MX2007008277A - 2-fenilindoles como antagonistas del receptor de la prostaglandina d2. - Google Patents
2-fenilindoles como antagonistas del receptor de la prostaglandina d2.Info
- Publication number
- MX2007008277A MX2007008277A MX2007008277A MX2007008277A MX2007008277A MX 2007008277 A MX2007008277 A MX 2007008277A MX 2007008277 A MX2007008277 A MX 2007008277A MX 2007008277 A MX2007008277 A MX 2007008277A MX 2007008277 A MX2007008277 A MX 2007008277A
- Authority
- MX
- Mexico
- Prior art keywords
- pharmaceutically acceptable
- solvate
- hydrate
- prodrug
- acceptable salt
- Prior art date
Links
- 102000009389 Prostaglandin D receptors Human genes 0.000 title description 5
- 108050000258 Prostaglandin D receptors Proteins 0.000 title description 5
- 229940044551 receptor antagonist Drugs 0.000 title description 5
- 239000002464 receptor antagonist Substances 0.000 title description 5
- KLLLJCACIRKBDT-UHFFFAOYSA-N 2-phenyl-1H-indole Chemical class N1C2=CC=CC=C2C=C1C1=CC=CC=C1 KLLLJCACIRKBDT-UHFFFAOYSA-N 0.000 title description 2
- 150000003839 salts Chemical class 0.000 claims abstract description 254
- 150000001875 compounds Chemical class 0.000 claims abstract description 234
- 229940002612 prodrug Drugs 0.000 claims abstract description 216
- 239000000651 prodrug Substances 0.000 claims abstract description 216
- 239000012453 solvate Substances 0.000 claims abstract description 206
- 238000000034 method Methods 0.000 claims abstract description 133
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 33
- 208000006673 asthma Diseases 0.000 claims abstract description 21
- 201000008937 atopic dermatitis Diseases 0.000 claims abstract description 19
- 208000035475 disorder Diseases 0.000 claims abstract description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
- BHMBVRSPMRCCGG-OUTUXVNYSA-N prostaglandin D2 Chemical compound CCCCC[C@H](O)\C=C\[C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@@H](O)CC1=O BHMBVRSPMRCCGG-OUTUXVNYSA-N 0.000 claims abstract description 17
- BHMBVRSPMRCCGG-UHFFFAOYSA-N prostaglandine D2 Natural products CCCCCC(O)C=CC1C(CC=CCCCC(O)=O)C(O)CC1=O BHMBVRSPMRCCGG-UHFFFAOYSA-N 0.000 claims abstract description 17
- 206010039085 Rhinitis allergic Diseases 0.000 claims abstract description 15
- 201000010105 allergic rhinitis Diseases 0.000 claims abstract description 15
- 208000010668 atopic eczema Diseases 0.000 claims abstract description 15
- 201000010099 disease Diseases 0.000 claims abstract description 15
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims abstract description 14
- 208000002205 allergic conjunctivitis Diseases 0.000 claims abstract description 14
- 208000024998 atopic conjunctivitis Diseases 0.000 claims abstract description 14
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract description 12
- 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 claims abstract description 12
- 101000988802 Homo sapiens Hematopoietic prostaglandin D synthase Proteins 0.000 claims abstract description 12
- 206010061218 Inflammation Diseases 0.000 claims abstract description 12
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- 230000004054 inflammatory process Effects 0.000 claims abstract description 12
- 206010012438 Dermatitis atopic Diseases 0.000 claims abstract description 11
- 208000024780 Urticaria Diseases 0.000 claims abstract description 11
- 239000003937 drug carrier Substances 0.000 claims abstract description 10
- 210000003630 histaminocyte Anatomy 0.000 claims abstract description 10
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims abstract description 8
- 230000009885 systemic effect Effects 0.000 claims abstract description 7
- 206010009900 Colitis ulcerative Diseases 0.000 claims abstract description 6
- 201000004624 Dermatitis Diseases 0.000 claims abstract description 6
- 201000006704 Ulcerative Colitis Diseases 0.000 claims abstract description 6
- 206010006451 bronchitis Diseases 0.000 claims abstract description 6
- 230000001684 chronic effect Effects 0.000 claims abstract description 6
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- 230000001404 mediated effect Effects 0.000 claims abstract description 5
- 206010006482 Bronchospasm Diseases 0.000 claims abstract description 4
- 208000004262 Food Hypersensitivity Diseases 0.000 claims abstract description 4
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- 206010008190 Cerebrovascular accident Diseases 0.000 claims abstract 2
- 208000026106 cerebrovascular disease Diseases 0.000 claims abstract 2
- -1 cyano, carboxy Chemical group 0.000 claims description 355
- 125000000217 alkyl group Chemical group 0.000 claims description 193
- 239000002253 acid Substances 0.000 claims description 179
- 239000001257 hydrogen Substances 0.000 claims description 156
- 229910052739 hydrogen Inorganic materials 0.000 claims description 156
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 116
- 150000002431 hydrogen Chemical class 0.000 claims description 111
- 125000003118 aryl group Chemical group 0.000 claims description 72
- 125000001072 heteroaryl group Chemical group 0.000 claims description 72
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 64
- 125000003545 alkoxy group Chemical group 0.000 claims description 63
- 125000000623 heterocyclic group Chemical group 0.000 claims description 62
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 61
- 125000005843 halogen group Chemical group 0.000 claims description 61
- 125000003342 alkenyl group Chemical group 0.000 claims description 50
- 125000000304 alkynyl group Chemical group 0.000 claims description 50
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 39
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 38
- 125000001424 substituent group Chemical group 0.000 claims description 38
- 125000001188 haloalkyl group Chemical group 0.000 claims description 37
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
- 125000002252 acyl group Chemical group 0.000 claims description 29
- 125000004350 aryl cycloalkyl group Chemical group 0.000 claims description 27
- 125000004367 cycloalkylaryl group Chemical group 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 26
- 125000001931 aliphatic group Chemical group 0.000 claims description 25
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 24
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 24
- DMEGYFMYUHOHGS-UHFFFAOYSA-N cycloheptane Chemical compound C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 24
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
- 125000003282 alkyl amino group Chemical group 0.000 claims description 23
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 22
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 21
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 20
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 20
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 16
- 150000002148 esters Chemical class 0.000 claims description 16
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 15
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 15
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 15
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 15
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 15
- 239000000460 chlorine Substances 0.000 claims description 14
- 125000005349 heteroarylcycloalkyl group Chemical group 0.000 claims description 12
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 12
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 11
- 125000003435 aroyl group Chemical group 0.000 claims description 11
- 125000001769 aryl amino group Chemical group 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 11
- 125000000232 haloalkynyl group Chemical group 0.000 claims description 10
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 10
- 230000007803 itching Effects 0.000 claims description 10
- KIGUGIFQHCUKBU-UHFFFAOYSA-N 2-[2-[4-chloro-3-(cyclohexylsulfamoyl)phenyl]-1h-indol-3-yl]acetic acid Chemical compound N1C2=CC=CC=C2C(CC(=O)O)=C1C(C=1)=CC=C(Cl)C=1S(=O)(=O)NC1CCCCC1 KIGUGIFQHCUKBU-UHFFFAOYSA-N 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000000262 haloalkenyl group Chemical group 0.000 claims description 9
- 125000005292 haloalkynyloxy group Chemical group 0.000 claims description 9
- 125000001318 4-trifluoromethylbenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C(F)(F)F 0.000 claims description 8
- RWCJSIMCWSEALS-UHFFFAOYSA-N C=C.C1CCCCC1.C=C1CCCCC1 Chemical group C=C.C1CCCCC1.C=C1CCCCC1 RWCJSIMCWSEALS-UHFFFAOYSA-N 0.000 claims description 8
- 206010012434 Dermatitis allergic Diseases 0.000 claims description 8
- 239000005557 antagonist Substances 0.000 claims description 8
- 125000005215 cycloalkylheteroaryl group Chemical group 0.000 claims description 8
- WCCDYNCDGZUTMV-UHFFFAOYSA-N cycloheptane methylidenecyclohexane Chemical compound C=C1CCCCC1.C1CCCCCC1 WCCDYNCDGZUTMV-UHFFFAOYSA-N 0.000 claims description 8
- 125000005291 haloalkenyloxy group Chemical group 0.000 claims description 8
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 8
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 8
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 8
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 claims description 8
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 8
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
- 239000003981 vehicle Substances 0.000 claims description 8
- 230000004913 activation Effects 0.000 claims description 5
- 230000006399 behavior Effects 0.000 claims description 5
- 150000004677 hydrates Chemical class 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- JDEGCYUKNLKEKH-UHFFFAOYSA-N 2-[2-[3-(cyclohexylsulfamoyl)phenyl]-1h-indol-3-yl]acetic acid Chemical compound N1C2=CC=CC=C2C(CC(=O)O)=C1C(C=1)=CC=CC=1S(=O)(=O)NC1CCCCC1 JDEGCYUKNLKEKH-UHFFFAOYSA-N 0.000 claims description 4
- 206010002199 Anaphylactic shock Diseases 0.000 claims description 4
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
- 239000000739 antihistaminic agent Substances 0.000 claims description 4
- 125000005140 aralkylsulfonyl group Chemical group 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 4
- VNDDPMCZAIPHMO-UHFFFAOYSA-N methyl 2-[2-[4-chloro-3-(cyclohexylsulfamoyl)phenyl]-1h-indol-3-yl]acetate Chemical compound N1C2=CC=CC=C2C(CC(=O)OC)=C1C(C=1)=CC=C(Cl)C=1S(=O)(=O)NC1CCCCC1 VNDDPMCZAIPHMO-UHFFFAOYSA-N 0.000 claims description 4
- 208000019116 sleep disease Diseases 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims description 3
- KZCCIJZBJRBWMG-UHFFFAOYSA-N 2-[2-[3-(benzylsulfamoyl)-4-chlorophenyl]-1h-indol-3-yl]acetic acid Chemical compound N1C2=CC=CC=C2C(CC(=O)O)=C1C(C=1)=CC=C(Cl)C=1S(=O)(=O)NCC1=CC=CC=C1 KZCCIJZBJRBWMG-UHFFFAOYSA-N 0.000 claims description 3
- ODQRPEPELMKXOZ-UHFFFAOYSA-N 2-[2-[3-chloro-4-(cyclohexylsulfamoyl)phenyl]-1h-indol-3-yl]acetic acid Chemical compound N1C2=CC=CC=C2C(CC(=O)O)=C1C(C=C1Cl)=CC=C1S(=O)(=O)NC1CCCCC1 ODQRPEPELMKXOZ-UHFFFAOYSA-N 0.000 claims description 3
- XLQRWCMKWOKBRB-UHFFFAOYSA-N 2-[2-[4-chloro-3-(cyclohexylsulfamoyl)phenyl]-1-methylindol-3-yl]acetic acid Chemical compound OC(=O)CC=1C2=CC=CC=C2N(C)C=1C(C=1)=CC=C(Cl)C=1S(=O)(=O)NC1CCCCC1 XLQRWCMKWOKBRB-UHFFFAOYSA-N 0.000 claims description 3
- NRCCDAGERPEEML-UHFFFAOYSA-N 2-[2-[4-chloro-3-(cyclohexylsulfamoyl)phenyl]-5-hydroxy-1h-indol-3-yl]acetic acid Chemical compound N1C2=CC=C(O)C=C2C(CC(=O)O)=C1C(C=1)=CC=C(Cl)C=1S(=O)(=O)NC1CCCCC1 NRCCDAGERPEEML-UHFFFAOYSA-N 0.000 claims description 3
- ZVTVOTKPLIIPCV-UHFFFAOYSA-N 2-[2-[4-chloro-3-(cyclohexylsulfamoyl)phenyl]-5-methoxy-1h-indol-3-yl]acetic acid Chemical compound OC(=O)CC=1C2=CC(OC)=CC=C2NC=1C(C=1)=CC=C(Cl)C=1S(=O)(=O)NC1CCCCC1 ZVTVOTKPLIIPCV-UHFFFAOYSA-N 0.000 claims description 3
- NQEPMFVZEBPBSE-UHFFFAOYSA-N 2-[2-[4-chloro-3-(cyclopentylsulfamoyl)phenyl]-1h-indol-3-yl]acetic acid Chemical compound N1C2=CC=CC=C2C(CC(=O)O)=C1C(C=1)=CC=C(Cl)C=1S(=O)(=O)NC1CCCC1 NQEPMFVZEBPBSE-UHFFFAOYSA-N 0.000 claims description 3
- XWYJQVOFBMQLQF-UHFFFAOYSA-N 2-[2-[4-chloro-3-(hexylsulfamoyl)phenyl]-1h-indol-3-yl]acetic acid Chemical compound C1=C(Cl)C(S(=O)(=O)NCCCCCC)=CC(C2=C(C3=CC=CC=C3N2)CC(O)=O)=C1 XWYJQVOFBMQLQF-UHFFFAOYSA-N 0.000 claims description 3
- KYIINTGTZURUIV-UHFFFAOYSA-N 2-[2-[4-chloro-3-(methylsulfamoyl)phenyl]-1h-indol-3-yl]acetic acid Chemical compound C1=C(Cl)C(S(=O)(=O)NC)=CC(C2=C(C3=CC=CC=C3N2)CC(O)=O)=C1 KYIINTGTZURUIV-UHFFFAOYSA-N 0.000 claims description 3
- NXXKXKSPXZGLAG-UHFFFAOYSA-N 2-[2-[4-chloro-3-(phenylsulfamoyl)phenyl]-1h-indol-3-yl]acetic acid Chemical compound N1C2=CC=CC=C2C(CC(=O)O)=C1C(C=1)=CC=C(Cl)C=1S(=O)(=O)NC1=CC=CC=C1 NXXKXKSPXZGLAG-UHFFFAOYSA-N 0.000 claims description 3
- XUHOVEDHEDNXIE-UHFFFAOYSA-N 2-[2-[4-chloro-3-(propan-2-ylsulfamoyl)phenyl]-1h-indol-3-yl]acetic acid Chemical compound C1=C(Cl)C(S(=O)(=O)NC(C)C)=CC(C2=C(C3=CC=CC=C3N2)CC(O)=O)=C1 XUHOVEDHEDNXIE-UHFFFAOYSA-N 0.000 claims description 3
- WDEKCKWZKZVGDZ-UHFFFAOYSA-N 2-chloro-n-cyclohexyl-5-[3-(2-hydroxyethyl)-1-methylindol-2-yl]benzenesulfonamide Chemical compound OCCC=1C2=CC=CC=C2N(C)C=1C(C=1)=CC=C(Cl)C=1S(=O)(=O)NC1CCCCC1 WDEKCKWZKZVGDZ-UHFFFAOYSA-N 0.000 claims description 3
- 208000034656 Contusions Diseases 0.000 claims description 3
- LDXDSHIEDAPSSA-OAHLLOKOSA-N Ramatroban Chemical group N([C@@H]1CCC=2N(C3=CC=CC=C3C=2C1)CCC(=O)O)S(=O)(=O)C1=CC=C(F)C=C1 LDXDSHIEDAPSSA-OAHLLOKOSA-N 0.000 claims description 3
- 229940125388 beta agonist Drugs 0.000 claims description 3
- 230000009519 contusion Effects 0.000 claims description 3
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 3
- 229960003592 fexofenadine Drugs 0.000 claims description 3
- 239000003199 leukotriene receptor blocking agent Substances 0.000 claims description 3
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 claims description 3
- 229960003088 loratadine Drugs 0.000 claims description 3
- QMCBHLLJXYUPLP-UHFFFAOYSA-N methyl 2-[2-[3-(cyclohexylsulfamoyl)-5-(trifluoromethyl)phenyl]-1h-indol-3-yl]acetate Chemical compound N1C2=CC=CC=C2C(CC(=O)OC)=C1C(C=1)=CC(C(F)(F)F)=CC=1S(=O)(=O)NC1CCCCC1 QMCBHLLJXYUPLP-UHFFFAOYSA-N 0.000 claims description 3
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 claims description 2
- WBOMXMVCPVYAJI-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-[2-[4-chloro-3-(cyclohexylsulfamoyl)phenyl]-1h-indol-3-yl]acetate Chemical compound N1C2=CC=CC=C2C(CC(=O)OCCN(C)C)=C1C(C=1)=CC=C(Cl)C=1S(=O)(=O)NC1CCCCC1 WBOMXMVCPVYAJI-UHFFFAOYSA-N 0.000 claims description 2
- CXCCZEPELUUFDD-UHFFFAOYSA-N 2-[2-(4-chloro-3-sulfamoylphenyl)-1h-indol-3-yl]acetic acid Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C2=C(C3=CC=CC=C3N2)CC(O)=O)=C1 CXCCZEPELUUFDD-UHFFFAOYSA-N 0.000 claims description 2
- RVWOCMSWEFASHI-UHFFFAOYSA-N 2-[2-[3-(benzenesulfonamido)-4-chlorophenyl]-1h-indol-3-yl]acetic acid Chemical compound N1C2=CC=CC=C2C(CC(=O)O)=C1C(C=1)=CC=C(Cl)C=1NS(=O)(=O)C1=CC=CC=C1 RVWOCMSWEFASHI-UHFFFAOYSA-N 0.000 claims description 2
- LSTFMDGUHBPESB-UHFFFAOYSA-N 2-[2-[3-(cyclohexylsulfamoyl)-4-methoxyphenyl]-1h-indol-3-yl]acetic acid Chemical compound COC1=CC=C(C2=C(C3=CC=CC=C3N2)CC(O)=O)C=C1S(=O)(=O)NC1CCCCC1 LSTFMDGUHBPESB-UHFFFAOYSA-N 0.000 claims description 2
- RVSDWKUYNSUGQC-UHFFFAOYSA-N 2-[2-[3-(cyclohexylsulfamoyl)-4-methylphenyl]-1h-indol-3-yl]acetic acid Chemical compound CC1=CC=C(C2=C(C3=CC=CC=C3N2)CC(O)=O)C=C1S(=O)(=O)NC1CCCCC1 RVSDWKUYNSUGQC-UHFFFAOYSA-N 0.000 claims description 2
- VKMOKQSYAVVHEY-UHFFFAOYSA-N 2-[2-[3-(cyclohexylsulfamoyl)-5-(trifluoromethyl)phenyl]-1h-indol-3-yl]acetic acid Chemical compound N1C2=CC=CC=C2C(CC(=O)O)=C1C(C=1)=CC(C(F)(F)F)=CC=1S(=O)(=O)NC1CCCCC1 VKMOKQSYAVVHEY-UHFFFAOYSA-N 0.000 claims description 2
- JXVFLISNIFHMNZ-UHFFFAOYSA-N 2-[2-[3-(cyclohexylsulfamoyl)phenyl]-1h-indol-3-yl]propanoic acid Chemical compound N1C2=CC=CC=C2C(C(C(O)=O)C)=C1C(C=1)=CC=CC=1S(=O)(=O)NC1CCCCC1 JXVFLISNIFHMNZ-UHFFFAOYSA-N 0.000 claims description 2
- YLTZBNUVCVPBCN-UHFFFAOYSA-N 2-[2-[4-(cyclohexylsulfamoyl)phenyl]-1h-indol-3-yl]acetic acid Chemical compound N1C2=CC=CC=C2C(CC(=O)O)=C1C(C=C1)=CC=C1S(=O)(=O)NC1CCCCC1 YLTZBNUVCVPBCN-UHFFFAOYSA-N 0.000 claims description 2
- RTJZYWCMRYZVJT-UHFFFAOYSA-N 2-[2-[4-chloro-3-(cycloheptylsulfamoyl)phenyl]-1h-indol-3-yl]acetic acid Chemical compound N1C2=CC=CC=C2C(CC(=O)O)=C1C(C=1)=CC=C(Cl)C=1S(=O)(=O)NC1CCCCCC1 RTJZYWCMRYZVJT-UHFFFAOYSA-N 0.000 claims description 2
- UKCNHXSLUKIVLK-UHFFFAOYSA-N 2-[2-[4-chloro-3-(cyclohexylsulfamoyl)phenyl]-5-(trifluoromethoxy)-1h-indol-3-yl]acetic acid Chemical compound N1C2=CC=C(OC(F)(F)F)C=C2C(CC(=O)O)=C1C(C=1)=CC=C(Cl)C=1S(=O)(=O)NC1CCCCC1 UKCNHXSLUKIVLK-UHFFFAOYSA-N 0.000 claims description 2
- AHKWGWWFOOHMBE-UHFFFAOYSA-N 2-[2-[4-chloro-3-(cyclohexylsulfamoyl)phenyl]-5-methyl-1h-indol-3-yl]acetic acid Chemical compound OC(=O)CC=1C2=CC(C)=CC=C2NC=1C(C=1)=CC=C(Cl)C=1S(=O)(=O)NC1CCCCC1 AHKWGWWFOOHMBE-UHFFFAOYSA-N 0.000 claims description 2
- JYQQECGODKQQRF-UHFFFAOYSA-N 2-[2-[4-chloro-3-(cyclohexylsulfamoyl)phenyl]-5-propan-2-yl-1h-indol-3-yl]acetic acid Chemical compound OC(=O)CC=1C2=CC(C(C)C)=CC=C2NC=1C(C=1)=CC=C(Cl)C=1S(=O)(=O)NC1CCCCC1 JYQQECGODKQQRF-UHFFFAOYSA-N 0.000 claims description 2
- JEBAWCRMSLGTPK-UHFFFAOYSA-N 2-[4-chloro-3-(cyclohexylsulfamoyl)phenyl]-1h-indole-6-carboxylic acid Chemical compound N1C2=CC(C(=O)O)=CC=C2C=C1C(C=1)=CC=C(Cl)C=1S(=O)(=O)NC1CCCCC1 JEBAWCRMSLGTPK-UHFFFAOYSA-N 0.000 claims description 2
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- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
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- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
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- A—HUMAN NECESSITIES
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/22—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an aralkyl radical attached to the ring nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an alkyl or cycloalkyl radical attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
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- Dermatology (AREA)
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- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
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- Hospice & Palliative Care (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US64730705P | 2005-01-26 | 2005-01-26 | |
| PCT/US2006/002736 WO2006081343A1 (en) | 2005-01-26 | 2006-01-25 | 2-phenyl-indoles as prostaglandin d2 receptor antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2007008277A true MX2007008277A (es) | 2007-09-07 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2007008277A MX2007008277A (es) | 2005-01-26 | 2006-01-25 | 2-fenilindoles como antagonistas del receptor de la prostaglandina d2. |
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| Country | Link |
|---|---|
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| EP (1) | EP1844011A1 (enExample) |
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| BR (1) | BRPI0607079A2 (enExample) |
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| GT (1) | GT200600030A (enExample) |
| IL (1) | IL184816A0 (enExample) |
| MA (1) | MA29259B1 (enExample) |
| MX (1) | MX2007008277A (enExample) |
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| PE (1) | PE20060878A1 (enExample) |
| RU (1) | RU2007132166A (enExample) |
| SG (1) | SG158918A1 (enExample) |
| TN (1) | TNSN07251A1 (enExample) |
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| EP2066628B1 (en) * | 2006-07-25 | 2010-10-20 | Sanofi-Aventis | 2-phenyl-indoles as prostaglandin d2 receptor antagonists |
| CN101500996B (zh) | 2006-08-07 | 2012-07-04 | 埃科特莱茵药品有限公司 | (3-胺基-1,2,3,4-四氢-9h-咔唑-9-基)-乙酸衍生物 |
| WO2008061006A1 (en) * | 2006-11-10 | 2008-05-22 | Wyeth | Substituted indan-2-yl, tetrahydronaphthalen-2-yl, or dihydr0-2h-chr0men-3-yl arylsulfonamides and methods of their use |
| WO2009061730A2 (en) * | 2007-11-05 | 2009-05-14 | Array Biopharma Inc. | 4-heteroaryl-substituted phenoxyphenylacetic acid |
| MX2012010820A (es) | 2010-03-22 | 2012-10-10 | Actelion Pharmaceuticals Ltd | Derivados de 3-(heteroaril-amino)-1, 2, 3, 4-tetrahidro-9h-carbazo l y sus uso como moduladores del receptor de prostaglandina d2. |
| WO2012046653A1 (ja) * | 2010-10-06 | 2012-04-12 | 株式会社クレハ | アミン系化合物とその用途 |
| WO2012140612A1 (en) | 2011-04-14 | 2012-10-18 | Actelion Pharmaceuticals Ltd | 7-(heteroaryl-amino)-6,7,8,9-tetrahydropyrido[1,2-a]indol acetic acid derivatives and their use as prostaglandin d2 receptor modulators |
| EP2548863A1 (en) * | 2011-07-18 | 2013-01-23 | Almirall, S.A. | New CRTh2 antagonists. |
| AR088204A1 (es) * | 2011-09-29 | 2014-05-14 | Shionogi & Co | Medicamentos para el tratamiento de la rinitis alergica que comprenden un antagonista de pgd2 y un antagonista de histamina |
| US9255090B2 (en) | 2011-12-21 | 2016-02-09 | Actelion Pharmaceuticals Ltd. | Heterocyclyl derivatives and their use as prostaglandin D2 receptor modulators |
| US9169270B2 (en) | 2012-07-05 | 2015-10-27 | Actelion Pharmaceuticals Ltd. | 1-phenyl-substituted heterocyclyl derivatives and their use as prostaglandin D2 receptor modulators |
| EP2912458B1 (en) | 2012-10-24 | 2018-07-18 | NYU Winthrop Hospital | Non-invasive biomarker to identify subjects at risk of preterm delivery |
| JP6168520B2 (ja) * | 2013-09-17 | 2017-07-26 | 国立大学法人 千葉大学 | インドール化合物、ｄｐプロスタノイド受容体アンタゴニスト、それを用いた薬剤、及びｄｐプロスタノイド受容体アンタゴニストの使用。 |
| JP2015089886A (ja) * | 2013-11-06 | 2015-05-11 | 国立大学法人名古屋大学 | 嵩高い置換基を有する化合物を用いた植物成長調整剤 |
| UA117780C2 (uk) | 2014-03-17 | 2018-09-25 | Ідорсія Фармасьютікалз Лтд | Похідні азаіндолоцтової кислоти та їх застосування як модуляторів рецепторів простагландину d2 |
| RU2016140708A (ru) | 2014-03-18 | 2018-04-18 | Идорсиа Фармасьютиклз Лтд | Производные азаиндол уксусной кислоты и их применение в качестве модуляторов рецептора простагландина d2 |
| UA123156C2 (uk) | 2015-09-15 | 2021-02-24 | Ідорсія Фармасьютікалз Лтд | КРИСТАЛІЧНА ФОРМА (S)-2-(8-((5-ХЛОРПІРИМІДИН-2-ІЛ)(МЕТИЛ)АМІНО)-2-ФТОР-6,7,8,9-ТЕТРАГІДРО-5H-ПІРИДО[3,2-b]ІНДОЛ-5-ІЛ)ОЦТОВОЇ КИСЛОТИ, ЇЇ ЗАСТОСУВАННЯ ТА ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ, ЩО ЇЇ МІСТИТЬ |
| US20200264188A1 (en) | 2017-09-13 | 2020-08-20 | Progenity, Inc. | Preeclampsia biomarkers and related systems and methods |
| WO2019166629A1 (en) | 2018-03-02 | 2019-09-06 | Inflazome Limited | Novel compounds |
| EP4070113A4 (en) | 2019-12-04 | 2023-12-20 | Biora Therapeutics, Inc. | ASSESSMENT OF PREECAMPSIA USING FREE AND DISSOCIATE PLACENTAL GROWTH FACTOR ASSAYS |
| CN113173877B (zh) * | 2020-10-30 | 2023-10-27 | 江西师范大学 | 吲哚乙酰基亚氨基砜系列化合物及其制备方法 |
| CN115925606B (zh) * | 2023-01-05 | 2023-10-13 | 宁夏医科大学 | 一种5-（3-（磺酰胺基）苯基）-1h-吡咯-2-羧酸衍生物及其制备方法和应用 |
| CN117599052A (zh) * | 2023-07-25 | 2024-02-27 | 温州医科大学附属眼视光医院 | Ptgds的抑制剂在制备治疗白内障药物上的应用 |
| US12220411B1 (en) | 2023-07-25 | 2025-02-11 | The Eye Hospital Of Wenzhou Medical University | Application of PTGDS inhibitor in preparation of drug for treating cataracts |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR950701317A (ko) * | 1992-05-08 | 1995-03-23 | 오오쓰까 아끼히꼬 | 인돌 유도체(Indole Derivative) |
| FR2751966B1 (fr) * | 1996-08-01 | 1998-10-30 | Union Pharma Scient Appl | Nouveaux derives 1,2-diarylindoles, leurs procedes de preparation, et leurs utilisations en therapeutique |
| US6500853B1 (en) * | 1998-02-28 | 2002-12-31 | Genetics Institute, Llc | Inhibitors of phospholipase enzymes |
| DE10204462A1 (de) * | 2002-02-05 | 2003-08-07 | Boehringer Ingelheim Pharma | Verwendung von Tyrosinkinase-Inhibitoren zur Behandlung inflammatorischer Prozesse |
| JP2004024655A (ja) * | 2002-06-27 | 2004-01-29 | Aruze Corp | 遊技機 |
| JPWO2004078719A1 (ja) * | 2003-03-06 | 2006-06-08 | 小野薬品工業株式会社 | インドール誘導体化合物およびその化合物を有効成分とする薬剤 |
| SE0301569D0 (sv) * | 2003-05-27 | 2003-05-27 | Astrazeneca Ab | Novel compounds |
| SE0303180D0 (sv) * | 2003-11-26 | 2003-11-26 | Astrazeneca Ab | Novel compounds |
| EA200700243A1 (ru) * | 2004-07-14 | 2007-08-31 | ПиТиСи ТЕРАПЬЮТИКС, ИНК. | Способы лечения гепатита с |
| US7868037B2 (en) * | 2004-07-14 | 2011-01-11 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
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2006
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- 2006-01-25 CN CNA2006800097886A patent/CN101146770A/zh active Pending
- 2006-01-25 GT GT200600030A patent/GT200600030A/es unknown
- 2006-01-25 WO PCT/US2006/002736 patent/WO2006081343A1/en not_active Ceased
- 2006-01-25 JP JP2007553221A patent/JP2008528606A/ja active Pending
- 2006-01-25 AR ARP060100278A patent/AR054726A1/es not_active Application Discontinuation
- 2006-01-25 SG SG201000540-3A patent/SG158918A1/en unknown
- 2006-01-25 RU RU2007132166/04A patent/RU2007132166A/ru not_active Application Discontinuation
- 2006-01-25 AU AU2006209213A patent/AU2006209213A1/en not_active Abandoned
- 2006-01-25 BR BRPI0607079-5A patent/BRPI0607079A2/pt not_active IP Right Cessation
- 2006-01-25 KR KR1020077017292A patent/KR20070110277A/ko not_active Withdrawn
- 2006-01-25 EP EP06719551A patent/EP1844011A1/en not_active Withdrawn
- 2006-01-25 MX MX2007008277A patent/MX2007008277A/es not_active Application Discontinuation
- 2006-01-25 CA CA002595728A patent/CA2595728A1/en not_active Abandoned
- 2006-01-26 PA PA20068661201A patent/PA8661201A1/es unknown
- 2006-01-26 TW TW095102967A patent/TW200639151A/zh unknown
- 2006-01-26 UY UY29346A patent/UY29346A1/es unknown
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2007
- 2007-06-28 CR CR9214A patent/CR9214A/es not_active Application Discontinuation
- 2007-07-03 TN TNP2007000251A patent/TNSN07251A1/en unknown
- 2007-07-04 ZA ZA200705449A patent/ZA200705449B/xx unknown
- 2007-07-24 IL IL184816A patent/IL184816A0/en unknown
- 2007-07-25 US US11/782,890 patent/US20070265278A1/en not_active Abandoned
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| IL184816A0 (en) | 2007-12-03 |
| TNSN07251A1 (en) | 2008-12-31 |
| GT200600030A (es) | 2006-09-27 |
| PA8661201A1 (es) | 2006-09-08 |
| US20070265278A1 (en) | 2007-11-15 |
| TW200639151A (en) | 2006-11-16 |
| AU2006209213A1 (en) | 2006-08-03 |
| NO20074336L (no) | 2007-10-23 |
| KR20070110277A (ko) | 2007-11-16 |
| UY29346A1 (es) | 2006-08-31 |
| CN101146770A (zh) | 2008-03-19 |
| ZA200705449B (en) | 2009-01-28 |
| BRPI0607079A2 (pt) | 2009-08-04 |
| AR054726A1 (es) | 2007-07-11 |
| DOP2006000016A (es) | 2006-07-31 |
| MA29259B1 (fr) | 2008-02-01 |
| JP2008528606A (ja) | 2008-07-31 |
| RU2007132166A (ru) | 2009-03-10 |
| EP1844011A1 (en) | 2007-10-17 |
| CR9214A (es) | 2007-11-23 |
| WO2006081343A1 (en) | 2006-08-03 |
| PE20060878A1 (es) | 2006-10-18 |
| CA2595728A1 (en) | 2006-08-03 |
| SG158918A1 (en) | 2010-02-26 |
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