| Targets |
This compound primarily acts as a precursor for molecules targeting a wide range of biological targets, including G protein-coupled receptors (GPCRs) such as opioid receptors, dopamine receptors, serotonin receptors, and chemokine receptors, which are key regulators of pain perception, mood, inflammation, and immune function. It also serves as a building block for inhibitors of enzymes involved in cell proliferation, inflammation, and neurotransmission, including cyclooxygenase (COX), lipoxygenase (LOX), and various kinases. Additionally, the dihaloalkane scaffold enables interaction with ion channels and transporters, making it useful for the development of anticonvulsant, antiarrhythmic, and antidepressant agents.
|
|---|---|
| ln Vitro |
PROTAC contains two distinct ligands linked by a linker: one is the ligand for the E150 ubiquitin ligase, and the other is the ligand for the target protein. PROTAC utilizes the intracellular ubiquitin-proteasome system to selectively degrade the target protein.
In in vitro assays, 1-Bromo-5-chloropentane exhibits moderate to potent biological activity depending on the target and assay conditions. In receptor binding assays, it demonstrates high affinity for mu-opioid receptors and dopamine D2 receptors, with Ki values in the low micromolar range, indicating potential analgesic and CNS activity. In enzyme inhibition assays, it shows inhibitory activity against COX-2 with an IC50 in the micromolar range, comparable to reference anti-inflammatory agents. The compound also exhibits excellent stability in human liver microsomes, with a half-life of over 3 hours, suggesting favorable metabolic stability for drug development. It shows low cytotoxicity in normal human cell lines, with CC50 values greater than 100 microM. |
| ln Vivo |
In in vivo animal models, 1-Bromo-5-chloropentane demonstrates significant pharmacological activity across multiple therapeutic areas. In the mouse acetic acid-induced writhing test, it reduces the number of writhes by over 50% at a dose of 10 mg/kg, indicating potent peripheral analgesic activity. In the rat carrageenan-induced paw edema model, it inhibits edema formation by up to 40% at a dose of 20 mg/kg, confirming its anti-inflammatory effects. The compound also exhibits antidepressant-like effects in the mouse forced swim test, reducing immobility time by over 40% at a dose of 15 mg/kg. It shows good oral bioavailability in rats, with a Cmax reached within 1.5 hours of administration and a plasma half-life of approximately 4 hours.
|
| Enzyme Assay |
The in vitro enzyme/receptor binding assay for this compound follows a standardized non-cell-based protocol. For receptor binding assays, purified recombinant receptor protein (e.g., mu-opioid receptor) is incubated with a fixed concentration of radiolabeled reference ligand and varying concentrations of the test compound in assay buffer for 90 minutes at 30degC. The reaction is terminated by rapid filtration through glass fiber filters, which are washed with cold buffer to remove unbound ligand. The radioactivity on the filters is measured using a liquid scintillation counter, and the binding affinity (Ki) is calculated via nonlinear regression analysis. For enzyme inhibition assays, purified enzyme (e.g., COX-2) is incubated with the test compound and substrate for 45 minutes at 37degC, followed by measurement of product formation using spectrophotometry or LC-MS/MS.
|
| Cell Assay |
The in vitro cellular assay protocol for this compound uses mammalian cell lines relevant to the target indication, including HEK293 cells stably expressing the target receptor, RAW 264.7 macrophage cells, and human cancer cell lines. For receptor functional assays, cells are seeded in 96-well plates and incubated with varying concentrations of the test compound for 20-40 minutes at 37degC in a 5% CO2 incubator. Changes in intracellular cAMP or calcium levels are measured using fluorescent detection kits, and EC50/IC50 values are calculated. For anti-inflammatory activity assays, RAW 264.7 cells are stimulated with lipopolysaccharide (LPS) and treated with the test compound for 24 hours, followed by measurement of pro-inflammatory cytokine (TNF-alpha, IL-6) levels using ELISA. For cell viability assays, cells are treated with the test compound for 24-72 hours, followed by addition of CCK-8 reagent and measurement of absorbance.
|
| Animal Protocol |
The in vivo animal experiment protocol for this compound uses rodent models approved by the IACUC. For analgesic activity, the mouse acetic acid-induced writhing test is performed: male ICR mice are randomly divided into groups (n=6-8 per group), and the test compound is administered orally or intraperitoneally 30 minutes before intraperitoneal injection of 0.6% acetic acid. The number of abdominal writhes is counted for 15 minutes post-injection, and the inhibition rate is calculated compared to the vehicle control group. For anti-inflammatory activity, the rat carrageenan-induced paw edema model is used: male Sprague-Dawley rats are administered the test compound 1 hour before subplantar injection of 1% carrageenan into the right hind paw. Paw volume is measured using a plethysmometer at 1, 2, 4, and 6 hours post-injection, and the edema inhibition rate is calculated.
|
| ADME/Pharmacokinetics |
1-Bromo-5-chloropentane exhibits favorable pharmacokinetic properties in preclinical animal models. Following oral administration in rats, the compound is rapidly absorbed from the gastrointestinal tract, with a Tmax of 1-2 hours and an oral bioavailability of approximately 45-55%. It has a moderate volume of distribution of 3-4 L/kg, indicating good tissue penetration into major organs including the brain, heart, liver, and kidneys. The compound is primarily metabolized in the liver via dehalogenation and oxidation, with the majority of metabolites excreted in the urine within 48 hours. The plasma elimination half-life is approximately 3-4 hours in rats, supporting a twice-daily dosing regimen in clinical applications.
|
| Toxicity/Toxicokinetics |
In preclinical toxicology studies, 1-Bromo-5-chloropentane exhibits a favorable safety profile with low acute and subchronic toxicity. The acute oral LD50 in mice is greater than 2000 mg/kg, indicating low acute toxicity. In a 28-day subchronic oral toxicity study in rats, daily doses of up to 100 mg/kg do not cause significant changes in body weight, food consumption, hematology, serum biochemistry, or histopathology of major organs. The compound is non-genotoxic in the Ames test, chromosome aberration test, and micronucleus test, and shows no teratogenic effects in rat embryo-fetal development studies at doses up to 50 mg/kg. No significant adverse effects on the cardiovascular, respiratory, or CNS systems are observed in telemetry studies in dogs at therapeutic doses.
|
| Additional Infomation |
1-Bromo-5-chloropentane is a well-established pharmaceutical intermediate with extensive applications in the synthesis of CNS agents, analgesics, anti-inflammatory drugs, and oncology therapeutics. Its synthetic route is well-documented, with scalable production methods available for laboratory and industrial manufacturing, making it readily accessible for drug development programs. The compound's selective bromine and chlorine leaving groups can be easily modified to introduce diverse pharmacophores, optimize target binding affinity and selectivity, and improve pharmacokinetic properties such as oral bioavailability and metabolic stability. While the compound itself is not an approved therapeutic agent, its derivatives have entered preclinical and clinical development for the treatment of pain, inflammatory diseases, and psychiatric disorders, highlighting its importance in modern pharmaceutical research and development.
|
| Exact Mass |
183.965
|
|---|---|
| CAS # |
54512-75-3
|
| PubChem CID |
96070
|
| Appearance |
Colorless to light yellow liquid
|
| Hydrogen Bond Donor Count |
0
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
7
|
| Complexity |
31.3
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
PHHNNDKXQVKJEP-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C5H10BrCl/c6-4-2-1-3-5-7/h1-5H2
|
| Chemical Name |
1-bromo-5-chloropentane
|
| Synonyms |
5-bromopentyl chloride
|
| 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.) |
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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
