BRPI0809238A2 - Derivados de piridazinonas úteis como inibidores de glican sintase - Google Patents

Info

Publication number

BRPI0809238A2

BRPI0809238A2 BRPI0809238-9A BRPI0809238A BRPI0809238A2 BR PI0809238 A2 BRPI0809238 A2 BR PI0809238A2 BR PI0809238 A BRPI0809238 A BR PI0809238A BR PI0809238 A2 BRPI0809238 A2 BR PI0809238A2

Authority

BR

Brazil

Prior art keywords

alkyl

alkenyl

formula

group

original document

Prior art date

2007-03-15

Links

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• Global Dossier
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• AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 title description 11
• 239000003112 inhibitor Substances 0.000 title description 10
• ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 title description 3
• 150000001875 compounds Chemical class 0.000 claims description 353
• 239000000203 mixture Substances 0.000 claims description 195
• -1 cycloenylalkyl Chemical group 0.000 claims description 159
• 125000000217 alkyl group Chemical group 0.000 claims description 147
• 238000000034 method Methods 0.000 claims description 91
• 125000003118 aryl group Chemical group 0.000 claims description 81
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 75
• 229910052757 nitrogen Inorganic materials 0.000 claims description 74
• 125000001072 heteroaryl group Chemical group 0.000 claims description 68
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 61
• 125000003342 alkenyl group Chemical group 0.000 claims description 54
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 44
• 150000003839 salts Chemical class 0.000 claims description 43
• 241000222120 Candida <Saccharomycetales> Species 0.000 claims description 42
• 125000001424 substituent group Chemical group 0.000 claims description 42
• 125000000623 heterocyclic group Chemical group 0.000 claims description 41
• 239000012453 solvate Substances 0.000 claims description 35
• 239000000651 prodrug Substances 0.000 claims description 33
• 229940002612 prodrug Drugs 0.000 claims description 33
• 125000004432 carbon atom Chemical group C* 0.000 claims description 30
• 229910052739 hydrogen Inorganic materials 0.000 claims description 30
• 239000011230 binding agent Substances 0.000 claims description 28
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 28
• 229910052760 oxygen Inorganic materials 0.000 claims description 25
• 125000000304 alkynyl group Chemical group 0.000 claims description 24
• 150000002148 esters Chemical class 0.000 claims description 24
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 24
• 229940121375 antifungal agent Drugs 0.000 claims description 23
• 229910052799 carbon Inorganic materials 0.000 claims description 23
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 23
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 22
• 125000004385 trihaloalkyl group Chemical group 0.000 claims description 22
• 229910052717 sulfur Inorganic materials 0.000 claims description 21
• 206010017533 Fungal infection Diseases 0.000 claims description 19
• 208000031888 Mycoses Diseases 0.000 claims description 19
• 125000003545 alkoxy group Chemical group 0.000 claims description 19
• 229910052736 halogen Inorganic materials 0.000 claims description 19
• 150000002367 halogens Chemical class 0.000 claims description 19
• 125000005018 aryl alkenyl group Chemical group 0.000 claims description 18
• 125000006682 monohaloalkyl group Chemical group 0.000 claims description 18
• 239000008194 pharmaceutical composition Substances 0.000 claims description 18
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
• 125000005356 cycloalkylalkenyl group Chemical group 0.000 claims description 17
• 125000004982 dihaloalkyl group Chemical group 0.000 claims description 17
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 17
• 239000003429 antifungal agent Substances 0.000 claims description 16
• 150000004676 glycans Chemical class 0.000 claims description 14
• 125000005842 heteroatom Chemical group 0.000 claims description 14
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
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• 241001465754 Metazoa Species 0.000 claims description 13
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 13
• 239000001257 hydrogen Substances 0.000 claims description 13
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
• 241000228212 Aspergillus Species 0.000 claims description 11
• 241000235527 Rhizopus Species 0.000 claims description 11
• 125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 11
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
• UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 claims description 10
• 241000223218 Fusarium Species 0.000 claims description 10
• 241000223230 Trichosporon Species 0.000 claims description 10
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 9
• 239000003937 drug carrier Substances 0.000 claims description 9
• 125000001188 haloalkyl group Chemical group 0.000 claims description 9
• 125000004449 heterocyclylalkenyl group Chemical group 0.000 claims description 9
• 125000005020 hydroxyalkenyl group Chemical group 0.000 claims description 9
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• 241000223682 Exophiala Species 0.000 claims description 6
• 235000014680 Saccharomyces cerevisiae Nutrition 0.000 claims description 6
• HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical group CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 claims description 6
• 125000004858 cycloalkoxyalkyl group Chemical group 0.000 claims description 6
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 6
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• 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 5
• 230000002401 inhibitory effect Effects 0.000 claims description 5
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• 235000013752 Rhizopus oryzae Nutrition 0.000 claims description 4
• 241001149962 Sporothrix Species 0.000 claims description 4
• 125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims description 4
• APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 claims description 4
• 125000005127 aryl alkoxy alkyl group Chemical group 0.000 claims description 4
• JYIKNQVWKBUSNH-WVDDFWQHSA-N caspofungin Chemical compound C1([C@H](O)[C@@H](O)[C@H]2C(=O)N[C@H](C(=O)N3CC[C@H](O)[C@H]3C(=O)N[C@H](NCCN)[C@H](O)C[C@@H](C(N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)N2)[C@@H](C)O)=O)NC(=O)CCCCCCCC[C@@H](C)C[C@@H](C)CC)[C@H](O)CCN)=CC=C(O)C=C1 JYIKNQVWKBUSNH-WVDDFWQHSA-N 0.000 claims description 4
• 229960003034 caspofungin Drugs 0.000 claims description 4
• 238000009472 formulation Methods 0.000 claims description 4
• 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 4
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• 241000222122 Candida albicans Species 0.000 claims description 3
• IIUZTXTZRGLYTI-UHFFFAOYSA-N Dihydrogriseofulvin Natural products COC1CC(=O)CC(C)C11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 IIUZTXTZRGLYTI-UHFFFAOYSA-N 0.000 claims description 3
• UXWOXTQWVMFRSE-UHFFFAOYSA-N Griseoviridin Natural products O=C1OC(C)CC=C(C(NCC=CC=CC(O)CC(O)C2)=O)SCC1NC(=O)C1=COC2=N1 UXWOXTQWVMFRSE-UHFFFAOYSA-N 0.000 claims description 3
• 241000228402 Histoplasma Species 0.000 claims description 3
• 241000124008 Mammalia Species 0.000 claims description 3
• 108010021062 Micafungin Proteins 0.000 claims description 3
• 241000893980 Microsporum canis Species 0.000 claims description 3
• 101150020251 NR13 gene Proteins 0.000 claims description 3
• DDUHZTYCFQRHIY-UHFFFAOYSA-N Negwer: 6874 Natural products COC1=CC(=O)CC(C)C11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 DDUHZTYCFQRHIY-UHFFFAOYSA-N 0.000 claims description 3
• 241000228143 Penicillium Species 0.000 claims description 3
• 241000132889 Scedosporium Species 0.000 claims description 3
• 125000005082 alkoxyalkenyl group Chemical group 0.000 claims description 3
• 238000011161 development Methods 0.000 claims description 3
• RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 claims description 3
• 229960004884 fluconazole Drugs 0.000 claims description 3
• DDUHZTYCFQRHIY-RBHXEPJQSA-N griseofulvin Chemical compound COC1=CC(=O)C[C@@H](C)[C@@]11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 DDUHZTYCFQRHIY-RBHXEPJQSA-N 0.000 claims description 3
• 229960002867 griseofulvin Drugs 0.000 claims description 3
• 230000005764 inhibitory process Effects 0.000 claims description 3
• 229960002159 micafungin Drugs 0.000 claims description 3
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 3
• VHVPQPYKVGDNFY-DFMJLFEVSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2r,4s)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 VHVPQPYKVGDNFY-DFMJLFEVSA-N 0.000 claims description 2
• 241001019659 Acremonium <Plectosphaerellaceae> Species 0.000 claims description 2
• 241000251468 Actinopterygii Species 0.000 claims description 2
• APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 claims description 2
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• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 2
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• BYBLEWFAAKGYCD-UHFFFAOYSA-N Miconazole Chemical compound ClC1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 BYBLEWFAAKGYCD-UHFFFAOYSA-N 0.000 claims description 2
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• JHVAMHSQVVQIOT-MFAJLEFUSA-N anidulafungin Chemical compound C1=CC(OCCCCC)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=O)N[C@@H]2C(N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)N[C@H](C(=O)N[C@H](C(=O)N3C[C@H](C)[C@H](O)[C@H]3C(=O)N[C@H](O)[C@H](O)C2)[C@@H](C)O)[C@H](O)[C@@H](O)C=2C=CC(O)=CC=2)[C@@H](C)O)=O)C=C1 JHVAMHSQVVQIOT-MFAJLEFUSA-N 0.000 claims description 2
• 229960003348 anidulafungin Drugs 0.000 claims description 2
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• RAGOYPUPXAKGKH-XAKZXMRKSA-N posaconazole Chemical compound O=C1N([C@H]([C@H](C)O)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@H]3C[C@@](CN4N=CN=C4)(OC3)C=3C(=CC(F)=CC=3)F)=CC=2)C=C1 RAGOYPUPXAKGKH-XAKZXMRKSA-N 0.000 claims description 2
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