| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
| Targets |
PDE5
cis-ent-Tadalafil is a potent and selective inhibitor of phosphodiesterase 5 (PDE5), with an IC₅₀ of 5 nM. As an impurity standard, it is used to identify and quantify this specific stereoisomer in tadalafil drug substance and finished products. Its mechanism of action involves the inhibition of PDE5, leading to vasodilation and reduced blood pressure. |
|---|---|
| ln Vitro |
In vitro, cis-ent-Tadalafil acts as a potent PDE5 inhibitor. Its activity is characterized by its ability to bind to the catalytic site of the PDE5 enzyme, preventing the hydrolysis of cyclic GMP. This leads to an accumulation of cGMP and subsequent vasodilation. It is used in research to differentiate the pharmacological effects of the active tadalafil enantiomer from its inactive isomers.
|
| ln Vivo |
In vivo, cis-ent-Tadalafil, as an isomer of tadalafil, is expected to exhibit PDE5 inhibitory activity and hypotensive effects. It may be present as an impurity in tadalafil formulations and could contribute to or interfere with the therapeutic effects of the drug. Its specific in vivo pharmacokinetic and pharmacodynamic profile is not as well-characterized as the parent drug.
|
| Enzyme Assay |
In vitro enzyme assays for PDE5 inhibition typically involve incubating cis-ent-Tadalafil with the PDE5 enzyme and a substrate such as cGMP in a buffer solution. The enzymatic activity is measured by quantifying the amount of hydrolyzed product (GMP) using radiometric or fluorescence-based methods. IC₅₀ values, such as the reported 5 nM for this compound, are determined from dose-response curves.
|
| Cell Assay |
For in vitro cell assays, cis-ent-Tadalafil is evaluated for its effects on cell lines expressing PDE5. Cells are treated with the compound, and the accumulation of intracellular cGMP is measured by ELISA or LC-MS. The compound's potency is compared to that of the active tadalafil enantiomer to assess its potential biological activity and toxicological profile as an impurity.
|
| Animal Protocol |
For in vivo animal studies, cis-ent-Tadalafil may be administered to rodents to study its pharmacokinetics and pharmacodynamics. Blood pressure is monitored to assess its vasodilatory effects. The compound's distribution, metabolism, and excretion are studied to understand its behavior as an impurity in pharmaceutical formulations. It may also be used in toxicology studies.
|
| ADME/Pharmacokinetics |
cis-ent-Tadalafil has a molecular weight of 389.4 and a molecular formula of C₂₂H₁₉N₃O₄. It is typically a white solid. The compound is stable under recommended storage conditions and is used as a neat reference standard for HPLC and LC-MS methods. It is soluble in DMSO and other organic solvents.
|
| Toxicity/Toxicokinetics |
cis-ent-Tadalafil is for research use only. No specific toxicity data are available for this compound. As an impurity standard, its toxicological profile is assessed in the context of pharmaceutical quality control to ensure patient safety. Standard laboratory safety precautions should be followed when handling this compound.
|
| References | |
| Additional Infomation |
Modification of the hydantoin ring in the previously described lead compound 2a led to the discovery of compound 12a, tadalafil, a highly potent and selective PDE5 inhibitor. Substituting the hydantoin ring in compound 2a with a piperazine dione ring yielded compound cis-11a, which exhibits similar PDE5 inhibitory activity to 2a. Introducing a 3,4-methylenedioxy group at the 6-position of the benzene ring resulted in cis-11c, a highly potent PDE5 inhibitor with enhanced cellular activity. Chain optimization on the piperazine dione ring identified the racemic cis-N-methyl derivative 11i. The piperazine dione series of compounds exhibits high diastereoselectivity for PDE5 inhibition, with the cis-(6R,12aR) enantiomer showing the highest PDE5 inhibitory activity. Piperazine dione compound 12a, namely tadalafil (GF196960), has been proven to be a highly potent PDE5 inhibitor (IC50 = 5 nM), with a much higher selectivity for PDE5 than for PDE1-4 and PDE6. Compound 12a has an 85-fold higher selectivity for PDE6 than sildenafil. In a spontaneously hypertensive rat model, oral administration of 12a (5 mg/kg) resulted in a significant and sustained decrease in blood pressure (30 mmHg/>7 h).
cis-ent-Tadalafil (CAS# 171596-28-4) is a designated European Pharmacopoeia (EP) impurity of the PDE5 inhibitor tadalafil. It has not been approved as a therapeutic agent. The compound is used as a reference standard in pharmaceutical quality control for impurity profiling and chiral analysis of tadalafil formulations. It is also known as Tadalafil EP Impurity C. |
| Molecular Formula |
C22H19N3O4
|
|---|---|
| Molecular Weight |
389.40
|
| Exact Mass |
389.138
|
| Elemental Analysis |
C, 67.86; H, 4.92; N, 10.79; O, 16.43
|
| CAS # |
171596-28-4
|
| Related CAS # |
Nortadalafil;171596-36-4;Tadalafil;171596-29-5;cis-Tadalafil;171596-27-3;ent-Tadalafil;629652-72-8
|
| PubChem CID |
9865139
|
| Appearance |
White to off-white solid powder
|
| Density |
1.51±0.1 g/cm3 (20 ºC 760 Torr)
|
| Melting Point |
290-292 ºC
|
| LogP |
2.087
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
29
|
| Complexity |
702
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
CN1CC(=O)N2[C@@H](C1=O)CC3=C([C@@H]2C4=CC5=C(C=C4)OCO5)NC6=CC=CC=C36
|
| InChi Key |
WOXKDUGGOYFFRN-IERDGZPVSA-N
|
| InChi Code |
InChI=1S/C22H19N3O4/c1-24-10-19(26)25-16(22(24)27)9-14-13-4-2-3-5-15(13)23-20(14)21(25)12-6-7-17-18(8-12)29-11-28-17/h2-8,16,21,23H,9-11H2,1H3/t16-,21+/m1/s1
|
| Chemical Name |
(2S,8R)-2-(1,3-benzodioxol-5-yl)-6-methyl-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraene-4,7-dione
|
| Synonyms |
cis-ent-Tadalafil; 171596-28-4; cis-Tadalafil; Tadalafil, (6S ,12aR)-; (6S,12aR)-6-(Benzo[d][1,3]dioxol-5-yl)-2-methyl-2,3,12,12a-tetrahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4(6H,7H)-dione; Tadalafil 6S ,12ar diastereomer; (+)-Tadalafil 6S ,12ar diastereomer; MGY23Z94HY;
|
| 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 | 2.5681 mL | 12.8403 mL | 25.6805 mL | |
| 5 mM | 0.5136 mL | 2.5681 mL | 5.1361 mL | |
| 10 mM | 0.2568 mL | 1.2840 mL | 2.5681 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
