAALAY-UHFFFAOYSA-N 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 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
241000283973 Oryctolagus cuniculus Species 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
RWRDLPDLKQPQOW-UHFFFAOYSA-O Pyrrolidinium ion Chemical compound C1CC[NH2+]C1 RWRDLPDLKQPQOW-UHFFFAOYSA-O 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
229930006000 Sucrose Natural products 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
235000009470 Theobroma cacao Nutrition 0.000 description 1
241000906446 Theraps Species 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
239000002250 absorbent Substances 0.000 description 1
230000002745 absorbent Effects 0.000 description 1
229960000583 acetic acid Drugs 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
150000003998 acyclic ketones Chemical class 0.000 description 1
239000012790 adhesive layer Substances 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
125000005263 alkylenediamine group Chemical group 0.000 description 1
201000009961 allergic asthma Diseases 0.000 description 1
230000007815 allergy Effects 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
238000010640 amide synthesis reaction Methods 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
229940121363 anti-inflammatory agent Drugs 0.000 description 1
239000002260 anti-inflammatory agent Substances 0.000 description 1
229940124599 anti-inflammatory drug Drugs 0.000 description 1
229940124346 antiarthritic agent Drugs 0.000 description 1
239000003435 antirheumatic agent Substances 0.000 description 1
229940114079 arachidonic acid Drugs 0.000 description 1
150000005840 aryl radicals Chemical class 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
238000010533 azeotropic distillation Methods 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
150000007514 bases Chemical class 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
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-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
SUMDYPCJJOFFON-UHFFFAOYSA-N beta-hydroxyethanesulfonic acid Natural products OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
239000012455 biphasic mixture Substances 0.000 description 1
230000037396 body weight Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
238000005282 brightening Methods 0.000 description 1
150000001649 bromium compounds Chemical class 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
244000240602 cacao Species 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
125000001589 carboacyl group Chemical group 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
239000000679 carrageenan Substances 0.000 description 1
229940113118 carrageenan Drugs 0.000 description 1
239000000969 carrier Substances 0.000 description 1
210000004027 cell Anatomy 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
CELCMWUXMBTJRP-UHFFFAOYSA-N chlorobenzene;hydrochloride Chemical compound Cl.ClC1=CC=CC=C1 CELCMWUXMBTJRP-UHFFFAOYSA-N 0.000 description 1
238000007813 chromatographic assay Methods 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
238000003501 co-culture Methods 0.000 description 1
238000000576 coating method Methods 0.000 description 1
239000003086 colorant Substances 0.000 description 1
239000010949 copper Substances 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
150000001879 copper Chemical class 0.000 description 1
239000012043 crude product Substances 0.000 description 1
OAOPDYUHWPBJCW-UHFFFAOYSA-N cyanoboron;sodium Chemical compound [Na].[B]C#N OAOPDYUHWPBJCW-UHFFFAOYSA-N 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
ZWWWLCMDTZFSOO-UHFFFAOYSA-N diethoxyphosphorylformonitrile Chemical compound CCOP(=O)(C#N)OCC ZWWWLCMDTZFSOO-UHFFFAOYSA-N 0.000 description 1
230000002500 effect on skin Effects 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
150000002085 enols Chemical class 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
210000003743 erythrocyte Anatomy 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000012530 fluid Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
239000006260 foam Substances 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
238000009472 formulation Methods 0.000 description 1
238000004508 fractional distillation Methods 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
210000000224 granular leucocyte Anatomy 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
229940071870 hydroiodic acid Drugs 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
125000005113 hydroxyalkoxy group Chemical group 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
230000004968 inflammatory condition Effects 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
230000004941 influx Effects 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
239000011630 iodine Substances 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
239000000644 isotonic solution Substances 0.000 description 1
230000002045 lasting effect Effects 0.000 description 1
239000010985 leather Substances 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
159000000003 magnesium salts Chemical class 0.000 description 1
239000000463 material Substances 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 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
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
AEPIHYWYPKENIN-UHFFFAOYSA-N methyl 2-[2-[(4-chlorophenyl)methyl-(2-ethoxy-2-oxoethyl)sulfonylamino]phenyl]acetate Chemical compound C=1C=CC=C(CC(=O)OC)C=1N(S(=O)(=O)CC(=O)OCC)CC1=CC=C(Cl)C=C1 AEPIHYWYPKENIN-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
210000005087 mononuclear cell Anatomy 0.000 description 1
208000031225 myocardial ischemia Diseases 0.000 description 1
FEBGCUIOXLPWOJ-UHFFFAOYSA-N n-(4-chlorophenyl)-1-[(4-chlorophenyl)methyl]-4-hydroxy-3-methyl-2,2-dioxo-3h-2$l^{6},1-benzothiazepine-5-carboxamide Chemical compound C12=CC=CC=C2N(CC=2C=CC(Cl)=CC=2)S(=O)(=O)C(C)C(O)=C1C(=O)NC1=CC=C(Cl)C=C1 FEBGCUIOXLPWOJ-UHFFFAOYSA-N 0.000 description 1
BTIDJFFESQUSBK-UHFFFAOYSA-N n-(4-chlorophenyl)-4-hydroxy-2,2-dioxo-1-(2-phenylethyl)-3h-2$l^{6},1-benzothiazepine-5-carboxamide Chemical compound C12=CC=CC=C2N(CCC=2C=CC=CC=2)S(=O)(=O)CC(O)=C1C(=O)NC1=CC=C(Cl)C=C1 BTIDJFFESQUSBK-UHFFFAOYSA-N 0.000 description 1
PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
230000010807 negative regulation of binding Effects 0.000 description 1
230000003472 neutralizing effect Effects 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
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
230000003287 optical effect Effects 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000006072 paste Substances 0.000 description 1
229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000005544 phthalimido group Chemical group 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
239000011505 plaster Substances 0.000 description 1
210000003281 pleural cavity Anatomy 0.000 description 1
208000008423 pleurisy Diseases 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920002635 polyurethane Polymers 0.000 description 1
239000004814 polyurethane Substances 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000011241 protective layer Substances 0.000 description 1
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000011552 rat model Methods 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
239000002002 slurry Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
241000894007 species Species 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical class O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
210000001258 synovial membrane Anatomy 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
230000002861 ventricular Effects 0.000 description 1
230000007279 water homeostasis Effects 0.000 description 1
238000009736 wetting Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
235000014101 wine Nutrition 0.000 description 1
210000002268 wool Anatomy 0.000 description 1
239000008096 xylene Substances 0.000 description 1
150000003751 zinc Chemical class 0.000 description 1
UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical class [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- 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
- 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
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D281/02—Seven-membered rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pulmonology (AREA)
Immunology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

DD88312142A 1987-01-12 1988-01-08 Verfahren zur herstellung von 2,1-benzothiazepin-2,2-dioxid-5-carbonsaeurederivaten DD270909A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US07/002,074 US4803197A (en)	1987-01-12	1987-01-12	2,1-benzothiazepine-2,2-dioxide-5-carboxylic acid derivatives

Publications (1)

Publication Number	Publication Date
DD270909A5 true DD270909A5 (de)	1989-08-16

Family

ID=21699148

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD88312142A DD270909A5 (de)	1987-01-12	1988-01-08	Verfahren zur herstellung von 2,1-benzothiazepin-2,2-dioxid-5-carbonsaeurederivaten

Country Status (15)

Country	Link
US (1)	US4803197A (da)
EP (1)	EP0276194A1 (da)
JP (1)	JPS63174980A (da)
KR (1)	KR880009002A (da)
AU (1)	AU1016288A (da)
DD (1)	DD270909A5 (da)
DK (1)	DK9588A (da)
FI (1)	FI880081A7 (da)
HU (1)	HU198917B (da)
IL (1)	IL85037A0 (da)
NO (1)	NO880088L (da)
NZ (1)	NZ223138A (da)
PH (1)	PH23637A (da)
PT (1)	PT86519B (da)
ZA (1)	ZA88145B (da)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ES2046941B1 (es) *	1991-10-24	1994-08-16	Consejo Superior Investigacion	Procedimiento de obtencion de trioxo-pirazolo, (2,1) benzotiazepinas>
ES2040629B1 (es) *	1991-12-18	1994-06-16	Consejo Superior Investigacion	Procedimiento de obtencion de derivados triciclicos de la benzotiazepina farmacologicamente activos.
UA59384C2 (uk) *	1996-12-20	2003-09-15	Пфайзер, Інк.	Похідні сульфонамідів та амідів як агоністи простагландину, фармацевтична композиція та способи лікування на їх основі

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3962261A (en) *	1974-02-04	1976-06-08	Warner-Lambert Company	2,3,4,5-tetra hydro-5-oxo-1-benzothiepi n-4-carboxamide 1,1-dioxides
SE420725B (sv) *	1974-09-26	1981-10-26	Ciba Geigy Ag	Sett att framstella 2,3-dihydro-1-benstiepin-4-karboxylsyraamider
DE2756113A1 (de) *	1977-12-16	1979-06-21	Thomae Gmbh Dr K	Neue 4-hydroxy-2h-1,2-benzothiazin- 3-carboxamid-1,1-dioxide, verfahren zu ihrer herstellung und diese enthaltende arzneimittel
US4605665A (en) *	1985-02-28	1986-08-12	Ciba-Geigy Corporation	Systemic treatment of splanchnic ischemia shock using 7-chloro-N-(3,4-dichlorophenyl)-2,3-dihydro-5-hydroxy-1-benzothiepin-4-carboxamide 1,1-dioxide and pharmaceutically acceptable salts thereof
US4582850A (en) *	1985-02-28	1986-04-15	Ciba-Geigy Corporation	Topical and systemic treatment of psoriasis using 7-chloro-N-(3,4-dichlorophenyl)-2,3-dihydro-5-hydroxy-1-benzothiepin-4-carboxamide 1,1-dioxide and pharmaceutically acceptable salts thereof

1987
- 1987-01-12 US US07/002,074 patent/US4803197A/en not_active Expired - Fee Related
1988
- 1988-01-06 IL IL85037A patent/IL85037A0/xx unknown
- 1988-01-06 PH PH36325A patent/PH23637A/en unknown
- 1988-01-06 EP EP88810004A patent/EP0276194A1/de not_active Withdrawn
- 1988-01-08 NZ NZ223138A patent/NZ223138A/xx unknown
- 1988-01-08 FI FI880081A patent/FI880081A7/fi not_active IP Right Cessation
- 1988-01-08 DD DD88312142A patent/DD270909A5/de unknown
- 1988-01-11 JP JP63002643A patent/JPS63174980A/ja active Pending
- 1988-01-11 NO NO880088A patent/NO880088L/no unknown
- 1988-01-11 AU AU10162/88A patent/AU1016288A/en not_active Abandoned
- 1988-01-11 PT PT86519A patent/PT86519B/pt not_active IP Right Cessation
- 1988-01-11 DK DK009588A patent/DK9588A/da not_active Application Discontinuation
- 1988-01-11 ZA ZA880145A patent/ZA88145B/xx unknown
- 1988-01-11 HU HU8891A patent/HU198917B/hu not_active IP Right Cessation
- 1988-01-12 KR KR1019880000148A patent/KR880009002A/ko not_active Withdrawn

Also Published As

Publication number	Publication date
HU198917B (en)	1989-12-28
AU1016288A (en)	1988-07-14
NO880088L (no)	1988-07-13
EP0276194A1 (de)	1988-07-27
HUT47262A (en)	1989-02-28
DK9588A (da)	1988-07-13
DK9588D0 (da)	1988-01-11
NO880088D0 (no)	1988-01-11
NZ223138A (en)	1990-02-26
FI880081A7 (fi)	1988-07-13
JPS63174980A (ja)	1988-07-19
PT86519B (pt)	1991-12-31
IL85037A0 (en)	1988-06-30
FI880081A0 (fi)	1988-01-08
PT86519A (en)	1988-02-01
ZA88145B (en)	1988-07-12
KR880009002A (ko)	1988-09-13
US4803197A (en)	1989-02-07
PH23637A (en)	1989-09-27

Publication	Publication Date	Title
DE69805769T2 (de)	2003-03-06	Entzündungshemmende verbindungen
DE69222352T2 (de)	1998-04-09	N-(Aminoalkyl)piperidin-Verbindungen und ihre Enantiomere als Neurokinine-Receptoren Antagonisten, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zusammensetzungen
DE69130597T2 (de)	1999-05-20	Arylalkylamine, Verfahren zur Herstellung und diese enthaltende Arzneimittel
DE69905738T2 (de)	2004-03-18	Amidinderivate, ihre herstellung, ihre verwendung in medikamenten und sie enthaltende pharmazeutische zubereitungen
DE2705446C2 (da)	1989-10-12
DE60015296T2 (de)	2006-02-02	Indolderivate und ihre verwendung als mcp-1 rezeptor antagonisten
DE69118388T2 (de)	1996-11-14	Substituierte bizyklische arylderivate mit selektiver leukotrien b4 antagonistischer wirkung
DE19955794A1 (de)	2000-05-31	Pyrrolidin-Derivate-CCR-3-Rezeptor-Antagonisten
WO1995013266A1 (de)	1995-05-18	Acylpyrrolalkansäuren und indol-2-alkansäuren sowie ihre derivate als hemmstoffe der phospholipase a¿2?
DE602005005456T2 (de)	2009-04-09	Neue azabicyclische derivate, herstellungsverfahren dafür und sie enthaltende pharmazeutische zusammensetzungen
DE69730837T2 (de)	2005-09-29	Indolderivate zur behandlung von osteoporose
EP0287890A1 (de)	1988-10-26	Substituierte Pyrrole
EP1268422A1 (de)	2003-01-02	Indole zur behandlung von krankheiten die mit schilddrüsenhormonen behandeln werden können
DE2329430A1 (de)	1974-01-03	1-acyl-3-(amino-niedrig-alkyl)-indole
DE3739882A1 (de)	1989-06-08	Substituierte hydroxylamine
DE69408674T2 (de)	1998-09-10	Phenylpyrrol-derivate und ihre verwendung als dopamin d3 antagonisten
DD291551A5 (de)	1991-07-04	Verfahren zur herstellung von substituierten hydroxamsaeurederivaten
EP0200947B1 (de)	1990-09-12	1,3-Disubstituierte Imidazoliumsalze
EP0298921B1 (de)	1992-12-23	1,2-Benzisoxazole und 1,2-Benzisothiazole
EP0171645A1 (de)	1986-02-19	Neue 2H-1-Benzopyran-2-on-Derivate, Verfahren zu ihrer Herstellung und Arzneimittel, die diese Verbindungen enthalten
DE69110217T2 (de)	1996-02-29	Derivate der Kaffeinsäure und sie enthaltende pharmazeutische Zusammensetzungen.
EP0389425B1 (de)	1995-04-26	Neue Benzothiopyranylamine
DE69501791T2 (de)	1998-07-02	Indol-derivate als 5-ht1-like agonisten
EP0072961B1 (de)	1985-07-10	1-Phenylindazol-3-on-Verbindungen sowie Verfahren und Zwischenprodukte zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
DD270909A5 (de)	1989-08-16	Verfahren zur herstellung von 2,1-benzothiazepin-2,2-dioxid-5-carbonsaeurederivaten