JPWO2019118583A5 - - Google Patents
Download PDFInfo
- Publication number
- JPWO2019118583A5 JPWO2019118583A5 JP2020531724A JP2020531724A JPWO2019118583A5 JP WO2019118583 A5 JPWO2019118583 A5 JP WO2019118583A5 JP 2020531724 A JP2020531724 A JP 2020531724A JP 2020531724 A JP2020531724 A JP 2020531724A JP WO2019118583 A5 JPWO2019118583 A5 JP WO2019118583A5
- Authority
- JP
- Japan
- Prior art keywords
- compound
- pain
- composition
- pharmaceutically acceptable
- administered
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 claims description 26
- 208000002193 Pain Diseases 0.000 claims description 22
- 230000036407 pain Effects 0.000 claims description 19
- 102000002689 Toll-like receptor Human genes 0.000 claims description 11
- 108020000411 Toll-like receptor Proteins 0.000 claims description 11
- 208000014674 injury Diseases 0.000 claims description 9
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 208000004296 neuralgia Diseases 0.000 claims description 7
- 208000021722 neuropathic pain Diseases 0.000 claims description 6
- 230000008733 trauma Effects 0.000 claims description 6
- 208000012902 Nervous system disease Diseases 0.000 claims description 5
- 208000025966 Neurological disease Diseases 0.000 claims description 5
- 208000001294 Nociceptive Pain Diseases 0.000 claims description 5
- 230000001154 acute effect Effects 0.000 claims description 5
- 238000002512 chemotherapy Methods 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 claims description 4
- 208000026251 Opioid-Related disease Diseases 0.000 claims description 4
- 102100039360 Toll-like receptor 4 Human genes 0.000 claims description 4
- 201000005040 opiate dependence Diseases 0.000 claims description 4
- 208000000094 Chronic Pain Diseases 0.000 claims description 3
- 206010019233 Headaches Diseases 0.000 claims description 3
- 208000027418 Wounds and injury Diseases 0.000 claims description 3
- 230000036592 analgesia Effects 0.000 claims description 3
- 230000006378 damage Effects 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
- 230000000694 effects Effects 0.000 claims description 3
- 230000004914 glial activation Effects 0.000 claims description 3
- 231100000869 headache Toxicity 0.000 claims description 3
- 208000015181 infectious disease Diseases 0.000 claims description 3
- 230000001537 neural effect Effects 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- 230000000306 recurrent effect Effects 0.000 claims description 3
- 201000009032 substance abuse Diseases 0.000 claims description 3
- 231100000736 substance abuse Toxicity 0.000 claims description 3
- 208000011117 substance-related disease Diseases 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 206010010071 Coma Diseases 0.000 claims description 2
- 206010010904 Convulsion Diseases 0.000 claims description 2
- 206010012289 Dementia Diseases 0.000 claims description 2
- 208000016192 Demyelinating disease Diseases 0.000 claims description 2
- 208000023105 Huntington disease Diseases 0.000 claims description 2
- 208000016285 Movement disease Diseases 0.000 claims description 2
- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- 208000020307 Spinal disease Diseases 0.000 claims description 2
- 208000034799 Tauopathies Diseases 0.000 claims description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
- 208000002173 dizziness Diseases 0.000 claims description 2
- 210000003205 muscle Anatomy 0.000 claims description 2
- 210000000715 neuromuscular junction Anatomy 0.000 claims description 2
- 210000000578 peripheral nerve Anatomy 0.000 claims description 2
- 208000019116 sleep disease Diseases 0.000 claims description 2
- 208000022925 sleep disturbance Diseases 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims 12
- 229910052739 hydrogen Inorganic materials 0.000 claims 5
- 239000001257 hydrogen Substances 0.000 claims 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 5
- 230000037396 body weight Effects 0.000 claims 4
- 201000011510 cancer Diseases 0.000 claims 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 206010037779 Radiculopathy Diseases 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 125000002877 alkyl aryl group Chemical group 0.000 claims 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 2
- 150000002431 hydrogen Chemical group 0.000 claims 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- 201000006417 multiple sclerosis Diseases 0.000 claims 2
- 238000001356 surgical procedure Methods 0.000 claims 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- 208000008035 Back Pain Diseases 0.000 claims 1
- 208000010392 Bone Fractures Diseases 0.000 claims 1
- 208000034656 Contusions Diseases 0.000 claims 1
- 208000012514 Cumulative Trauma disease Diseases 0.000 claims 1
- 208000001640 Fibromyalgia Diseases 0.000 claims 1
- 206010017076 Fracture Diseases 0.000 claims 1
- 208000007514 Herpes zoster Diseases 0.000 claims 1
- 206010060820 Joint injury Diseases 0.000 claims 1
- 208000034693 Laceration Diseases 0.000 claims 1
- 206010024453 Ligament sprain Diseases 0.000 claims 1
- 208000002720 Malnutrition Diseases 0.000 claims 1
- 208000019155 Radiation injury Diseases 0.000 claims 1
- 208000008765 Sciatica Diseases 0.000 claims 1
- 208000010040 Sprains and Strains Diseases 0.000 claims 1
- 208000006011 Stroke Diseases 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 230000000202 analgesic effect Effects 0.000 claims 1
- 206010003246 arthritis Diseases 0.000 claims 1
- 125000004104 aryloxy group Chemical group 0.000 claims 1
- 208000034526 bruise Diseases 0.000 claims 1
- 208000003295 carpal tunnel syndrome Diseases 0.000 claims 1
- 230000001684 chronic effect Effects 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- 239000011737 fluorine Substances 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 230000004968 inflammatory condition Effects 0.000 claims 1
- 230000001071 malnutrition Effects 0.000 claims 1
- 235000000824 malnutrition Nutrition 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 210000005036 nerve Anatomy 0.000 claims 1
- 230000000926 neurological effect Effects 0.000 claims 1
- 208000015380 nutritional deficiency disease Diseases 0.000 claims 1
- 230000003389 potentiating effect Effects 0.000 claims 1
- 208000020431 spinal cord injury Diseases 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 239000003053 toxin Substances 0.000 claims 1
- 231100000765 toxin Toxicity 0.000 claims 1
- 108700012359 toxins Proteins 0.000 claims 1
- 101000763579 Homo sapiens Toll-like receptor 1 Proteins 0.000 description 1
- 101000763537 Homo sapiens Toll-like receptor 10 Proteins 0.000 description 1
- 101000831567 Homo sapiens Toll-like receptor 2 Proteins 0.000 description 1
- 101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 description 1
- 101000669460 Homo sapiens Toll-like receptor 5 Proteins 0.000 description 1
- 101000669406 Homo sapiens Toll-like receptor 6 Proteins 0.000 description 1
- 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 description 1
- 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 description 1
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 1
- 102100027010 Toll-like receptor 1 Human genes 0.000 description 1
- 102100027009 Toll-like receptor 10 Human genes 0.000 description 1
- 102100024333 Toll-like receptor 2 Human genes 0.000 description 1
- 102100024324 Toll-like receptor 3 Human genes 0.000 description 1
- 102100039357 Toll-like receptor 5 Human genes 0.000 description 1
- 102100039387 Toll-like receptor 6 Human genes 0.000 description 1
- 102100039390 Toll-like receptor 7 Human genes 0.000 description 1
- 102100033110 Toll-like receptor 8 Human genes 0.000 description 1
- 102100033117 Toll-like receptor 9 Human genes 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 208000013433 lightheadedness Diseases 0.000 description 1
- DAZSWUUAFHBCGE-KRWDZBQOSA-N n-[(2s)-3-methyl-1-oxo-1-pyrrolidin-1-ylbutan-2-yl]-3-phenylpropanamide Chemical group N([C@@H](C(C)C)C(=O)N1CCCC1)C(=O)CCC1=CC=CC=C1 DAZSWUUAFHBCGE-KRWDZBQOSA-N 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
Description
本発明のさらに別の実施形態は、Ｔｏｌｌ様受容体（ＴＬＲ）神経膠活性化に関連する臨床状態を有する対象を処置するための方法であって、対象に有効量の式Ｉの化合物を投与するステップを含む方法を提供する。この実施形態の一部の態様では、Ｔｏｌｌ様受容体（ＴＬＲ）は、ＴＬＲ－４である。同様に、この実施形態の一部の態様では、臨床状態は、急性侵害受容性疼痛；神経障害性疼痛；他の疼痛サブタイプ／混合型疼痛状態、例えば、火傷、骨関節炎、化学療法、外傷によって引き起こされる疼痛；急性および反復性オピオイド無痛覚；薬物乱用の報酬効果、慢性疼痛またはオピオイド依存に関連する他の疼痛を含む。本発明のある特定の実施形態の詳細は、以下に記載されているある特定の実施形態の発明を実施するための形態に記載されている。本発明の他の特色、目的および利点は、定義、実施例、図面および特許請求の範囲から明白となろう。 Yet another embodiment of the present invention is a method for treating a subject having a clinical condition associated with Toll-like receptor (TLR) glial activation, comprising administering to the subject an effective amount of a compound of formula I A method is provided that includes the step of: In some aspects of this embodiment, the Toll-like receptor (TLR) is TLR-4. Similarly, in some aspects of this embodiment, the clinical condition is acute nociceptive pain; neuropathic pain; other pain subtypes/mixed pain conditions, e.g., burns, osteoarthritis, chemotherapy, trauma acute and recurrent opioid analgesia; rewarding effects of substance abuse, chronic pain or other pain associated with opioid dependence. The details of certain embodiments of the invention are set forth in the detailed description of certain embodiments below. Other features, objects and advantages of the invention will become apparent from the definitions, examples, drawings and claims.
本開示の一態様では、本開示は、Ｔｏｌｌ様受容体（ＴＬＲ）神経膠活性化に関連する臨床状態を有する対象を処置するための方法であって、対象に有効量の本明細書に記載されている化合物を投与するステップを含む方法を提供する。一部の実施形態では、式Ｉの化合物が対象に投与される。ある特定の実施形態では、式Ｉの化合物のプロドラッグが対象に投与される。一部の実施形態では、Ｔｏｌｌ様受容体は、ＴＬＲ１、ＴＬＲ２、ＴＬＲ３、ＴＬＲ４、ＴＬＲ５、ＴＬＲ６、ＴＬＲ７、ＴＬＲ８、ＴＬＲ９およびＴＬＲ１０からなる群から選択される。ある特定の実施形態では、Ｔｏｌｌ様受容体は、ＴＬＲ－４である。一部の実施形態では、臨床状態は、急性侵害受容性疼痛、神経障害性疼痛、神経性疾患に関連する疼痛、ニューロン損傷に関連する疼痛、他の疼痛サブタイプ／混合型疼痛状態（例えば、火傷、骨関節炎、化学療法、外傷によって引き起こされる疼痛）、急性および反復性オピオイド無痛覚、薬物乱用の報酬効果、慢性疼痛またはオピオイド依存に関連する他の疼痛を含む。ある特定の実施形態では、臨床状態は、神経学的疾患に関連する疼痛を含む。ある特定の実施形態では、神経学的疾患は、アルツハイマー病、パーキンソン病、筋萎縮性側索硬化症、タウオパチー、ハンチントン病、頭痛、意識朦朧および昏睡、認知症、発作、睡眠障害、外傷、感染、新生物、神経眼科学、運動障害、脱髄性疾患、脊髄障害、ならびに末梢神経、筋肉および神経筋接合部の障害からなる群から選択される。一部の実施形態では、臨床状態は、ニューロン損傷に関連する疼痛を含む。 In one aspect of the present disclosure, the present disclosure provides a method for treating a subject having a clinical condition associated with Toll-like receptor (TLR) glial activation, comprising administering to the subject an effective amount of a drug as described herein. A method is provided comprising the step of administering the compound of the present invention. In some embodiments, a compound of Formula I is administered to a subject. In certain embodiments, a prodrug of the compound of Formula I is administered to the subject. In some embodiments, the Toll-like Receptor is selected from the group consisting of TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9 and TLR10. In certain embodiments, the Toll-like receptor is TLR-4. In some embodiments, the clinical condition is acute nociceptive pain, neuropathic pain, pain associated with neurological disease, pain associated with neuronal injury, other pain subtypes/mixed pain conditions (e.g., pain caused by burns, osteoarthritis, chemotherapy, trauma), acute and recurrent opioid analgesia, the rewarding effects of substance abuse, chronic pain or other pain associated with opioid dependence. In certain embodiments, the clinical condition comprises pain associated with neurological disease. In certain embodiments, the neurological disease is Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, tauopathy, Huntington's disease, headaches, lightheadedness and coma, dementia, seizures, sleep disturbances, trauma, infections , neoplasms, neuro-ophthalmology, movement disorders, demyelinating diseases, spinal disorders, and disorders of peripheral nerves, muscles and neuromuscular junctions. In some embodiments, the clinical condition comprises pain associated with neuronal injury.
Claims (23)
Ｒ１は、ヒドロキシル、アルコキシおよびアリールオキシからなる群から選択され、
Ｒ２は、水素、アルキル、アルキニル、アルケニル、アルコキシ、ヒドロカルビル、置換ヒドロカルビル、シクロアルキル、アルキルアリールおよび置換アルキルアリール、
Ｙは、水素およびヒドロキシルからなる群から選択され、
Ｘは、フッ素であり、そして
Ｚは、水素であり、
ただし、Ｒ１がヒドロキシルである場合、Ｒ２はシクロプロピルメチルではない、
化合物、またはその薬学的に許容される塩。 Compounds of Formula IC :
R 1 is selected from the group consisting of hydroxyl, alkoxy and aryloxy;
R2 is hydrogen, alkyl, alkynyl, alkenyl, alkoxy , hydrocarbyl, substituted hydrocarbyl, cycloalkyl, alkylaryl and substituted alkylaryl ;
Y is selected from the group consisting of hydrogen and hydroxyl ;
X is fluorine, and
Z is hydrogen;
with the proviso that when R 1 is hydroxyl, R 2 is not cyclopropylmethyl;
A compound, or a pharmaceutically acceptable salt thereof .
（ｂ）Ｙがヒドロキシルである、
請求項１に記載の化合物。 (a) Y is hydrogen, or
( b ) Y is hydroxyl ;
A compound according to claim 1 .
（ａ）ヒドロキシル、または
（ｂ）メトキシ
である、請求項１または２に記載の化合物。 3. The compound of claim 1 or 2 , wherein R1 is (a) hydroxyl, or (b) methoxy.
（ａ）シクロプロピルメチル、
（ｂ）２－プロペニル、または
（ｃ）フェネチル
である、請求項１から３のいずれか一項に記載の化合物。 R 2 is (a) cyclopropylmethyl,
4. A compound according to any one of claims 1 to 3 , which is (b) 2-propenyl, or (c) phenethyl.
（ａ）多発性硬化症、
（ｂ）がん、または
（ｃ）化学療法
によるものである、請求項１７または１８に記載の組成物。 wherein the neuropathic pain is
(a) multiple sclerosis,
19. The composition of claim 17 or 18 , wherein (b) cancer, or (c) is due to chemotherapy.
（ｉ）最大で約１５００ｍｇ／用量であり、１日あたり１～４回の別個の用量で投与される、 (i) up to about 1500 mg/dose, administered in 1-4 separate doses per day;
（ｉｉ）１日あたり約０．８ｍｇ／ｋｇ体重～約１００ｍｇ／ｋｇ体重であり、１回から数回の別個の用量で投与される、 (ii) from about 0.8 mg/kg body weight to about 100 mg/kg body weight per day, administered in one to several separate doses;
（ｉｉｉ）約３４ｍｇ／日～約５１０ｍｇ／日であり、１回から数回の別個の用量で投与される、 (iii) from about 34 mg/day to about 510 mg/day, administered in one to several discrete doses;
（ｉｖ）約６８～約４０８ｍｇ／日であり、１回から数回の別個の用量で投与される、 (iv) from about 68 to about 408 mg/day, administered in one to several separate doses;
（ｖ）１日あたり約０．５～約７．２ｍｇ／ｋｇ体重であり、１回から数回の別個の用量で投与される、または (v) from about 0.5 to about 7.2 mg/kg body weight per day, administered in one to several separate doses, or
（ｖｉ）１日あたり約１．０～約６ｍｇ／ｋｇ体重であり、１回から数回の別個の用量で投与される、 (vi) about 1.0 to about 6 mg/kg body weight per day, administered in one to several separate doses;
請求項１１から２１のいずれか一項に記載の組成物。22. A composition according to any one of claims 11-21.
および対象に請求項１から１０のいずれか一項に記載の化合物を投与するための指示書
を含む、キット。 a compound according to any one of claims 1 to 10 ,
and instructions for administering a compound of any one of claims 1-10 to a subject.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762597815P | 2017-12-12 | 2017-12-12 | |
| US62/597,815 | 2017-12-12 | ||
| PCT/US2018/065185 WO2019118583A1 (en) | 2017-12-12 | 2018-12-12 | Halogenated derivatives of morphinans and uses thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2021506768A JP2021506768A (en) | 2021-02-22 |
| JPWO2019118583A5 true JPWO2019118583A5 (en) | 2023-04-19 |
| JP7307067B2 JP7307067B2 (en) | 2023-07-11 |
Family
ID=66820629
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020531724A Active JP7307067B2 (en) | 2017-12-12 | 2018-12-12 | Halogenated derivatives of morphinans and uses thereof |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US11505556B2 (en) |
| EP (1) | EP3723749A4 (en) |
| JP (1) | JP7307067B2 (en) |
| KR (1) | KR102758290B1 (en) |
| CN (1) | CN111698987B (en) |
| AU (1) | AU2018383773A1 (en) |
| BR (1) | BR112020010901A2 (en) |
| CA (1) | CA3085321C (en) |
| IL (1) | IL274610B2 (en) |
| MX (1) | MX2020006068A (en) |
| WO (1) | WO2019118583A1 (en) |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4241065A (en) * | 1979-07-02 | 1980-12-23 | E. I. Du Pont De Nemours And Company | Fluoro analogs of hydrocodone and oxycodone useful as analgesics, narcotic antagonists or both |
| US4368326A (en) | 1980-07-03 | 1983-01-11 | Rice Kenner C | Short total synthesis of dihydrothebainone, dihydrocodeinone, and nordihydroccodeinone |
| US4556712A (en) | 1981-05-20 | 1985-12-03 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Preparation and racemization of chiral 1-benzyl-1,2,3,4-tetrahydroisoquinolines |
| US4410700A (en) | 1980-07-03 | 1983-10-18 | The United States Of America As Represented By The Department Of Health And Human Services | Preparation of chiral 1-benzyl-1,2,3,4-tetrahydroisoquinolines by optical resolution |
| US4521601A (en) | 1981-05-20 | 1985-06-04 | The United States Of America As Represented By The Department Of Health & Human Services | Practical total synthesis unnatural enantiomers of opium-derived morphinans |
| US4613668A (en) | 1983-12-22 | 1986-09-23 | The United States Of America As Represented By The Department Of Health And Human Services | Short total synthesis or morphinan compounds which uses cyclization of a cycloalkylcarbonyl compound selected from cyclopropylcarbonyl and cyclobutylcarbonyl |
| US4775759A (en) * | 1984-11-27 | 1988-10-04 | The United States Of America As Represented By The Department Of Health And Human Services | Synthesis and utilization of 17-methyl and 17-cyclopropylmethyl-3,14-dihydroxy-4,5α-epoxy 6β-fluoromorphinans (foxy and cyclofoxy) as (18F)-labeled opioid ligands for position emission transaxial tomography (PETT) |
| US5668285A (en) | 1986-10-31 | 1997-09-16 | The United States Of America As Represented By The Department Of Health And Human Services | Total synthesis of northebaine, normophine, noroxymorphone enantiomers and derivatives via N-Nor intermediates |
| US5008449A (en) | 1989-03-03 | 1991-04-16 | The United States Of America As Represented By The Department Of Health And Human Services | Method of synthesis of hydroxy-substituted-4-alkoxyphenylacetic acids |
| PT95069B (en) | 1989-08-24 | 1997-10-31 | Searle & Co | PROCESS FOR THE PREPARATION OF (+) - ISOMERS OF DERIVATIVES OF ENDOETANO / ENDOETANOEPOXIMOFINANO, UTEIS AS ANTI-TUSTIC AGENTS |
| EP1370570B1 (en) * | 2001-02-28 | 2007-01-24 | John H. Griffin | Plasma glucosylceramide deficiency as risk factor for thrombosis and modulator of anticoagulant protein c |
| DE602008004245D1 (en) * | 2007-05-04 | 2011-02-10 | Mallinckrodt Inc | IMPROVED METHOD FOR THE PRODUCTION OF 6-ALPHA-HYDROXY-N-ALKYLATED OPIATES |
| WO2009059050A2 (en) | 2007-10-30 | 2009-05-07 | The Regents Of The University Of Colorado | Tlr modulators and methods for using the same |
| WO2009059048A2 (en) | 2007-10-30 | 2009-05-07 | The Regents Of The University Of Colorado | (+)-opioids and methods of use |
| EP2222678B1 (en) * | 2007-12-17 | 2016-03-09 | Mallinckrodt LLC | Processes for the production of (+)-'nal' morphinan compounds |
| WO2010017573A1 (en) * | 2008-08-11 | 2010-02-18 | Tasmanian Alkaloids Pty Limited | PROCESS FOR MAKING MORPHINAN-6α-OLS |
| CA2676881C (en) * | 2008-09-30 | 2017-04-25 | Wyeth | Peripheral opioid receptor antagonists and uses thereof |
-
2018
- 2018-12-12 EP EP18889631.0A patent/EP3723749A4/en active Pending
- 2018-12-12 WO PCT/US2018/065185 patent/WO2019118583A1/en unknown
- 2018-12-12 US US16/772,108 patent/US11505556B2/en active Active
- 2018-12-12 MX MX2020006068A patent/MX2020006068A/en unknown
- 2018-12-12 CA CA3085321A patent/CA3085321C/en active Active
- 2018-12-12 BR BR112020010901-0A patent/BR112020010901A2/en unknown
- 2018-12-12 JP JP2020531724A patent/JP7307067B2/en active Active
- 2018-12-12 CN CN201880088637.7A patent/CN111698987B/en active Active
- 2018-12-12 KR KR1020207019701A patent/KR102758290B1/en active Active
- 2018-12-12 AU AU2018383773A patent/AU2018383773A1/en not_active Abandoned
- 2018-12-12 IL IL274610A patent/IL274610B2/en unknown
-
2022
- 2022-10-07 US US17/962,187 patent/US20230203053A1/en not_active Abandoned
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2022105175A5 (en) | ||
| US20040167226A1 (en) | Methods for the treatment of pain and traumatic injury using benzamides and compositions containing the same | |
| JP2019519503A5 (en) | ||
| JP2006510618A (en) | Analgesic use of norketamine and ketamine / norketamine prodrugs | |
| CN101257899B (en) | Application of alkamine compound in the preparation of drugs of autoimmune diseases | |
| SI2546233T1 (en) | Hydrobenzamide derivatives as inhibitors of hsp90 | |
| TW201924681A (en) | Combination use of KOR agonist and MOR agonist in the preparation of a medicament for the treatment of pain | |
| EP1009397A2 (en) | N,n-bis (phenylcarbamoylmethyl) dimethylammonium chloride and derivatives in the treatment of pain | |
| RU97104483A (en) | SUITABLE ACID SALT 4- [2-AMINO-6- (CYCLOPROPYLAMINO) -9H-PURIN-9-IL] -2- CYCLOPENTEN-1-METHANOL AS ANTI-VIRUS AGENT | |
| US4609647A (en) | Cytidyl diphosphocholine-drug composition and process | |
| CN105497020A (en) | Medical use of optical isomers of amine compounds in treating pain | |
| JPWO2019118583A5 (en) | ||
| TWI332007B (en) | Use of alkylphosphocholines in combination with antitumor medicaments for the treatment of benign and malignant oncoses in humans and animals | |
| CA1248454A (en) | Cytidyl diphosphocholine-drug composition and process | |
| CN109758452A (en) | Medicinal use of amine compounds in the treatment of pain | |
| JPS6310728A (en) | Disaccharide derivative-containing analgestic agent | |
| CA1295341C (en) | Trienamide compounds having anti-inflammatory and analgesic activity | |
| EP1734940B1 (en) | Combinations of deramciclane and opioids for use as analgesics | |
| IL274610B2 (en) | Halogenated derivatives of morphinans and uses thereof | |
| JPH11505851A (en) | Drugs for the treatment of radiation damage | |
| WO2024136755A1 (en) | Albumin binding compounds and methods of use thereof | |
| US4035491A (en) | Pharmaceutical composition having synergistic analgesic activity and containing azidomorphine or azidocodeine | |
| WO2021242711A1 (en) | Adjuvanted conjugate opioid vaccine | |
| CN112569238A (en) | Application of imatinib and derivative thereof and analgesic combined medicine or compound preparation in treating pain | |
| KR20060131933A (en) | Combination of Deramcyclane and Opioids as Analgesics |