JP2017502032A5 - - Google Patents
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- JP2017502032A5 JP2017502032A5 JP2016541508A JP2016541508A JP2017502032A5 JP 2017502032 A5 JP2017502032 A5 JP 2017502032A5 JP 2016541508 A JP2016541508 A JP 2016541508A JP 2016541508 A JP2016541508 A JP 2016541508A JP 2017502032 A5 JP2017502032 A5 JP 2017502032A5
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- JP
- Japan
- Prior art keywords
- pharmaceutical composition
- composition according
- modulator
- chloride
- transporter
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 claims 12
- 230000000051 modifying Effects 0.000 claims 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-M chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 7
- 239000003112 inhibitor Substances 0.000 claims 6
- 230000002401 inhibitory effect Effects 0.000 claims 6
- 210000002569 neurons Anatomy 0.000 claims 4
- 201000010374 Down syndrome Diseases 0.000 claims 3
- 101710025861 SLC12A2 Proteins 0.000 claims 3
- MAEIEVLCKWDQJH-UHFFFAOYSA-N Bumetanide Chemical compound CCCCNC1=CC(C(O)=O)=CC(S(N)(=O)=O)=C1OC1=CC=CC=C1 MAEIEVLCKWDQJH-UHFFFAOYSA-N 0.000 claims 2
- 229960004064 bumetanide Drugs 0.000 claims 2
- 239000000651 prodrug Substances 0.000 claims 2
- 229940002612 prodrugs Drugs 0.000 claims 2
- 239000003451 thiazide diuretic agent Substances 0.000 claims 2
- CYLWJCABXYDINA-UHFFFAOYSA-N 6-chloro-2-methyl-1,1-dioxo-3-{[(2,2,2-trifluoroethyl)sulfanyl]methyl}-3,4-dihydro-2H-1lambda^{6},2,4-benzothiadiazine-7-sulfonamide Polymers ClC1=C(S(N)(=O)=O)C=C2S(=O)(=O)N(C)C(CSCC(F)(F)F)NC2=C1 CYLWJCABXYDINA-UHFFFAOYSA-N 0.000 claims 1
- JBMKAUGHUNFTOL-UHFFFAOYSA-N Aldoclor Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC=NS2(=O)=O JBMKAUGHUNFTOL-UHFFFAOYSA-N 0.000 claims 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 claims 1
- 229920002395 Aptamer Polymers 0.000 claims 1
- UJEWTUDSLQGTOA-UHFFFAOYSA-N Arlix Chemical compound C=1C=CC=CC=1OC=1C(S(=O)(=O)N)=CC(C(O)=O)=CC=1N1CCCC1 UJEWTUDSLQGTOA-UHFFFAOYSA-N 0.000 claims 1
- IIOPLILENRZKRV-UHFFFAOYSA-N Azosemide Chemical compound C=1C=CSC=1CNC=1C=C(Cl)C(S(=O)(=O)N)=CC=1C1=NN=N[N]1 IIOPLILENRZKRV-UHFFFAOYSA-N 0.000 claims 1
- 229960004988 Azosemide Drugs 0.000 claims 1
- 229960003515 Bendroflumethiazide Drugs 0.000 claims 1
- NDTSRXAMMQDVSW-UHFFFAOYSA-N Benzthiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(S(N2)(=O)=O)=C1N=C2CSCC1=CC=CC=C1 NDTSRXAMMQDVSW-UHFFFAOYSA-N 0.000 claims 1
- 108090000994 Catalytic RNA Proteins 0.000 claims 1
- 229960002155 Chlorothiazide Drugs 0.000 claims 1
- JZUFKLXOESDKRF-UHFFFAOYSA-N Dichlothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 claims 1
- AVOLMBLBETYQHX-UHFFFAOYSA-N Etacrynic acid Chemical compound CCC(=C)C(=O)C1=CC=C(OCC(O)=O)C(Cl)=C1Cl AVOLMBLBETYQHX-UHFFFAOYSA-N 0.000 claims 1
- 229960002541 Ethacrynic Acid Drugs 0.000 claims 1
- RBBWCVQDXDFISW-UHFFFAOYSA-N Feprazone Chemical compound O=C1C(CC=C(C)C)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 RBBWCVQDXDFISW-UHFFFAOYSA-N 0.000 claims 1
- 229960003883 Furosemide Drugs 0.000 claims 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N Furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims 1
- UHLOVGKIEARANS-NIFPGPBJSA-N G36A0E9CVT Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(=O)NN2C[C@@H]3[C@@H]4CC[C@@H](C4)[C@@H]3C2)=C1 UHLOVGKIEARANS-NIFPGPBJSA-N 0.000 claims 1
- DMDGGSIALPNSEE-UHFFFAOYSA-N Hydroflumethiazide Chemical compound C1=C(C(F)(F)F)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O DMDGGSIALPNSEE-UHFFFAOYSA-N 0.000 claims 1
- NDDAHWYSQHTHNT-UHFFFAOYSA-N Indapamide Chemical compound CC1CC2=CC=CC=C2N1NC(=O)C1=CC=C(Cl)C(S(N)(=O)=O)=C1 NDDAHWYSQHTHNT-UHFFFAOYSA-N 0.000 claims 1
- 229960004569 Indapamide Drugs 0.000 claims 1
- RLWRMIYXDPXIEX-UHFFFAOYSA-N Muzolimine Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C)N1N=C(N)CC1=O RLWRMIYXDPXIEX-UHFFFAOYSA-N 0.000 claims 1
- 229920000272 Oligonucleotide Polymers 0.000 claims 1
- 108020004459 Small Interfering RNA Proteins 0.000 claims 1
- 229920001891 Small hairpin RNA Polymers 0.000 claims 1
- NGBFQHCMQULJNZ-UHFFFAOYSA-N Torsemide Chemical compound CC(C)NC(=O)NS(=O)(=O)C1=CN=CC=C1NC1=CC=CC(C)=C1 NGBFQHCMQULJNZ-UHFFFAOYSA-N 0.000 claims 1
- LMJSLTNSBFUCMU-UHFFFAOYSA-N Trichlormethiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC(C(Cl)Cl)NS2(=O)=O LMJSLTNSBFUCMU-UHFFFAOYSA-N 0.000 claims 1
- 206010044688 Trisomy 21 Diseases 0.000 claims 1
- 239000000074 antisense oligonucleotide Substances 0.000 claims 1
- HDWIHXWEUNVBIY-UHFFFAOYSA-N bendroflumethiazidum Chemical compound C1=C(C(F)(F)F)C(S(=O)(=O)N)=CC(S(N2)(=O)=O)=C1NC2CC1=CC=CC=C1 HDWIHXWEUNVBIY-UHFFFAOYSA-N 0.000 claims 1
- 229960001541 benzthiazide Drugs 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 229960000489 feprazone Drugs 0.000 claims 1
- 229960002003 hydrochlorothiazide Drugs 0.000 claims 1
- 229960003313 hydroflumethiazide Drugs 0.000 claims 1
- 238000001802 infusion Methods 0.000 claims 1
- 238000007918 intramuscular administration Methods 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 229960001788 muzolimine Drugs 0.000 claims 1
- 229960001085 piretanide Drugs 0.000 claims 1
- 229960005483 polythiazide Drugs 0.000 claims 1
- 229920000046 polythiazide Polymers 0.000 claims 1
- 229920002033 ribozyme Polymers 0.000 claims 1
- 239000002924 silencing RNA Substances 0.000 claims 1
- 239000004055 small Interfering RNA Substances 0.000 claims 1
- 238000007920 subcutaneous administration Methods 0.000 claims 1
- 230000000699 topical Effects 0.000 claims 1
- 229960002070 torsemide Drugs 0.000 claims 1
- 229960004813 trichlormethiazide Drugs 0.000 claims 1
- 229950004678 tripamide Drugs 0.000 claims 1
Claims (12)
- ダウン症の治療のための塩化物輸送体のモジュレータを含む、医薬組成物。
- 前記モジュレータが、塩化物のニューロンへの移入に関与する輸送体の阻害剤である、請求項１に記載の医薬組成物。
- 前記モジュレータが、塩化物のニューロンへの移入に関与する輸送体の発現の阻害剤である、請求項１に記載の医薬組成物。
- 前記モジュレータが、塩化物のニューロンへの移入に関与する塩化物輸送体のｓｉＲＮＡ、ｓｈＲＮＡ、アンチセンス・オリゴヌクレオチド、リボザイムおよびアプタマーからなる群から選択される、請求項３に記載の医薬組成物。
- 前記モジュレータが、塩化物のニューロンへの移入に関与する輸送体の活性の阻害剤である、請求項１に記載の医薬組成物。
- 前記モジュレータが、輸送体ＮＫＣＣの阻害剤である、請求項１に記載の医薬組成物。
- 前記輸送体ＮＫＣＣの阻害剤が、ブメタニド、フロセミド、エタクリン酸、トルセミド、アゾセミド、ムゾリミン、ピレタニド、トリパミドおよびその類似体、機能性誘導体および/またはプロドラッグ、ベンドロフルメチアジド、ベンズチアジド、クロロチアジド、ヒドロクロロチアジド、ヒドロフルメチアジド、メチルクロチアジド、ポリチアジド、トリクロロメチアジド、クロロタリドン、インダパミド、メトラゾンおよびキネタゾンなどのチアジドおよびチアジド系利尿薬、その類似体および/または機能性誘導体および/またはプロドラッグからなる群から選択される、請求項６に記載の医薬組成物。
- 前記輸送体ＮＫＣＣの阻害剤が、ブメタニドである、請求項７に記載の医薬組成物。
- 前記治療が、有効量の前記モジュレータの投与を必要とする患者への該モジュレータの投与を特徴とするものであって、前記有効量が、０．０１ｍｇから５００ｍｇである、請求項１から８のいずれか一項に記載の医薬組成物。
- 前記塩化物輸送体のモジュレータが、皮下、筋肉内、静脈内、眼球内、経皮、局所、非経口、鼻腔内もしくは経口投与、または注入によって該モジュレータの投与を必要とする患者に直接投与されることを特徴とする、請求項９に記載の医薬組成物。
- 患者が、ダウン症と診断されている、請求項１から１０のいずれか一項に記載の医薬組成物。
- 患者が、ダウン症にかかっている、請求項１から１１のいずれか一項に記載の医薬組成物。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361919195P | 2013-12-20 | 2013-12-20 | |
| US61/919,195 | 2013-12-20 | ||
| PCT/EP2014/078561 WO2015091857A1 (en) | 2013-12-20 | 2014-12-18 | Modulators of intracellular chloride concentration for treating down syndrome |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017502032A JP2017502032A (ja) | 2017-01-19 |
| JP2017502032A5 true JP2017502032A5 (ja) | 2018-01-25 |
| JP6490077B2 JP6490077B2 (ja) | 2019-03-27 |
Family
ID=52273127
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016541508A Active JP6490077B2 (ja) | 2013-12-20 | 2014-12-18 | ダウン症を治療するための細胞内塩化物濃度のモジュレータ |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US9822368B2 (ja) |
| EP (1) | EP3083959B1 (ja) |
| JP (1) | JP6490077B2 (ja) |
| WO (1) | WO2015091857A1 (ja) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016025778A1 (en) * | 2014-08-15 | 2016-02-18 | The Johns Hopkins University | Compositions and methods for treating refractory seizures |
| EP3388520A1 (en) | 2017-04-11 | 2018-10-17 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical composition for reducing the expression of nkcc1 in a subject in need thereof |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3985777A (en) | 1968-12-24 | 1976-10-12 | Lovens Kemiske Fabrik Produktionsaktieselskab | Sulphamyl-benzoic acid derivatives |
| US4247550A (en) | 1975-07-08 | 1981-01-27 | Leo Pharmaceutical Products Ltd. A/S (Lovens Kemiske Fabrik Produktionsaktieselskab) | Compositions and methods for the treatment of hypertension or oedemas |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| GB2207129A (en) | 1987-07-13 | 1989-01-25 | Leo Pharm Prod Ltd | N-(1-carboxy-3-phenylpropyl)alanyl derivatives |
| US6506559B1 (en) | 1997-12-23 | 2003-01-14 | Carnegie Institute Of Washington | Genetic inhibition by double-stranded RNA |
| AUPP249298A0 (en) | 1998-03-20 | 1998-04-23 | Ag-Gene Australia Limited | Synthetic genes and genetic constructs comprising same I |
| US6566131B1 (en) | 2000-10-04 | 2003-05-20 | Isis Pharmaceuticals, Inc. | Antisense modulation of Smad6 expression |
| US6410323B1 (en) | 1999-08-31 | 2002-06-25 | Isis Pharmaceuticals, Inc. | Antisense modulation of human Rho family gene expression |
| US6107091A (en) | 1998-12-03 | 2000-08-22 | Isis Pharmaceuticals Inc. | Antisense inhibition of G-alpha-16 expression |
| US5981732A (en) | 1998-12-04 | 1999-11-09 | Isis Pharmaceuticals Inc. | Antisense modulation of G-alpha-13 expression |
| US8008283B2 (en) | 1998-12-23 | 2011-08-30 | Neurotherapeutics Pharma, Inc. | Methods and compositions for the treatment of neuropsychiatric disorders |
| US6046321A (en) | 1999-04-09 | 2000-04-04 | Isis Pharmaceuticals Inc. | Antisense modulation of G-alpha-i1 expression |
| GB9927444D0 (en) | 1999-11-19 | 2000-01-19 | Cancer Res Campaign Tech | Inhibiting gene expression |
| EP1272630A2 (en) | 2000-03-16 | 2003-01-08 | Genetica, Inc. | Methods and compositions for rna interference |
| US6365354B1 (en) | 2000-07-31 | 2002-04-02 | Isis Pharmaceuticals, Inc. | Antisense modulation of lysophospholipase I expression |
| US6566135B1 (en) | 2000-10-04 | 2003-05-20 | Isis Pharmaceuticals, Inc. | Antisense modulation of caspase 6 expression |
| AU2004270162B2 (en) | 2003-08-28 | 2010-05-13 | Nicox S.A. | Nitrosated ad nitrosylated diuretic compouds, compositions and methods of use |
| EP1968603A4 (en) | 2006-01-03 | 2013-01-16 | Algebra Inc | THERAPEUTIC AMINARYLSULFONAMIDE CONJUGATE COMPOUNDS |
| EP2298296A1 (en) | 2009-08-25 | 2011-03-23 | CNRS Centre National De La Recherche Scientifique | Composition and method for treating cognitive impairments in down syndrome subjects |
| JP2011231094A (ja) * | 2009-11-02 | 2011-11-17 | Neurotherapeutics Pharma Inc | ブメタニド、フロセミド、ピレタニド、アゾセミド、およびトルセミドのアナログ、組成物および使用方法 |
| HUE034866T2 (hu) | 2010-01-15 | 2018-03-28 | Inst Nat Sante Rech Med | NKCC inhibitorok az autizmus kezelésére |
| WO2012018635A2 (en) | 2010-07-26 | 2012-02-09 | Neurotherapeutics Pharma, Inc. | Arylsulfonamide derivatives, compositions, and methods of use |
-
2014
- 2014-12-18 US US15/104,895 patent/US9822368B2/en active Active
- 2014-12-18 JP JP2016541508A patent/JP6490077B2/ja active Active
- 2014-12-18 EP EP14821154.3A patent/EP3083959B1/en active Active
- 2014-12-18 WO PCT/EP2014/078561 patent/WO2015091857A1/en active Application Filing
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