| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
β adrenergic receptor
(RS)-Butyryltimolol itself is not pharmacologically active; its target is the enzymes responsible for ester hydrolysis (e.g., esterases in the eye). Upon enzymatic cleavage of the butyryl ester group, the active metabolite timolol is released. Timolol is a non-selective beta-adrenergic receptor antagonist that blocks beta1 and beta2 adrenergic receptors, leading to reduced aqueous humor production and lowered intraocular pressure (IOP). |
|---|---|
| ln Vitro |
When it comes to improving ocular medication absorption, butyryltimolol, a prodrug of tipol, is just as effective as 240-min nasolacrimal blockade[1].
As a prodrug, (RS)-Butyryltimolol is designed to have enhanced corneal penetration compared to the parent drug timolol. In vitro studies demonstrate that butyryltimolol is hydrolyzed by esterases in ocular tissues to regenerate active timolol. The esterification improves the lipophilicity of the molecule, facilitating its diffusion across the corneal epithelium, a key barrier for ophthalmic drug absorption. |
| ln Vivo |
In vivo, (RS)-Butyryltimolol functions as an effective prodrug of timolol, improving corneal penetration and thus ocular bioavailability. After administration into the eye, butyryltimolol is rapidly hydrolyzed by tissue esterases to release timolol. The active timolol then exerts its pharmacological effect by blocking beta-adrenergic receptors in the ciliary body, reducing aqueous humor production and lowering intraocular pressure, making it useful for glaucoma research.
|
| Enzyme Assay |
Not applicable for the prodrug. For ester hydrolysis studies, a standard non-cellular protocol involves incubating (RS)-Butyryltimolol with purified esterases or ocular tissue homogenates (e.g., rabbit corneal or iris-ciliary body homogenates) in phosphate-buffered saline at 37degC. At various time points, aliquots are withdrawn, the reaction is stopped (e.g., with acetonitrile), and the formation of timolol is quantified by HPLC-UV or LC-MS to determine hydrolysis kinetics.
|
| Cell Assay |
Cell-based assays are not standard for prodrug characterization. However, the transcorneal permeability of (RS)-Butyryltimolol can be assessed using excised rabbit or porcine corneas mounted in a Franz diffusion cell apparatus. The prodrug is applied to the donor chamber, and samples are collected from the receptor chamber over time. Both intact prodrug and released timolol are quantified by HPLC to determine permeability coefficients and the rate of enzymatic conversion.
|
| Animal Protocol |
In an in vivo study for ophthalmic drug delivery, the prodrug is typically administered as a topical eye drop (e.g., 50-100 uL of a 0.1-1% solution) to rabbits. Intraocular pressure (IOP) is measured at baseline and at various time points (e.g., 0.5, 1, 2, 4, 6, 8 hours) post-administration using a tonometer. The reduction in IOP compared to vehicle-treated controls indicates successful prodrug conversion and beta-blockade activity.
|
| ADME/Pharmacokinetics |
No specific pharmacokinetic data for (RS)-Butyryltimolol is available in the provided references. As an ester prodrug, its key property is enhanced corneal permeability compared to timolol. Butyryltimolol is more lipophilic than timolol, which allows it to partition more readily into the corneal epithelium. Following corneal absorption, it is rapidly hydrolyzed to timolol, which then distributes to the ciliary body to exert its ocular hypotensive effect.
|
| Toxicity/Toxicokinetics |
No specific toxicological data is available for (RS)-Butyryltimolol. The safety profile of the active metabolite timolol is well-established; topical ocular administration of timolol can cause local irritation (stinging, burning), and systemic absorption can lead to cardiovascular and pulmonary adverse effects (bradycardia, hypotension, bronchospasm) due to beta-blockade. The prodrug strategy aims to reduce systemic exposure by improving local corneal absorption.
|
| References |
|
| Additional Infomation |
(RS)-Butyryltimolol is a research compound used as a reference standard for prodrug development in ophthalmology. Unlabeled timolol is a first-line therapy for open-angle glaucoma, but its low corneal permeability necessitates frequent dosing. The esterification prodrug strategy exemplified by butyryltimolol aims to enhance ocular bioavailability and reduce systemic side effects. The compound is useful for comparing hydrolysis kinetics, tissue distribution, and structure-activity relationships within timolol ester series and other beta-blocker analog libraries.
|
| Molecular Formula |
C17H30N4O4S
|
|---|---|
| Molecular Weight |
386.51
|
| Exact Mass |
386.198
|
| CAS # |
2320274-78-8
|
| Related CAS # |
Butyryltimolol;106351-79-5
|
| PubChem CID |
23276806
|
| Appearance |
Colorless to light yellow ointment
|
| Density |
1.169±0.06 g/cm3(Predicted)
|
| Boiling Point |
511.5±50.0 °C(Predicted)
|
| LogP |
3.2
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
11
|
| Heavy Atom Count |
26
|
| Complexity |
430
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
S1N=C(C(=N1)N1CCOCC1)OCC(CNC(C)(C)C)OC(CCC)=O
|
| InChi Key |
IGJCFKQCZRWRRM-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C17H30N4O4S/c1-5-6-14(22)25-13(11-18-17(2,3)4)12-24-16-15(19-26-20-16)21-7-9-23-10-8-21/h13,18H,5-12H2,1-4H3
|
| Chemical Name |
[1-(tert-butylamino)-3-[(4-morpholin-4-yl-1,2,5-thiadiazol-3-yl)oxy]propan-2-yl] butanoate
|
| 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) |
DMSO: ≥ 100 mg/mL (258.73 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (12.94 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 50.0 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: ≥ 5 mg/mL (12.94 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 50.0 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: ≥ 5 mg/mL (12.94 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 | 2.5873 mL | 12.9363 mL | 25.8726 mL | |
| 5 mM | 0.5175 mL | 2.5873 mL | 5.1745 mL | |
| 10 mM | 0.2587 mL | 1.2936 mL | 2.5873 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
