Tiagabine-d6 (hydrochloride)
目录号 : GC48178
An internal standard for the quantification of tiagabine
Cas No.:1217808-68-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Tiagabine-d6 is intended for use as an internal standard for the quantification of tiagabine by GC- or LC-MS. Tiagabine is an inhibitor of GABA transporter 1 (GAT-1; IC50 = 49 nM for GAT-1 expressed in CHO cells).1 It inhibits seizures induced by DMCM in mice (ED50 = 1.2 mg/kg, i.p.).2 Tiagabine reduces allodynia in a rodent model of neuropathic pain when used at a dose of 72.8 µmol/kg, and it acts synergistically with gabapentin to delay pain responses in mice in the hot plate test.3,4 Formulations containing tiagabine have been used as adjunctive therapies in the treatment of partial seizures.
1.Nakada, K., Yoshikawa, M., Ide, S., et al.Cyclopropane-based conformational restriction of GABA by a stereochemical diversity-oriented strategy: Identification of an efficient lead for potent inhibitors of GABA transportsBioorg. Med. Chem.21(17)4938-4950(2013) 2.Andersen, K.E., Braestrup, C., GrØnwald, F.C., et al.The synthesis of novel GABA uptake inhibitors. 1. Elucidation of the structure-activity studies leading to the choice of (R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid (tiagabine) as an anticonvulsant drug candidateJ. Med. Chem.36(12)1716-1725(1993) 3.Giardina, W.J., Decker, M.W., Porsolt, R.D., et al.An evaluation of the GABA uptake blocker tiagabine in animal models of neuropathic and nociceptive painDrug Dev. Res.44(2-3)106-113(1998) 4.?uszczki, J.J., Ko?acz, A., Wojda, E., et al.Synergistic interaction of gabapentin with tiagabine in the hot-plate test in mice: An isobolographic analysisPharmacol. Rep.61(3)459-467(2009)
| Cas No. | 1217808-68-8 | SDF | |
| Canonical SMILES | OC([C@@H]1CCCN(CC/C=C(C2=C(C([2H])([2H])[2H])C=CS2)\C3=C(C([2H])([2H])[2H])C=CS3)C1)=O.Cl | ||
| 分子式 | C20H19D6NO2S2.HCl | 分子量 | 418 |
| 溶解度 | DMSO: soluble,Methanol: soluble,Water: soluble | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3923 mL | 11.9617 mL | 23.9234 mL |
| 5 mM | 0.4785 mL | 2.3923 mL | 4.7847 mL |
| 10 mM | 0.2392 mL | 1.1962 mL | 2.3923 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Nalfurafine hydrochloride, a κ-Opioid Receptor Agonist, Induces Melanophagy via PKA Inhibition in B16F1 Cells
Cells 2022 Dec 29;12(1):146.PMID:36611940DOI:10.3390/cells12010146.
Selective autophagy controls cellular homeostasis by degrading unnecessary or damaged cellular components. Melanosomes are specialized organelles that regulate the biogenesis, storage, and transport of melanin in melanocytes. However, the mechanisms underlying melanosomal autophagy, known as the melanophagy pathway, are poorly understood. To better understand the mechanism of melanophagy, we screened an endocrine-hormone chemical library and identified nalfurafine hydrochlorides, a κ-opioid receptor agonist, as a potent inducer of melanophagy. Treatment with nalfurafine hydrochloride increased autophagy and reduced melanin content in alpha-melanocyte-stimulating hormone (α-MSH)-treated cells. Furthermore, inhibition of autophagy blocked melanosomal degradation and reversed the nalfurafine hydrochloride-induced decrease in melanin content in α-MSH-treated cells. Consistently, treatment with other κ-opioid receptor agonists, such as MCOPPB or mianserin, inhibited excessive melanin production but induced autophagy in B16F1 cells. Furthermore, nalfurafine hydrochloride inhibited protein kinase A (PKA) activation, which was notably restored by forskolin, a PKA activator. Additionally, forskolin treatment further suppressed melanosomal degradation as well as the anti-pigmentation activity of nalfurafine hydrochloride in α-MSH-treated cells. Collectively, our data suggest that stimulation of κ-opioid receptors induces melanophagy by inhibiting PKA activation in α-MSH-treated B16F1 cells.
Antiparasitic activities of new lawsone Mannich bases
Arch Pharm (Weinheim) 2019 Nov;352(11):e1900128.PMID:31536649DOI:10.1002/ardp.201900128.
A series of new lawsone Mannich bases derived from salicylaldehydes or nitrofurfural were prepared and tested for their activities against Leishmania major, Toxoplasma gondii, and Trypanosoma brucei brucei parasites. The hydrochloride salts 5a and 6a of the Mannich bases 2a and 3a, derived from unsubstituted salicylaldehyde and long-chained alkyl amines, were selectively and strongly active against T. gondii cells and appear to be new promising drug candidates against this parasite. Compound 6a showed an even higher activity against T. gondii than the known lawsone Mannich base 1b. Compound 4a, derived from salicylaldehyde and 2-methylaminopyridine, was also distinctly active against T. gondii cells. The derivatives 3a (salicyl derivative), 3b (3,5-dichloro-2-hydroxyphenyl derivative), and 3d (5-nitrofuranyl derivative) as well as the hydrochlorides 6a and 6b were also efficacious against T. b. brucei cells with compounds 3a and 3b being more selective for T. b. brucei over Vero cells when compared with the known control compound 1b. The derivatives 5a, 5c, 6a, and 6c proved to be up to five times more active than 1b against L. major promastigotes and up to four times more efficacious against L. major amastigotes.
Iodine-Catalyzed Diazenylation with Arylhydrazine Hydrochlorides in Air
J Org Chem 2018 Apr 6;83(7):3537-3546.PMID:29486127DOI:10.1021/acs.joc.7b03149.
A mild approach to diazenylation of active methylene compounds and N-heterocyclic compounds with arylhydrazine hydrochlorides in the presence of iodine under basic aerobic conditions was developed. The reaction could be executed either under heating or in the presence of blue LED light, though the latter condition was found to be relatively efficient. Presumably, the aryldiazene produced by oxidation of arylhydrazine hydrochloride acts as a nitrogen scavenger of the radical intermediate generated from the active methylene compound in the presence of iodine to produce the diazo compounds. The scope and limitations of the protocol are presented.
Green Formation of Novel Pyridinyltriazole-Salicylidene Schiff Bases
Curr Org Synth 2019;16(2):309-313.PMID:31975681DOI:10.2174/1570179416666181207145951.
Aim and objective: In this work, water was used as solvent for the eco-friendly synthesis of imines under microwave irradiation. In the first step of the study, 5-pyridinyl-3-amino-1,2,4-triazole hydrochlorides were synthesized in the reaction of amino guanidine hydrochloride with different pyridine carboxylic acids under acid catalysis. A green method for 5-pyridinyl-3-amino-1,2,4-triazoles was developed with the assistance of microwave synthesis. In the second step, the eco-friendly synthesis of imines was achieved by reacting 5- pyridinyl-2H-1,2,4-triazol-3-amine hydrochlorides with salicylic aldehyde derivatives to produce 2-(5- pyridinyl-2H-1,2,4-triazol-3-ylimino)methyl)phenol imines. Materials and methods: Microwave experiments were done using a monomode Anton Paar Monowave 300 microwave reactor (2.45 GHz). Reaction temperatures were monitored by an IR sensor. Microwave experiments were carried out in sealed microwave process vials G10 with maximum reaction volume of 10 mL. Results: When alternative methods were used, it was impossible to obtain good yields from ethanol. Nevertheless, the use of water was successful for this reaction. After 1-h microwave irritation, a yellow solid was obtained in 82% yield. Conclusion: In this work an eco-friendly protocol for the synthesis of Schiff bases from 5-(pyridin-2-, 3- or 4- yl)-3-amino-1,2,4-triazoles and substituted salicylic aldehydes in water under microwave irradiation was developed. Under the found conditions the high yields for the products were achieved at short reaction time and with an easy isolation procedure.
Liquid Co-crystals of Dual-Active Phenothiazine-NSAID Drugs: Synthesis, Spectroscopic, and Thermal Characterization
ACS Omega 2022 May 9;7(20):16990-17001.PMID:35647432DOI:10.1021/acsomega.1c07382.
Four aliphatic phenothiazine cations (promazinium, promethazinium, chlorpromazinium, and triflupromazinium) were each paired with docusate anions and three different NSAID anions (ibuprofen, salicylate, and naproxen) to form fifteen glassy materials and one solid. The compounds were prepared via the metathesis reaction between the corresponding phenothiazine hydrochloride salts and sodium docusate or sodium NSAID salts and were obtained as liquid co-crystals with various degrees of ionization. The self-diffusion coefficients of several derivatives in 0.06 M DMSO-d 6 solutions were determined using DOSY NMR spectroscopy. The influence of the size, shape of the compounds, and intermolecular forces has been investigated by using the four promazine and the four ibuprofen co-crystals. The ion pairs (or aggregates) were found to be maintained in six out of the seven compounds examined. All fifteen glassy compounds showed reversible glass transitions in the -25 to 10 °C range with the docusate derivatives exhibiting the highest thermal stability (T onset values being at least 40 °C higher than those of the corresponding phenothiazine hydrochlorides).