AU2010213936B2 - Methods of using and compositions comprising PDE4 modulators for treatment, prevention and management of tuberculosis - Google Patents
Methods of using and compositions comprising PDE4 modulators for treatment, prevention and management of tuberculosis Download PDFInfo
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- AU2010213936B2 AU2010213936B2 AU2010213936A AU2010213936A AU2010213936B2 AU 2010213936 B2 AU2010213936 B2 AU 2010213936B2 AU 2010213936 A AU2010213936 A AU 2010213936A AU 2010213936 A AU2010213936 A AU 2010213936A AU 2010213936 B2 AU2010213936 B2 AU 2010213936B2
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- carbon atoms
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- hydrogen
- phenyl
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- 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 title claims abstract description 116
- 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 title claims abstract description 116
- 201000008827 tuberculosis Diseases 0.000 title claims abstract description 56
- 238000000034 method Methods 0.000 title claims abstract description 43
- 239000000203 mixture Substances 0.000 title description 35
- 238000011282 treatment Methods 0.000 title description 24
- 230000002265 prevention Effects 0.000 title description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 72
- 239000012453 solvate Substances 0.000 claims abstract description 69
- 125000004432 carbon atom Chemical group C* 0.000 claims description 297
- 125000000217 alkyl group Chemical group 0.000 claims description 218
- -1 moxifloxicin Chemical compound 0.000 claims description 207
- 125000003545 alkoxy group Chemical group 0.000 claims description 93
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 90
- 229910052739 hydrogen Inorganic materials 0.000 claims description 88
- 239000001257 hydrogen Substances 0.000 claims description 82
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 82
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 77
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 73
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 68
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 58
- 125000001424 substituent group Chemical group 0.000 claims description 56
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 47
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- 208000015181 infectious disease Diseases 0.000 claims description 17
- 125000003282 alkyl amino group Chemical group 0.000 claims description 16
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 12
- 125000001624 naphthyl group Chemical group 0.000 claims description 11
- 125000004442 acylamino group Chemical group 0.000 claims description 10
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 10
- 125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims description 9
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 9
- 229960001225 rifampicin Drugs 0.000 claims description 5
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 claims description 4
- AEUTYOVWOVBAKS-UWVGGRQHSA-N ethambutol Chemical compound CC[C@@H](CO)NCCN[C@@H](CC)CO AEUTYOVWOVBAKS-UWVGGRQHSA-N 0.000 claims description 4
- 229960003350 isoniazid Drugs 0.000 claims description 4
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical group NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 claims description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 claims description 4
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical group OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 claims description 3
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 3
- VCOPTHOUUNAYKQ-WBTCAYNUSA-N (3s)-3,6-diamino-n-[[(2s,5s,8e,11s,15s)-15-amino-11-[(6r)-2-amino-1,4,5,6-tetrahydropyrimidin-6-yl]-8-[(carbamoylamino)methylidene]-2-(hydroxymethyl)-3,6,9,12,16-pentaoxo-1,4,7,10,13-pentazacyclohexadec-5-yl]methyl]hexanamide;(3s)-3,6-diamino-n-[[(2s,5s,8 Chemical compound N1C(=O)\C(=C/NC(N)=O)NC(=O)[C@H](CNC(=O)C[C@@H](N)CCCN)NC(=O)[C@H](C)NC(=O)[C@@H](N)CNC(=O)[C@@H]1[C@@H]1NC(N)=NCC1.N1C(=O)\C(=C/NC(N)=O)NC(=O)[C@H](CNC(=O)C[C@@H](N)CCCN)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CNC(=O)[C@@H]1[C@@H]1NC(N)=NCC1 VCOPTHOUUNAYKQ-WBTCAYNUSA-N 0.000 claims description 2
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 claims description 2
- 239000004475 Arginine Substances 0.000 claims description 2
- 108010065839 Capreomycin Proteins 0.000 claims description 2
- DYDCUQKUCUHJBH-UWTATZPHSA-N D-Cycloserine Chemical compound N[C@@H]1CONC1=O DYDCUQKUCUHJBH-UWTATZPHSA-N 0.000 claims description 2
- DYDCUQKUCUHJBH-UHFFFAOYSA-N D-Cycloserine Natural products NC1CONC1=O DYDCUQKUCUHJBH-UHFFFAOYSA-N 0.000 claims description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 2
- VRDIULHPQTYCLN-UHFFFAOYSA-N Prothionamide Chemical compound CCCC1=CC(C(N)=S)=CC=N1 VRDIULHPQTYCLN-UHFFFAOYSA-N 0.000 claims description 2
- 108010015940 Viomycin Proteins 0.000 claims description 2
- OZKXLOZHHUHGNV-UHFFFAOYSA-N Viomycin Natural products NCCCC(N)CC(=O)NC1CNC(=O)C(=CNC(=O)N)NC(=O)C(CO)NC(=O)C(CO)NC(=O)C(NC1=O)C2CC(O)NC(=N)N2 OZKXLOZHHUHGNV-UHFFFAOYSA-N 0.000 claims description 2
- 229930003270 Vitamin B Natural products 0.000 claims description 2
- ZWBTYMGEBZUQTK-PVLSIAFMSA-N [(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,32-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-1'-(2-methylpropyl)-6,23-dioxospiro[8,33-dioxa-24,27,29-triazapentacyclo[23.6.1.14,7.05,31.026,30]tritriaconta-1(32),2,4,9,19,21,24,26,30-nonaene-28,4'-piperidine]-13-yl] acetate Chemical compound CO[C@H]1\C=C\O[C@@]2(C)Oc3c(C2=O)c2c4NC5(CCN(CC(C)C)CC5)N=c4c(=NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)c(O)c2c(O)c3C ZWBTYMGEBZUQTK-PVLSIAFMSA-N 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- LKCWBDHBTVXHDL-RMDFUYIESA-N amikacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)[C@@H](O)[C@H](O)[C@H]1O LKCWBDHBTVXHDL-RMDFUYIESA-N 0.000 claims description 2
- 229960004821 amikacin Drugs 0.000 claims description 2
- 229960004909 aminosalicylic acid Drugs 0.000 claims description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 2
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- 229960003405 ciprofloxacin Drugs 0.000 claims description 2
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 claims description 2
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- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 claims description 2
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 229960000318 kanamycin Drugs 0.000 claims description 2
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- TYZROVQLWOKYKF-ZDUSSCGKSA-N linezolid Chemical compound O=C1O[C@@H](CNC(=O)C)CN1C(C=C1F)=CC=C1N1CCOCC1 TYZROVQLWOKYKF-ZDUSSCGKSA-N 0.000 claims description 2
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- NTIBXLBUWCCEBH-UHFFFAOYSA-N methyl 3-(3,4-dimethoxyphenyl)-3-(3-oxo-1h-isoindol-2-yl)propanoate Chemical group C1C2=CC=CC=C2C(=O)N1C(CC(=O)OC)C1=CC=C(OC)C(OC)=C1 NTIBXLBUWCCEBH-UHFFFAOYSA-N 0.000 claims description 2
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- SRVJKTDHMYAMHA-WUXMJOGZSA-N thioacetazone Chemical compound CC(=O)NC1=CC=C(\C=N\NC(N)=S)C=C1 SRVJKTDHMYAMHA-WUXMJOGZSA-N 0.000 claims description 2
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- 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
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| JP6143675B2 (ja) | 2010-12-16 | 2017-06-07 | セルジーン コーポレイション | 難溶性薬物の制御放出経口剤形及びその使用 |
| RU2627471C2 (ru) | 2011-09-14 | 2017-08-08 | Селджин Корпорейшн | Препараты { 2-[(1s)-1-(3-этокси-4-метоксифенил)-2-метансульфонилэтил]-3-оксо-2,3-дигидро-1h-изоиндол-4-ил} амида циклопропанкарбоновой кислоты |
| RS60415B1 (sr) | 2011-12-27 | 2020-07-31 | Amgen (Europe) GmbH | Formulacije (+)-2-[1-(3-etoksi-4-metoksi-fenil)-2-metansulfonil-etil]-4-acetil aminoizoindolin-1,3-diona |
| WO2013119607A2 (en) * | 2012-02-08 | 2013-08-15 | Celgene Corporation | Modified release formulations of (+)-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-4-acetyl aminoisoindoline-1,3-dione |
| EP2764866A1 (en) | 2013-02-07 | 2014-08-13 | IP Gesellschaft für Management mbH | Inhibitors of nedd8-activating enzyme |
| US10011611B2 (en) | 2015-08-14 | 2018-07-03 | Reaction Biology Corp. | Histone deacetylase inhibitors and methods for use thereof |
| WO2017070291A1 (en) * | 2015-10-21 | 2017-04-27 | Celgene Corporation | Pde4 modulators for treating and preventing immune reconstitution inflammatory syndrome (iris) |
| DE102018201827A1 (de) * | 2017-02-28 | 2018-08-30 | Aktiebolaget Skf | Wälzlager |
| CN112220785B (zh) * | 2020-09-22 | 2021-12-31 | 北京鑫开元医药科技有限公司 | 一种pde4抑制剂药物组合物及其制备方法与用途 |
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| CO6410289A2 (es) | 2012-03-30 |
| EP2818164A1 (en) | 2014-12-31 |
| CR20110411A (es) | 2012-01-06 |
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