| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Orexin receptor
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|---|---|
| ln Vitro |
As a novel orexin receptor antagonist, YZJ-1139 has a unique mechanism and fewer clinical side effects compared with other drugs used for the treatment of insomnia. It has completed Phase II clinical trials and will be expected to be marketed in the near future and become a potential agent for insomnia. [2]
As one of the most common sleep disorders in the clinic, insomnia affects a lot of people in the world. It has been estimated that the prevalence of at least one insomnia symptom is as high as 33% in the general population. Commonly, insomnia patients suffer from difficulty in falling asleep and maintaining sleep, which seriously affects people’s health and daily activities. The current medical therapies include benzodiazepines, non-benzodiazepines, melatonin receptor agonists, some antidepressants with sedation, and so on. These drugs have apparent shortcomings including hangover, insomnia rebound, drug dependence, cognitive decline, etc. Moreover, these drugs could not optimize sleep structure and are not suitable for long-term medication. Orexin is a kind of neuropeptide secreted by the hypothalamus and plays an important role in maintaining wakefulness. By blocking the interaction of orexin A and orexin B with orexin receptor 1 (OXR1) and orexin receptor 2 (OXR2), orexin receptor antagonists can inhibit wakefulness and increase NREM and REM (non-rapid eye movement and rapid eye movement) sleep, reduce anxiety and panic, and inhibit drug addiction. It is worth noting that the orexin receptor antagonist will not damage the patient’s cognitive ability. [2] |
| References | |
| Additional Infomation |
Tropane derivatives are widely used in the pharmaceutical field, but their catalytic asymmetric synthesis methods are still underdeveloped. This article reports a rhodium-catalyzed Suzuki-Miyaura-type asymmetric cross-coupling reaction between racemic N-Boc-nortropane-derived allyl chloride and (hetero)arylboronic ester. The reaction proceeds through an unexpected kinetic resolution, and the enantiomeric allyl chloride after resolution can react with nucleophiles containing N, O and S with high enantioselectivity. This method is applied to the synthesis of the highly stereoselective form of YZJ-1139(1), a potential insomnia treatment drug, which has recently completed a phase II clinical trial. This article reports an asymmetric catalytic method for the synthesis of YZJ-1139(1) and related compounds. [1]
This article also describes the synthesis and process development of the orexin receptor antagonist YZJ-1139(1). YZJ-1139(1) contains an azabicyclic nortropane structure with three chiral centers. According to the original process, high-purity intermediates or active pharmaceutical ingredients (APIs) can be obtained by chromatography with relatively low yield. In order to remove unwanted stereoisomers as early as possible, intermediate 13 with (R)-α-phenylethyl was synthesized by Robinson-Schöpf reaction and was easily purified in the form of hydrochloride. Single-crystal X-ray diffraction analysis was used to confirm the stereoconfigurations of 13·HCl and 18·HCl. The protecting group was easily removed by transfer hydrogenation reaction to obtain enantiomeric pure intermediate 3 (d-tartrate). The overall yield of YZJ-1139(1) was significantly improved, and this cost-effective process has the prospect of application in future commercial production. [2] |
| Molecular Formula |
C25H25FN4O2
|
|---|---|
| Molecular Weight |
432.490009069443
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| Exact Mass |
432.196
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| Elemental Analysis |
C, 69.43; H, 5.83; F, 4.39; N, 12.95; O, 7.40
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| CAS # |
1808918-69-5
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| PubChem CID |
156889652
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
32
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| Complexity |
645
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CC1=CC(=C(C=C1)C2=NC=CC=N2)C(=O)N3[C@H]4CC[C@H]([C@@H]3CC4)COC5=NC=C(C=C5)F
|
| InChi Key |
PMJPLAGTPPVSRL-JLMWRMLUSA-N
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| InChi Code |
InChI=1S/C25H25FN4O2/c1-16-3-8-20(24-27-11-2-12-28-24)21(13-16)25(31)30-19-6-4-17(22(30)9-7-19)15-32-23-10-5-18(26)14-29-23/h2-3,5,8,10-14,17,19,22H,4,6-7,9,15H2,1H3/t17-,19-,22-/m0/s1
|
| Chemical Name |
[(1S,2R,5S)-2-[(5-fluoropyridin-2-yl)oxymethyl]-8-azabicyclo[3.2.1]octan-8-yl]-(5-methyl-2-pyrimidin-2-ylphenyl)methanone
|
| Synonyms |
Fazamorexant; 1808918-69-5; YZJ-1139; fazamorexant [INN]; MDH4D7M594; CHEMBL5314459; SCHEMBL25191995;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (231.22 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.78 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.78 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.78 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3122 mL | 11.5610 mL | 23.1219 mL | |
| 5 mM | 0.4624 mL | 2.3122 mL | 4.6244 mL | |
| 10 mM | 0.2312 mL | 1.1561 mL | 2.3122 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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