JP2008518035A - 置換テトラサイクリン化合物 - Google Patents
置換テトラサイクリン化合物 Download PDFInfo
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- JP2008518035A JP2008518035A JP2007539189A JP2007539189A JP2008518035A JP 2008518035 A JP2008518035 A JP 2008518035A JP 2007539189 A JP2007539189 A JP 2007539189A JP 2007539189 A JP2007539189 A JP 2007539189A JP 2008518035 A JP2008518035 A JP 2008518035A
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- Prior art keywords
- substituted
- compound
- alkyl
- hydrogen
- halogen
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- -1 tetracycline compounds Chemical class 0.000 title claims abstract description 515
- 239000004098 Tetracycline Substances 0.000 title claims abstract description 239
- 235000019364 tetracycline Nutrition 0.000 title claims abstract description 238
- 229960002180 tetracycline Drugs 0.000 title claims abstract description 231
- 229930101283 tetracycline Natural products 0.000 title claims abstract description 231
- 150000003522 tetracyclines Chemical class 0.000 claims abstract description 47
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 12
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims description 301
- 229910052739 hydrogen Inorganic materials 0.000 claims description 235
- 239000001257 hydrogen Substances 0.000 claims description 235
- 125000000217 alkyl group Chemical group 0.000 claims description 225
- 125000003342 alkenyl group Chemical group 0.000 claims description 128
- 125000003118 aryl group Chemical group 0.000 claims description 127
- 150000002431 hydrogen Chemical class 0.000 claims description 121
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 116
- 125000000304 alkynyl group Chemical group 0.000 claims description 113
- 125000003545 alkoxy group Chemical group 0.000 claims description 112
- 229910052736 halogen Inorganic materials 0.000 claims description 110
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 102
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 101
- 150000002367 halogens Chemical class 0.000 claims description 93
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 87
- 125000004414 alkyl thio group Chemical group 0.000 claims description 80
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 79
- 150000003839 salts Chemical class 0.000 claims description 78
- 125000003282 alkyl amino group Chemical group 0.000 claims description 74
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 72
- 239000000651 prodrug Substances 0.000 claims description 63
- 229940002612 prodrug Drugs 0.000 claims description 63
- 125000000623 heterocyclic group Chemical group 0.000 claims description 62
- 125000002252 acyl group Chemical class 0.000 claims description 61
- 150000002148 esters Chemical class 0.000 claims description 59
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 57
- 238000000034 method Methods 0.000 claims description 50
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- 125000004103 aminoalkyl group Chemical group 0.000 claims description 46
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 43
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 39
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 38
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 37
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 35
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 34
- 125000001072 heteroaryl group Chemical group 0.000 claims description 33
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 32
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- 150000007942 carboxylates Chemical class 0.000 claims description 27
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 24
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 24
- 125000005015 aryl alkynyl group Chemical group 0.000 claims description 24
- 125000004093 cyano group Chemical class *C#N 0.000 claims description 24
- 125000002541 furyl group Chemical group 0.000 claims description 23
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 21
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- 229910052731 fluorine Inorganic materials 0.000 claims description 20
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 19
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- 125000005199 aryl carbonyloxy group Chemical group 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 18
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- 125000005084 alkoxyalkylaminoalkyl group Chemical group 0.000 claims description 17
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
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- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 15
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 15
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 14
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 13
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 12
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 12
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 12
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 12
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 11
- 125000004442 acylamino group Chemical group 0.000 claims description 11
- 125000003277 amino group Chemical group 0.000 claims description 11
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 11
- 125000004702 alkoxy alkyl carbonyl group Chemical group 0.000 claims description 10
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 10
- 125000003435 aroyl group Chemical group 0.000 claims description 10
- 239000000460 chlorine Substances 0.000 claims description 10
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- 125000005094 alkyl carbonyl amino alkyl group Chemical group 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 claims description 9
- 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 8
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 8
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 8
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- 229910052727 yttrium Inorganic materials 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 7
- 241000588724 Escherichia coli Species 0.000 claims description 6
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 125000004946 alkenylalkyl group Chemical group 0.000 claims description 6
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 6
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 6
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 6
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000002971 oxazolyl group Chemical group 0.000 claims description 5
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 241000282414 Homo sapiens Species 0.000 claims description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 201000004792 malaria Diseases 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 229940072172 tetracycline antibiotic Drugs 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- 208000030852 Parasitic disease Diseases 0.000 claims description 3
- 125000004689 alkyl amino carbonyl alkyl group Chemical group 0.000 claims description 3
- 150000001349 alkyl fluorides Chemical class 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
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- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000003963 dichloro group Chemical group Cl* 0.000 claims description 2
- 125000006001 difluoroethyl group Chemical group 0.000 claims description 2
- 125000004212 difluorophenyl group Chemical group 0.000 claims description 2
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 claims description 2
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 2
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
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- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims 2
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 241000495778 Escherichia faecalis Species 0.000 claims 1
- 125000006534 ethyl amino methyl group Chemical group [H]N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims 1
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- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 84
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 53
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 49
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 49
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- 229950000614 sancycline Drugs 0.000 description 41
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2016130243A (ja) * | 2009-08-28 | 2016-07-21 | テトラフェース ファーマシューティカルズ,インコーポレイテッド | テトラサイクリン化合物 |
| JP2023526258A (ja) * | 2020-05-13 | 2023-06-21 | ルネラ・バイオテック・インコーポレーテッド | 癌幹細胞の標的化及び転移の防止のための、9‐アミノ‐ドキシサイクリンのミリストイル誘導体 |
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| US6756365B2 (en) * | 1991-11-06 | 2004-06-29 | Trustees Of Tufts College | Reducing tetracycline resistance in living cells |
| AU2466099A (en) * | 1998-01-23 | 1999-08-09 | Trustees Of Tufts College | Pharmaceutically active compounds and methods of use thereof |
| US8106225B2 (en) * | 1999-09-14 | 2012-01-31 | Trustees Of Tufts College | Methods of preparing substituted tetracyclines with transition metal-based chemistries |
| EP1666453A1 (en) * | 1999-09-14 | 2006-06-07 | Trustees Of Tufts College | Methods of preparing substituted tetracyclines with transition metal-based chemistries |
| AU2001268475A1 (en) * | 2000-06-16 | 2002-01-02 | Trustees Of Tufts College | 7-phenyl-substituted tetracycline compounds |
| US20020132798A1 (en) * | 2000-06-16 | 2002-09-19 | Nelson Mark L. | 7-phenyl-substituted tetracycline compounds |
| US20040224927A1 (en) * | 2000-06-16 | 2004-11-11 | Trustees Of Tufts College | 7-N-substituted phenyl tetracycline compounds |
| EA006170B1 (ru) * | 2000-07-07 | 2005-10-27 | Трастис Оф Тафтс Коллидж | Замещенные соединения тетрациклина (варианты), фармацевтическая композиция и способ лечения чувствительного к тетрациклину состояния субъекта |
| US7094806B2 (en) | 2000-07-07 | 2006-08-22 | Trustees Of Tufts College | 7, 8 and 9-substituted tetracycline compounds |
| SI1301467T1 (sl) | 2000-07-07 | 2007-02-28 | Tufts College | 9-substituirane minociklinske spojine |
| US7553828B2 (en) | 2001-03-13 | 2009-06-30 | Paratek Pharmaceuticals, Inc. | 9-aminomethyl substituted minocycline compounds |
| AU2002250331A1 (en) * | 2001-03-13 | 2002-09-24 | Paratek Pharmaceuticals, Inc. | 7-pyrollyl tetracycline compounds and methods of use thereof |
| US8088820B2 (en) * | 2001-04-24 | 2012-01-03 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds for the treatment of malaria |
| JP2005514410A (ja) * | 2002-01-08 | 2005-05-19 | パラテック ファーマシューティカルズ インコーポレイテッド | 4−デジメチルアミノテトラサイクリン化合物 |
| JP2005526754A (ja) * | 2002-03-08 | 2005-09-08 | パラテック ファーマシューティカルズ インコーポレイテッド | アミノメチル置換されたテトラサイクリン化合物 |
| EP1534300A4 (en) * | 2002-07-12 | 2008-04-23 | Paratek Pharm Innc | TETRACYCLINE COMPOUNDS SUBSTITUTED IN 3, 10, AND 12A |
| US20060287283A1 (en) * | 2003-07-09 | 2006-12-21 | Paratek Pharmaceuticals, Inc. | Prodrugs of 9-aminomethyl tetracycline compounds |
| EP2319828A3 (en) | 2003-07-09 | 2011-07-06 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
| EP2287148A3 (en) | 2004-10-25 | 2011-10-26 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
| JP2008530023A (ja) * | 2005-02-04 | 2008-08-07 | パラテック ファーマシューティカルズ インコーポレイテッド | テトラサイクリン化合物の11a,12−誘導体 |
| WO2007014154A2 (en) * | 2005-07-21 | 2007-02-01 | Paratek Pharmaceuticals, Inc. | 10-substituted tetracyclines and methods of use thereof |
| AU2007249695A1 (en) | 2006-05-15 | 2007-11-22 | Paratek Pharmaceuticals, Inc. | Methods of regulating expression of genes or of gene products using substituted tetracycline compounds |
| PT2109602E (pt) * | 2006-12-21 | 2014-05-23 | Paratek Pharm Innc | Derivados de tetraciclina para o tratamento de infecções bacterianas, virais e parasitárias |
| SI2120963T1 (sl) | 2006-12-21 | 2019-02-28 | Paratek Pharmaceuticals, Inc. | Substituirane spojine tetraciklina za zdravljenje vnetnih kožnih motenj |
| CN102688492A (zh) * | 2007-03-23 | 2012-09-26 | 分子研究中心公司 | 包含四环素类的抗炎组合物及其用途 |
| US7935687B2 (en) | 2007-04-12 | 2011-05-03 | Paratek Pharmaceuticals, Inc. | Methods for treating spinal muscular atrophy using tetracycline compounds |
| CA2688662A1 (en) * | 2007-04-27 | 2008-11-06 | Paratek Pharmaceuticals, Inc. | Methods for synthesizing and purifying aminoalkyl tetracycline compounds |
| ATE555079T1 (de) | 2007-07-06 | 2012-05-15 | Paratek Pharm Innc | Verfahren zur synthese von 9-substituiertem minocyclin |
| CN102015602A (zh) | 2008-03-05 | 2011-04-13 | 帕拉特克药品公司 | 米诺环素化合物及其使用方法 |
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| CA2730377C (en) | 2008-07-11 | 2017-09-19 | Neumedics | Tetracycline derivatives with reduced antibiotic activity and neuroprotective benefits |
| AP2011005631A0 (en) * | 2008-09-19 | 2011-04-30 | Paratek Pharmaceuticals Ind | Tetracycline compounds for the treatment of rheumatoid arthritis and related methods of treatment. |
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| CN102603683B (zh) * | 2012-02-10 | 2014-04-09 | 山东大学 | 一种呋喃类化合物及其制备方法与应用 |
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| CN110087655A (zh) | 2016-11-01 | 2019-08-02 | 帕拉特克药品公司 | 9-氨基甲基米诺环素化合物及其在治疗社区获得性细菌性肺炎(cabp)中的用途 |
| CA3078540A1 (en) | 2017-11-30 | 2019-06-06 | Arrakis Therapeutics, Inc. | Nucleic acid-binding photoprobes and uses thereof |
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- 2005-10-25 US US11/258,622 patent/US8466132B2/en not_active Expired - Fee Related
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| JP7761590B2 (ja) | 2020-05-13 | 2025-10-28 | ルネラ・バイオテック・インコーポレーテッド | 癌幹細胞の標的化及び転移の防止のための、9‐アミノ‐ドキシサイクリンのミリストイル誘導体 |
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