DE19613976C1 - Thalidomid-Prodrugs mit immunmodulatorischer Wirkung - Google Patents
Thalidomid-Prodrugs mit immunmodulatorischer WirkungInfo
- Publication number
- DE19613976C1 DE19613976C1 DE19613976A DE19613976A DE19613976C1 DE 19613976 C1 DE19613976 C1 DE 19613976C1 DE 19613976 A DE19613976 A DE 19613976A DE 19613976 A DE19613976 A DE 19613976A DE 19613976 C1 DE19613976 C1 DE 19613976C1
- Authority
- DE
- Germany
- Prior art keywords
- thalidomide
- prodrugs
- amino
- acid
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 title claims abstract description 36
- 229960003433 thalidomide Drugs 0.000 title claims abstract description 33
- 229940002612 prodrug Drugs 0.000 title claims abstract description 24
- 239000000651 prodrug Substances 0.000 title claims abstract description 24
- 230000002519 immonomodulatory effect Effects 0.000 title description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 15
- 125000006239 protecting group Chemical group 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 8
- -1 R<2> is H Chemical group 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- 239000002253 acid Substances 0.000 claims abstract description 5
- 230000008569 process Effects 0.000 claims abstract description 5
- 150000007513 acids Chemical class 0.000 claims abstract description 4
- 150000003839 salts Chemical class 0.000 claims abstract description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 4
- 150000001413 amino acids Chemical class 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 150000008065 acid anhydrides Chemical class 0.000 claims description 3
- 150000001718 carbodiimides Chemical class 0.000 claims description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical class C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 2
- 238000003776 cleavage reaction Methods 0.000 claims description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 2
- 230000007017 scission Effects 0.000 claims description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 239000008186 active pharmaceutical agent Substances 0.000 abstract description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
- 229940088679 drug related substance Drugs 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 25
- 150000001875 compounds Chemical class 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 102000000588 Interleukin-2 Human genes 0.000 description 10
- 108010002350 Interleukin-2 Proteins 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 210000001744 T-lymphocyte Anatomy 0.000 description 9
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 9
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 9
- LZHQPJSJEITGHB-UHFFFAOYSA-N 2-[1-(hydroxymethyl)-2,6-dioxopiperidin-3-yl]isoindole-1,3-dione Chemical compound O=C1N(CO)C(=O)CCC1N1C(=O)C2=CC=CC=C2C1=O LZHQPJSJEITGHB-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 7
- RGUKYNXWOWSRET-UHFFFAOYSA-N 4-pyrrolidin-1-ylpyridine Chemical compound C1CCCN1C1=CC=NC=C1 RGUKYNXWOWSRET-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000013459 approach Methods 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 208000002399 aphthous stomatitis Diseases 0.000 description 5
- 239000002158 endotoxin Substances 0.000 description 5
- 229920006008 lipopolysaccharide Polymers 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 210000001616 monocyte Anatomy 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- FTLCOOXASLJZOG-UHFFFAOYSA-N 2-[3-(1,3-dioxoisoindol-2-yl)-2,6-dioxopiperidin-1-yl]-3-methoxy-2-methyl-3-oxopropanoic acid Chemical compound O=C1N(C(C)(C(=O)OC)C(O)=O)C(=O)CCC1N1C(=O)C2=CC=CC=C2C1=O FTLCOOXASLJZOG-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 206010052779 Transplant rejections Diseases 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 235000011054 acetic acid Nutrition 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000006143 cell culture medium Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 229960000443 hydrochloric acid Drugs 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 229940126701 oral medication Drugs 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid group Chemical group C(CCC(=O)O)(=O)O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 3
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 206010062016 Immunosuppression Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000003608 fece Anatomy 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 239000010871 livestock manure Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 229940086542 triethylamine Drugs 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- SZXBQTSZISFIAO-ZETCQYMHSA-N (2s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)OC(C)(C)C SZXBQTSZISFIAO-ZETCQYMHSA-N 0.000 description 1
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
- VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 1
- IMFASZSXAQHCHV-UHFFFAOYSA-N 2-[1-(morpholin-4-ylmethyl)-2,6-dioxopiperidin-3-yl]isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C(C1=O)CCC(=O)N1CN1CCOCC1 IMFASZSXAQHCHV-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 206010001488 Aggression Diseases 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 241000973621 Concinnum ten Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 101000867232 Escherichia coli Heat-stable enterotoxin II Proteins 0.000 description 1
- 206010017711 Gangrene Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 101000686985 Mouse mammary tumor virus (strain C3H) Protein PR73 Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010030201 Oesophageal ulcer Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- BYPFEZZEUUWMEJ-UHFFFAOYSA-N Pentoxifylline Chemical compound O=C1N(CCCCC(=O)C)C(=O)N(C)C2=C1N(C)C=N2 BYPFEZZEUUWMEJ-UHFFFAOYSA-N 0.000 description 1
- 208000006311 Pyoderma Diseases 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 238000011579 SCID mouse model Methods 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 206010070517 Type 2 lepra reaction Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- SYOIWFNFUFXXMV-UHFFFAOYSA-N [Br].Cl Chemical compound [Br].Cl SYOIWFNFUFXXMV-UHFFFAOYSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 208000004921 cutaneous lupus erythematosus Diseases 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 231100000655 enterotoxin Toxicity 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 229940013688 formic acid Drugs 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229960002598 fumaric acid Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000007124 immune defense Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 230000001031 immunopharmacological effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229940057952 methanol Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229940116315 oxalic acid Drugs 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229960001476 pentoxifylline Drugs 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- KNCYXPMJDCCGSJ-UHFFFAOYSA-N piperidine-2,6-dione Chemical group O=C1CCCC(=O)N1 KNCYXPMJDCCGSJ-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 235000011044 succinic acid Nutrition 0.000 description 1
- 229960005137 succinic acid Drugs 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 229940032330 sulfuric acid Drugs 0.000 description 1
- 231100000617 superantigen Toxicity 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
-
- 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
-
- 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)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrrole Compounds (AREA)
Priority Applications (16)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19613976A DE19613976C1 (de) | 1996-04-09 | 1996-04-09 | Thalidomid-Prodrugs mit immunmodulatorischer Wirkung |
| SI9730242T SI0892794T1 (en) | 1996-04-09 | 1997-03-22 | Acylated n-hydroxy methyl thalidomide prodrugs with immunomodulator action |
| DK97916380T DK0892794T3 (da) | 1996-04-09 | 1997-03-22 | Acylerede N-hydroxymethyl thalidomid-promedikamenter med immunmodulatorisk virkning |
| PT97916380T PT892794E (pt) | 1996-04-09 | 1997-03-22 | Prodrogas de n-hidroximetil-talidomida aciladas de efeito imunomodulador |
| AU25052/97A AU707144B2 (en) | 1996-04-09 | 1997-03-22 | Acylated N-hydroxymethyl thalidomide prodrugs having an immunomodulatory effect |
| CA002251060A CA2251060C (en) | 1996-04-09 | 1997-03-22 | Acylated n-hydroxy methyl thalidomide prodrugs with immunomodulator action |
| EP97916380A EP0892794B1 (de) | 1996-04-09 | 1997-03-22 | Acylierte n-hydroxymethyl thalidomid-prodrugs mit immunomodulatorischer wirkung |
| CN97193682A CN1102931C (zh) | 1996-04-09 | 1997-03-22 | 具有免疫调解剂作用的酰化n－羟甲基酞胺哌啶酮－前药 |
| JP9535786A JP2000508298A (ja) | 1996-04-09 | 1997-03-22 | 免疫調節作用を有するアシル化ｎ―ヒドロキシメチルサリドマイドプロドラッグ |
| US09/155,896 US6417197B1 (en) | 1996-04-09 | 1997-03-22 | Acylated n-hydroxy methyl thalidomide prodrugs with immunomodulator action |
| ES97916380T ES2171923T3 (es) | 1996-04-09 | 1997-03-22 | Profarmacos de la talidomida, su procedimiento de preparacion y su utilizacion como principios activos en medicamentos. |
| HK99102396.8A HK1017350B (en) | 1996-04-09 | 1997-03-22 | Acylated n-hydroxy methyl thalidomide prodrugs with immunomodulator action |
| HU9902181A HUP9902181A3 (en) | 1996-04-09 | 1997-03-22 | Acylated n-hydroxy methyl thalidomide prodrugs with immunomodulator action |
| AT97916380T ATE212989T1 (de) | 1996-04-09 | 1997-03-22 | Acylierte n-hydroxymethyl thalidomid-prodrugs mit immunomodulatorischer wirkung |
| DE59706313T DE59706313D1 (de) | 1996-04-09 | 1997-03-22 | Acylierte n-hydroxymethyl thalidomid-prodrugs mit immunomodulatorischer wirkung |
| PCT/EP1997/001475 WO1997037988A1 (de) | 1996-04-09 | 1997-03-22 | Acylierte n-hydroxymethyl thalidomid-prodrugs mit immunomodulatorischer wirkung |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19613976A DE19613976C1 (de) | 1996-04-09 | 1996-04-09 | Thalidomid-Prodrugs mit immunmodulatorischer Wirkung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE19613976C1 true DE19613976C1 (de) | 1997-11-20 |
Family
ID=7790778
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19613976A Expired - Fee Related DE19613976C1 (de) | 1996-04-09 | 1996-04-09 | Thalidomid-Prodrugs mit immunmodulatorischer Wirkung |
| DE59706313T Expired - Fee Related DE59706313D1 (de) | 1996-04-09 | 1997-03-22 | Acylierte n-hydroxymethyl thalidomid-prodrugs mit immunomodulatorischer wirkung |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE59706313T Expired - Fee Related DE59706313D1 (de) | 1996-04-09 | 1997-03-22 | Acylierte n-hydroxymethyl thalidomid-prodrugs mit immunomodulatorischer wirkung |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US6417197B1 (cg-RX-API-DMAC7.html) |
| EP (1) | EP0892794B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP2000508298A (cg-RX-API-DMAC7.html) |
| CN (1) | CN1102931C (cg-RX-API-DMAC7.html) |
| AT (1) | ATE212989T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU707144B2 (cg-RX-API-DMAC7.html) |
| DE (2) | DE19613976C1 (cg-RX-API-DMAC7.html) |
| DK (1) | DK0892794T3 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2171923T3 (cg-RX-API-DMAC7.html) |
| HU (1) | HUP9902181A3 (cg-RX-API-DMAC7.html) |
| PT (1) | PT892794E (cg-RX-API-DMAC7.html) |
| WO (1) | WO1997037988A1 (cg-RX-API-DMAC7.html) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001041755A3 (en) * | 1999-12-02 | 2002-02-21 | Univ Michigan | Topical compositions comprising thalidomide for the treatment of inflammatory diseases |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19613976C1 (de) * | 1996-04-09 | 1997-11-20 | Gruenenthal Gmbh | Thalidomid-Prodrugs mit immunmodulatorischer Wirkung |
| AU3224997A (en) * | 1996-05-29 | 1998-01-05 | Prototek, Inc | Prodrugs of thalidomide and methods for using same as modulators of t-cell function |
| HU228769B1 (en) * | 1996-07-24 | 2013-05-28 | Celgene Corp | Substituted 2(2,6-dioxopiperidin-3-yl)phthalimides and -1-oxoisoindolines and their use for production of pharmaceutical compositions for mammals to reduce the level of tnf-alpha |
| DE19743968C2 (de) * | 1997-10-06 | 2002-07-11 | Gruenenthal Gmbh | Intravenöse Applikationsform von Thalidomid zur Therapie immunologischer Erkrankungen |
| DE69834668T2 (de) * | 1997-11-18 | 2007-01-11 | Celgene Corp. | Substituierte 2-(2,6-dioxo-3-fluoropiperidine-3-yl)-isoindoline und ihre Verwendung zum reduzieren des TNF-alpha spiegels |
| US5955476A (en) * | 1997-11-18 | 1999-09-21 | Celgene Corporation | Substituted 2-(2,6-dioxo-3-fluoropiperidin-3-yl)-isoindolines and method of reducing inflammatory cytokine levels |
| US7091353B2 (en) | 2000-12-27 | 2006-08-15 | Celgene Corporation | Isoindole-imide compounds, compositions, and uses thereof |
| EP1389203B8 (en) * | 2001-02-27 | 2010-03-10 | The Governement of the United States of America, represented by The Secretary Department of Health and Human services | Analogs of thalidomide as angiogenesis inhibitors |
| CN100488959C (zh) * | 2003-03-27 | 2009-05-20 | 天津和美生物技术有限公司 | 水溶性的酞胺哌啶酮衍生物 |
| WO2005016326A2 (en) * | 2003-07-11 | 2005-02-24 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Analogs of thalidomide as potential angiogenesis inhibitors |
| CN100398534C (zh) * | 2003-09-15 | 2008-07-02 | 天津和美生物技术有限公司 | 合成酞胺哌啶酮及其衍生物的方法 |
| US7973057B2 (en) * | 2003-09-17 | 2011-07-05 | The United States Of America As Represented By The Department Of Health And Human Services | Thalidomide analogs |
| US8952895B2 (en) | 2011-06-03 | 2015-02-10 | Apple Inc. | Motion-based device operations |
| US7423150B2 (en) * | 2003-10-16 | 2008-09-09 | Novartis Ag | Substituted benzazoles and methods of their use as inhibitors of Raf kinase |
| ITMI20041113A1 (it) * | 2004-06-01 | 2004-09-01 | Antibioticos Spa | Processo per la sintesi della talidomide |
| US20070155791A1 (en) * | 2005-12-29 | 2007-07-05 | Zeldis Jerome B | Methods for treating cutaneous lupus using aminoisoindoline compounds |
| WO2007120669A1 (en) | 2006-04-13 | 2007-10-25 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Tetrahalogenated compounds useful as inhibitors of angiogenesis |
| EP3354646A1 (en) * | 2008-10-29 | 2018-08-01 | Celgene Corporation | Isoindoline compounds for use in the treatment of cancer |
| US8927725B2 (en) | 2011-12-02 | 2015-01-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Thio compounds |
| TWI782395B (zh) * | 2016-01-08 | 2022-11-01 | 美商西建公司 | 抗增生化合物，及其醫藥組合物及用途 |
| US20200199097A1 (en) * | 2017-08-21 | 2020-06-25 | Nanjing Noratech Pharmaceuticals Co., Ltd | Pomalidomide derivative and preparation method therefor |
| CN111499610A (zh) * | 2019-01-31 | 2020-08-07 | 南京诺瑞特医药科技有限公司 | 泊马度胺前体药物盐的多晶型物 |
| EP3771711A1 (en) | 2019-07-29 | 2021-02-03 | Bayer Animal Health GmbH | Pyrazole derivatives for controlling arthropods |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4211812C2 (de) * | 1991-04-17 | 1994-05-05 | Gruenenthal Gmbh | Thalidomidderivate, ein Verfahren zu deren Herstellung sowie die Verwendung derselben in Arzneimitteln |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU1531492A (en) * | 1991-02-14 | 1992-09-15 | Rockefeller University, The | Method for controlling abnormal concentration tnf alpha in human tissues |
| DE19613976C1 (de) * | 1996-04-09 | 1997-11-20 | Gruenenthal Gmbh | Thalidomid-Prodrugs mit immunmodulatorischer Wirkung |
-
1996
- 1996-04-09 DE DE19613976A patent/DE19613976C1/de not_active Expired - Fee Related
-
1997
- 1997-03-22 AU AU25052/97A patent/AU707144B2/en not_active Ceased
- 1997-03-22 EP EP97916380A patent/EP0892794B1/de not_active Expired - Lifetime
- 1997-03-22 US US09/155,896 patent/US6417197B1/en not_active Expired - Fee Related
- 1997-03-22 AT AT97916380T patent/ATE212989T1/de not_active IP Right Cessation
- 1997-03-22 HU HU9902181A patent/HUP9902181A3/hu unknown
- 1997-03-22 DE DE59706313T patent/DE59706313D1/de not_active Expired - Fee Related
- 1997-03-22 PT PT97916380T patent/PT892794E/pt unknown
- 1997-03-22 DK DK97916380T patent/DK0892794T3/da active
- 1997-03-22 ES ES97916380T patent/ES2171923T3/es not_active Expired - Lifetime
- 1997-03-22 JP JP9535786A patent/JP2000508298A/ja not_active Withdrawn
- 1997-03-22 CN CN97193682A patent/CN1102931C/zh not_active Expired - Fee Related
- 1997-03-22 WO PCT/EP1997/001475 patent/WO1997037988A1/de not_active Ceased
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4211812C2 (de) * | 1991-04-17 | 1994-05-05 | Gruenenthal Gmbh | Thalidomidderivate, ein Verfahren zu deren Herstellung sowie die Verwendung derselben in Arzneimitteln |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001041755A3 (en) * | 1999-12-02 | 2002-02-21 | Univ Michigan | Topical compositions comprising thalidomide for the treatment of inflammatory diseases |
Also Published As
| Publication number | Publication date |
|---|---|
| US6417197B1 (en) | 2002-07-09 |
| HK1017350A1 (en) | 1999-11-19 |
| PT892794E (pt) | 2002-07-31 |
| WO1997037988A1 (de) | 1997-10-16 |
| AU2505297A (en) | 1997-10-29 |
| HUP9902181A3 (en) | 2002-11-28 |
| DK0892794T3 (da) | 2002-04-15 |
| AU707144B2 (en) | 1999-07-01 |
| CN1102931C (zh) | 2003-03-12 |
| ATE212989T1 (de) | 2002-02-15 |
| EP0892794A1 (de) | 1999-01-27 |
| JP2000508298A (ja) | 2000-07-04 |
| HUP9902181A2 (hu) | 2000-04-28 |
| DE59706313D1 (de) | 2002-03-21 |
| EP0892794B1 (de) | 2002-02-06 |
| CN1215397A (zh) | 1999-04-28 |
| ES2171923T3 (es) | 2002-09-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE19613976C1 (de) | Thalidomid-Prodrugs mit immunmodulatorischer Wirkung | |
| DE68910421T2 (de) | DC-88A-Derivate. | |
| DE69228627T2 (de) | Langkettiger Carbonsäureimidester | |
| DE2655500C2 (cg-RX-API-DMAC7.html) | ||
| EP0150263A1 (de) | Derivate der cis, endo-2-Azabicyclo-[3.3.0]-octan-3-carbonsäure, Verfahren zu ihrer Herstellung, diese enthaltende Mittel und deren Verwendung | |
| DE3249054T1 (de) | (1-(2-benzoxazolyl)-hydrazino)-alkylnitril-derivate | |
| EP0548024A2 (de) | Aminosulfonsäurederivate und Verfahren zu ihrer Herstellung | |
| DE3306006A1 (de) | Pyrrolessigsaeureamide mit antiinflammatorischer aktivitaet, verfahren zu deren herstellung und arzneimittel, die dieselben enthalten | |
| DE3872127T2 (de) | 4-aminopyridin-derivate und ihre saueradditionssalze. | |
| DE68910211T2 (de) | Estramustin-ester. | |
| DE2455353B2 (de) | Substituierte a -Aminooxycarbonsäurehydrazidderivate und ihre Säureadditionssalze sowie ihre Verwendung und Verfahren zur Herstellung derselben | |
| DE68909815T2 (de) | Beta-carbonyl-carboxyamide von 1,3-Thiazolidinen. | |
| DE1913199B2 (de) | Mannichbasen aus alpha-Tetralon bzw. dessen Derivaten und Arylalkylaminen und deren Salze | |
| DE19703763C1 (de) | Thalidomidanaloge Verbindungen aus der Klasse der Piperidin-2,6-Dione | |
| DE2063996C3 (de) | Alpha-Aminoxyhydroxamsäurederivate, Verfahren zur Herstellung derselben und diese enthaltende Arzneimittel | |
| DE3014813A1 (de) | 2-hydroxy-5-(1-hydroxy-2-piperazinylethyl)benzoesaeure-derivate | |
| DE2064061C3 (de) | Neue tuberkulostatisch wirkende alpha-Aminoxycarbonsäurederivate, Verfahren zur Herstellung derselben und diese enthaltende pharmazeutische Präparate | |
| WO2007031343A1 (de) | 2-(AMINOMETHYL)-5-CHLOR-BENZYLAMID-DERIVATE UND IHRE VERWENDUNG ALS HEMMSTOFFE DES GERINNUNGSFAKTORS Xa | |
| CA2251060C (en) | Acylated n-hydroxy methyl thalidomide prodrugs with immunomodulator action | |
| DE69002959T2 (de) | Pyridinium-Nitrat, seine Herstellung und Anwendung. | |
| EP0203450B1 (de) | Neue Derivate bicyclischer Aminosäuren, Verfahren zu ihrer Herstellung, diese enthaltende Mittel und deren Verwendung | |
| CH617691A5 (cg-RX-API-DMAC7.html) | ||
| EP0139627A1 (de) | Verfahren zur Herstellung von neuen in 5-Stellung substituierten 5,10-Dihydro-11H-dibenzo(b,e)(1,4)diazepin-11-onen | |
| DD210909A5 (de) | Verfahren zur herstellung von substituierten 3,4-diamino-1,2,5-thiadiazolverbindungen | |
| EP0716658B1 (de) | Glycosylamide von 2-aminoacylamino-2-desoxy-zuckern |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8100 | Publication of the examined application without publication of unexamined application | ||
| D1 | Grant (no unexamined application published) patent law 81 | ||
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |