| Size | Price | Stock | Qty |
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| 5mg |
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| 25mg |
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| Targets |
SSRI; tricyclic antidepressant (TCA)
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| ln Vitro |
Pipofezine has sedative, antihistamine, anticholinergic and antiadrenergic activity in addition to its antidepressant action.
Pipofezine Dihydrochloride Monohydrate 2 [5] The MicroED structure 2 was solved in a monoclinic P 21/c space group at the resolution of 0.82 Å (Figure 2b and Figure 3), with the unit cell parameters of a = 6.88 Å, b = 15.61 Å, c = 15.93 Å, α = 90.0°, β = 97.2°, γ = 90.0°. Two conforms, namely 2a and 2b were identified in the uniFig t cell. Each can be transformed by inversion symmetry or 180° rotation of C11‒N4/C11′‒N4′ bond. The crystal packing is formed mainly by hydrogen bonds and ion-dipole interactions between 2a/2b and chloride anions along b- and c-axes, i.e. hydrogen bonds N5/N5′─H···Cl1 (3.01 Å) and N3/N3′─H···O2 (2.67 Å); ion-dipole interactions between CH atoms and chloride anions (Figure S3, Supporting Information). The water molecules serve as hydrogen bond donors to Cl1 or Cl2 anions that bridge 2a and 2b molecules together (Figure S3, Supporting Information). The packing along the a-axis is facilitated by strong parallel-displaced pi-stacking interactions between the phenyl and pyridazine rings in 2a and 2b (3.65 Å). In 2, bond angles are mostly fixed, with only one freely rotating bond (C10‒C11‒N4‒C15 and C10′‒C11′‒N4′‒C15′, measured at ±178.60° in 2a and 2b), generating a co-planar arrangement of piperazine ring and tricyclic moiety (Figure S4, Supporting Information).[5] |
| Enzyme Assay |
2‒hSERT Complexes[5]
2 was tested at the central (S1) and allosteric (S2) sites in hSERT (Figure S12c, Supporting Information),[32] however the final docking center was found near S2 site due to the weak binding observed in S1 site (i.e., only the hydrophobic interactions). A salt bridge between Asp98 and piperazine ring, together with one pi-stacking (Phe335), one pi-cation interaction (Arg104), and three hydrophobic interactions (Phe335, Phe556) to the tricyclic moiety stabilized the binding complex of 2/hERT (Figure 4c). The structures of 2 in its drug-formulation state and biologically active state are very similar, with only 3–6° rotation C11′‒N4′ bond (Figure S4, Supporting Information), and maintain the piperazine ring and tricyclic moiety in a nearly co-planar geometry (C10‒C11‒N4‒C15≈180°) for both states. The minimum conformational changes ensure small entropy differences upon binding which is beneficial for the binding of 2 to the receptor. |
| References |
[1]. Azaphen: a return to clinical practice.Zh Nevrol Psikhiatr Im S S Korsakova. 2005;105(10):55-6.
[2]. Azaphen in the treatment of enuresis in children.Psychiatr Pol. 1977 Jan-Feb;11(1):29-33. [3]. A comparison of the effect of the tricyclic antidepressants azaphen and imizin on the gastrointestinal tracts of experimental animals.Farmakol Toksikol. 1975 Jan-Feb;38(1):29-32. [4]. Proceedings: Influence of azaphen, a new antidepressive drug, on the human EEG. Act Nerv Super (Praha). 1974;16(4):245-6. [5]. Uncovering the Elusive Structures and Mechanisms of Prevalent Antidepressants. Advanced Therapeutics 2024, 2400117. https://onlinelibrary.wiley.com/doi/full/10.1002/adtp.202400117 |
| Additional Infomation |
Most treatments to alleviate major depression work by either inhibiting human monoamine transporters, vital for the reuptake of monoamine neurotransmitters, or by inhibiting monoamine oxidases, which are vital for their degradation. The analysis of the experimental 3D structures of those antidepressants in their drug formulation state is key to precision drug design and development. In this study, microcrystal electron diffraction (MicroED) is applied to reveal the atomic 3D structures for the first time of five of the most prevalent antidepressants (reboxetine, pipofezine, ansofaxine, phenelzine, and bifemelane) directly from the commercially available powder of the active ingredients. Their modes of binding are investigated by molecular docking, revealing the essential contacts and conformational changes into the biologically active state. This study underscores the combined use of MicroED and molecular docking to uncover elusive drug structures and mechanisms to aid in further drug development pipelines.[5]
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| Molecular Formula |
C16H20CLN5O
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|---|---|
| Molecular Weight |
333.82
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| Exact Mass |
369.112
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| Elemental Analysis |
C, 57.57; H, 6.04; Cl, 10.62; N, 20.98; O, 4.79
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| CAS # |
24853-80-3
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| Related CAS # |
Azaphen dihydrochloride monohydrate;63302-99-8
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| PubChem CID |
159976
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| Appearance |
Typically exists as solids at room temperature
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| Boiling Point |
536ºC at 760 mmHg
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| Flash Point |
278ºC
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| Vapour Pressure |
1.46E-11mmHg at 25°C
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| LogP |
3.773
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
24
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| Complexity |
387
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[H]Cl.[H]Cl.CN1C2=CC=CC=C2OC3=C1C=C(N4CCN(C)CC4)N=N3
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| InChi Key |
ZZVWCKAYZSAUKR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H19N5O.2ClH/c1-19-7-9-21(10-8-19)15-11-13-16(18-17-15)22-14-6-4-3-5-12(14)20(13)2;;/h3-6,11H,7-10H2,1-2H3;2*1H
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| Chemical Name |
5-methyl-3-(4-methylpiperazin-1-yl)pyridazino[3,4-b][1,4]benzoxazine;dihydrochloride
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| Synonyms |
Azaphen; 24853-80-3; Azafen; Pipofezine HCl; Pipofezine hydrochloride; MFB4TD413U; Azaphen hydrochloride; 5-methyl-3-(4-methylpiperazin-1-yl)pyridazino[3,4-b][1,4]benzoxazine;dihydrochloride;
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9956 mL | 14.9781 mL | 29.9563 mL | |
| 5 mM | 0.5991 mL | 2.9956 mL | 5.9913 mL | |
| 10 mM | 0.2996 mL | 1.4978 mL | 2.9956 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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