HRP20000493A2 - Novel sulfonamide derivatives as inhibitors of bone resorption and as inhibitors of cell adhesion - Google Patents
Novel sulfonamide derivatives as inhibitors of bone resorption and as inhibitors of cell adhesion Download PDFInfo
- Publication number
- HRP20000493A2 HRP20000493A2 HR20000493A HRP20000493A HRP20000493A2 HR P20000493 A2 HRP20000493 A2 HR P20000493A2 HR 20000493 A HR20000493 A HR 20000493A HR P20000493 A HRP20000493 A HR P20000493A HR P20000493 A2 HRP20000493 A2 HR P20000493A2
- Authority
- HR
- Croatia
- Prior art keywords
- alkyl
- radical
- aryl
- formula
- heteroaryl
- Prior art date
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- 208000006386 Bone Resorption Diseases 0.000 title claims description 18
- 230000024279 bone resorption Effects 0.000 title claims description 18
- 239000003112 inhibitor Substances 0.000 title description 11
- 229940124530 sulfonamide Drugs 0.000 title description 4
- 150000003456 sulfonamides Chemical class 0.000 title description 4
- 230000021164 cell adhesion Effects 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 147
- -1 cyano, hydroxyl Chemical group 0.000 claims description 144
- 150000003254 radicals Chemical class 0.000 claims description 102
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 64
- 150000003839 salts Chemical class 0.000 claims description 64
- 239000000651 prodrug Substances 0.000 claims description 56
- 229940002612 prodrug Drugs 0.000 claims description 56
- 239000000203 mixture Substances 0.000 claims description 54
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 52
- 239000001257 hydrogen Substances 0.000 claims description 50
- 229910052739 hydrogen Inorganic materials 0.000 claims description 50
- 238000000034 method Methods 0.000 claims description 45
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 39
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 38
- 229920006395 saturated elastomer Polymers 0.000 claims description 37
- 125000006708 (C5-C14) heteroaryl group Chemical group 0.000 claims description 32
- 125000002837 carbocyclic group Chemical group 0.000 claims description 30
- 229910052736 halogen Inorganic materials 0.000 claims description 26
- 150000002367 halogens Chemical class 0.000 claims description 26
- 125000004043 oxo group Chemical group O=* 0.000 claims description 24
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 23
- 238000011321 prophylaxis Methods 0.000 claims description 19
- 102100022337 Integrin alpha-V Human genes 0.000 claims description 18
- 108010048673 Vitronectin Receptors Proteins 0.000 claims description 18
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 16
- 150000005840 aryl radicals Chemical class 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 13
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 12
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims description 11
- 208000001132 Osteoporosis Diseases 0.000 claims description 11
- 230000015572 biosynthetic process Effects 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 230000008569 process Effects 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 150000001450 anions Chemical class 0.000 claims description 10
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 125000000524 functional group Chemical group 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- XLQRIUSFTHXJOG-QFIPXVFZSA-N (2s)-2-(naphthalen-1-ylsulfonylamino)-3-[[4-[3-oxo-3-(1,4,5,6-tetrahydropyrimidin-2-ylamino)propyl]benzoyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NS(=O)(=O)C=1C2=CC=CC=C2C=CC=1)NC(=O)C(C=C1)=CC=C1CCC(=O)NC1=NCCCN1 XLQRIUSFTHXJOG-QFIPXVFZSA-N 0.000 claims description 9
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 9
- 206010028980 Neoplasm Diseases 0.000 claims description 9
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 9
- 150000002357 guanidines Chemical class 0.000 claims description 9
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 7
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 7
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 206010027476 Metastases Diseases 0.000 claims description 4
- 230000004614 tumor growth Effects 0.000 claims description 4
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 208000017442 Retinal disease Diseases 0.000 claims description 3
- 206010038923 Retinopathy Diseases 0.000 claims description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 208000037803 restenosis Diseases 0.000 claims description 3
- 125000004494 ethyl ester group Chemical group 0.000 claims description 2
- 239000012634 fragment Substances 0.000 claims description 2
- 208000017169 kidney disease Diseases 0.000 claims description 2
- 239000002243 precursor Substances 0.000 claims 2
- 206010061218 Inflammation Diseases 0.000 claims 1
- 239000005864 Sulphur Substances 0.000 claims 1
- 230000000903 blocking effect Effects 0.000 claims 1
- 230000004054 inflammatory process Effects 0.000 claims 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims 1
- 239000000047 product Substances 0.000 description 100
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 93
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 42
- 239000002904 solvent Substances 0.000 description 42
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 28
- 239000000243 solution Substances 0.000 description 27
- 210000004027 cell Anatomy 0.000 description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 19
- 210000002997 osteoclast Anatomy 0.000 description 19
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- 239000002253 acid Substances 0.000 description 15
- 238000002560 therapeutic procedure Methods 0.000 description 15
- 239000004480 active ingredient Substances 0.000 description 14
- 239000000872 buffer Substances 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 125000005842 heteroatom Chemical group 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 210000000988 bone and bone Anatomy 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 8
- 150000001735 carboxylic acids Chemical class 0.000 description 8
- 239000000969 carrier Substances 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 230000009471 action Effects 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 229910052717 sulfur Inorganic materials 0.000 description 7
- PEHDFSFYZKSKGH-UHFFFAOYSA-N 1,4,5,6-tetrahydropyrimidin-2-amine Chemical compound NC1=NCCCN1 PEHDFSFYZKSKGH-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 125000002619 bicyclic group Chemical group 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- 229940011871 estrogen Drugs 0.000 description 6
- 239000000262 estrogen Substances 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
- 208000020084 Bone disease Diseases 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 125000002252 acyl group Chemical group 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 210000002805 bone matrix Anatomy 0.000 description 5
- 125000002950 monocyclic group Chemical group 0.000 description 5
- 239000002464 receptor antagonist Substances 0.000 description 5
- 229940044551 receptor antagonist Drugs 0.000 description 5
- CZXTYIYINDZRAD-AWEZNQCLSA-N tert-butyl (2s)-2-amino-3-[[4-(3-methoxy-3-oxopropyl)benzoyl]amino]propanoate Chemical compound COC(=O)CCC1=CC=C(C(=O)NC[C@H](N)C(=O)OC(C)(C)C)C=C1 CZXTYIYINDZRAD-AWEZNQCLSA-N 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- 101000803709 Homo sapiens Vitronectin Proteins 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 4
- FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 230000033115 angiogenesis Effects 0.000 description 4
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- 201000011510 cancer Diseases 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- XSOIIFAHTXDPCI-QFIPXVFZSA-N (2s)-2-[(4-tert-butylphenyl)sulfonylamino]-3-[[4-[3-oxo-3-(1,4,5,6-tetrahydropyrimidin-2-ylamino)propyl]benzoyl]amino]propanoic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1S(=O)(=O)N[C@H](C(O)=O)CNC(=O)C(C=C1)=CC=C1CCC(=O)NC1=NCCCN1 XSOIIFAHTXDPCI-QFIPXVFZSA-N 0.000 description 3
- SYDPQTZOZHZQRA-FQEVSTJZSA-N (2s)-3-[[4-[3-oxo-3-(1,4,5,6-tetrahydropyrimidin-2-ylamino)propyl]benzoyl]amino]-2-(quinolin-8-ylsulfonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NS(=O)(=O)C=1C2=NC=CC=C2C=CC=1)NC(=O)C(C=C1)=CC=C1CCC(=O)NC1=NCCCN1 SYDPQTZOZHZQRA-FQEVSTJZSA-N 0.000 description 3
- FUJPHFYUOLGWNC-NRFANRHFSA-N (2s)-3-[[4-[3-oxo-3-(1,4,5,6-tetrahydropyrimidin-2-ylamino)propyl]benzoyl]amino]-2-[[2-(1,4,5,6-tetrahydropyrimidin-2-ylcarbamoyl)phenyl]sulfonylamino]propanoic acid Chemical compound C([C@@H](C(=O)O)NS(=O)(=O)C=1C(=CC=CC=1)C(=O)NC=1NCCCN=1)NC(=O)C(C=C1)=CC=C1CCC(=O)NC1=NCCCN1 FUJPHFYUOLGWNC-NRFANRHFSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
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- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
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- ZHZZWIQPCAMTIM-UHFFFAOYSA-N [C]1=CC=CC2=CC=CC=C12 Chemical group [C]1=CC=CC2=CC=CC=C12 ZHZZWIQPCAMTIM-UHFFFAOYSA-N 0.000 description 3
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- 150000001602 bicycloalkyls Chemical group 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
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- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
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- 230000030991 negative regulation of bone resorption Effects 0.000 description 3
- 238000011275 oncology therapy Methods 0.000 description 3
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C311/19—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/06—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D239/08—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms directly attached in position 2
- C07D239/12—Nitrogen atoms not forming part of a nitro radical
- C07D239/16—Nitrogen atoms not forming part of a nitro radical acylated on said nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms
-
- 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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1248998A | 1998-01-23 | 1998-01-23 | |
| PCT/EP1999/000242 WO1999037621A1 (en) | 1998-01-23 | 1999-01-16 | Novel sulfonamide derivatives as inhibitors of bone resorption and as inhibitors of cell adhesion |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20000493A2 true HRP20000493A2 (en) | 2001-06-30 |
Family
ID=21755208
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20000493A HRP20000493A2 (en) | 1998-01-23 | 2000-07-21 | Novel sulfonamide derivatives as inhibitors of bone resorption and as inhibitors of cell adhesion |
Country Status (25)
| Country | Link |
|---|---|
| EP (1) | EP1049677A1 (id) |
| JP (1) | JP2002501054A (id) |
| KR (1) | KR20010034319A (id) |
| CN (1) | CN1177832C (id) |
| AP (1) | AP1269A (id) |
| AR (1) | AR014456A1 (id) |
| AU (1) | AU752882B2 (id) |
| BG (1) | BG104630A (id) |
| BR (1) | BR9907735A (id) |
| CA (1) | CA2318221A1 (id) |
| EA (1) | EA003102B1 (id) |
| HR (1) | HRP20000493A2 (id) |
| HU (1) | HUP0100520A3 (id) |
| ID (1) | ID26219A (id) |
| IL (1) | IL137423A0 (id) |
| NO (1) | NO318795B1 (id) |
| NZ (1) | NZ505613A (id) |
| PL (1) | PL341871A1 (id) |
| SK (1) | SK10632000A3 (id) |
| TR (1) | TR200002160T2 (id) |
| TW (1) | TWI247742B (id) |
| UA (1) | UA63990C2 (id) |
| WO (1) | WO1999037621A1 (id) |
| YU (1) | YU47200A (id) |
| ZA (1) | ZA99476B (id) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1100506A4 (en) * | 1998-07-29 | 2002-06-26 | Merck & Co Inc | INTEGRIN RECEPTOR ANTAGONISTS |
| EP1028114A1 (en) | 1999-02-13 | 2000-08-16 | Aventis Pharma Deutschland GmbH | Novel guanidine derivatives as inhibitors of cell adhesion |
| EP1065208A1 (en) * | 1999-07-02 | 2001-01-03 | Aventis Pharma Deutschland GmbH | Substituted purine derivatives as inhibitors of cell adhesion |
| EP1065207A1 (en) | 1999-07-02 | 2001-01-03 | Aventis Pharma Deutschland GmbH | Naphthyridine derivatives, processes for their preparation, their use, and pharmaceutical compositions comprising them |
| EP1070707A1 (en) | 1999-07-21 | 2001-01-24 | Aventis Pharma Deutschland GmbH | 1,4,5,6-tetrahydropyrimidine derivative as a vitronectin inhibitor |
| US6849639B2 (en) | 1999-12-14 | 2005-02-01 | Amgen Inc. | Integrin inhibitors and their methods of use |
| EP1108721A1 (en) * | 1999-12-15 | 2001-06-20 | Aventis Pharma Deutschland GmbH | Thienylalanine derivatives as inhibitors of cell adhesion |
| JP2003519119A (ja) * | 1999-12-24 | 2003-06-17 | スミスクライン ビーチャム パブリック リミテッド カンパニー | （ヘテロ）ビシクリルメタンスルホニルアミノ置換ヒドロキサム酸誘導体 |
| FR2808798A1 (fr) * | 2000-05-09 | 2001-11-16 | Hoechst Marion Roussel Inc | Nouveaux derives antagonistes du recepteur de la vitronectine |
| FR2847254B1 (fr) | 2002-11-19 | 2005-01-28 | Aventis Pharma Sa | Nouveaux derives antagonistes du recepteur de la vitronectine, leur procede de preparation, leur application comme medicaments et les compositions pharmaceutiques les refermant |
| SG151303A1 (en) * | 2004-03-24 | 2009-04-30 | Jerini Ag | New compounds for the inhibition of angiogenesis and use thereof |
| FR2870541B1 (fr) | 2004-05-18 | 2006-07-14 | Proskelia Sas | Derives de pyrimidines antigonistes du recepteur de la vitronectine |
| GB0412553D0 (en) * | 2004-06-04 | 2004-07-07 | Univ Aberdeen | Therapeutic agents for the treatment of bone conditions |
| UA87854C2 (en) | 2004-06-07 | 2009-08-25 | Мерк Энд Ко., Инк. | N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators |
| FR2873585B1 (fr) * | 2004-07-27 | 2006-11-17 | Aventis Pharma Sa | Nouvelles formulations galeniques de principes actifs |
| GB0705400D0 (en) | 2007-03-21 | 2007-05-02 | Univ Aberdeen | Therapeutic compounds andm their use |
| GB0817208D0 (en) | 2008-09-19 | 2008-10-29 | Pimco 2664 Ltd | Therapeutic apsap compounds and their use |
| GB0817207D0 (en) | 2008-09-19 | 2008-10-29 | Pimco 2664 Ltd | therapeutic apsac compounds and their use |
| GB201311361D0 (en) | 2013-06-26 | 2013-08-14 | Pimco 2664 Ltd | Compounds and their therapeutic use |
| KR20160147007A (ko) | 2014-05-30 | 2016-12-21 | 화이자 인코포레이티드 | 선택적인 안드로겐 수용체 조절제로서의 카보니트릴 유도체 |
| CA2970578C (en) | 2014-12-17 | 2024-01-02 | Pimco 2664 Limited | N-(4-hydroxy-4-methyl-cyclohexyl)-4-phenyl-benzenesulfonamide and n-(4-hydroxy-4-methyl-cyclohexyl)-4-(2-pyridyl)-benzenesulfonamide compounds and their therapeutic use |
| WO2023275715A1 (en) | 2021-06-30 | 2023-01-05 | Pfizer Inc. | Metabolites of selective androgen receptor modulators |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2190870A1 (en) * | 1994-05-27 | 1995-12-07 | George D. Hartman | Compounds for inhibiting osteoclast-mediated bone resorption |
| JP3895792B2 (ja) * | 1995-12-08 | 2007-03-22 | プロスケリア・エス・ア・エス | 骨形成促進剤 |
-
1999
- 1999-01-16 SK SK1063-2000A patent/SK10632000A3/sk unknown
- 1999-01-16 HU HU0100520A patent/HUP0100520A3/hu unknown
- 1999-01-16 EA EA200000785A patent/EA003102B1/ru not_active IP Right Cessation
- 1999-01-16 NZ NZ505613A patent/NZ505613A/xx unknown
- 1999-01-16 KR KR1020007008041A patent/KR20010034319A/ko active IP Right Grant
- 1999-01-16 YU YU47200A patent/YU47200A/sh unknown
- 1999-01-16 CA CA002318221A patent/CA2318221A1/en not_active Abandoned
- 1999-01-16 PL PL99341871A patent/PL341871A1/xx unknown
- 1999-01-16 TR TR2000/02160T patent/TR200002160T2/xx unknown
- 1999-01-16 AU AU25181/99A patent/AU752882B2/en not_active Ceased
- 1999-01-16 JP JP2000528545A patent/JP2002501054A/ja not_active Abandoned
- 1999-01-16 EP EP99904789A patent/EP1049677A1/en not_active Withdrawn
- 1999-01-16 WO PCT/EP1999/000242 patent/WO1999037621A1/en not_active Application Discontinuation
- 1999-01-16 UA UA2000084983A patent/UA63990C2/uk unknown
- 1999-01-16 IL IL13742399A patent/IL137423A0/xx unknown
- 1999-01-16 BR BR9907735-3A patent/BR9907735A/pt not_active IP Right Cessation
- 1999-01-16 CN CNB998040894A patent/CN1177832C/zh not_active Expired - Fee Related
- 1999-01-16 ID IDW20001407A patent/ID26219A/id unknown
- 1999-01-16 AP APAP/P/2000/001863A patent/AP1269A/en active
- 1999-01-22 ZA ZA9900476A patent/ZA99476B/xx unknown
- 1999-01-29 AR ARP990100244A patent/AR014456A1/es not_active Application Discontinuation
- 1999-04-30 TW TW088100862A patent/TWI247742B/zh active
-
2000
- 2000-07-21 NO NO20003765A patent/NO318795B1/no unknown
- 2000-07-21 BG BG104630A patent/BG104630A/xx unknown
- 2000-07-21 HR HR20000493A patent/HRP20000493A2/hr not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| NO318795B1 (no) | 2005-05-09 |
| AP1269A (en) | 2004-04-03 |
| NZ505613A (en) | 2002-11-26 |
| JP2002501054A (ja) | 2002-01-15 |
| HUP0100520A3 (en) | 2002-11-28 |
| AP2000001863A0 (en) | 2000-09-30 |
| AR014456A1 (es) | 2001-02-28 |
| WO1999037621A1 (en) | 1999-07-29 |
| EP1049677A1 (en) | 2000-11-08 |
| NO20003765D0 (no) | 2000-07-21 |
| NO20003765L (no) | 2000-09-25 |
| AU2518199A (en) | 1999-08-09 |
| YU47200A (sh) | 2002-11-15 |
| BG104630A (en) | 2001-04-30 |
| PL341871A1 (en) | 2001-05-07 |
| KR20010034319A (ko) | 2001-04-25 |
| UA63990C2 (uk) | 2004-02-16 |
| HUP0100520A1 (hu) | 2001-07-30 |
| EA200000785A1 (ru) | 2001-02-26 |
| CA2318221A1 (en) | 1999-07-29 |
| EA003102B1 (ru) | 2002-12-26 |
| ZA99476B (en) | 1999-08-05 |
| BR9907735A (pt) | 2000-10-17 |
| ID26219A (id) | 2000-12-07 |
| TWI247742B (en) | 2006-01-21 |
| IL137423A0 (en) | 2001-07-24 |
| SK10632000A3 (sk) | 2001-02-12 |
| CN1177832C (zh) | 2004-12-01 |
| CN1293662A (zh) | 2001-05-02 |
| AU752882B2 (en) | 2002-10-03 |
| TR200002160T2 (tr) | 2001-07-23 |
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