MXPA02008375A - Derivados de indano. - Google Patents
Derivados de indano.Info
- Publication number
- MXPA02008375A MXPA02008375A MXPA02008375A MXPA02008375A MXPA02008375A MX PA02008375 A MXPA02008375 A MX PA02008375A MX PA02008375 A MXPA02008375 A MX PA02008375A MX PA02008375 A MXPA02008375 A MX PA02008375A MX PA02008375 A MXPA02008375 A MX PA02008375A
- Authority
- MX
- Mexico
- Prior art keywords
- alkyl
- group
- aryl
- heteroaryl
- compounds
- Prior art date
Links
- 230000021164 cell adhesion Effects 0.000 title claims description 9
- 239000003112 inhibitor Substances 0.000 title claims description 9
- 125000003392 indanyl group Chemical class C1(CCC2=CC=CC=C12)* 0.000 title description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 221
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 154
- 125000003118 aryl group Chemical group 0.000 claims abstract description 75
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 72
- 239000001257 hydrogen Substances 0.000 claims abstract description 72
- 239000002253 acid Chemical group 0.000 claims abstract description 70
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 64
- 150000003839 salts Chemical class 0.000 claims abstract description 62
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 54
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 45
- 229940002612 prodrug Drugs 0.000 claims abstract description 45
- 239000000651 prodrug Substances 0.000 claims abstract description 45
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 34
- 239000012453 solvate Substances 0.000 claims abstract description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 21
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 17
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 17
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 10
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 10
- -1 cycloalkenylalkyl Chemical group 0.000 claims description 108
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 claims description 52
- 239000000203 mixture Substances 0.000 claims description 42
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
- 125000002947 alkylene group Chemical group 0.000 claims description 34
- 238000011282 treatment Methods 0.000 claims description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 32
- 125000003545 alkoxy group Chemical group 0.000 claims description 32
- 150000002431 hydrogen Chemical group 0.000 claims description 31
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 29
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 21
- 125000003342 alkenyl group Chemical group 0.000 claims description 20
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 18
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 17
- 230000002378 acidificating effect Effects 0.000 claims description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000000524 functional group Chemical group 0.000 claims description 14
- 125000004450 alkenylene group Chemical group 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 11
- 125000004043 oxo group Chemical group O=* 0.000 claims description 11
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 10
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 9
- 125000004414 alkyl thio group Chemical group 0.000 claims description 9
- 125000004419 alkynylene group Chemical group 0.000 claims description 9
- 125000004104 aryloxy group Chemical group 0.000 claims description 9
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 8
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 8
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 7
- 125000003435 aroyl group Chemical group 0.000 claims description 7
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 7
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 7
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 7
- 125000005110 aryl thio group Chemical group 0.000 claims description 7
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 7
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 7
- 125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 7
- 125000004442 acylamino group Chemical group 0.000 claims description 6
- 125000005239 aroylamino group Chemical group 0.000 claims description 6
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 6
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 6
- 125000005114 heteroarylalkoxy group Chemical group 0.000 claims description 6
- 125000005835 indanylene group Chemical group 0.000 claims description 6
- 230000001404 mediated effect Effects 0.000 claims description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
- 125000005015 aryl alkynyl group Chemical group 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 125000002619 bicyclic group Chemical group 0.000 claims description 5
- 125000005724 cycloalkenylene group Chemical group 0.000 claims description 5
- 125000005356 cycloalkylalkenyl group Chemical group 0.000 claims description 5
- 125000005357 cycloalkylalkynyl group Chemical group 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 5
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 5
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims description 4
- 125000000732 arylene group Chemical group 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 3
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 2
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical group C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims description 2
- 125000005518 carboxamido group Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 2
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 2
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims 1
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims 1
- 125000004404 heteroalkyl group Chemical group 0.000 claims 1
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims 1
- RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 abstract description 19
- 108010067306 Fibronectins Proteins 0.000 abstract description 12
- 102000016359 Fibronectins Human genes 0.000 abstract description 12
- 230000003993 interaction Effects 0.000 abstract description 10
- 108010008212 Integrin alpha4beta1 Proteins 0.000 abstract 1
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 57
- 238000000034 method Methods 0.000 description 52
- 239000000243 solution Substances 0.000 description 41
- 238000006243 chemical reaction Methods 0.000 description 39
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- 210000004027 cell Anatomy 0.000 description 26
- 150000002148 esters Chemical class 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 125000004432 carbon atom Chemical group C* 0.000 description 20
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 108010044426 integrins Proteins 0.000 description 18
- 102000006495 integrins Human genes 0.000 description 18
- 125000001309 chloro group Chemical group Cl* 0.000 description 16
- 229910052799 carbon Inorganic materials 0.000 description 15
- 150000004677 hydrates Chemical class 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 230000008569 process Effects 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 239000002585 base Substances 0.000 description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 230000007062 hydrolysis Effects 0.000 description 10
- 238000006460 hydrolysis reaction Methods 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 239000012634 fragment Substances 0.000 description 9
- 239000012458 free base Substances 0.000 description 9
- 238000005984 hydrogenation reaction Methods 0.000 description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- 239000012442 inert solvent Substances 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- 150000003254 radicals Chemical class 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 210000001744 T-lymphocyte Anatomy 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 150000007513 acids Chemical class 0.000 description 8
- 229910052801 chlorine Inorganic materials 0.000 description 8
- 238000005859 coupling reaction Methods 0.000 description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 8
- 125000002950 monocyclic group Chemical group 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 7
- 125000001931 aliphatic group Chemical group 0.000 description 7
- 150000001721 carbon Chemical group 0.000 description 7
- 230000008878 coupling Effects 0.000 description 7
- 238000010168 coupling process Methods 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 125000001153 fluoro group Chemical group F* 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 239000003960 organic solvent Substances 0.000 description 7
- 230000003647 oxidation Effects 0.000 description 7
- 238000007254 oxidation reaction Methods 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 230000006978 adaptation Effects 0.000 description 6
- 238000000105 evaporative light scattering detection Methods 0.000 description 6
- 125000005843 halogen group Chemical group 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
- 239000002243 precursor Substances 0.000 description 6
- 239000011347 resin Substances 0.000 description 6
- 229920005989 resin Polymers 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 206010003246 arthritis Diseases 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 239000007853 buffer solution Substances 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 238000005886 esterification reaction Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 229910052751 metal Inorganic materials 0.000 description 5
- 239000002184 metal Substances 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 4
- 239000005977 Ethylene Substances 0.000 description 4
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 4
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 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
- 241001465754 Metazoa Species 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 239000012980 RPMI-1640 medium Substances 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 150000001450 anions Chemical class 0.000 description 4
- OBNCKNCVKJNDBV-UHFFFAOYSA-N butanoic acid ethyl ester Natural products CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 125000004979 cyclopentylene group Chemical group 0.000 description 4
- 125000004980 cyclopropylene group Chemical group 0.000 description 4
- 230000032050 esterification Effects 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 150000002596 lactones Chemical class 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 229940086542 triethylamine Drugs 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 125000000355 1,3-benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical group C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 3
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- 108010058846 Ovalbumin Proteins 0.000 description 3
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 230000001476 alcoholic effect Effects 0.000 description 3
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N anhydrous n-heptane Natural products CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000003125 aqueous solvent Substances 0.000 description 3
- 125000005135 aryl sulfinyl group Chemical group 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
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- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000005897 peptide coupling reaction Methods 0.000 description 1
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- 229910052700 potassium Inorganic materials 0.000 description 1
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- 238000009117 preventive therapy Methods 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
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- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
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- 235000011803 sesame oil Nutrition 0.000 description 1
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- 108010085082 sigma receptors Proteins 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- XMVONEAAOPAGAO-UHFFFAOYSA-N sodium tungstate Chemical compound [Na+].[Na+].[O-][W]([O-])(=O)=O XMVONEAAOPAGAO-UHFFFAOYSA-N 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-N sodium;5-ethyl-5-pentan-2-yl-1,3-diazinane-2,4,6-trione Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)NC1=O QGMRQYFBGABWDR-UHFFFAOYSA-N 0.000 description 1
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- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
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- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
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- 125000001544 thienyl group Chemical group 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
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- ZFDIRQKJPRINOQ-UHFFFAOYSA-N transbutenic acid ethyl ester Natural products CCOC(=O)C=CC ZFDIRQKJPRINOQ-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles 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 in position 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles 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 in position 2
- C07D235/30—Nitrogen atoms not forming part of a nitro radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0004686.2A GB0004686D0 (en) | 2000-02-28 | 2000-02-28 | Chemical compounds |
| PCT/GB2001/000844 WO2001064659A2 (en) | 2000-02-28 | 2001-02-28 | Indane derivatives and their use as cell adhesion inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA02008375A true MXPA02008375A (es) | 2002-12-13 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA02008375A MXPA02008375A (es) | 2000-02-28 | 2001-02-28 | Derivados de indano. |
Country Status (13)
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|---|---|
| US (1) | US6762199B2 (https=) |
| EP (1) | EP1259495B1 (https=) |
| JP (1) | JP5021133B2 (https=) |
| AR (1) | AR027578A1 (https=) |
| AT (1) | ATE277023T1 (https=) |
| AU (1) | AU3579001A (https=) |
| CA (1) | CA2401441C (https=) |
| DE (1) | DE60105771T2 (https=) |
| ES (1) | ES2227137T3 (https=) |
| GB (1) | GB0004686D0 (https=) |
| IL (1) | IL150724A0 (https=) |
| MX (1) | MXPA02008375A (https=) |
| WO (1) | WO2001064659A2 (https=) |
Families Citing this family (14)
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| JP4212358B2 (ja) | 2000-12-28 | 2009-01-21 | 第一三共株式会社 | Ｖｌａ−４阻害薬 |
| GB0123765D0 (en) * | 2001-10-03 | 2001-11-21 | Bayer Ag | Para-amino benzoic acids |
| US8005919B2 (en) | 2002-11-18 | 2011-08-23 | Aol Inc. | Host-based intelligent results related to a character stream |
| CA2506585A1 (en) | 2002-11-18 | 2004-06-03 | Valerie Kucharewski | People lists |
| CA2528586A1 (en) | 2003-07-24 | 2005-02-03 | Daiichi Pharmaceutical Co., Ltd. | Cyclohexanecarboxylic acid compound |
| JP2006056830A (ja) * | 2004-08-20 | 2006-03-02 | Dai Ichi Seiyaku Co Ltd | ２−アリールアミノベンゾオキサゾール誘導体 |
| WO2012074980A2 (en) * | 2010-12-01 | 2012-06-07 | Dara Biosciences, Inc. | Methods of treating or preventing autoimmune disorders and liver disorders using indane acetic acid derivatives |
| US12522583B2 (en) | 2018-11-07 | 2026-01-13 | Dana-Farber Cancer Institute, Inc. | Benzimidazole derivatives and aza-benzimidazole derivatives as Janus kinase 2 inhibitors and uses thereof |
| EP3877371A4 (en) | 2018-11-07 | 2022-07-27 | Dana-Farber Cancer Institute, Inc. | IMIDAZOPYRIDINE DERIVATIVES AND AZA-IMIDAZOPYRIDINE DERIVATIVES AS JANUS KINASE 2 INHIBITORS AND USES THEREOF |
| EP3876939A4 (en) | 2018-11-07 | 2022-08-10 | Dana-Farber Cancer Institute, Inc. | Benzothiazole derivatives and 7-aza-benzothiazole derivatives as janus kinase 2 inhibitors and uses thereof |
| US11691963B2 (en) | 2020-05-06 | 2023-07-04 | Ajax Therapeutics, Inc. | 6-heteroaryloxy benzimidazoles and azabenzimidazoles as JAK2 inhibitors |
| US12043632B2 (en) | 2020-12-23 | 2024-07-23 | Ajax Therapeutics, Inc. | 6-heteroaryloxy benzimidazoles and azabenzimidazoles as JAK2 inhibitors |
| US12162881B2 (en) | 2021-11-09 | 2024-12-10 | Ajax Therapeutics, Inc. | Forms and compositions of inhibitors of JAK2 |
| WO2023086319A1 (en) | 2021-11-09 | 2023-05-19 | Ajax Therapeutics, Inc. | 6-he tero aryloxy benzimidazoles and azabenzimidazoles as jak2 inhibitors |
Family Cites Families (93)
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| FR2041594A5 (https=) * | 1969-04-30 | 1971-01-29 | Expanscience | |
| US4331692A (en) * | 1971-07-23 | 1982-05-25 | Ulla Drevici | Cocoa fruits and products |
| GB1541463A (en) * | 1975-10-11 | 1979-02-28 | Lion Dentifrice Co Ltd | Process for prparing a multiple emulsion having a dispersing form of water-phase/oil-phase/water-phase |
| US4151304A (en) * | 1976-11-05 | 1979-04-24 | Lever Brothers Company | Method and composition for moisturizing the skin |
| FR2380775A1 (fr) * | 1977-02-22 | 1978-09-15 | Sederma Sarl | Composition " apres-epilation " favorisant un ralentissement progressif de la repousse des poils |
| US4190671A (en) * | 1977-03-17 | 1980-02-26 | Biorex Laboratories Limited | Chalcone derivatives |
| US4279930A (en) * | 1978-10-10 | 1981-07-21 | The Upjohn Company | Process for treating inflammation |
| DE3040246C2 (de) * | 1979-10-29 | 1985-01-10 | Osaka Chemical Laboratory Co., Ltd., Osaka | Sojasaponine A↓1↓ und A↓2↓ und ihre Verwendung |
| JPS56135416A (en) * | 1980-03-27 | 1981-10-22 | Mitsubishi Chem Ind Ltd | Pharmaceutical preparation for skin |
| US4272544A (en) * | 1980-08-20 | 1981-06-09 | Eli Lilly And Company | Skin cell renewal regime |
| US4278570A (en) * | 1980-08-20 | 1981-07-14 | Eli Lilly And Company | Cosmetic cleanser formulation |
| DE3109420A1 (de) * | 1981-03-12 | 1982-09-23 | Kastell, Wolfgang, 2000 Hamburg | Mittel zum anhalten des haarausfalls und zum foerdern des haarwuchses |
| FR2509988B1 (fr) * | 1981-07-23 | 1986-05-30 | Oreal | Melange d'huiles vegetales a base d'huile de jojoba comme agent de stabilisation a l'oxydation et compositions cosmetiques le contenant |
| DE3129867A1 (de) * | 1981-07-29 | 1983-02-17 | Henkel Kgaa | "ungesaettigte arylketone als antiseborrhoische zusaetze fuer kosmetische mittel" |
| US4382960A (en) * | 1981-08-03 | 1983-05-10 | Eli Lilly And Company | Cosmetic cleanser formulation |
| US4368187A (en) * | 1981-08-03 | 1983-01-11 | Eli Lilly And Company | Sensitive-skin care regime |
| US4578267A (en) * | 1981-09-15 | 1986-03-25 | Morton Thiokol, Inc. | Skin conditioning polymer containing alkoxylated nitrogen salts of sulfonic acid |
| US4462981A (en) * | 1982-12-10 | 1984-07-31 | Creative Products Resource, Associates Ltd. | Cosmetic applicator useful for skin moisturizing and deodorizing |
| US5192332A (en) * | 1983-10-14 | 1993-03-09 | L'oreal | Cosmetic temporary coloring compositions containing protein derivatives |
| JPS60109544A (ja) * | 1983-11-17 | 1985-06-15 | Kao Corp | 新規カルコン誘導体及びこれを含有する紫外線吸収剤 |
| FR2580478B1 (fr) * | 1985-04-17 | 1989-05-12 | Christian Chapoton | Dispositif de traitement capillaire liberant une substance active et procede de fabrication |
| US4760096A (en) * | 1985-09-27 | 1988-07-26 | Schering Corporation | Moisturizing skin preparation |
| US4847267A (en) * | 1986-03-17 | 1989-07-11 | Charles Of The Ritz Group Ltd. | Skin treatment composition and method |
| IT1203515B (it) * | 1987-02-26 | 1989-02-15 | Indena Spa | Complessi di saponine con fosfolipidi e composizioni farmaceutiche e cosmetiche che li contengono |
| US4824662A (en) * | 1987-06-15 | 1989-04-25 | Vi-Jon Laboratories, Inc. | Nail polish remover |
| IT1222012B (it) * | 1987-07-10 | 1990-08-31 | Indena Spa | Composizioni farmaceutiche e cosmetiche contenenti complessi di flavonolignani con fosfolipidi |
| IT1223290B (it) * | 1987-07-27 | 1990-09-19 | Indena Spa | Acidi poliinsaturi ad azione vasocinetica e relative formulazioni farmaceutiche e cosmetiche |
| LU86997A1 (fr) * | 1987-09-21 | 1989-04-06 | Oreal | Composition cosmetique filtrante photostable contenant de la bixine associee a un filtre uv liposoluble et son utilisation pour la protection de l'epiderme humain contre les radiations ultraviolettes |
| EP0317667B1 (en) * | 1987-11-24 | 1993-02-17 | Agfa-Gevaert N.V. | Magnetic carrier particles |
| CH676470A5 (https=) * | 1988-02-03 | 1991-01-31 | Nestle Sa | |
| DE3814839A1 (de) * | 1988-05-02 | 1989-11-16 | Henkel Kgaa | Haarbehandlungsmittel mit natuerlichen inhaltsstoffen |
| US4906457A (en) * | 1988-09-06 | 1990-03-06 | Washington State University Research Foundation, Inc. | Compositions and methods for reducing the risk of sunlight and ultraviolet induced skin cancer |
| US4851214A (en) * | 1988-09-07 | 1989-07-25 | Ici Americas Inc. | Deodorants containing N-soya-N-ethyl morpholinium ethosulfate |
| US4943462A (en) * | 1989-01-17 | 1990-07-24 | Semex Medical, Inc. | Nail treatment device |
| US5116605A (en) * | 1989-03-09 | 1992-05-26 | Alt John P | Composition and skin treatment method therewith for mitigating acne and male-pattern baldness |
| US5194252A (en) * | 1989-07-27 | 1993-03-16 | Vijon Laboratories, Inc. | Moisture retaining aftershave |
| US5032400A (en) * | 1989-11-02 | 1991-07-16 | Erie Laboratories | Shark liver oil and garlic oil topical analgesic |
| US5622690A (en) * | 1990-04-05 | 1997-04-22 | Nurture, Inc. | Seed-derived proteinaceous compositions for reduction of sunburn cell formation |
| FR2663633B1 (fr) * | 1990-06-22 | 1994-06-17 | Adir | Nouvelles chalcones, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
| US5231090A (en) * | 1990-07-30 | 1993-07-27 | University Of Miami | Treatment for hypercholesterolemia |
| US5407675A (en) * | 1990-08-10 | 1995-04-18 | Etemad-Moghadam; Parviz | Method and composition for use on the scalp and eyebrow region of a subject |
| CA2049728A1 (en) * | 1990-08-24 | 1992-02-25 | Kenji Kitamura | Washing composition capable of preventing and ameliorating skin irritation |
| US5217717A (en) * | 1990-09-06 | 1993-06-08 | Central Soya Company, Inc. | Method of making soybean Bowman-Birk inhibitor concentrate and use of same as a human cancer preventative and therapy |
| EP0510165B1 (fr) * | 1990-11-14 | 1995-01-25 | L'oreal | Composes amphiphiles non-ioniques derives du glycerol, leur procede de preparation, composes intermediaires correspondants et compositions contenant lesdits composes |
| US5110603A (en) * | 1991-01-31 | 1992-05-05 | Kao Corporation | Bathing preparation for colloidal material |
| US5188823A (en) * | 1991-02-07 | 1993-02-23 | Stepan Company | Antiperspirant formulations |
| US5498420A (en) * | 1991-04-12 | 1996-03-12 | Merz & Co. Gmbh & Co. | Stable small particle liposome preparations, their production and use in topical cosmetic, and pharmaceutical compositions |
| US5229104A (en) * | 1991-04-29 | 1993-07-20 | Richardson-Vicks Inc. | Artificial tanning compositions containing positively charged paucilamellar vesicles |
| EP0514576A1 (fr) * | 1991-05-24 | 1992-11-25 | Societe Des Produits Nestle S.A. | Mélange antioxydant liposoluble |
| US5310734A (en) * | 1991-07-05 | 1994-05-10 | Rhone-Poulenc Rorer | Phospholipid composition |
| ES2179038T3 (es) * | 1991-09-13 | 2003-01-16 | Pentapharm Ag | Fraccion porteinica para el tratamiento cosmetico y dermatologico de la piel. |
| WO1993010755A1 (en) * | 1991-11-25 | 1993-06-10 | Richardson-Vicks, Inc. | Compositions for regulating skin wrinkles and/or skin atrophy |
| WO1993010756A1 (en) * | 1991-11-25 | 1993-06-10 | Richardson-Vicks, Inc. | Use of salicylic acid for regulating skin wrinkles and/or skin atrophy |
| FR2687314A1 (fr) * | 1992-02-18 | 1993-08-20 | Oreal | Dispersion de vesicules lipidiques, composition cosmetique et/ou pharmaceutique la contenant et procede de preparation de ladite dispersion. |
| US5766628A (en) * | 1992-02-24 | 1998-06-16 | Merz + Co. Gmbh & Co. | Bath and shower composition having vesicle-forming properties and method for the production and use thereof |
| US5393519A (en) * | 1992-03-27 | 1995-02-28 | Helene Curtis, Inc. | Shampoo compositions |
| DE4226173A1 (de) * | 1992-08-07 | 1994-02-10 | Solvay Fluor & Derivate | Badezusatzpräparat |
| FR2694934B1 (fr) * | 1992-08-24 | 1994-11-10 | Oreal | Composition pour le traitement de l'acné contenant un dérivé d'acide salicylique et dérivés d'acide salicylique. |
| US6048520A (en) * | 1992-09-24 | 2000-04-11 | Helene Curtis, Inc. | Clear leave-on hair treatment composition and method |
| US5753612A (en) * | 1992-10-27 | 1998-05-19 | Yissum Research Development Co. Of The Hebrew University Of Jerusalem | Pharmaceutical composition and method for inhibiting hair growth by administration of activin or activin agonists |
| CA2119064A1 (en) * | 1993-03-17 | 1994-09-18 | Richard A. Berg | Dermal-epidermal in vitro test system |
| US5276058A (en) * | 1993-06-09 | 1994-01-04 | Nippon Hypox Laboratories Incorporated | 3,4-dihydroxychalcone derivatives |
| FR2710264B1 (fr) * | 1993-09-21 | 1995-12-08 | Rocher Yves Biolog Vegetale | Utilisation pour le traitement des peaux mixtes d'une quantité efficace de substances actives. |
| DE4343431C1 (de) * | 1993-12-18 | 1995-05-04 | Henkel Kgaa | Kosmetische und/oder pharamzeutische Zubereitungen |
| FR2714596B1 (fr) * | 1993-12-30 | 1996-02-09 | Oreal | Composition cosmétique pour le traitement simultané des couches superficielles et profondes de la peau, son utilisation. |
| US6013255A (en) * | 1994-04-18 | 2000-01-11 | Gist-Brocades B.V. | Stable water-in-oil emulsions |
| GB9414045D0 (en) * | 1994-07-12 | 1994-08-31 | Berwind Pharma Service | Moisture barrier film coating composition, method, and coated form |
| DE4444238A1 (de) * | 1994-12-13 | 1996-06-20 | Beiersdorf Ag | Kosmetische oder dermatologische Wirkstoffkombinationen aus Zimtsäurederivaten und Flavonglycosiden |
| US5523308A (en) * | 1995-06-07 | 1996-06-04 | Costanzo; Michael J. | Peptidyl heterocycles useful in the treatment of thrombin related disorders |
| US5639785A (en) * | 1995-06-07 | 1997-06-17 | Global Pharma, Ltd. | Methods for the treatment of baldness and gray hair using isoflavonoid derivatives |
| US6013250A (en) * | 1995-06-28 | 2000-01-11 | L'oreal S. A. | Composition for treating hair against chemical and photo damage |
| US6063398A (en) * | 1995-09-20 | 2000-05-16 | L'oreal | Cosmetic or dermopharmaceutical patch containing, in an anhydrous polymeric matrix, at least one active compound which is, in particular, unstable in oxidizing mediums, and at least one water-absorbing agent |
| US5885593A (en) * | 1995-09-28 | 1999-03-23 | The Andrew Jergens Company | Skin care composition including cyclodextrin materials and method for treating skin therewith |
| US6019962A (en) * | 1995-11-07 | 2000-02-01 | The Procter & Gamble Co. | Compositions and methods for improving cosmetic products |
| ES2154844T3 (es) * | 1995-11-24 | 2001-04-16 | Mitsui Chemicals Inc | Derivados de hidrocalcona, composiciones cosmeticas que contienen dichos derivados y procedimientos para producir los mismos. |
| US5643587A (en) * | 1996-02-15 | 1997-07-01 | Avon Products, Inc. | Composition and method for under-eye skin lightening |
| FR2747568B1 (fr) * | 1996-04-17 | 1999-09-17 | Oreal | Utilisation d'au moins un inhibiteur de lipoxygenase et d'au moins un inhibiteur de cyclo-oxygenase pour modifier la pousse des poils et/ou des cheveux |
| IL119535A (en) * | 1996-10-31 | 2001-01-11 | Chajuss Daniel | Soy molasses and modified soy molasses for topical application |
| FR2757767B1 (fr) * | 1996-12-27 | 1999-02-05 | Oreal | Composition topique contenant au moins une proteine d'origine vegetale et/ou une proteine d'origine animale et une poly(acide 2-acrylamido 2-methylpropane sulfonique) reticule |
| US5863546A (en) * | 1997-03-02 | 1999-01-26 | Swinehart; James M | Cosmetic composition |
| US5885600A (en) * | 1997-04-01 | 1999-03-23 | Burlington Bio-Medical & Scientific Corp. | Natural insect repellent formula and method of making same |
| US5885596A (en) * | 1997-07-23 | 1999-03-23 | Bristol-Myers Squibb Company | Methods and compositions for fine lines and/or wrinkles |
| US6017893A (en) * | 1997-08-29 | 2000-01-25 | Natures Sunshine Products, Inc. | Use of isoflavones to prevent hair loss and preserve the integrity of existing hair |
| US5928658A (en) * | 1997-12-05 | 1999-07-27 | U.S. Cosmetics | Oil-free wax-free solid cosmetic composition |
| FR2772613B1 (fr) * | 1997-12-19 | 2003-05-09 | Oreal | Utilisation du phloroglucinol dans une composition cosmetique |
| US6030931A (en) * | 1998-02-03 | 2000-02-29 | Chesebrough-Pond's Usa Co., Division Of Conopco, Inc. | Foaming cleansing skin product |
| US5928889A (en) * | 1998-02-13 | 1999-07-27 | S.C. Johnson & Son, Inc. | Protocol for simulated natural biofilm formation |
| BR9908870A (pt) * | 1998-03-16 | 2000-11-21 | Procter & Gamble | Processos para regularizarem a aparência da pele |
| CO5090829A1 (es) * | 1998-07-21 | 2001-10-30 | Novartis Ag | Compuestos organicos de la formula i, utiles como inhibido res de la proteina de transferencia de triglicerido microso mal y de la secrecion de la apolipoproteina b. |
| GB9916374D0 (en) * | 1998-07-23 | 1999-09-15 | Zeneca Ltd | Chemical compounds |
| JP2002521375A (ja) * | 1998-07-23 | 2002-07-16 | アストラゼネカ アクチエボラーク | 化合物 |
| WO2000049005A1 (en) * | 1999-02-16 | 2000-08-24 | Aventis Pharma Limited | Bicyclic compounds and their use as integrin receptor ligands |
| ES2321055T3 (es) * | 1999-05-05 | 2009-06-02 | Aventis Pharma Limited | Compuestos biblicos sustituidos. |
-
2000
- 2000-02-28 GB GBGB0004686.2A patent/GB0004686D0/en not_active Ceased
-
2001
- 2001-02-28 AR ARP010100942A patent/AR027578A1/es unknown
- 2001-02-28 DE DE60105771T patent/DE60105771T2/de not_active Expired - Lifetime
- 2001-02-28 ES ES01907923T patent/ES2227137T3/es not_active Expired - Lifetime
- 2001-02-28 JP JP2001563500A patent/JP5021133B2/ja not_active Expired - Lifetime
- 2001-02-28 EP EP01907923A patent/EP1259495B1/en not_active Expired - Lifetime
- 2001-02-28 CA CA2401441A patent/CA2401441C/en not_active Expired - Lifetime
- 2001-02-28 AT AT01907923T patent/ATE277023T1/de not_active IP Right Cessation
- 2001-02-28 WO PCT/GB2001/000844 patent/WO2001064659A2/en not_active Ceased
- 2001-02-28 MX MXPA02008375A patent/MXPA02008375A/es active IP Right Grant
- 2001-02-28 IL IL15072401A patent/IL150724A0/xx unknown
- 2001-02-28 AU AU35790/01A patent/AU3579001A/en not_active Abandoned
-
2002
- 2002-08-28 US US10/229,592 patent/US6762199B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JP5021133B2 (ja) | 2012-09-05 |
| WO2001064659A3 (en) | 2001-12-27 |
| GB0004686D0 (en) | 2000-04-19 |
| AR027578A1 (es) | 2003-04-02 |
| CA2401441C (en) | 2011-11-15 |
| EP1259495A2 (en) | 2002-11-27 |
| WO2001064659A2 (en) | 2001-09-07 |
| DE60105771T2 (de) | 2006-02-16 |
| CA2401441A1 (en) | 2001-09-07 |
| JP2003525281A (ja) | 2003-08-26 |
| IL150724A0 (en) | 2003-02-12 |
| EP1259495B1 (en) | 2004-09-22 |
| ES2227137T3 (es) | 2005-04-01 |
| US20030199564A1 (en) | 2003-10-23 |
| DE60105771D1 (de) | 2004-10-28 |
| US6762199B2 (en) | 2004-07-13 |
| ATE277023T1 (de) | 2004-10-15 |
| AU3579001A (en) | 2001-09-12 |
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