SK101399A3 - Arylsulfonyl hydroxamic acid derivatives - Google Patents

Arylsulfonyl hydroxamic acid derivatives Download PDF

Info

Publication number: SK101399A3
Authority: SK; Slovakia
Prior art keywords: carbon atoms; alkyl; aryl; heteroaryl; moiety
Prior art date: 1997-02-11

Application number

SK1013-99A

Other languages

English (en)

Slovak (sk)

Inventor

Kim Francis Mcclure

Original Assignee

Pfizer

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.)

1997-02-11

Filing date

1998-01-16

Publication date

2001-09-11

1998-01-16 Application filed by Pfizer filed Critical Pfizer

2001-09-11 Publication of SK101399A3 publication Critical patent/SK101399A3/sk

Links

-1 Arylsulfonyl hydroxamic Chemical compound 0.000 title claims abstract description 145
239000002253 acid Substances 0.000 title claims description 68
150000001875 compounds Chemical class 0.000 claims abstract description 91
201000010099 disease Diseases 0.000 claims abstract description 15
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 15
238000004519 manufacturing process Methods 0.000 claims abstract description 14
238000011282 treatment Methods 0.000 claims abstract description 14
102000002274 Matrix Metalloproteinases Human genes 0.000 claims abstract description 13
108010000684 Matrix Metalloproteinases Proteins 0.000 claims abstract description 13
230000000694 effects Effects 0.000 claims abstract description 10
206010028980 Neoplasm Diseases 0.000 claims abstract description 8
208000025865 Ulcer Diseases 0.000 claims abstract description 8
206010003246 arthritis Diseases 0.000 claims abstract description 8
201000011510 cancer Diseases 0.000 claims abstract description 8
230000036269 ulceration Effects 0.000 claims abstract description 8
206010040047 Sepsis Diseases 0.000 claims abstract description 7
206010040070 Septic Shock Diseases 0.000 claims abstract description 7
208000028169 periodontal disease Diseases 0.000 claims abstract description 7
230000036303 septic shock Effects 0.000 claims abstract description 7
208000030507 AIDS Diseases 0.000 claims abstract description 6
229940035676 analgesics Drugs 0.000 claims abstract description 6
239000000730 antalgic agent Substances 0.000 claims abstract description 6
208000037803 restenosis Diseases 0.000 claims abstract description 6
206010039705 Scleritis Diseases 0.000 claims abstract description 5
231100000433 cytotoxic Toxicity 0.000 claims abstract description 5
230000001472 cytotoxic effect Effects 0.000 claims abstract description 5
208000002780 macular degeneration Diseases 0.000 claims abstract description 5
239000003814 drug Substances 0.000 claims abstract description 4
125000004432 carbon atom Chemical group C* 0.000 claims description 235
125000003118 aryl group Chemical group 0.000 claims description 144
125000001072 heteroaryl group Chemical group 0.000 claims description 109
125000000217 alkyl group Chemical group 0.000 claims description 107
125000003545 alkoxy group Chemical group 0.000 claims description 59
239000001257 hydrogen Substances 0.000 claims description 53
229910052739 hydrogen Inorganic materials 0.000 claims description 53
150000003839 salts Chemical class 0.000 claims description 52
229910052799 carbon Inorganic materials 0.000 claims description 50
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 44
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 42
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 40
125000005842 heteroatom Chemical group 0.000 claims description 32
229910052760 oxygen Inorganic materials 0.000 claims description 30
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 29
229910052757 nitrogen Inorganic materials 0.000 claims description 28
229910052717 sulfur Inorganic materials 0.000 claims description 27
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 25
239000001301 oxygen Substances 0.000 claims description 25
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 25
108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 24
ZXKINMCYCKHYFR-UHFFFAOYSA-N aminooxidanide Chemical compound [O-]N ZXKINMCYCKHYFR-UHFFFAOYSA-N 0.000 claims description 24
102000003390 tumor necrosis factor Human genes 0.000 claims description 23
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 22
239000011593 sulfur Substances 0.000 claims description 22
125000003710 aryl alkyl group Chemical group 0.000 claims description 19
125000001424 substituent group Chemical group 0.000 claims description 18
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 17
125000000041 C6-C10 aryl group Chemical group 0.000 claims description 16
241000282414 Homo sapiens Species 0.000 claims description 16
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 14
125000002757 morpholinyl group Chemical group 0.000 claims description 14
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 14
125000004568 thiomorpholinyl group Chemical group 0.000 claims description 14
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 13
125000004104 aryloxy group Chemical group 0.000 claims description 12
125000002393 azetidinyl group Chemical group 0.000 claims description 12
125000002252 acyl group Chemical group 0.000 claims description 11
150000002431 hydrogen Chemical class 0.000 claims description 11
241000124008 Mammalia Species 0.000 claims description 10
125000004423 acyloxy group Chemical group 0.000 claims description 10
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
125000005936 piperidyl group Chemical group 0.000 claims description 10
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 8
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 8
125000004429 atom Chemical group 0.000 claims description 8
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
125000004193 piperazinyl group Chemical group 0.000 claims description 8
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 7
125000005127 aryl alkoxy alkyl group Chemical group 0.000 claims description 7
125000005110 aryl thio group Chemical group 0.000 claims description 7
125000001153 fluoro group Chemical group F* 0.000 claims description 7
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 6
125000006537 (C6-C10)-aryl alkyl group Chemical group 0.000 claims description 6
125000005241 heteroarylamino group Chemical group 0.000 claims description 6
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 6
125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 6
HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 claims description 6
HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 claims description 6
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
150000007513 acids Chemical class 0.000 claims description 5
125000005035 acylthio group Chemical group 0.000 claims description 5
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 5
125000005418 aryl aryl group Chemical group 0.000 claims description 5
239000011737 fluorine Substances 0.000 claims description 5
229910052731 fluorine Inorganic materials 0.000 claims description 5
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 5
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 4
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 4
150000008575 L-amino acids Chemical class 0.000 claims description 4
125000004442 acylamino group Chemical group 0.000 claims description 4
125000004171 alkoxy aryl group Chemical group 0.000 claims description 4
239000002246 antineoplastic agent Substances 0.000 claims description 4
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 4
239000000460 chlorine Substances 0.000 claims description 4
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 4
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 4
125000005368 heteroarylthio group Chemical group 0.000 claims description 4
125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
125000003386 piperidinyl group Chemical group 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
241000282412 Homo Species 0.000 claims description 3
125000001931 aliphatic group Chemical group 0.000 claims description 3
125000004948 alkyl aryl alkyl group Chemical group 0.000 claims description 3
125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 3
125000005018 aryl alkenyl group Chemical group 0.000 claims description 3
125000005015 aryl alkynyl group Chemical group 0.000 claims description 3
125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 3
125000005135 aryl sulfinyl group Chemical group 0.000 claims description 3
229910052801 chlorine Inorganic materials 0.000 claims description 3
125000004122 cyclic group Chemical group 0.000 claims description 3
229910052736 halogen Inorganic materials 0.000 claims description 3
150000002367 halogens Chemical class 0.000 claims description 3
125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 3
125000005326 heteroaryloxy alkyl group Chemical group 0.000 claims description 3
125000005553 heteroaryloxy group Chemical group 0.000 claims description 3
125000000623 heterocyclic group Chemical group 0.000 claims description 3
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 3
230000002401 inhibitory effect Effects 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 3
DCNAGTIFBSSTEQ-CZUORRHYSA-N (2R,4R)-1-(4-methoxyphenyl)sulfonyl-4-(piperazine-1-carbonyl)piperidine-2-carboxylic acid Chemical compound COC1=CC=C(C=C1)S(=O)(=O)N2CC[C@H](C[C@@H]2C(=O)O)C(=O)N3CCNCC3 DCNAGTIFBSSTEQ-CZUORRHYSA-N 0.000 claims description 2
125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 2
125000004414 alkyl thio group Chemical group 0.000 claims description 2
125000005164 aryl thioalkyl group Chemical group 0.000 claims description 2
150000001721 carbon Chemical group 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
125000005114 heteroarylalkoxy group Chemical group 0.000 claims description 2
DFFFQSWTAXMMBT-UHFFFAOYSA-N n-hydroxypiperidine-2-carboxamide Chemical compound ONC(=O)C1CCCCN1 DFFFQSWTAXMMBT-UHFFFAOYSA-N 0.000 claims description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 8
125000004390 alkyl sulfonyl group Chemical group 0.000 claims 3
125000001769 aryl amino group Chemical group 0.000 claims 3
125000006663 (C1-C6) perfluoroalkyl group Chemical group 0.000 claims 2
UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims 2
125000003282 alkyl amino group Chemical group 0.000 claims 2
125000004644 alkyl sulfinyl group Chemical group 0.000 claims 2
229940124599 anti-inflammatory drug Drugs 0.000 claims 2
125000004430 oxygen atom Chemical group O* 0.000 claims 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 claims 2
125000004149 thio group Chemical group *S* 0.000 claims 2
KCBCIFNWFHZSGL-QFBILLFUSA-N (2r,3s)-1-[4-(1,3-benzothiazol-2-ylmethoxy)phenyl]sulfonyl-n,3-dihydroxypiperidine-2-carboxamide Chemical compound ONC(=O)[C@H]1[C@@H](O)CCCN1S(=O)(=O)C(C=C1)=CC=C1OCC1=NC2=CC=CC=C2S1 KCBCIFNWFHZSGL-QFBILLFUSA-N 0.000 claims 1
JOLNGWZCQMJSCD-ZWKOTPCHSA-N (2r,3s)-n,3-dihydroxy-1-[4-(2-pyridin-4-ylethoxy)phenyl]sulfonylpiperidine-2-carboxamide Chemical compound ONC(=O)[C@H]1[C@@H](O)CCCN1S(=O)(=O)C(C=C1)=CC=C1OCCC1=CC=NC=C1 JOLNGWZCQMJSCD-ZWKOTPCHSA-N 0.000 claims 1
JMBOAEVTEXTTPO-BXUZGUMPSA-N (2r,4r)-1-[3-(4-fluorophenoxy)propylsulfonyl]-2-(hydroxycarbamoyl)piperidine-4-carboxylic acid Chemical compound ONC(=O)[C@H]1C[C@H](C(O)=O)CCN1S(=O)(=O)CCCOC1=CC=C(F)C=C1 JMBOAEVTEXTTPO-BXUZGUMPSA-N 0.000 claims 1
ACEUKQZDNBIUHG-CRAIPNDOSA-N (2r,4r)-n,4-dihydroxy-1-(4-phenylmethoxyphenyl)sulfonylpiperidine-2-carboxamide Chemical compound ONC(=O)[C@H]1C[C@H](O)CCN1S(=O)(=O)C(C=C1)=CC=C1OCC1=CC=CC=C1 ACEUKQZDNBIUHG-CRAIPNDOSA-N 0.000 claims 1
UUSUIALWMWHMSS-CRAIPNDOSA-N (2r,5r)-1-[4-[(4-fluorophenyl)methoxy]phenyl]sulfonyl-n,5-dihydroxypiperidine-2-carboxamide Chemical compound ONC(=O)[C@H]1CC[C@@H](O)CN1S(=O)(=O)C(C=C1)=CC=C1OCC1=CC=C(F)C=C1 UUSUIALWMWHMSS-CRAIPNDOSA-N 0.000 claims 1
GIGWICZCQGBJDH-MAUKXSAKSA-N (2r,5s)-n,5-dihydroxy-1-(4-phenylmethoxyphenyl)sulfonylpiperidine-2-carboxamide Chemical compound ONC(=O)[C@H]1CC[C@H](O)CN1S(=O)(=O)C(C=C1)=CC=C1OCC1=CC=CC=C1 GIGWICZCQGBJDH-MAUKXSAKSA-N 0.000 claims 1
125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims 1
125000006720 (C1-C6) alkyl (C6-C10) aryl group Chemical group 0.000 claims 1
125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims 1
PDFDFBYWRAAPBF-UHFFFAOYSA-N 1-[4-[(4-fluorophenyl)methoxy]phenyl]sulfonyl-2-(hydroxycarbamoyl)piperidine-4-carboxylic acid Chemical compound ONC(=O)C1CC(C(O)=O)CCN1S(=O)(=O)C(C=C1)=CC=C1OCC1=CC=C(F)C=C1 PDFDFBYWRAAPBF-UHFFFAOYSA-N 0.000 claims 1
UAISREBYDOFHJY-UHFFFAOYSA-N 4-oxopiperidin-1-ium-2-carboxylate Chemical compound OC(=O)C1CC(=O)CCN1 UAISREBYDOFHJY-UHFFFAOYSA-N 0.000 claims 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
206010053177 Epidermolysis Diseases 0.000 claims 1
101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 claims 1
102000010750 Metalloproteins Human genes 0.000 claims 1
108010063312 Metalloproteins Proteins 0.000 claims 1
125000005041 acyloxyalkyl group Chemical group 0.000 claims 1
125000004183 alkoxy alkyl group Chemical group 0.000 claims 1
125000006430 alkyl cyclopropyl group Chemical group 0.000 claims 1
230000009286 beneficial effect Effects 0.000 claims 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
229910052794 bromium Inorganic materials 0.000 claims 1
KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims 1
125000004663 dialkyl amino group Chemical group 0.000 claims 1
NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 claims 1
102000057041 human TNF Human genes 0.000 claims 1
125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 1
125000005010 perfluoroalkyl group Chemical group 0.000 claims 1
125000004001 thioalkyl group Chemical group 0.000 claims 1
KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 claims 1
GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 claims 1
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 abstract description 5
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 abstract description 4
206010014989 Epidermolysis bullosa Diseases 0.000 abstract description 4
STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 abstract description 2
WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 abstract description 2
ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 abstract description 2
229930012538 Paclitaxel Natural products 0.000 abstract description 2
229940009456 adriamycin Drugs 0.000 abstract description 2
229930013930 alkaloid Natural products 0.000 abstract description 2
238000002648 combination therapy Methods 0.000 abstract description 2
STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 abstract description 2
229940079593 drug Drugs 0.000 abstract description 2
VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 abstract description 2
229960005420 etoposide Drugs 0.000 abstract description 2
229960001592 paclitaxel Drugs 0.000 abstract description 2
RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 abstract description 2
229940063683 taxotere Drugs 0.000 abstract description 2
OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 abstract description 2
229960004528 vincristine Drugs 0.000 abstract description 2
OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 abstract description 2
239000000041 non-steroidal anti-inflammatory agent Substances 0.000 abstract 1
229910052697 platinum Inorganic materials 0.000 abstract 1
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 88
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 65
239000000203 mixture Substances 0.000 description 53
239000000243 solution Substances 0.000 description 52
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 44
238000006243 chemical reaction Methods 0.000 description 43
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 34
239000007787 solid Substances 0.000 description 30
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 29
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
125000006239 protecting group Chemical group 0.000 description 22
238000003556 assay Methods 0.000 description 21
239000011541 reaction mixture Substances 0.000 description 21
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
230000002829 reductive effect Effects 0.000 description 18
108060005980 Collagenase Proteins 0.000 description 17
102000029816 Collagenase Human genes 0.000 description 17
229960002424 collagenase Drugs 0.000 description 17
239000000706 filtrate Substances 0.000 description 17
239000003112 inhibitor Substances 0.000 description 17
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CNCJXVCCTNQTQC-ZEQKJWHPSA-N tert-butyl 4-[(2r,4r)-1-(4-methoxyphenyl)sulfonyl-2-(phenylmethoxycarbamoyl)piperidine-4-carbonyl]piperazine-1-carboxylate Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N1[C@@H](C(=O)NOCC=2C=CC=CC=2)C[C@H](C(=O)N2CCN(CC2)C(=O)OC(C)(C)C)CC1 CNCJXVCCTNQTQC-ZEQKJWHPSA-N 0.000 description 1
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CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
- C07D211/96—Sulfur atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/12—1,4-Thiazines; Hydrogenated 1,4-thiazines not condensed with other rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Rheumatology (AREA)
Virology (AREA)
Dermatology (AREA)
AIDS & HIV (AREA)
Oncology (AREA)
Molecular Biology (AREA)
Diabetes (AREA)
Hematology (AREA)
Tropical Medicine & Parasitology (AREA)
Pain & Pain Management (AREA)
Orthopedic Medicine & Surgery (AREA)
Immunology (AREA)
Communicable Diseases (AREA)
Physical Education & Sports Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Hydrogenated Pyridines (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

SK1013-99A 1997-02-11 1998-01-16 Arylsulfonyl hydroxamic acid derivatives SK101399A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US3760097P	1997-02-11	1997-02-11
PCT/IB1998/000064 WO1998034918A1 (en)	1997-02-11	1998-01-16	Arylsulfonyl hydroxamic acid derivatives

Publications (1)

Publication Number	Publication Date
SK101399A3 true SK101399A3 (en)	2001-09-11

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ID=21895216

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SK1013-99A SK101399A3 (en)	1997-02-11	1998-01-16	Arylsulfonyl hydroxamic acid derivatives

Country Status (37)

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US (1)	US6599890B1 (is)
EP (1)	EP0960098A1 (is)
JP (1)	JP3710489B2 (is)
KR (1)	KR20000070923A (is)
CN (1)	CN1247531A (is)
AP (1)	AP958A (is)
AR (1)	AR011123A1 (is)
AU (1)	AU722784B2 (is)
BG (1)	BG63430B1 (is)
BR (1)	BR9807678A (is)
CA (1)	CA2280151C (is)
CO (1)	CO4950619A1 (is)
DZ (1)	DZ2416A1 (is)
EA (1)	EA002546B1 (is)
GT (1)	GT199800026A (is)
HN (1)	HN1998000020A (is)
HR (1)	HRP980070B1 (is)
HU (1)	HUP0000657A3 (is)
ID (1)	ID22809A (is)
IL (1)	IL131123A0 (is)
IS (1)	IS5130A (is)
MA (1)	MA24469A1 (is)
NO (1)	NO993836L (is)
NZ (1)	NZ336836A (is)
OA (1)	OA11142A (is)
PA (1)	PA8446101A1 (is)
PE (1)	PE58699A1 (is)
PL (1)	PL334997A1 (is)
SA (1)	SA98180856A (is)
SK (1)	SK101399A3 (is)
TN (1)	TNSN98025A1 (is)
TR (1)	TR199901926T2 (is)
TW (1)	TW502020B (is)
UY (1)	UY24880A1 (is)
WO (1)	WO1998034918A1 (is)
YU (1)	YU37499A (is)
ZA (1)	ZA981061B (is)

Families Citing this family (317)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0960098A1 (en) *	1997-02-11	1999-12-01	Pfizer Inc.	Arylsulfonyl hydroxamic acid derivatives
CN1301265A (zh) *	1998-05-14	2001-06-27	杜邦药品公司	新的用作金属蛋白酶抑制剂的取代的芳基异羟肟酸
ES2242402T3 (es) *	1998-08-12	2005-11-01	Pfizer Products Inc.	Inhibidores de tace.
UA59453C2 (uk) *	1998-08-12	2003-09-15	Пфайзер Продактс Інк.	Похідні гідроксипіпеколат гідроксамової кислоти як інгібітори матричних металопротеїназ
AU6228499A (en) *	1998-10-22	2000-05-08	Akzo Nobel N.V.	Tetrahydropyridopyridine derivatives and intermediates for producing the same
US6225311B1 (en)	1999-01-27	2001-05-01	American Cyanamid Company	Acetylenic α-amino acid-based sulfonamide hydroxamic acid tace inhibitors
US6313123B1 (en)	1999-01-27	2001-11-06	American Cyanamid Company	Acetylenic sulfonamide thiol tace inhibitors
US6200996B1 (en)	1999-01-27	2001-03-13	American Cyanamid Company	Heteroaryl acetylenic sulfonamide and phosphinic acid amide hydroxamic acid tace inhibitors
US6753337B2 (en)	1999-01-27	2004-06-22	Wyeth Holdings Corporation	Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase/tace inhibitors
US6358980B1 (en)	1999-01-27	2002-03-19	American Cyanamid Company	Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase/tace inhibitors
US6946473B2 (en)	1999-01-27	2005-09-20	Wyeth Holdings Corporation	Preparation and use of acetylenic ortho-sulfonamido and phosphinic acid amido bicyclic heteroaryl hydroxamic acids as TACE inhibitors
US6277885B1 (en)	1999-01-27	2001-08-21	American Cyanamid Company	Acetylenic aryl sulfonamide and phosphinic acid amide hydroxamic acid TACE inhibitors
US6762178B2 (en)	1999-01-27	2004-07-13	Wyeth Holdings Corporation	Acetylenic aryl sulfonamide and phosphinic acid amide hydroxamic acid TACE inhibitors
US6340691B1 (en)	1999-01-27	2002-01-22	American Cyanamid Company	Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase and tace inhibitors
US6326516B1 (en)	1999-01-27	2001-12-04	American Cyanamid Company	Acetylenic β-sulfonamido and phosphinic acid amide hydroxamic acid TACE inhibitors
EP1081137A1 (en) *	1999-08-12	2001-03-07	Pfizer Products Inc.	Selective inhibitors of aggrecanase in osteoarthritis treatment
UA74803C2 (uk)	1999-11-11	2006-02-15	Осі Фармасьютікалз, Інк.	Стійкий поліморф гідрохлориду n-(3-етинілфеніл)-6,7-біс(2-метоксіетокси)-4-хіназолінаміну, спосіб його одержання (варіанти) та фармацевтичне застосування
US6462063B1 (en)	2000-02-04	2002-10-08	Fibrogen, Inc.	C-proteinase inhibitors
US6458822B2 (en)	2000-03-13	2002-10-01	Pfizer Inc.	2-oxo-imidazolidine-4-carboxylic acid hydroxamide compounds that inhibit matrix metalloproteinases
EP1138680A1 (en) *	2000-03-29	2001-10-04	Pfizer Products Inc.	Gem substituted sulfonyl hydroxamic acids as MMP inhibitors
GB0011409D0 (en) *	2000-05-11	2000-06-28	Smithkline Beecham Plc	Novel compounds
JP2001322977A (ja) *	2000-05-12	2001-11-20	Kotobuki Seiyaku Kk	ピペコリン酸誘導体及びその製造方法並びにこれを含有する医薬組成物
ME00502B (me)	2001-01-05	2011-10-10	Amgen Fremont Inc	Antitjela za insulinu sličan receptor faktora i rasta
MXPA01013172A (es)	2001-02-14	2002-08-21	Warner Lambert Co	Inhibidores sulfonamida de metaloproteinasa de matriz.
MXPA01013171A (es)	2001-02-14	2004-05-21	Warner Lambert Co	Inhibidores triciclicos de sulfonamida de metaloproteinasa de matriz.
MXPA01013326A (es) *	2001-02-14	2002-08-26	Warner Lambert Co	Bifenil sulfonamidas utiles como inhibisdores de metaloproteinasa de matriz.
WO2003000194A2 (en)	2001-06-21	2003-01-03	Pfizer Inc.	Thienopyridine and thienopyrimidine anticancer agents
AUPR726201A0 (en) *	2001-08-24	2001-09-20	Fujisawa Pharmaceutical Co., Ltd.	New use of a cyclic compound
BR0213736A (pt)	2001-11-01	2004-10-19	Wyeth Corp	ácidos hidroxâmicos de sulfonamida de arila alênica como metaloproteinase matriz e inibidores de tace
AR039067A1 (es)	2001-11-09	2005-02-09	Pfizer Prod Inc	Anticuerpos para cd40
AU2003206068A1 (en)	2002-03-01	2003-09-16	Pfizer Inc.	Indolyl-urea derivatives of thienopyridines useful as anti-angiogenic agents
KR100984595B1 (ko)	2002-03-13	2010-09-30	어레이 바이오파마 인크.	Ｍｅｋ 억제제로서의 ｎ3 알킬화 벤즈이미다졸 유도체
EP2436676A1 (en)	2002-06-12	2012-04-04	Symphony Evolution, Inc.	Human adam-10 inhibitors
UA77303C2 (en)	2002-06-14	2006-11-15	Pfizer	Derivatives of thienopyridines substituted by benzocondensed heteroarylamide useful as therapeutic agents, pharmaceutical compositions and methods for their use
WO2004056806A1 (en)	2002-12-19	2004-07-08	Pfizer Inc.	2-(1h-indazol-6-ylamino)-benzamide compounds as protein kinases inhibitors useful for the treatment of ophtalmic diseases
US7199155B2 (en)	2002-12-23	2007-04-03	Wyeth Holdings Corporation	Acetylenic aryl sulfonate hydroxamic acid TACE and matrix metalloproteinase inhibitors
DK1603570T5 (da)	2003-02-26	2013-12-09	Sugen Inc	Aminoheteroarylforbindelser som proteinkinaseinhibitorer
HN2004000285A (es)	2003-08-04	2006-04-27	Pfizer Prod Inc	ANTICUERPOS DIRIGIDOS A c-MET
ES2314444T3 (es)	2003-08-29	2009-03-16	Pfizer Inc.	Tienopiridina-fenilacetaminasy sus derivados utiles como nuevos agentes antiangiogenicos.
US7144907B2 (en)	2003-09-03	2006-12-05	Array Biopharma Inc.	Heterocyclic inhibitors of MEK and methods of use thereof
AR045563A1 (es)	2003-09-10	2005-11-02	Warner Lambert Co	Anticuerpos dirigidos a m-csf
CN1905873A (zh)	2003-11-19	2007-01-31	阵列生物制药公司	Mek的杂环抑制剂及其使用方法
GT200500139A (es)	2004-06-08	2005-07-25		Metodo para la preparacion de acidos hidroxamicos
KR20080019733A (ko)	2004-07-16	2008-03-04	화이자 프로덕츠 인코포레이티드	항-아이지에프-1알 항체를 사용하는 비-혈액학적악성종양에 대한 조합 치료
DE602005020465D1 (de)	2004-08-26	2010-05-20	Pfizer	Enantiomerenreine aminoheteroaryl-verbindungen als proteinkinasehemmer
MY146381A (en)	2004-12-22	2012-08-15	Amgen Inc	Compositions and methods relating relating to anti-igf-1 receptor antibodies
US7429667B2 (en)	2005-01-20	2008-09-30	Ardea Biosciences, Inc.	Phenylamino isothiazole carboxamidines as MEK inhibitors
ES2405785T3 (es)	2005-05-18	2013-06-03	Array Biopharma Inc.	Inhibidores heterocíclicos de MEK y métodos de uso de los mismos
US8101799B2 (en)	2005-07-21	2012-01-24	Ardea Biosciences	Derivatives of N-(arylamino) sulfonamides as inhibitors of MEK
CA2623125A1 (en)	2005-09-20	2007-03-29	Osi Pharmaceuticals, Inc.	Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors
TWI405756B (zh)	2005-12-21	2013-08-21	Array Biopharma Inc	新穎硫酸氫鹽
US7842836B2 (en)	2006-04-11	2010-11-30	Ardea Biosciences	N-aryl-N'alkyl sulfamides as MEK inhibitors
JP5269762B2 (ja)	2006-04-18	2013-08-21	アーディア・バイオサイエンシーズ・インコーポレイテッド	Ｍｅｋ阻害剤としてのピリドンスルホンアミドおよびピリドンスルファミド
CA2672815A1 (en)	2006-12-15	2008-06-26	Pfizer Products Inc.	Benzimidazole derivatives for use in treating abnormal cell growth
KR20090111847A (ko)	2007-01-19	2009-10-27	아디아 바이오사이언스즈 인크.	Ｍｅｋ 억제제
CN101678215B (zh)	2007-04-18	2014-10-01	辉瑞产品公司	用于治疗异常细胞生长的磺酰胺衍生物
US8530463B2 (en)	2007-05-07	2013-09-10	Hale Biopharma Ventures Llc	Multimodal particulate formulations
CA2924436A1 (en)	2007-07-30	2009-02-05	Ardea Biosciences, Inc.	Pharmaceutical combinations of n-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide as inhibitors of mek and methods of use
JP5421925B2 (ja)	2007-12-19	2014-02-19	ジェネンテック，インコーポレイテッド	５−アニリノイミダゾピリジン及び使用の方法
MX2010007419A (es)	2008-01-04	2010-11-12	Intellikine Inc	Ciertas entidades quimicas, composiciones y metodos.
US8193182B2 (en)	2008-01-04	2012-06-05	Intellikine, Inc.	Substituted isoquinolin-1(2H)-ones, and methods of use thereof
EP2252293B1 (en)	2008-03-14	2018-06-27	Intellikine, LLC	Kinase inhibitors and methods of use
US20090258865A1 (en)	2008-03-28	2009-10-15	Hale Biopharma Ventures, Llc	Administration of benzodiazepine compositions
BRPI0915231A2 (pt)	2008-07-08	2018-06-12	Intellikine Inc	compostos inibidores de quinase e métodos de uso
WO2010045495A2 (en)	2008-10-16	2010-04-22	University Of Pittsburgh-Of The Commonwealth System Of Higher Education	Fully human antibodies to high molecular weight-melanoma associated antigen and uses thereof
US8476431B2 (en)	2008-11-03	2013-07-02	Itellikine LLC	Benzoxazole kinase inhibitors and methods of use
RU2683325C2 (ru)	2009-02-05	2019-03-28	Иммьюноджен, Инк.	Новые производные бензодиазепина
TW201041892A (en)	2009-02-09	2010-12-01	Supergen Inc	Pyrrolopyrimidinyl Axl kinase inhibitors
WO2010099139A2 (en)	2009-02-25	2010-09-02	Osi Pharmaceuticals, Inc.	Combination anti-cancer therapy
JP2012519170A (ja)	2009-02-26	2012-08-23	オーエスアイ・ファーマシューティカルズ，エルエルシー	生体内の腫瘍細胞のｅｍｔステータスをモニターするためのｉｎｓｉｔｕ法
WO2010099363A1 (en)	2009-02-27	2010-09-02	Osi Pharmaceuticals, Inc.	Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation
WO2010099138A2 (en)	2009-02-27	2010-09-02	Osi Pharmaceuticals, Inc.	Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation
WO2010098866A1 (en)	2009-02-27	2010-09-02	Supergen, Inc.	Cyclopentathiophene/cyclohexathiophene dna methyltransferase inhibitors
WO2010099364A2 (en)	2009-02-27	2010-09-02	Osi Pharmaceuticals, Inc.	Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation
CN102448938A (zh)	2009-03-27	2012-05-09	阿迪生物科学公司	作为mek抑制剂的二氢吡啶磺酰胺和二氢吡啶硫酰胺
JP5789252B2 (ja)	2009-05-07	2015-10-07	インテリカイン，エルエルシー	複素環式化合物およびその使用
EP2459191A1 (en)	2009-07-31	2012-06-06	OSI Pharmaceuticals, LLC	Mtor inhibitor and angiogenesis inhibitor combination therapy
NZ598220A (en)	2009-08-17	2014-02-28	Intellikine Llc	Heterocyclic compounds and uses thereof
JP2013503846A (ja)	2009-09-01	2013-02-04	ファイザー・インク	ベンズイミダゾール誘導体
CN102666512B (zh)	2009-10-13	2014-11-26	奥斯特姆医疗公司	对疾病治疗有用的mek抑制剂
WO2011049625A1 (en)	2009-10-20	2011-04-28	Mansour Samadpour	Method for aflatoxin screening of products
NZ599830A (en)	2009-11-05	2014-08-29	Rhizen Pharmaceuticals Sa	Novel kinase modulators
KR20130009760A (ko)	2010-02-10	2013-01-23	이뮤노젠 아이엔씨	Ｃｄ２０ 항체 및 이의 용도
EP4166558A1 (en)	2010-02-12	2023-04-19	Pfizer Inc.	Salts and polymorphs of 8-fluoro-2-{4- [(methylamino)methyl]phenyl}-1 ,3,4,5-tetrahydro-6h-azepino[5,4,3- cd]indol-6-one
WO2011109572A2 (en)	2010-03-03	2011-09-09	OSI Pharmaceuticals, LLC	Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors
CA2783665A1 (en)	2010-03-03	2011-09-09	OSI Pharmaceuticals, LLC	Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors
NZ604306A (en)	2010-05-17	2015-02-27	Incozen Therapeutics Pvt Ltd	Novel 3,5-disubstitued-3h-imidazo[4,5-b]pyridine and 3,5- disubstitued -3h-[1,2,3]triazolo[4,5-b] pyridine compounds as modulators of protein kinases
CA2799579A1 (en)	2010-05-21	2011-11-24	Intellikine, Inc.	Chemical compounds, compositions and methods for kinase modulation
EP2582727B8 (en)	2010-06-16	2017-04-19	University of Pittsburgh- Of the Commonwealth System of Higher Education	Antibodies to endoplasmin and their use
CA2813162C (en)	2010-10-20	2015-06-16	Pfizer Inc.	Pyridine-2- derivatives as smoothened receptor modulators
JP2013545749A (ja)	2010-11-10	2013-12-26	インフィニティーファーマシューティカルズ，インコーポレイテッド	複素環化合物及びその使用
ES2637113T3 (es)	2011-01-10	2017-10-10	Infinity Pharmaceuticals, Inc.	Procedimientos para preparar isoquinolinonas y formas sólidas de isoquinolinonas
MX2013008833A (es)	2011-02-02	2013-12-06	Amgen Inc	Metodos y composiciones relacionadas con la inhibicion de receptor del factor de crecimiento similar a la insulina 1 (igf-1r).
JP5826863B2 (ja)	2011-02-15	2015-12-02	イミュノジェン・インコーポレーテッド	細胞傷害性ベンゾジアゼピン誘導体
WO2012116040A1 (en)	2011-02-22	2012-08-30	OSI Pharmaceuticals, LLC	Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors in hepatocellular carcinoma
WO2012116237A2 (en)	2011-02-23	2012-08-30	Intellikine, Llc	Heterocyclic compounds and uses thereof
US9150644B2 (en)	2011-04-12	2015-10-06	The United States Of America, As Represented By The Secretary, Department Of Health And Human Services	Human monoclonal antibodies that bind insulin-like growth factor (IGF) I and II
DK2699598T3 (en)	2011-04-19	2019-04-23	Pfizer	COMBINATIONS OF ANTI-4-1BB ANTIBODIES AND ADCC-INducing ANTIBODIES FOR TREATMENT OF CANCER
WO2012149014A1 (en)	2011-04-25	2012-11-01	OSI Pharmaceuticals, LLC	Use of emt gene signatures in cancer drug discovery, diagnostics, and treatment
PH12013502240B1 (en)	2011-05-04	2018-06-27	Rhizen Pharmaceuticals Sa	Novel compounds as modulators of protein kinase
ES2683902T3 (es)	2011-06-14	2018-09-28	Hale Biopharma Ventures, Llc	Administración de benzodiacepina
HK1198443A1 (en)	2011-07-19	2015-04-24	无限药品股份有限公司	Heterocyclic compounds and uses thereof
AR088218A1 (es)	2011-07-19	2014-05-21	Infinity Pharmaceuticals Inc	Compuestos heterociclicos utiles como inhibidores de pi3k
EP3812387A1 (en)	2011-07-21	2021-04-28	Sumitomo Dainippon Pharma Oncology, Inc.	Heterocyclic protein kinase inhibitors
MX2014002542A (es)	2011-08-29	2014-07-09	Infinity Pharmaceuticals Inc	Compuestos heterociclicos y usos de los mismos.
EP2758402B9 (en)	2011-09-22	2016-09-14	Pfizer Inc	Pyrrolopyrimidine and purine derivatives
WO2013049332A1 (en)	2011-09-29	2013-04-04	Infinity Pharmaceuticals, Inc.	Inhibitors of monoacylglycerol lipase and methods of their use
EP2763972A1 (en) *	2011-10-04	2014-08-13	Institut National de la Santé et de la Recherche Médicale (INSERM)	New apoptosis inducing compounds
EP2764025B1 (en)	2011-10-04	2017-11-29	IGEM Therapeutics Limited	Ige-antibodies against hmw-maa
WO2013068902A1 (en)	2011-11-08	2013-05-16	Pfizer Inc.	Methods of treating inflammatory disorders using anti-m-csf antibodies
WO2013126617A1 (en)	2012-02-22	2013-08-29	The Regents Of The University Of Colorado, A Body Corporate	Bouvardin derivatives and therapeutic uses thereof
US9452215B2 (en)	2012-02-22	2016-09-27	The Regents Of The University Of Colorado	Bourvadin derivatives and therapeutic uses thereof
CN107082779A (zh)	2012-03-30	2017-08-22	理森制药股份公司	作为c‑met 蛋白激酶调节剂的新化合物
WO2013152252A1 (en)	2012-04-06	2013-10-10	OSI Pharmaceuticals, LLC	Combination anti-cancer therapy
US8940742B2 (en)	2012-04-10	2015-01-27	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
EP2859017B1 (en)	2012-06-08	2019-02-20	Sutro Biopharma, Inc.	Antibodies comprising site-specific non-natural amino acid residues, methods of their preparation and methods of their use
WO2014004639A1 (en)	2012-06-26	2014-01-03	Sutro Biopharma, Inc.	Modified fc proteins comprising site-specific non-natural amino acid residues, conjugates of the same, methods of their preparation and methods of their use
HK1211208A1 (zh)	2012-08-22	2016-05-20	Immunogen, Inc.	細胞毒性苯並二氮呯衍生物
EP2890402B1 (en)	2012-08-31	2019-04-17	Sutro Biopharma, Inc.	Modified amino acids comprising an azido group
EP2909181B1 (en)	2012-10-16	2017-08-09	Tolero Pharmaceuticals, Inc.	Pkm2 modulators and methods for their use
AU2013337717B2 (en)	2012-11-01	2018-10-25	Infinity Pharmaceuticals, Inc.	Treatment of cancers using PI3 kinase isoform modulators
JP6423804B2 (ja)	2013-02-28	2018-11-14	イミュノジェン・インコーポレーテッド	細胞結合剤及び細胞毒性剤を含む複合体
EP3566750A3 (en)	2013-02-28	2020-04-08	ImmunoGen, Inc.	Conjugates comprising cell-binding agents and cytotoxic agents
MX394360B (es)	2013-03-14	2025-03-24	Sumitomo Pharma Oncology Inc	Inhibidores de jak2 y alk2 y metodos para su uso.
CA2904393A1 (en)	2013-03-15	2014-09-25	Araxes Pharma Llc	Covalent inhibitors of kras g12c
US9745319B2 (en)	2013-03-15	2017-08-29	Araxes Pharma Llc	Irreversible covalent inhibitors of the GTPase K-Ras G12C
EP2968340A4 (en)	2013-03-15	2016-08-10	Intellikine Llc	COMBINING KINASE INHIBITORS AND USES THEREOF
WO2014151386A1 (en)	2013-03-15	2014-09-25	Infinity Pharmaceuticals, Inc.	Salts and solid forms of isoquinolinones and composition comprising and methods of using the same
US9227978B2 (en)	2013-03-15	2016-01-05	Araxes Pharma Llc	Covalent inhibitors of Kras G12C
CA2914284A1 (en)	2013-05-30	2014-12-04	Infinity Pharmaceuticals, Inc.	Treatment of cancers using pi3 kinase isoform modulators
WO2014194030A2 (en)	2013-05-31	2014-12-04	Immunogen, Inc.	Conjugates comprising cell-binding agents and cytotoxic agents
WO2015006555A2 (en)	2013-07-10	2015-01-15	Sutro Biopharma, Inc.	Antibodies comprising multiple site-specific non-natural amino acid residues, methods of their preparation and methods of their use
SG11201602572YA (en)	2013-10-03	2016-04-28	Kura Oncology Inc	Inhibitors of erk and methods of use
PT3052485T (pt)	2013-10-04	2021-10-22	Infinity Pharmaceuticals Inc	Compostos heterocíclicos e suas utilizações
US9751888B2 (en)	2013-10-04	2017-09-05	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
EP3055290B1 (en)	2013-10-10	2019-10-02	Araxes Pharma LLC	Inhibitors of kras g12c
JO3805B1 (ar)	2013-10-10	2021-01-31	Araxes Pharma Llc	مثبطات كراس جي12سي
EP3055298B1 (en)	2013-10-11	2020-04-29	Sutro Biopharma, Inc.	Modified amino acids comprising tetrazine functional groups, methods of preparation, and methods of their use
US20160244452A1 (en)	2013-10-21	2016-08-25	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
UA115388C2 (uk)	2013-11-21	2017-10-25	Пфайзер Інк.	2,6-заміщені пуринові похідні та їх застосування в лікуванні проліферативних захворювань
WO2015155624A1 (en)	2014-04-10	2015-10-15	Pfizer Inc.	Dihydropyrrolopyrimidine derivatives
WO2015168079A1 (en)	2014-04-29	2015-11-05	Infinity Pharmaceuticals, Inc.	Pyrimidine or pyridine derivatives useful as pi3k inhibitors
CR20160497A (es)	2014-04-30	2016-12-20	Pfizer	Derivados de diheterociclo enlazado a cicloalquilo
EP3778584A1 (en)	2014-06-19	2021-02-17	ARIAD Pharmaceuticals, Inc.	Production process of 2-chloro-4-heteroaryl-pyrimidine derivatives
WO2016001789A1 (en)	2014-06-30	2016-01-07	Pfizer Inc.	Pyrimidine derivatives as pi3k inhibitors for use in the treatment of cancer
JP6811706B2 (ja)	2014-07-31	2021-01-13	ザホンコンユニヴァーシティオブサイエンスアンドテクノロジー	Ｅｐｈａ４に対するヒトモノクローナル抗体及びそれらの使用
JO3556B1 (ar)	2014-09-18	2020-07-05	Araxes Pharma Llc	علاجات مدمجة لمعالجة السرطان
JP2017528498A (ja)	2014-09-25	2017-09-28	アラクセスファーマエルエルシー	Ｋｒａｓｇ１２ｃ変異体タンパク質のインヒビター
WO2016049568A1 (en)	2014-09-25	2016-03-31	Araxes Pharma Llc	Methods and compositions for inhibition of ras
JP6621477B2 (ja)	2014-12-18	2019-12-18	ファイザー・インク	ピリミジンおよびトリアジン誘導体ならびにａｘｌ阻害薬としてのそれらの使用
ES2898765T3 (es)	2015-04-10	2022-03-08	Araxes Pharma Llc	Compuestos de quinazolina sustituidos y métodos de uso de los mismos
US10428064B2 (en)	2015-04-15	2019-10-01	Araxes Pharma Llc	Fused-tricyclic inhibitors of KRAS and methods of use thereof
HK1251655A1 (zh)	2015-04-20	2019-02-01	Tolero Pharmaceuticals, Inc.	通过线粒体分析预测对阿伏西地的应答
CA2984421C (en)	2015-05-01	2024-04-09	Cocrystal Pharma, Inc.	Nucleoside analogs for treatment of the flaviviridae family of viruses and cancer
KR102608921B1 (ko)	2015-05-18	2023-12-01	스미토모 파마 온콜로지, 인크.	생체 이용률이 증가된 알보시딥 프로드러그
TWI703150B (zh)	2015-06-04	2020-09-01	美商庫拉腫瘤技術股份有限公司	用於抑制ｍｅｎｉｎ及ｍｌｌ蛋白之交互作用的方法及組合物
WO2017009751A1 (en)	2015-07-15	2017-01-19	Pfizer Inc.	Pyrimidine derivatives
US10144724B2 (en)	2015-07-22	2018-12-04	Araxes Pharma Llc	Substituted quinazoline compounds and methods of use thereof
JP7083497B2 (ja)	2015-08-03	2022-06-13	スミトモファーマオンコロジー，インコーポレイテッド	がんの処置のための併用療法
WO2017048702A1 (en)	2015-09-14	2017-03-23	Infinity Pharmaceuticals, Inc.	Solid forms of isoquinolinone derivatives, process of making, compositions comprising, and methods of using the same
EP3356351A1 (en)	2015-09-28	2018-08-08	Araxes Pharma LLC	Inhibitors of kras g12c mutant proteins
WO2017058805A1 (en)	2015-09-28	2017-04-06	Araxes Pharma Llc	Inhibitors of kras g12c mutant proteins
WO2017058902A1 (en)	2015-09-28	2017-04-06	Araxes Pharma Llc	Inhibitors of kras g12c mutant proteins
EP3356359B1 (en)	2015-09-28	2021-10-20	Araxes Pharma LLC	Inhibitors of kras g12c mutant proteins
EP3356349A1 (en)	2015-09-28	2018-08-08	Araxes Pharma LLC	Inhibitors of kras g12c mutant proteins
EP3356347A1 (en)	2015-09-28	2018-08-08	Araxes Pharma LLC	Inhibitors of kras g12c mutant proteins
WO2017058728A1 (en)	2015-09-28	2017-04-06	Araxes Pharma Llc	Inhibitors of kras g12c mutant proteins
WO2017070256A2 (en)	2015-10-19	2017-04-27	Araxes Pharma Llc	Method for screening inhibitors of ras
KR20180081596A (ko)	2015-11-16	2018-07-16	아락세스 파마 엘엘씨	치환된 헤테로사이클릭 그룹을 포함하는 2-치환된 퀴나졸린 화합물 및 이의 사용 방법
WO2017096165A1 (en)	2015-12-03	2017-06-08	Agios Pharmaceuticals, Inc.	Mat2a inhibitors for treating mtap null cancer
US9988357B2 (en)	2015-12-09	2018-06-05	Araxes Pharma Llc	Methods for preparation of quinazoline derivatives
WO2017132615A1 (en)	2016-01-27	2017-08-03	Sutro Biopharma, Inc.	Anti-cd74 antibody conjugates, compositions comprising anti-cd74 antibody conjugates and methods of using anti-cd74 antibody conjugates
PH12018501955B1 (en)	2016-03-16	2024-01-24	Kura Oncology Inc	Bridged bicyclic inhibitors of menin-mll and methods of use
PL3429591T3 (pl)	2016-03-16	2023-07-17	Kura Oncology, Inc.	Podstawione pochodne tieno[2,3-d]pirymidyny jako inhibitory meniny-mll i metody ich zastosowania
WO2017172979A1 (en)	2016-03-30	2017-10-05	Araxes Pharma Llc	Substituted quinazoline compounds and methods of use
ES2910787T3 (es)	2016-05-12	2022-05-13	Univ Michigan Regents	Inhibidores de ASH1L y métodos de tratamiento con los mismos
US11118233B2 (en)	2016-05-18	2021-09-14	The University Of Chicago	BTK mutation and ibrutinib resistance
WO2017214269A1 (en)	2016-06-08	2017-12-14	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
US10646488B2 (en)	2016-07-13	2020-05-12	Araxes Pharma Llc	Conjugates of cereblon binding compounds and G12C mutant KRAS, HRAS or NRAS protein modulating compounds and methods of use thereof
CA3035081A1 (en)	2016-09-02	2018-03-08	Dana-Farber Cancer Institute, Inc.	Composition and methods of treating b cell disorders
WO2018064510A1 (en)	2016-09-29	2018-04-05	Araxes Pharma Llc	Inhibitors of kras g12c mutant proteins
EP3523289A1 (en)	2016-10-07	2019-08-14	Araxes Pharma LLC	Heterocyclic compounds as inhibitors of ras and methods of use thereof
WO2018094275A1 (en)	2016-11-18	2018-05-24	Tolero Pharmaceuticals, Inc.	Alvocidib prodrugs and their use as protein kinase inhibitors
WO2018098352A2 (en)	2016-11-22	2018-05-31	Jun Oishi	Targeting kras induced immune checkpoint expression
AU2017379847B2 (en)	2016-12-19	2022-05-26	Sumitomo Pharma Oncology, Inc.	Profiling peptides and methods for sensitivity profiling
CN110366550A (zh)	2016-12-22	2019-10-22	美国安进公司	作为用于治疗肺癌、胰腺癌或结直肠癌的KRAS G12C抑制剂的苯并异噻唑、异噻唑并[3,4-b]吡啶、喹唑啉、酞嗪、吡啶并[2,3-d]哒嗪和吡啶并[2,3-d]嘧啶衍生物
EP3573966A1 (en)	2017-01-26	2019-12-04	Araxes Pharma LLC	Fused n-heterocyclic compounds and methods of use thereof
WO2018140599A1 (en)	2017-01-26	2018-08-02	Araxes Pharma Llc	Benzothiophene and benzothiazole compounds and methods of use thereof
JP7327802B2 (ja)	2017-01-26	2023-08-16	アラクセスファーマエルエルシー	縮合ヘテロ－ヘテロ二環式化合物およびその使用方法
EP3573954A1 (en)	2017-01-26	2019-12-04	Araxes Pharma LLC	Fused bicyclic benzoheteroaromatic compounds and methods of use thereof
WO2018140513A1 (en)	2017-01-26	2018-08-02	Araxes Pharma Llc	1-(3-(6-(3-hydroxynaphthalen-1-yl)benzofuran-2-yl)azetidin-1yl)prop-2-en-1-one derivatives and similar compounds as kras g12c modulators for treating cancer
WO2018137705A1 (en)	2017-01-26	2018-08-02	Zai Lab (Shanghai) Co., Ltd.	Cd47 antigen binding unit and uses thereof
US11136308B2 (en)	2017-01-26	2021-10-05	Araxes Pharma Llc	Substituted quinazoline and quinazolinone compounds and methods of use thereof
WO2018175746A1 (en)	2017-03-24	2018-09-27	Kura Oncology, Inc.	Methods for treating hematological malignancies and ewing's sarcoma
AU2018273356B2 (en)	2017-05-22	2021-09-16	Amgen Inc.	KRAS G12C inhibitors and methods of using the same
WO2018218069A1 (en)	2017-05-25	2018-11-29	Araxes Pharma Llc	Quinazoline derivatives as modulators of mutant kras, hras or nras
CN110869357A (zh)	2017-05-25	2020-03-06	亚瑞克西斯制药公司	化合物及其用于治疗癌症的使用方法
US10745385B2 (en)	2017-05-25	2020-08-18	Araxes Pharma Llc	Covalent inhibitors of KRAS
WO2018226976A1 (en)	2017-06-08	2018-12-13	Kura Oncology, Inc.	Methods and compositions for inhibiting the interaction of menin with mll proteins
WO2019023316A1 (en)	2017-07-26	2019-01-31	Sutro Biopharma, Inc.	METHODS OF USING ANTI-CD74 ANTIBODIES AND ANTIBODY CONJUGATES IN THE TREATMENT OF A T CELL LYMPHOMA
AU2018329920B2 (en)	2017-09-08	2022-12-01	Amgen Inc.	Inhibitors of KRAS G12C and methods of using the same
JP7196160B2 (ja)	2017-09-12	2022-12-26	スミトモファーマオンコロジー，インコーポレイテッド	Ｍｃｌ－１阻害剤アルボシジブを用いた、ｂｃｌ－２阻害剤に対して非感受性である癌の治療レジメン
KR20250035037A (ko)	2017-09-18	2025-03-11	서트로 바이오파마, 인크.	항-엽산 수용체 알파 항체 접합체 및 이의 용도
EP3684361A4 (en)	2017-09-20	2021-09-08	Kura Oncology, Inc.	SUBSTITUTED INHIBITORS OF MENIN-MLL AND METHOD OF USING
US20200237766A1 (en)	2017-10-13	2020-07-30	Tolero Pharmaceuticals, Inc.	Pkm2 activators in combination with reactive oxygen species for treatment of cancer
WO2019094773A1 (en)	2017-11-10	2019-05-16	The Regents Of The University Of Michigan	Ash1l inhibitors and methods of treatment therewith
CN112040947A (zh)	2017-12-07	2020-12-04	密歇根大学董事会	Nsd家族抑制剂及用其进行治疗的方法
KR20210003780A (ko)	2018-04-05	2021-01-12	스미토모 다이니폰 파마 온콜로지, 인크.	Axl 키나제 억제제 및 그의 용도
CA3098574A1 (en)	2018-05-04	2019-11-07	Amgen Inc.	Kras g12c inhibitors and methods of using the same
EP3788053B1 (en)	2018-05-04	2024-07-10	Amgen Inc.	Kras g12c inhibitors and methods of using the same
MA52564A (fr)	2018-05-10	2021-03-17	Amgen Inc	Inhibiteurs de kras g12c pour le traitement du cancer
US11096939B2 (en)	2018-06-01	2021-08-24	Amgen Inc.	KRAS G12C inhibitors and methods of using the same
WO2019236957A1 (en)	2018-06-07	2019-12-12	The Regents Of The University Of Michigan	Prc1 inhibitors and methods of treatment therewith
MX2020012204A (es)	2018-06-11	2021-03-31	Amgen Inc	Inhibidores de kras g12c para tratar el cáncer.
US11285156B2 (en)	2018-06-12	2022-03-29	Amgen Inc.	Substituted piperazines as KRAS G12C inhibitors
AU2019310590A1 (en)	2018-07-26	2021-01-14	Sumitomo Pharma Oncology, Inc.	Methods for treating diseases associated with abnormal acvr1 expression and acvr1 inhibitors for use in the same
MX2021000887A (es)	2018-08-01	2021-03-31	Araxes Pharma Llc	Compuestos espiroheterociclicos y metodos de uso de los mismos para el tratamiento de cancer.
JP2022500454A (ja)	2018-09-17	2022-01-04	ストロバイオファーマインコーポレーテッド	抗葉酸受容体抗体コンジュゲートによる併用療法
CN113207291A (zh)	2018-10-24	2021-08-03	亚瑞克西斯制药公司	2-(2-丙烯酰基-2,6-二氮杂螺[3.4]辛-6-基)-6-(1h-吲唑-4-基)苄腈衍生物及相关化合物作为用于抑制肿瘤转移的g12c突变kras蛋白的抑制剂
JP7516029B2 (ja)	2018-11-16	2024-07-16	アムジエン・インコーポレーテツド	Ｋｒａｓｇ１２ｃ阻害剤化合物の重要な中間体の改良合成法
AU2019384118B2 (en)	2018-11-19	2025-06-12	Amgen Inc.	KRAS G12C inhibitors and methods of using the same
JP7377679B2 (ja)	2018-11-19	2023-11-10	アムジエン・インコーポレーテツド	がん治療のためのｋｒａｓｇ１２ｃ阻害剤及び１種以上の薬学的に活性な追加の薬剤を含む併用療法
EP3887373A1 (en)	2018-11-29	2021-10-06	Araxes Pharma LLC	Compounds and methods of use thereof for treatment of cancer
US11034710B2 (en)	2018-12-04	2021-06-15	Sumitomo Dainippon Pharma Oncology, Inc.	CDK9 inhibitors and polymorphs thereof for use as agents for treatment of cancer
JP7686559B2 (ja)	2018-12-20	2025-06-02	アムジエン・インコーポレーテツド	Ｋｉｆ１８ａ阻害剤
JP2022513967A (ja)	2018-12-20	2022-02-09	アムジエン・インコーポレーテツド	Ｋｉｆ１８ａ阻害剤として有用なヘテロアリールアミド
AU2019401495B2 (en)	2018-12-20	2025-06-26	Amgen Inc.	Heteroaryl amides useful as KIF18A inhibitors
MA54543A (fr)	2018-12-20	2022-03-30	Amgen Inc	Inhibiteurs de kif18a
KR20260008165A (ko)	2019-02-12	2026-01-15	스미토모 파마 아메리카, 인크.	헤테로시클릭 단백질 키나제 억제제를 포함하는 제제
MX2021010319A (es)	2019-03-01	2021-12-10	Revolution Medicines Inc	Compuestos biciclicos de heteroarilo y usos de estos.
MX2021010323A (es)	2019-03-01	2021-12-10	Revolution Medicines Inc	Compuestos bicíclicos de heterociclilo y usos de este.
WO2020191326A1 (en)	2019-03-20	2020-09-24	Sumitomo Dainippon Pharma Oncology, Inc.	Treatment of acute myeloid leukemia (aml) with venetoclax failure
KR20210141621A (ko)	2019-03-22	2021-11-23	스미토모 다이니폰 파마 온콜로지, 인크.	Pkm2 조정제를 포함하는 조성물 및 그를 사용한 치료 방법
WO2020227105A1 (en)	2019-05-03	2020-11-12	Sutro Biopharma, Inc.	Anti-bcma antibody conjugates
EP3738593A1 (en)	2019-05-14	2020-11-18	Amgen, Inc	Dosing of kras inhibitor for treatment of cancers
WO2020236947A1 (en)	2019-05-21	2020-11-26	Amgen Inc.	Solid state forms
EP3994132A1 (en)	2019-07-03	2022-05-11	Sumitomo Dainippon Pharma Oncology, Inc.	Tyrosine kinase non-receptor 1 (tnk1) inhibitors and uses thereof
EP4007638A1 (en)	2019-08-02	2022-06-08	Amgen Inc.	Pyridine derivatives as kif18a inhibitors
EP4007752B1 (en)	2019-08-02	2025-09-24	Amgen Inc.	Kif18a inhibitors
EP4007756B1 (en)	2019-08-02	2025-12-24	Amgen Inc.	Kif18a inhibitors
EP4007753B1 (en)	2019-08-02	2025-09-24	Amgen Inc.	Kif18a inhibitors
US20220402916A1 (en)	2019-09-18	2022-12-22	Merck Sharp & Dohme Corp.	Small molecule inhibitors of kras g12c mutant
WO2021067215A1 (en)	2019-09-30	2021-04-08	Agios Pharmaceuticals, Inc.	Piperidine compounds as menin inhibitors
EP4048671B1 (en)	2019-10-24	2026-03-18	Amgen Inc.	Pyridopyrimidine derivatives useful as kras g12c and kras g12d inhibitors in the treatment of cancer
UA129778C2 (uk)	2019-10-28	2025-07-30	Мерк Шарп Енд Доум Елелсі	Низькомолекулярні інгібітори g12c-мутантного kras
US20230023023A1 (en)	2019-10-31	2023-01-26	Taiho Pharmaceutical Co., Ltd.	4-aminobut-2-enamide derivatives and salts thereof
IL322454A (en)	2019-11-04	2025-09-01	Revolution Medicines Inc	ras inhibitors
AU2020377925A1 (en)	2019-11-04	2022-05-05	Revolution Medicines, Inc.	Ras inhibitors
TW202132316A (zh)	2019-11-04	2021-09-01	美商銳新醫藥公司	Ｒａｓ抑制劑
CA3156359A1 (en)	2019-11-08	2021-05-14	Adrian Liam Gill	Bicyclic heteroaryl compounds and uses thereof
JP2023501528A (ja)	2019-11-14	2023-01-18	アムジエン・インコーポレーテツド	Ｋｒａｓｇ１２ｃ阻害剤化合物の改善された合成
JP7837865B2 (ja)	2019-11-14	2026-03-31	アムジエン・インコーポレーテツド	Ｋｒａｓｇ１２ｃ阻害剤化合物の改良合成法
EP4065231A1 (en)	2019-11-27	2022-10-05	Revolution Medicines, Inc.	Covalent ras inhibitors and uses thereof
WO2021106231A1 (en)	2019-11-29	2021-06-03	Taiho Pharmaceutical Co., Ltd.	A compound having inhibitory activity against kras g12d mutation
WO2021142026A1 (en)	2020-01-07	2021-07-15	Revolution Medicines, Inc.	Shp2 inhibitor dosing and methods of treating cancer
WO2021155006A1 (en)	2020-01-31	2021-08-05	Les Laboratoires Servier Sas	Inhibitors of cyclin-dependent kinases and uses thereof
US20230095053A1 (en)	2020-03-03	2023-03-30	Sutro Biopharma, Inc.	Antibodies comprising site-specific glutamine tags, methods of their preparation and methods of their use
WO2021207310A1 (en)	2020-04-08	2021-10-14	Agios Pharmaceuticals, Inc.	Menin inhibitors and methods of use for treating cancer
TW202204333A (zh)	2020-04-08	2022-02-01	美商阿吉歐斯製藥公司	Menin抑制劑及治療癌症之使用方法
WO2021215544A1 (en)	2020-04-24	2021-10-28	Taiho Pharmaceutical Co., Ltd.	Kras g12d protein inhibitors
WO2021215545A1 (en)	2020-04-24	2021-10-28	Taiho Pharmaceutical Co., Ltd.	Anticancer combination therapy with n-(1-acryloyl-azetidin-3-yl)-2-((1h-indazol-3-yl)amino)methyl)-1h-imidazole-5-carboxamide inhibitor of kras-g12c
IL299131A (en)	2020-06-18	2023-02-01	Revolution Medicines Inc	Methods for delaying, preventing and treating acquired resistance to RAS inhibitors
CA3185209A1 (en)	2020-07-10	2021-01-27	Alyssa WINKLER	Gas41 inhibitors and methods of use thereof
EP4183395A4 (en)	2020-07-15	2024-07-24	Taiho Pharmaceutical Co., Ltd.	PYRIMIDINE COMPOUND-CONTAINING COMBINATION FOR USE IN TUMOR TREATMENT
WO2022019920A1 (en)	2020-07-24	2022-01-27	Verastem, Inc.	Treatment of cancers using pi3 kinase isoform modulators
US20250195521A1 (en)	2020-09-03	2025-06-19	Revolution Medicines, Inc.	Use of sos1 inhibitors to treat malignancies with shp2 mutations
CA3194067A1 (en)	2020-09-15	2022-03-24	Revolution Medicines, Inc.	Ras inhibitors
TW202237119A (zh)	2020-12-10	2022-10-01	美商住友製藥腫瘤公司	Ａｌｋ﹘５抑制劑和彼之用途
JP7849366B2 (ja)	2020-12-22	2026-04-21	キル・レガー・セラピューティクス・インコーポレーテッド	Ｓｏｓ１阻害剤およびその使用
TW202309022A (zh)	2021-04-13	2023-03-01	美商努法倫特公司	用於治療具egfr突變之癌症之胺基取代雜環
WO2022232488A1 (en)	2021-04-30	2022-11-03	Celgene Corporation	Combination therapies using an anti-bcma antibody drug conjugate (adc) in combination with a gamma secretase inhibitor (gsi)
JP2024516450A (ja)	2021-05-05	2024-04-15	レボリューションメディシンズインコーポレイテッド	共有結合性ｒａｓ阻害剤及びその使用
KR20240017811A (ko)	2021-05-05	2024-02-08	레볼루션 메디슨즈, 인크.	암의 치료를 위한 ras 억제제
TW202309052A (zh)	2021-05-05	2023-03-01	美商銳新醫藥公司	Ｒａｓ抑制劑
EP4347041A1 (en)	2021-05-28	2024-04-10	Taiho Pharmaceutical Co., Ltd.	Small molecule inhibitors of kras mutated proteins
JP2024521399A (ja)	2021-06-10	2024-05-31	ニューレリス、インク．	小児患者における発作性障害を治療するための組成物および方法
AR127308A1 (es)	2021-10-08	2024-01-10	Revolution Medicines Inc	Inhibidores ras
WO2023056589A1 (en)	2021-10-08	2023-04-13	Servier Pharmaceuticals Llc	Menin inhibitors and methods of use for treating cancer
US20240294548A1 (en)	2021-10-12	2024-09-05	Peloton Therapeutics Inc.	Tricyclic sultams and sulfamides as antitumor agents
CN119212994A (zh)	2021-12-17	2024-12-27	建新公司	作为shp2抑制剂的吡唑并吡嗪化合物
EP4227307A1 (en)	2022-02-11	2023-08-16	Genzyme Corporation	Pyrazolopyrazine compounds as shp2 inhibitors
KR20240156373A (ko)	2022-03-07	2024-10-29	암젠 인크	4-메틸-2-프로판-2-일-피리딘-3-카르보니트릴의 제조 방법
JP2025510572A (ja)	2022-03-08	2025-04-15	レボリューションメディシンズインコーポレイテッド	免疫不応性肺癌を治療するための方法
TW202412755A (zh)	2022-04-25	2024-04-01	美商耐斯泰德醫療公司	促分裂原活化蛋白激酶（ｍｅｋ）抑制劑
WO2023240263A1 (en)	2022-06-10	2023-12-14	Revolution Medicines, Inc.	Macrocyclic ras inhibitors
CA3259758A1 (en)	2022-06-30	2024-01-04	Sutro Biopharma, Inc.	Anti-ROR1 antibodies and antibody conjugates, compositions comprising anti-ROR1 antibodies or antibody conjugates, and methods of manufacturing and using anti-ROR1 antibodies and antibody conjugates
JP2025521928A (ja)	2022-07-08	2025-07-10	ネステッド・セラピューティクス・インコーポレイテッド	マイトジェン活性化プロテインキナーゼ（ｍｅｋ）阻害剤
AU2023358792A1 (en)	2022-10-14	2025-04-17	Black Diamond Therapeutics, Inc.	Methods of treating cancers using isoquinoline or 6-aza-quinoline derivatives
AU2024241633A1 (en)	2023-03-30	2025-11-06	Revolution Medicines, Inc.	Compositions for inducing ras gtp hydrolysis and uses thereof
CR20250420A (es)	2023-04-07	2025-11-20	Revolution Medicines Inc	Inhibidores macrocíclicos de ras
AR132338A1 (es)	2023-04-07	2025-06-18	Revolution Medicines Inc	Inhibidores de ras
CN121100123A (zh)	2023-04-14	2025-12-09	锐新医药公司	Ras抑制剂的结晶形式
CN121464140A (zh)	2023-04-14	2026-02-03	锐新医药公司	Ras抑制剂的结晶形式、含有其的组合物及其使用方法
CN121889153A (zh)	2023-04-24	2026-04-17	耐斯泰德医疗公司	作为促分裂原活化蛋白激酶(mek)抑制剂的杂环衍生物
TW202508595A (zh)	2023-05-04	2025-03-01	美商銳新醫藥公司	用於ｒａｓ相關疾病或病症之組合療法
US20250049810A1 (en)	2023-08-07	2025-02-13	Revolution Medicines, Inc.	Methods of treating a ras protein-related disease or disorder
WO2025043187A1 (en)	2023-08-24	2025-02-27	Otsuka Pharmaceutical Co., Ltd.	Fixed dose combinations of cedazuridine and azacitidine
AU2024360465A1 (en)	2023-10-12	2026-04-09	Revolution Medicines, Inc.	Macrocyclic ras inhibitors
AU2024358957A1 (en)	2023-10-13	2026-04-02	Sutro Biopharma, Inc.	Anti-tissue factor antibodies and antibody conjugates, compositions comprising anti-tissue factor antibodies or antibody conjugates, and methods of making and using anti-tissue factor antibodies and antibody conjugates
AU2024361909A1 (en)	2023-10-20	2026-03-26	Merck Sharp & Dohme Llc	Small molecule inhibitors of kras proteins
WO2025090905A1 (en)	2023-10-26	2025-05-01	Nested Therapeutics, Inc.	Crystalline forms of 3-[[3-fluoro-2-(methylsulfamoylamino)-4-pyridyl]methyl]-7-[(3-fluoro-2-pyridyl)oxy]-4-methyl-chromen-2-one
TW202542151A (zh)	2023-12-22	2025-11-01	美商銳格醫藥有限公司	Ｓｏｓ１抑制劑及其用途
TW202547461A (zh)	2024-05-17	2025-12-16	美商銳新醫藥公司	Ｒａｓ抑制劑
WO2025250825A1 (en)	2024-05-30	2025-12-04	Sutro Biopharma, Inc.	Anti-trop2 antibodies, compositions comprising anti-trop2 antibodies and methods of making and using anti-trop2 antibodies
WO2025255438A1 (en)	2024-06-07	2025-12-11	Revolution Medicines, Inc.	Methods of treating a ras protein-related disease or disorder
WO2025259841A1 (en)	2024-06-13	2025-12-18	Nested Therapeutics, Inc.	Crystalline forms of 3-[[3-fluoro-2-(methylsulfamoylamino)-4-pyridyl]jmethyl]-7-[(3-fluoro-2-pyridyl)oxy]-4-methyl-chromen-2-one
WO2025265060A1 (en)	2024-06-21	2025-12-26	Revolution Medicines, Inc.	Therapeutic compositions and methods for managing treatment-related effects
WO2026006747A1 (en)	2024-06-28	2026-01-02	Revolution Medicines, Inc.	Ras inhibitors
WO2026015825A1 (en)	2024-07-12	2026-01-15	Revolution Medicines, Inc.	Use of ras inhibitor for treating pancreatic cancer
WO2026015790A1 (en)	2024-07-12	2026-01-15	Revolution Medicines, Inc.	Methods of treating a ras related disease or disorder
WO2026015796A1 (en)	2024-07-12	2026-01-15	Revolution Medicines, Inc.	Methods of treating a ras related disease or disorder
WO2026015801A1 (en)	2024-07-12	2026-01-15	Revolution Medicines, Inc.	Methods of treating a ras related disease or disorder
WO2026035750A1 (en)	2024-08-05	2026-02-12	Pivot Therapeutics, Inc.	Inhibitors of akt and uses thereof
WO2026043823A2 (en)	2024-08-19	2026-02-26	Sutro Biopharma, Inc.	Antibodies comprising site-specific non-natural amino acid residues, methods of preparation and uses thereof
WO2026050446A1 (en)	2024-08-29	2026-03-05	Revolution Medicines, Inc.	Ras inhibitors
WO2026072904A2 (en)	2024-09-26	2026-04-02	Revolution Medicines, Inc.	Compositions and methods for treating lung cancer
WO2026080697A1 (en)	2024-10-09	2026-04-16	Sutro Biopharma, Inc.	Antibody conjugates with high payload to antibody ratios, compositions comprising the same, and methods of their use

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5455258A (en)	1993-01-06	1995-10-03	Ciba-Geigy Corporation	Arylsulfonamido-substituted hydroxamic acids
ES2153031T4 (es) *	1995-04-20	2001-05-16	Pfizer	Derivados del acido arilsulfonil hidroxamico como inhibidores de mmp y tnf.
US5753653A (en)	1995-12-08	1998-05-19	Agouron Pharmaceuticals, Inc.	Metalloproteinase inhibitors, pharmaceutical compositions containing them and their pharmaceutical uses
KR100339296B1 (ko)	1996-08-28	2002-06-03	데이비드 엠 모이어	헤테로고리성 메탈로프로테아제 억제제
ATE226193T1 (de)	1996-08-28	2002-11-15	Procter & Gamble	Substituierte zyklische amine als metalloproteaseinhibitoren
EP0960098A1 (en) *	1997-02-11	1999-12-01	Pfizer Inc.	Arylsulfonyl hydroxamic acid derivatives
JPH11199512A (ja) *	1997-10-24	1999-07-27	Pfizer Prod Inc	変形性関節症および他のｍｍｐ媒介疾患の治療のためのｍｍｐ−１３選択的阻害剤の使用

1998
- 1998-01-16 EP EP98900124A patent/EP0960098A1/en not_active Withdrawn
- 1998-01-16 YU YU37499A patent/YU37499A/sh unknown
- 1998-01-16 EA EA199900641A patent/EA002546B1/ru not_active IP Right Cessation
- 1998-01-16 IL IL13112398A patent/IL131123A0/xx not_active IP Right Cessation
- 1998-01-16 KR KR1019997007188A patent/KR20000070923A/ko not_active Ceased
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- 1998-01-16 JP JP53404098A patent/JP3710489B2/ja not_active Expired - Fee Related
- 1998-01-16 WO PCT/IB1998/000064 patent/WO1998034918A1/en not_active Ceased
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- 1998-01-16 CN CN98802460A patent/CN1247531A/zh active Pending
- 1998-01-16 AU AU53366/98A patent/AU722784B2/en not_active Ceased
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1999
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2000
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Also Published As

Publication number	Publication date
US6599890B1 (en)	2003-07-29
UY24880A1 (es)	2000-09-29
NZ336836A (en)	2001-02-23
NO993836D0 (no)	1999-08-10
JP2000510162A (ja)	2000-08-08
PE58699A1 (es)	1999-06-21
MA24469A1 (fr)	1998-10-01
HRP980070A2 (en)	1998-12-31
BG63430B1 (bg)	2002-01-31
ZA981061B (en)	1999-08-10
BG103641A (en)	2000-02-29
AP958A (en)	2001-04-17
CO4950619A1 (es)	2000-09-01
CA2280151C (en)	2005-12-13
TW502020B (en)	2002-09-11
DZ2416A1 (fr)	2003-01-04
CA2280151A1 (en)	1998-08-13
JP3710489B2 (ja)	2005-10-26
EA199900641A1 (ru)	2000-04-24
NO993836L (no)	1999-10-08
KR20000070923A (ko)	2000-11-25
YU37499A (sh)	2002-09-19
ID22809A (id)	1999-12-09
CN1247531A (zh)	2000-03-15
BR9807678A (pt)	2000-02-15
PL334997A1 (en)	2000-03-27
IL131123A0 (en)	2001-01-28
EA002546B1 (ru)	2002-06-27
SA98180856A (ar)	2005-12-03
PA8446101A1 (es)	2000-05-24
OA11142A (en)	2003-04-25
TNSN98025A1 (fr)	2005-03-15
HUP0000657A2 (hu)	2000-09-28
GT199800026A (es)	1999-07-27
IS5130A (is)	1999-07-23
HRP980070B1 (en)	2002-10-31
HUP0000657A3 (en)	2000-10-30
AU722784B2 (en)	2000-08-10
EP0960098A1 (en)	1999-12-01
WO1998034918A1 (en)	1998-08-13
TR199901926T2 (xx)	1999-12-21
HN1998000020A (es)	1999-01-08
AR011123A1 (es)	2000-08-02
AU5336698A (en)	1998-08-26

Publication	Publication Date	Title
SK101399A3 (en)	2001-09-11	Arylsulfonyl hydroxamic acid derivatives
US6153609A (en)	2000-11-28	Arylsulfonylamino hydroxamic acid derivatives
KR100219976B1 (ko)	1999-09-01	아릴설포닐 하이드록삼산 유도체
CN1122662C (zh)	2003-10-01	芳基磺酰氨基异羟肟酸衍生物
KR100317146B1 (ko)	2001-12-22	아릴술포닐아미노 히드록삼산 유도체
US6380219B1 (en)	2002-04-30	Arylsulfonylamino hydroxamic acid derivatives
US6509337B1 (en)	2003-01-21	Arylsulfonyl Hydroxamic Acid derivatives as MMP and TNF inhibitors
CZ9902833A3 (cs)	2000-10-11	Deriváty arylsulfonylhydroxamových kyselin, farmaceutický prostředek, způsob inhibice matričních metalloproteinas nebo produkce faktoru nekrosy nádorů a způsob léčení
KR100194258B1 (ko)	1999-06-15	아릴설포닐 하이드록삼산 유도체
MXPA99007385A (en)	2000-07-01	Arylsulfonyl hydroxamic acid derivatives
CZ58999A3 (cs)	2000-03-15	Deriváty arylsulfonylaminohydroxamové kyseliny, farmaceutický prostředek, způsob inhibice matričních metalloproteinas nebo produkce faktoru nekrosy nádorů a způsob léčení
MXPA99001808A (en)	1999-09-20	Arylsulfonylamino hydroxamic acid derivatives
MXPA99006301A (en)	2000-07-01	Cyclic sulfone derivatives
CZ267699A3 (cs)	2000-09-13	Deriváty arylsulfonylaminohydroxamové kyseliny, farmaceutický prostředek, způsob inhibice matričních metalloproteinas nebo produkce faktoru nekrosy nádorů a způsob léčení