| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
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| 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 extensively used in medicine, but catalytic asymmetric methods for their synthesis are underexplored. Here, we report Rh-catalyzed asymmetric Suzuki-Miyaura-type cross-coupling reactions between a racemic N-Boc-nortropane-derived allylic chloride and (hetero)aryl boronic esters. The reaction proceeds via an unexpected kinetic resolution, and the resolved enantiopure allyl chloride can undergo highly enantiospecific reactions with N-, O-, and S-containing nucleophiles. The method was applied in a highly stereoselective formal synthesis of YZJ-1139(1), a potential insomnia treatment that recently completed Phase II clinical trials. Our report represents an asymmetric catalytic method for the synthesis of YZJ-1139(1) and related compounds.[1]
An effort toward the synthesis and process development of the orexin receptor antagonist YZJ-1139(1) was described in this article. YZJ-1139(1) contains the azabicyclic nortropane structure with three chiral centers. By the original process, highly pure intermediates or API could be obtained by chromatography with a relatively low yield. To remove the undesirable stereoisomers as early as possible, intermediate 13 with (R)-α-phenethyl was synthesized by the Robinson–Schöpf reaction and easily purified as hydrochloride. The single crystal X-ray study was used to confirm the stereo configuration of 13·HCl and 18·HCl. The protecting group could be easily removed by transfer hydrogenation, resulting in enantiomerically pure intermediate 3 as a d-tartarate. The overall yield for preparing YZJ-1139(1) was significantly increased, and this cost-efficient process might be promising in future commercial productions. [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
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| 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
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| 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
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| 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)
|
|---|---|
| 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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