| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
1. 5-HT₂ₐ receptor (Ki = 1.2 nM for receptor binding, IC50 = 3.5 nM for functional antagonism) [1]
2. 5-HT₂c receptor (Ki = 2.8 nM for receptor binding, IC50 = 7.2 nM for functional antagonism) [1] 3. 5-HT₂b receptor (Ki = 15.6 nM for receptor binding) [1] |
|---|---|
| ln Vitro |
In guinea pig mesenteric arteries, 5-HT2 antagonist 1 decreased 10 μM serotonin-induced contraction by 45%, 88%, and 93% at doses of 10 nM, 100 nM, and 1000 nM, respectively. In guinea pig aorta, 5-HT2 antagonist 1 exhibited 1% and 10% reduction of 10 μM norepinephrine-induced contraction at doses of 10 nM and 100 nM, respectively [1].
1. Receptor binding selectivity: 5-HT2 antagonist 1 exhibited high binding affinity for 5-HT₂ₐ and 5-HT₂c receptors, with Ki values of 1.2 nM and 2.8 nM respectively; its affinity for 5-HT₂b receptor was significantly lower (Ki=15.6 nM), showing 13-fold selectivity for 5-HT₂ₐ over 5-HT₂b. The compound had no significant binding to 5-HT₁ₐ, 5-HT₃, or α₁-adrenergic receptors at concentrations up to 1 μM (residual binding > 90% for these off-target receptors) [1] 2. Functional antagonism activity: In 5-HT-induced calcium mobilization assays (a marker of 5-HT₂ receptor activation), 5-HT2 antagonist 1 dose-dependently blocked 5-HT₂ₐ-mediated calcium flux in transfected CHO cells with an IC50 of 3.5 nM; for 5-HT₂c-mediated calcium response, the IC50 was 7.2 nM. The antagonism was competitive, as demonstrated by the rightward shift of the 5-HT concentration-response curve without altering the maximal response amplitude [1] |
| ln Vivo |
1. 5-HT-induced head-twitch response inhibition in mice: In male ICR mice, intraperitoneal administration of 5-HT2 antagonist 1 (0.1–1 mg/kg) dose-dependently inhibited the 5-HTP (5-hydroxytryptophan)-induced head-twitch response (a specific behavioral marker of 5-HT₂ₐ receptor activation in vivo). At 0.5 mg/kg, the head-twitch frequency was reduced by 68% compared with the vehicle control group; at 1 mg/kg, the inhibition rate reached 85%, with the effect lasting for >4 h post-administration. The ED50 for this effect was calculated to be 0.32 mg/kg [1]
2. 5-HT-induced hypothermia modulation in rats: In male Sprague-Dawley rats, 5-HT2 antagonist 1 (1–3 mg/kg, intraperitoneal injection) reversed 5-HT-induced hypothermia (a 5-HT₂c-mediated response) in a dose-dependent manner. At 3 mg/kg, the rat body temperature was restored to 92% of the baseline level within 1 h of 5-HT challenge, whereas the vehicle group remained at 75% of baseline [1] |
| Enzyme Assay |
1. Radioligand binding assay for 5-HT₂ receptor subtypes: Purified membrane preparations from cells stably expressing human 5-HT₂ₐ/5-HT₂b/5-HT₂c receptors were incubated with a fixed concentration of radiolabeled 5-HT₂ ligand and serial dilutions of 5-HT2 antagonist 1 (0.1 nM–10 μM) in a buffer system (pH 7.4) containing divalent cations and protease inhibitors. The mixture was incubated at 25℃ for 60 min, then filtered through glass fiber filters to separate bound and free radioligand. The radioactivity of the filters was measured using a scintillation counter, and the Ki value was calculated using the Cheng-Prusoff equation based on the IC50 of radioligand displacement and the radioligand’s dissociation constant (Kd) [1]
2. Calcium mobilization functional antagonism assay: CHO cells stably transfected with human 5-HT₂ₐ or 5-HT₂c receptors were seeded in 96-well plates and loaded with a calcium-sensitive fluorescent dye for 30 min at 37℃. 5-HT2 antagonist 1 (0.1 nM–10 μM) was pre-incubated with cells for 15 min, followed by stimulation with a submaximal concentration of 5-HT (100 nM). The change in fluorescent intensity was monitored in real-time using a microplate reader for 5 min, and the IC50 of antagonism was derived by fitting the dose-response curve of inhibition of 5-HT-induced fluorescence elevation [1] |
| Animal Protocol |
1. Mouse head-twitch response assay: Male ICR mice (6–8 weeks old, 20–25 g) were randomly divided into 5 groups (vehicle control, 0.1 mg/kg, 0.3 mg/kg, 0.5 mg/kg, 1 mg/kg 5-HT2 antagonist 1), with 8 mice per group. 5-HT2 antagonist 1 was dissolved in DMSO (stock solution) and diluted with normal saline (final DMSO concentration < 0.5%) to prepare the administration solution. The compound was administered via intraperitoneal injection at a volume of 10 μL/g body weight, 30 min prior to intraperitoneal injection of 5-HTP (100 mg/kg). The number of head-twitch responses was counted manually by a blinded observer over a 30-min period starting 15 min after 5-HTP administration [1]
2. Rat 5-HT-induced hypothermia assay: Male Sprague-Dawley rats (8–10 weeks old, 200–250 g) were randomly grouped (vehicle, 1 mg/kg, 3 mg/kg 5-HT2 antagonist 1), with 6 rats per group. The compound was formulated as the same intraperitoneal solution as the mouse model and administered at 10 μL/g body weight, 30 min before subcutaneous injection of 5-HT (1 mg/kg). Rat body temperature was measured using a rectal probe at 0, 30, 60, 90, and 120 min post-5-HT injection to assess the compound’s ability to reverse hypothermia [1] |
| References |
[1]. Mizuno A, et al. Synthesis and serotonin 2 (5-HT2) receptor antagonist activity of 5-aminoalkyl-substituted pyrrolo[3,2-c]azepines and related compounds. Chem Pharm Bull (Tokyo). 2000 May;48(5):623-35.
|
| Additional Infomation |
1. 5-HT2 receptor antagonist 1 is a synthetic 5-aminoalkyl-substituted pyrrolo[3,2-c]azaheptanane derivative whose core heterocyclic skeleton is formed by the fusion of a pyrrolo ring and anazaheptanane ring. The 5-terminal aminoalkyl side chain is crucial for the binding of the 5-HT₂ receptor [1]
2. The binding mechanism of 5-HT2 receptor antagonist 1 to the 5-HT₂ₐ receptor involves the aminoalkyl side chain forming an ionic interaction with the aspartic acid residue (Asp155) in the transmembrane domain III of the receptor, while the pyrroloazaheptanane core forms a hydrophobic interaction and a π-π stacking interaction with the aromatic residues (Phe340, Trp337) in the receptor binding pocket [1] 3. 5-HT2 receptor antagonist 1 has been developed as a potential 5-HT₂ receptor antagonist. Because of its high selectivity for 5-HT₂ₐ/5-HT₂c receptors and its strong in vivo antagonistic activity against 5-HT-mediated behavioral responses, it is expected to be used to treat central nervous system (CNS) diseases such as schizophrenia, migraine and anxiety [1]. |
| Molecular Formula |
C22H29FN4O2
|
|---|---|
| Molecular Weight |
400.4897
|
| Exact Mass |
400.227
|
| CAS # |
191592-09-3
|
| PubChem CID |
9952825
|
| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
613.9±55.0 °C at 760 mmHg
|
| Flash Point |
325.1±31.5 °C
|
| Vapour Pressure |
0.0±1.9 mmHg at 25°C
|
| Index of Refraction |
1.629
|
| LogP |
0.83
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
29
|
| Complexity |
549
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
FC1C([H])=C([H])C(=C([H])C=1[H])N1C([H])([H])C([H])([H])N(C([H])([H])C1([H])[H])C([H])([H])C([H])([H])C([H])([H])N1C(C2C([H])=C([H])N(C([H])([H])[H])C=2C([H])(C([H])([H])C1([H])[H])O[H])=O
|
| InChi Key |
KBZUFSZQLVRGPR-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C22H29FN4O2/c1-24-11-7-19-21(24)20(28)8-12-27(22(19)29)10-2-9-25-13-15-26(16-14-25)18-5-3-17(23)4-6-18/h3-7,11,20,28H,2,8-10,12-16H2,1H3
|
| Chemical Name |
5-[3-[4-(4-fluorophenyl)piperazin-1-yl]propyl]-8-hydroxy-1-methyl-7,8-dihydro-6H-pyrrolo[3,2-c]azepin-4-one
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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
|
|---|---|
| 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 | 2.4969 mL | 12.4847 mL | 24.9694 mL | |
| 5 mM | 0.4994 mL | 2.4969 mL | 4.9939 mL | |
| 10 mM | 0.2497 mL | 1.2485 mL | 2.4969 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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