CA2589648A1 - Fused pyrazole derivatives and methods of treatment of metabolic-relateddisorders thereof - Google Patents
Fused pyrazole derivatives and methods of treatment of metabolic-relateddisorders thereof Download PDFInfo
- Publication number
- CA2589648A1 CA2589648A1 CA002589648A CA2589648A CA2589648A1 CA 2589648 A1 CA2589648 A1 CA 2589648A1 CA 002589648 A CA002589648 A CA 002589648A CA 2589648 A CA2589648 A CA 2589648A CA 2589648 A1 CA2589648 A1 CA 2589648A1
- Authority
- CA
- Canada
- Prior art keywords
- tetrahydro
- cyclopropa
- diaza
- pentalene
- compound according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 114
- 238000011282 treatment Methods 0.000 title claims abstract description 66
- 150000003217 pyrazoles Chemical class 0.000 title abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 589
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 92
- 150000003839 salts Chemical class 0.000 claims abstract description 51
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 50
- 230000002503 metabolic effect Effects 0.000 claims abstract description 46
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 40
- 239000003112 inhibitor Substances 0.000 claims abstract description 35
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 33
- 206010022489 Insulin Resistance Diseases 0.000 claims abstract description 28
- 239000000556 agonist Substances 0.000 claims abstract description 27
- 208000032928 Dyslipidaemia Diseases 0.000 claims abstract description 22
- 208000017170 Lipid metabolism disease Diseases 0.000 claims abstract description 22
- 208000029078 coronary artery disease Diseases 0.000 claims abstract description 19
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 16
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 15
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims abstract description 14
- 239000003623 enhancer Substances 0.000 claims abstract description 13
- 239000002464 receptor antagonist Substances 0.000 claims abstract description 13
- 229940044551 receptor antagonist Drugs 0.000 claims abstract description 13
- 229940123208 Biguanide Drugs 0.000 claims abstract description 12
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims abstract description 12
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 claims abstract description 10
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 claims abstract description 10
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229940031439 squalene Drugs 0.000 claims abstract description 10
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 claims abstract description 10
- 208000011580 syndromic disease Diseases 0.000 claims abstract description 9
- 229940125753 fibrate Drugs 0.000 claims abstract description 8
- 230000015556 catabolic process Effects 0.000 claims abstract description 7
- 230000003914 insulin secretion Effects 0.000 claims abstract description 7
- 239000003288 aldose reductase inhibitor Substances 0.000 claims abstract description 6
- -1 C4-7 oxo-cycloalkyl Chemical group 0.000 claims description 148
- GUVXZFRDPCKWEM-UHFFFAOYSA-N pentalene Chemical compound C1=CC2=CC=CC2=C1 GUVXZFRDPCKWEM-UHFFFAOYSA-N 0.000 claims description 66
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 47
- 239000012453 solvate Substances 0.000 claims description 45
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
- 239000003814 drug Substances 0.000 claims description 34
- 229910052736 halogen Inorganic materials 0.000 claims description 32
- 150000002367 halogens Chemical class 0.000 claims description 31
- 241001465754 Metazoa Species 0.000 claims description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- 201000010099 disease Diseases 0.000 claims description 28
- 229910052799 carbon Inorganic materials 0.000 claims description 27
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 21
- 125000002252 acyl group Chemical group 0.000 claims description 20
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 20
- 125000004423 acyloxy group Chemical group 0.000 claims description 19
- 125000004995 haloalkylthio group Chemical group 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 17
- 239000003937 drug carrier Substances 0.000 claims description 17
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 17
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 16
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
- 150000003857 carboxamides Chemical class 0.000 claims description 15
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 14
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 238000002560 therapeutic procedure Methods 0.000 claims description 14
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 13
- 125000004741 (C1-C6) haloalkylsulfonyl group Chemical group 0.000 claims description 13
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 13
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 12
- 125000004749 (C1-C6) haloalkylsulfinyl group Chemical group 0.000 claims description 12
- 125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 11
- 125000005432 dialkylcarboxamide group Chemical group 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 11
- 229920002554 vinyl polymer Polymers 0.000 claims description 11
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 10
- 125000005431 alkyl carboxamide group Chemical group 0.000 claims description 10
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 10
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 claims description 10
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 10
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 10
- 239000005541 ACE inhibitor Substances 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 9
- 208000008589 Obesity Diseases 0.000 claims description 9
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 9
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 235000020824 obesity Nutrition 0.000 claims description 9
- 239000004031 partial agonist Substances 0.000 claims description 9
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 9
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 8
- 206010020772 Hypertension Diseases 0.000 claims description 8
- 208000006011 Stroke Diseases 0.000 claims description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 7
- 208000019622 heart disease Diseases 0.000 claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- 201000009104 prediabetes syndrome Diseases 0.000 claims description 7
- ABDMQSFNJPYOLA-UHFFFAOYSA-N NS(=O)(=O)[N+]([O-])=O Chemical compound NS(=O)(=O)[N+]([O-])=O ABDMQSFNJPYOLA-UHFFFAOYSA-N 0.000 claims description 6
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 6
- 229940124530 sulfonamide Drugs 0.000 claims description 6
- 150000003456 sulfonamides Chemical class 0.000 claims description 6
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims description 5
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 5
- 229940123464 Thiazolidinedione Drugs 0.000 claims description 5
- 125000005110 aryl thio group Chemical group 0.000 claims description 5
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
- 229940118148 Aldose reductase inhibitor Drugs 0.000 claims description 4
- 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 claims description 4
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 claims description 4
- 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 claims description 4
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- ZYICRESAGWVMJD-UHFFFAOYSA-N C=1C=CC=CC=1CC(C12)C2CC=2C1=NNC=2C=1N=NNN=1 Chemical compound C=1C=CC=CC=1CC(C12)C2CC=2C1=NNC=2C=1N=NNN=1 ZYICRESAGWVMJD-UHFFFAOYSA-N 0.000 claims description 3
- 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 3
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- WVIAXGYIVDKKEC-UHFFFAOYSA-N (+/-)-1,1-dimethyl-1a,3,5,5a-tetrahydro-1h-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid Chemical compound C12C(C)(C)C2CC=2C1=NNC=2C(O)=O WVIAXGYIVDKKEC-UHFFFAOYSA-N 0.000 claims description 2
- UKQFEWRNKWDNBW-UHFFFAOYSA-N 7,8-diazatricyclo[4.3.0.02,4]nona-1(6),8-diene-9-carboxylic acid Chemical compound C1C2CC2C2=C(C(=O)O)NN=C21 UKQFEWRNKWDNBW-UHFFFAOYSA-N 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 10
- 125000003396 thiol group Chemical class [H]S* 0.000 claims 4
- OTMHRRBDBDERSZ-UHFFFAOYSA-N 3-benzyl-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxylic acid Chemical compound C12CC3=C(C(=O)O)NN=C3C2C1CC1=CC=CC=C1 OTMHRRBDBDERSZ-UHFFFAOYSA-N 0.000 claims 2
- DVJZLBFGLLGJNR-UHFFFAOYSA-N ethyl 3-ethyl-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxylate Chemical compound C1C2=C(C(=O)OCC)NN=C2C2C(CC)C21 DVJZLBFGLLGJNR-UHFFFAOYSA-N 0.000 claims 2
- RAILBMQEZUOZPY-UHFFFAOYSA-N (+/-)-1,1-dimethyl-1a,3,5,5a-tetrahydro-1h-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ethyl ester Chemical compound C1C2=C(C(=O)OCC)NN=C2C2C(C)(C)C12 RAILBMQEZUOZPY-UHFFFAOYSA-N 0.000 claims 1
- VSBDNNUJQGUHKD-UHFFFAOYSA-N (+/-)-1,1-dimethyl-4-(2h-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1h-2,3-diaza-cyclopropa[a]pentalene Chemical compound C12C(C)(C)C2CC=2C1=NNC=2C=1N=NNN=1 VSBDNNUJQGUHKD-UHFFFAOYSA-N 0.000 claims 1
- ZNSMRESAJQMQFB-UHFFFAOYSA-N 3-(2-methylpropyl)-7-(2H-tetrazol-5-yl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene Chemical compound C12C(CC(C)C)C2CC=2C1=NNC=2C=1N=NNN=1 ZNSMRESAJQMQFB-UHFFFAOYSA-N 0.000 claims 1
- JQOLBGNVBHBYTN-UHFFFAOYSA-N 3-(2-methylpropyl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxylic acid Chemical compound C12C(CC(C)C)C2CC=2C1=NNC=2C(O)=O JQOLBGNVBHBYTN-UHFFFAOYSA-N 0.000 claims 1
- UZFHZWKLQQVCHG-UHFFFAOYSA-N 3-(ethoxymethyl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxylic acid Chemical compound C12C(COCC)C2CC=2C1=NNC=2C(O)=O UZFHZWKLQQVCHG-UHFFFAOYSA-N 0.000 claims 1
- ODUVQBROUWOBDH-UHFFFAOYSA-N 3-(hydroxymethyl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxylic acid Chemical compound C12C(CO)C2CC=2C1=NNC=2C(O)=O ODUVQBROUWOBDH-UHFFFAOYSA-N 0.000 claims 1
- SNHAYNGAPALUSS-UHFFFAOYSA-N 3-(methoxymethyl)-7-(2H-tetrazol-5-yl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene Chemical compound C12C(COC)C2CC=2C1=NNC=2C=1N=NNN=1 SNHAYNGAPALUSS-UHFFFAOYSA-N 0.000 claims 1
- APQANBAOGDTTDE-UHFFFAOYSA-N 3-(methoxymethyl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxylic acid Chemical compound C12C(COC)C2CC=2C1=NNC=2C(O)=O APQANBAOGDTTDE-UHFFFAOYSA-N 0.000 claims 1
- UDQHREJCGBMEQZ-UHFFFAOYSA-N 3-(methylsulfanylmethyl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxylic acid Chemical compound C12C(CSC)C2CC=2C1=NNC=2C(O)=O UDQHREJCGBMEQZ-UHFFFAOYSA-N 0.000 claims 1
- XJNZFQMEFRFJIV-UHFFFAOYSA-N 3-(phenoxymethyl)-7-(2H-tetrazol-5-yl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene Chemical compound C12CC(=C(NN=3)C4=NNN=N4)C=3C2C1COC1=CC=CC=C1 XJNZFQMEFRFJIV-UHFFFAOYSA-N 0.000 claims 1
- LUCHJPWHYQGXLE-NSCUHMNNSA-N 3-[(E)-prop-1-enyl]-7-(2H-tetrazol-5-yl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene Chemical compound C12C(/C=C/C)C2CC=2C1=NNC=2C=1N=NNN=1 LUCHJPWHYQGXLE-NSCUHMNNSA-N 0.000 claims 1
- VIQDOSDFYBSVKH-NSCUHMNNSA-N 3-[(E)-prop-1-enyl]-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxylic acid Chemical compound C12C(/C=C/C)C2CC=2C1=NNC=2C(O)=O VIQDOSDFYBSVKH-NSCUHMNNSA-N 0.000 claims 1
- LUCHJPWHYQGXLE-IHWYPQMZSA-N 3-[(Z)-prop-1-enyl]-7-(2H-tetrazol-5-yl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene Chemical compound C12C(\C=C/C)C2CC=2C1=NNC=2C=1N=NNN=1 LUCHJPWHYQGXLE-IHWYPQMZSA-N 0.000 claims 1
- VIQDOSDFYBSVKH-IHWYPQMZSA-N 3-[(Z)-prop-1-enyl]-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxylic acid Chemical compound C12C(\C=C/C)C2CC=2C1=NNC=2C(O)=O VIQDOSDFYBSVKH-IHWYPQMZSA-N 0.000 claims 1
- VYWKYLOLYLNJFO-UHFFFAOYSA-N 3-butyl-7-(2H-tetrazol-5-yl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene Chemical compound C12C(CCCC)C2CC=2C1=NNC=2C=1N=NNN=1 VYWKYLOLYLNJFO-UHFFFAOYSA-N 0.000 claims 1
- HZGMLBXSQLGHIS-UHFFFAOYSA-N 3-butyl-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxylic acid Chemical compound C12C(CCCC)C2CC=2C1=NNC=2C(O)=O HZGMLBXSQLGHIS-UHFFFAOYSA-N 0.000 claims 1
- BUTFUADABNFVEZ-UHFFFAOYSA-N 3-cyclopropyl-7-(2H-tetrazol-5-yl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene Chemical compound C1CC1C1C2C3=NNC(C4=NNN=N4)=C3CC21 BUTFUADABNFVEZ-UHFFFAOYSA-N 0.000 claims 1
- KRGVFHQAOMELTE-UHFFFAOYSA-N 3-cyclopropyl-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxylic acid Chemical compound C1C2=C(C(=O)O)NN=C2C2C1C2C1CC1 KRGVFHQAOMELTE-UHFFFAOYSA-N 0.000 claims 1
- UCNBXLZANXGQAD-UHFFFAOYSA-N 3-ethenyl-7-(2H-tetrazol-5-yl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene Chemical compound C12C(C=C)C2CC=2C1=NNC=2C=1N=NNN=1 UCNBXLZANXGQAD-UHFFFAOYSA-N 0.000 claims 1
- RTJPVQFTNJBAAO-UHFFFAOYSA-N 3-ethenyl-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxylic acid Chemical compound C1C2=C(C(=O)O)NN=C2C2C(C=C)C12 RTJPVQFTNJBAAO-UHFFFAOYSA-N 0.000 claims 1
- SYZZVQFBZIIAPM-UHFFFAOYSA-N 3-ethyl-7-(2H-tetrazol-5-yl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene Chemical compound C12C(CC)C2CC=2C1=NNC=2C=1N=NNN=1 SYZZVQFBZIIAPM-UHFFFAOYSA-N 0.000 claims 1
- TWKUMVSEPLJJQZ-UHFFFAOYSA-N 3-ethyl-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxylic acid Chemical compound C12C(CC)C2CC=2C1=NNC=2C(O)=O TWKUMVSEPLJJQZ-UHFFFAOYSA-N 0.000 claims 1
- NFZMLDIEJQTJDW-UHFFFAOYSA-N 3-methyl-7,8-diazatricyclo[4.3.0.02,4]nona-1(6),8-diene-9-carboxylic acid Chemical compound N1C(C(O)=O)=C2C3C(C)C3CC2=N1 NFZMLDIEJQTJDW-UHFFFAOYSA-N 0.000 claims 1
- SOPWSSMPKDHAFO-UHFFFAOYSA-N 3-methyl-7-(2H-tetrazol-5-yl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene Chemical compound C12C(C)C2CC=2C1=NNC=2C=1N=NNN=1 SOPWSSMPKDHAFO-UHFFFAOYSA-N 0.000 claims 1
- RTKOUBUTPYWYHC-UHFFFAOYSA-N 3-methyl-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxylic acid Chemical compound C12C(C)C2CC=2C1=NNC=2C(O)=O RTKOUBUTPYWYHC-UHFFFAOYSA-N 0.000 claims 1
- HGMKQXPTBSXDTB-UHFFFAOYSA-N 3-pentyl-7-(2H-tetrazol-5-yl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene Chemical compound C12C(CCCCC)C2CC=2C1=NNC=2C=1N=NNN=1 HGMKQXPTBSXDTB-UHFFFAOYSA-N 0.000 claims 1
- LRSWOBPCCZMIMT-UHFFFAOYSA-N 3-pentyl-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxylic acid Chemical compound C12C(CCCCC)C2CC=2C1=NNC=2C(O)=O LRSWOBPCCZMIMT-UHFFFAOYSA-N 0.000 claims 1
- ADDWQSJBENMLJW-UHFFFAOYSA-N 3-phenyl-7-(2H-tetrazol-5-yl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene Chemical compound C12=NNC(C3=NNN=N3)=C2CC2C1C2C1=CC=CC=C1 ADDWQSJBENMLJW-UHFFFAOYSA-N 0.000 claims 1
- HJVDLDUXOXOQJX-UHFFFAOYSA-N 3-phenyl-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxylic acid Chemical compound C1C2=C(C(=O)O)NN=C2C2C1C2C1=CC=CC=C1 HJVDLDUXOXOQJX-UHFFFAOYSA-N 0.000 claims 1
- ULNGMOCVPKLURH-UHFFFAOYSA-N 3-propan-2-yl-7-(2H-tetrazol-5-yl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene Chemical compound C12C(C(C)C)C2CC=2C1=NNC=2C=1N=NNN=1 ULNGMOCVPKLURH-UHFFFAOYSA-N 0.000 claims 1
- ZAKPZERPWYRHOO-UHFFFAOYSA-N 3-propan-2-yl-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxylic acid Chemical compound C12C(C(C)C)C2CC=2C1=NNC=2C(O)=O ZAKPZERPWYRHOO-UHFFFAOYSA-N 0.000 claims 1
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- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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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
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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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
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
-
- 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
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/88—Carbazoles; Hydrogenated carbazoles 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 carbon atoms of the ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
- C07D265/36—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
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- Organic Chemistry (AREA)
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- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Hematology (AREA)
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- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
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- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US63866804P | 2004-12-23 | 2004-12-23 | |
| US60/638,668 | 2004-12-23 | ||
| US67652105P | 2005-04-29 | 2005-04-29 | |
| US60/676,521 | 2005-04-29 | ||
| PCT/US2005/046599 WO2006069242A2 (en) | 2004-12-23 | 2005-12-22 | Fused pyrazole derivatives and uses thereof in methods of treatment of metabolic-related?disorders |
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| CA2589648A1 true CA2589648A1 (en) | 2006-06-29 |
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| CA002589648A Abandoned CA2589648A1 (en) | 2004-12-23 | 2005-12-22 | Fused pyrazole derivatives and methods of treatment of metabolic-relateddisorders thereof |
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| PE20050483A1 (es) | 2003-10-31 | 2005-08-25 | Arena Pharm Inc | Derivados de tetrazol de formula (i), sus composiciones farmaceuticas y procesos para producir composiciones farmaceuticas |
| AU2004293415A1 (en) | 2003-11-21 | 2005-06-09 | Arena Pharmaceuticals, Inc. | 4-oxo-4,5-dihydro-furan-2-carboxylic and acid derivatives and methods of treatment of metabolic-related disorders thereof |
| PE20060949A1 (es) * | 2004-12-23 | 2006-10-11 | Arena Pharm Inc | Derivados fusionados de pirazol como agonistas del receptor de niacina |
| SI1901731T1 (sl) | 2005-06-28 | 2011-07-29 | Merck Sharp & Dohme | Niacin receptorski antagonisti, sestavki vsebujoäśi take spojine in postopki zdravljenja |
| EP2061767B1 (de) | 2006-08-08 | 2014-12-17 | Sanofi | Arylaminoaryl-alkyl-substituierte Imidazolidin-2,4-dione, Verfahren zu ihrer Herstellung, diese Verbindungen enthaltende Arzneimittel und ihre Verwendung |
| DE102007005045B4 (de) | 2007-01-26 | 2008-12-18 | Sanofi-Aventis | Phenothiazin Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| DE102007054497B3 (de) | 2007-11-13 | 2009-07-23 | Sanofi-Aventis Deutschland Gmbh | Neue kristalline Diphenylazetidinonhydrate und Verfahren zu deren Herstellung |
| US8470841B2 (en) | 2008-07-09 | 2013-06-25 | Sanofi | Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof |
| WO2010068601A1 (en) | 2008-12-08 | 2010-06-17 | Sanofi-Aventis | A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof |
| CN102482312A (zh) | 2009-08-26 | 2012-05-30 | 赛诺菲 | 新颖的杂芳族氟代糖苷结晶水合物、含有这些化合物的药物和它们的用途 |
| CN102596913B (zh) * | 2009-08-28 | 2016-11-09 | 艾尼纳制药公司 | 大麻素受体调节剂 |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP2582709B1 (de) | 2010-06-18 | 2018-01-24 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| WO2012116278A1 (en) * | 2011-02-25 | 2012-08-30 | Arena Pharmaceuticals, Inc. | Cannabinoid receptor modulators |
| WO2012116277A1 (en) | 2011-02-25 | 2012-08-30 | Arena Pharmaceuticals, Inc. | Cannabinoid receptor modulators |
| EA035989B1 (ru) | 2011-02-25 | 2020-09-09 | Арена Фармасьютикалз, Инк. | Кристаллические формы и способы получения модуляторов каннабиноидного рецептора |
| JP6043733B2 (ja) | 2011-02-25 | 2016-12-14 | アリーナ ファーマシューティカルズ， インコーポレイテッド | カンナビノイド受容体モジュレーター |
| EP2683702B1 (de) | 2011-03-08 | 2014-12-24 | Sanofi | Neue substituierte phenyl-oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP2683705B1 (de) | 2011-03-08 | 2015-04-22 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2683699B1 (de) | 2011-03-08 | 2015-06-24 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2012120053A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| US8846666B2 (en) | 2011-03-08 | 2014-09-30 | Sanofi | Oxathiazine derivatives which are substituted with benzyl or heteromethylene groups, method for producing them, their use as medicine and drug containing said derivatives and the use thereof |
| US8901114B2 (en) | 2011-03-08 | 2014-12-02 | Sanofi | Oxathiazine derivatives substituted with carbocycles or heterocycles, method for producing same, drugs containing said compounds, and use thereof |
| WO2012120056A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2012120051A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Mit adamantan- oder noradamantan substituierte benzyl-oxathiazinderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP2683703B1 (de) | 2011-03-08 | 2015-05-27 | Sanofi | Neue substituierte phenyl-oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2760862B1 (en) | 2011-09-27 | 2015-10-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| AR091739A1 (es) | 2012-07-11 | 2015-02-25 | Elcelyx Therapeutics Inc | Composiciones y metodos para reducir el riesgo cardiometabolico |
| MX2019013311A (es) | 2017-05-08 | 2020-08-03 | Arena Pharm Inc | Compuestos y metodos para el tratamiento del dolor visceral. |
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| US3105336A (en) * | 1961-05-16 | 1963-10-01 | Package Machinery Co | Converting wrapping machines to wrap different size articles |
| US4613610A (en) * | 1984-06-22 | 1986-09-23 | Sandoz Pharmaceuticals Corp. | Cholesterol biosynthesis inhibiting pyrazole analogs of mevalonolactone and its derivatives |
| US5134155A (en) * | 1991-08-08 | 1992-07-28 | Ortho Pharmaceutical Corporation | Tetrahydroindazole, tetrahydrocyclopentapyrazole, and hexahydrocycloheptapyrazole compounds and their use as HMG-coA reductase inhibitors |
| DE69935335T2 (de) * | 1998-08-07 | 2007-11-22 | Novartis Vaccines and Diagnostics, Inc., Emeryville | Pyrazole als modulatoren des östrogenrezeptors |
| WO2003022814A1 (en) | 2001-09-07 | 2003-03-20 | Ono Pharmaceutical Co., Ltd. | Indole derivatives |
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| US6410583B1 (en) | 2000-07-25 | 2002-06-25 | Merck Frosst Canada & Co. | Cyclopentanoindoles, compositions containing such compounds and methods of treatment |
| AU2002302248B2 (en) | 2001-05-23 | 2008-03-06 | Merck Frosst Canada Ltd. | Dihydropyrrolo[1,2-A]indole and tetrahydropyrido[1,2-A]-indole derivatives as prostaglandin D2 receptor antagonists |
| DE60200346T2 (de) | 2001-06-27 | 2005-03-24 | Rs Tech Corp. | Neuer chiraler salen-katalysator und verfahren zur herstellung chiraler verbindungen aus racemischen epoxiden unter verwendung des neuen katalysators |
| DE10148617A1 (de) * | 2001-09-25 | 2003-04-24 | Schering Ag | Substituierte N-(1,4,5,6-Tetrahydro-cyclopentapyrazol-3-yl)-Derivate, deren Herstellung und Verwendung als Arzneimittel |
| AR038136A1 (es) | 2002-01-24 | 2004-12-29 | Merck Frosst Canada Inc | Cicloalcanindoles con sustitucion con fluor composiciones que contienen estos compuestos y metodos de tratamiento |
| MXPA04009095A (es) | 2002-03-19 | 2004-12-06 | Ono Pharmaceutical Co | Compuesto de acido carboxilico y agente farmaceutico que comprende el compuesto como ingrediente activo. |
| WO2004033431A2 (en) | 2002-10-04 | 2004-04-22 | Arena Pharmaceuticals, Inc. | Hydroxypyrazoles for use against metabolic-related disorders |
| CA2501134A1 (en) * | 2002-10-10 | 2004-04-22 | Arena Pharmaceuticals, Inc. | 5-substituted 2h-pyrazole-3-carboxylic acid derivatives as antilipolytic agents for the treatment of metabolic-related disorders such as dyslipidemia |
| AR041089A1 (es) | 2003-05-15 | 2005-05-04 | Merck & Co Inc | Procedimiento y composiciones farmaceutiicas para tratar aterosclerosis, dislipidemias y afecciones relacionadas |
| WO2005011677A1 (en) * | 2003-06-13 | 2005-02-10 | Arena Pharmaceuticals, Inc. | 5-substituted 2h-pyrazole-3-carboxylic acid derivatives as agonists for the nicotinic acid receptor rup25 for the treatment of dyslipidemia and related diseases |
| GB0319126D0 (en) | 2003-08-14 | 2003-09-17 | Smithkline Beecham Corp | Chemical compounds |
| GB0319124D0 (en) | 2003-08-14 | 2003-09-17 | Smithkline Beecham Corp | Chemical compounds |
| PE20050483A1 (es) * | 2003-10-31 | 2005-08-25 | Arena Pharm Inc | Derivados de tetrazol de formula (i), sus composiciones farmaceuticas y procesos para producir composiciones farmaceuticas |
| CN101103030B (zh) | 2004-02-14 | 2010-10-13 | 史密丝克莱恩比彻姆公司 | 具有hm74a受体活性的药物 |
| PE20060949A1 (es) * | 2004-12-23 | 2006-10-11 | Arena Pharm Inc | Derivados fusionados de pirazol como agonistas del receptor de niacina |
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2005
- 2005-12-15 PE PE2005001472A patent/PE20060949A1/es not_active Application Discontinuation
- 2005-12-20 GT GT200500379A patent/GT200500379A/es unknown
- 2005-12-21 HN HN2005036256A patent/HN2005036256A/es unknown
- 2005-12-21 AR ARP050105438A patent/AR055015A1/es not_active Application Discontinuation
- 2005-12-21 TW TW094145549A patent/TW200635904A/zh unknown
- 2005-12-22 US US11/315,753 patent/US7241792B2/en active Active
- 2005-12-22 KR KR1020077016787A patent/KR20070088808A/ko not_active Ceased
- 2005-12-22 JP JP2007548472A patent/JP2008525476A/ja not_active Withdrawn
- 2005-12-22 NZ NZ555721A patent/NZ555721A/en not_active IP Right Cessation
- 2005-12-22 CN CN2011102214054A patent/CN102311378A/zh active Pending
- 2005-12-22 EA EA200701361A patent/EA013184B1/ru not_active IP Right Cessation
- 2005-12-22 EP EP05857182A patent/EP1831178A2/en not_active Withdrawn
- 2005-12-22 CN CN2011102214069A patent/CN102321024A/zh active Pending
- 2005-12-22 GE GEAP200510188A patent/GEP20105126B/en unknown
- 2005-12-22 AU AU2005319121A patent/AU2005319121A1/en not_active Abandoned
- 2005-12-22 BR BRPI0519262-5A patent/BRPI0519262A2/pt not_active IP Right Cessation
- 2005-12-22 WO PCT/US2005/046599 patent/WO2006069242A2/en not_active Ceased
- 2005-12-22 CA CA002589648A patent/CA2589648A1/en not_active Abandoned
- 2005-12-23 PA PA20058658301A patent/PA8658301A1/es unknown
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2006
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2007
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- 2007-07-12 MA MA30071A patent/MA29148B1/fr unknown
- 2007-07-19 NO NO20073766A patent/NO20073766L/no not_active Application Discontinuation
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2009
- 2009-04-30 US US12/433,704 patent/US20090258892A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| KR20070088808A (ko) | 2007-08-29 |
| TW200635904A (en) | 2006-10-16 |
| US7241792B2 (en) | 2007-07-10 |
| BRPI0519262A2 (pt) | 2009-01-06 |
| CN102321024A (zh) | 2012-01-18 |
| PA8658301A1 (es) | 2006-10-13 |
| TNSN07236A1 (en) | 2008-11-21 |
| NZ555721A (en) | 2011-02-25 |
| MA29148B1 (fr) | 2008-01-02 |
| JP2008525476A (ja) | 2008-07-17 |
| AR055015A1 (es) | 2007-08-01 |
| CU23691B7 (es) | 2011-09-21 |
| WO2006069242A3 (en) | 2006-08-31 |
| CU20070144A7 (es) | 2010-01-22 |
| CN102311378A (zh) | 2012-01-11 |
| GT200500379A (es) | 2006-10-25 |
| PE20060949A1 (es) | 2006-10-11 |
| EA200701361A1 (ru) | 2007-12-28 |
| US20090258892A1 (en) | 2009-10-15 |
| GEP20105126B (en) | 2010-12-10 |
| US20060205955A1 (en) | 2006-09-14 |
| US7612106B2 (en) | 2009-11-03 |
| NO20073766L (no) | 2007-09-21 |
| HN2005036256A (es) | 2010-02-08 |
| AU2005319121A1 (en) | 2006-06-29 |
| EA013184B1 (ru) | 2010-02-26 |
| EP1831178A2 (en) | 2007-09-12 |
| US20070073062A1 (en) | 2007-03-29 |
| WO2006069242A2 (en) | 2006-06-29 |
| IL183654A0 (en) | 2007-09-20 |
| NI200700161A (es) | 2008-04-21 |
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| Date | Code | Title | Description |
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| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20131001 |