JP2019135271A - 疼痛の治療または予防に使用されるtrpc4調節因子 - Google Patents
疼痛の治療または予防に使用されるtrpc4調節因子 Download PDFInfo
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
- C07D215/38—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Quinoline Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
本発明は、以下の、本発明の好適な実施形態の詳細な説明およびそれに含まれる実施例、ならびに、それらの任意の図面および説明を参照することで、さらに容易に理解され得る。本明細書に記載されるものに類似するかまたは等価である任意の方法および材料を、本発明の実施または試験に使用することができるが、好適な方法、装置、および材料について説明する。本明細書で言及する、すべての参考文献、刊行物、特許、特許出願、および市販材料は、本発明と関連して使用され得る、刊行物で報告された材料および/または方法を説明し開示する目的で、参照により本明細書に組み込まれる。本明細書中の何物も、本発明が先行発明によってそのような開示に先行することはできないことを認めるものとして、解釈されないものとする。
化合物の、疼痛を治療する能力は、本明細書に記載するようなさまざまな周知のアッセイを使用して確認され得る。
式1a)のキノリン構造が、細胞およびラットにおいて試験される。式1a)が投与される野生型ラットは、用量反応性の疼痛抑制を示し(図1)、心臓毒性がないことを含め、明らかな副作用はない。
A.(式1aによる)結腸へのアブラナの注入(colon mustard infusion)後の、自発性疼痛に関連する行動および50%の収縮閾値(足における)
(1) 化合物であって、
式中、Rは、
R’は、H、CH3、Et、またはXから選択され、
R”は、Hまたはアルキルから選択され、
ヒトまたは動物の身体を治療する方法で使用される、化合物。
(2) 実施態様1に記載の化合物において、
Rは、
R’は、H、CH3、Et、またはXから選択され、
R”は、Hまたはアルキルから選択される、化合物。
(3) 実施態様1または2に記載の化合物において、
Rは、
R’は、Hであり、
R”は、CH3である、化合物。
(4) 実施態様1〜3のいずれかに記載の化合物において、
哺乳動物の疼痛を治療、低減、または防止するのに使用される、化合物。
(5) 実施態様4に記載の化合物において、
前記疼痛は、急性疼痛、慢性疼痛、神経障害性疼痛、侵害受容性疼痛、内臓痛、およびそれらの組み合わせから選択される、化合物。
前記疼痛は、内臓痛を含む、化合物。
(7) 実施態様5に記載の化合物において、
前記疼痛は、神経障害性疼痛を含む、化合物。
(8) 実施態様4〜7のいずれかに記載の化合物において、
前記化合物は、経口投与される、化合物。
(9) 実施態様4〜7のいずれかに記載の化合物において、
前記化合物は、局所投与される、化合物。
(10) 医薬組成物において、
実施態様1〜7のいずれかに記載の化合物と、
医薬品賦形剤と、
を含む、医薬組成物。
1つまたは複数の追加の薬学的活性物質をさらに含む、医薬組成物。
(12) 実施態様9に記載の医薬組成物において、
前記1つまたは複数の追加の薬学的活性物質は、非オピオイド鎮痛剤、オピオイド鎮痛剤、抗てんかん薬、NMDAアンタゴニスト、リドカイン、三環系抗鬱薬、またはそれらの組み合わせから選択される、医薬組成物。
(13) 哺乳動物の疼痛を治療、低減、または防止する方法において、
治療上有効量の組成物を前記哺乳動物に投与する工程を含み、
前記組成物は化合物を含み、前記化合物は、
式中、Rは、
R’は、H、CH3、Et、またはXから選択され、
R”は、Hまたはアルキルから選択されるものと、
式中、Rは、アリール、ヘテロアリール、アルキル、シクロアルキル、Hから選択され、
R’は、必要としている被験者に対する、H、アリール、ヘテロアリール、アルキル、シクロアルキルから選択されるものと、
から選択され、
前記化合物は、Trpc4活性を調節することができる、方法。
(14) 実施態様13に記載の方法において、
前記化合物は、
式中、Rは、
R’は、H、CH3、Et、またはXから選択され、
R”は、Hまたはアルキルから選択される、方法。
(15) 実施態様13または14に記載の方法において、
前記化合物は、
式中、Rは、
R’は、Hであり、
R”は、CH3である、方法。
前記Trpc4は、ヒトのものである、方法。
(17) 実施態様13〜16のいずれかに記載の方法において、
前記化合物は、Trpc4活性の増加を引き起こす、方法。
(18) 実施態様13〜16のいずれかに記載の方法において、
前記化合物は、Trpc4活性の減少を引き起こす、方法。
(19) 実施態様13〜16のいずれかに記載の方法において、
前記化合物は、Trpc4アンタゴニストとして機能する、方法。
(20) 実施態様13〜16のいずれかに記載の方法において、
前記化合物は、Trpc4アゴニストとして機能する、方法。
前記化合物は、Trpc4アンタゴニストとして機能する、方法。
(22) 実施態様14に記載の方法において、
前記化合物は、Trpc4アゴニストとして機能する、方法。
(23) 実施態様13〜22のいずれかに記載の方法において、
前記疼痛は、急性疼痛、慢性疼痛、神経障害性疼痛、侵害受容性疼痛、内臓痛、およびそれらの組み合わせからなる群から選択される、方法。
(24) 実施態様13に記載の方法において、
前記疼痛は、内臓痛を含む、方法。
(25) 実施態様13に記載の方法において、
前記疼痛は、神経障害性疼痛を含む、方法。
前記組成物は、第2の薬学的活性物質をさらに含む、方法。
(27) 実施態様13〜26のいずれかに記載の方法において、
前記組成物は、非オピオイド鎮痛剤、オピオイド鎮痛剤、抗てんかん薬、NMDAアンタゴニスト、リドカイン、三環系抗鬱薬、またはそれらの組み合わせから選択される、1つまたは複数の追加の薬学的活性物質をさらに含む、方法。
(28) 実施態様13〜27のいずれかに記載の方法において、
前記化合物は、経口投与される、方法。
(29) 実施態様13〜27のいずれかに記載の方法において、
前記化合物は、局所投与される、方法。
Claims (24)
- TRPC4活性を調節することにより哺乳動物の疼痛を低減または防止するのに使用される、請求項1−3のいずれか1項に記載の医薬組成物であって、
前記疼痛は、急性疼痛、慢性疼痛、神経障害性疼痛、侵害受容性疼痛、内臓痛、およびそれらの組み合わせから選択される、医薬組成物。 - 請求項4に記載の医薬組成物であって、
前記疼痛は、内臓痛を含む、医薬組成物。 - 請求項4に記載の医薬組成物であって、
前記疼痛は、神経障害性疼痛を含む、医薬組成物。 - 請求項4に記載の医薬組成物であって、
前記慢性疼痛は、癌と関連している、医薬組成物。 - 請求項4に記載の医薬組成物であって、
前記急性疼痛は、軟組織損傷、感染、または炎症と関連している、医薬組成物。 - 請求項4に記載の医薬組成物であって、
前記医薬組成物は、経口投与され、
前記化合物の有効量は、テールフリックモデル、ラットテール浸漬モデルおよびカラギーナン誘発性足痛覚過敏モデルから選択される、インビトロおよびインビボのアッセイから補外される、医薬組成物。 - 請求項4に記載の医薬組成物であって、
前記医薬組成物は、局所投与され、
前記化合物の有効量は、テールフリックモデル、ラットテール浸漬モデルおよびカラギーナン誘発性足痛覚過敏モデルから選択される、インビトロおよびインビボのアッセイから補外される、医薬組成物。 - 請求項1−3のいずれか1項に記載の医薬組成物であって、
少なくとも1つの追加の薬学的活性物質をさらに含む、医薬組成物。 - 請求項11に記載の医薬組成物であって、
前記少なくとも1つの追加の薬学的活性物質は、非オピオイド鎮痛剤、オピオイド鎮痛剤、抗てんかん薬、NMDAアンタゴニスト、リドカイン、三環系抗鬱薬、またはそれらの組み合わせから選択される、医薬組成物。 - 請求項13−15のいずれか1項に記載の医薬組成物であって、
前記疼痛は、急性疼痛、慢性疼痛、神経障害性疼痛、侵害受容性疼痛、内臓痛、およびそれらの組み合わせから選択される、医薬組成物。 - 請求項16に記載の医薬組成物であって、
前記疼痛は、内臓痛を含む、医薬組成物。 - 請求項16に記載の医薬組成物であって、
前記疼痛は、神経障害性疼痛を含む、医薬組成物。 - 請求項16に記載の医薬組成物であって、
前記慢性疼痛は、癌と関連している、医薬組成物。 - 請求項16に記載の医薬組成物であって、
前記急性疼痛は、軟組織損傷、感染、または炎症と関連している、医薬組成物。 - 請求項16に記載の医薬組成物であって、
前記医薬組成物は、経口投与され、
前記化合物の有効量は、テールフリックモデル、ラットテール浸漬モデルおよびカラギーナン誘発性足痛覚過敏モデルから選択される、インビトロおよびインビボのアッセイから補外される、医薬組成物。 - 請求項16に記載の医薬組成物であって、
前記医薬組成物は、局所投与され、
前記化合物の有効量は、テールフリックモデル、ラットテール浸漬モデルおよびカラギーナン誘発性足痛覚過敏モデルから選択される、インビトロおよびインビボのアッセイから補外される、医薬組成物。 - 請求項13−15のいずれか1項に記載の医薬組成物であって、
少なくとも1つの追加の薬学的活性物質をさらに含む、医薬組成物。 - 請求項23に記載の医薬組成物であって、
前記少なくとも1つの追加の薬学的活性物質は、非オピオイド鎮痛剤、オピオイド鎮痛剤、抗てんかん薬、NMDAアンタゴニスト、リドカイン、三環系抗鬱薬、またはそれらの組み合わせから選択される、医薬組成物。
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RS57919B1 (sr) | 2019-01-31 |
JP6858808B2 (ja) | 2021-04-14 |
SI2790687T1 (sl) | 2019-01-31 |
HRP20181746T1 (hr) | 2018-12-28 |
JP2018030875A (ja) | 2018-03-01 |
AU2012352083A1 (en) | 2014-07-17 |
WO2013090722A1 (en) | 2013-06-20 |
TR201815535T4 (tr) | 2018-11-21 |
DK2790687T3 (en) | 2018-11-19 |
CA2859283C (en) | 2021-03-09 |
US10131634B2 (en) | 2018-11-20 |
AU2012352083B2 (en) | 2018-01-04 |
ES2692546T3 (es) | 2018-12-04 |
EP3485889A1 (en) | 2019-05-22 |
PL2790687T3 (pl) | 2019-03-29 |
EP3485889B1 (en) | 2023-09-06 |
US20190135759A1 (en) | 2019-05-09 |
CA2859283A1 (en) | 2013-06-20 |
JP6534716B2 (ja) | 2019-06-26 |
AU2018202172A1 (en) | 2018-04-26 |
HUE041294T2 (hu) | 2019-05-28 |
EP2790687B1 (en) | 2018-08-29 |
CY1121293T1 (el) | 2020-05-29 |
PT2790687T (pt) | 2018-11-13 |
US20140329856A1 (en) | 2014-11-06 |
LT2790687T (lt) | 2018-12-10 |
AU2018202172B2 (en) | 2019-12-19 |
JP2015500345A (ja) | 2015-01-05 |
EP2790687A1 (en) | 2014-10-22 |
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