| Identification | More | [Name]
Cialis | [CAS]
171596-29-5 | [Synonyms]
(6r,12ar)-6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methyl-pyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
CIALIS
IC 351
TADALAFIL
TADALAFIL(CIALIS)
Taladafil (cialis)
Cialis/taladafil
Cialis(IC351)
Tadanafil
TADALAFIL 99 %
TADALAFIL (CIALIS,USP)
CIALIS/TADALAFIL
(6R,12aR)-6-(1,3-Benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methyl-pyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
Tadalafei
GF 196960
ICOS 351
Tildenafil
UK 336017 | [EINECS(EC#)]
687-782-2 | [Molecular Formula]
C22H19N3O4 | [MDL Number]
MFCD07771966 | [Molecular Weight]
389.4 | [MOL File]
171596-29-5.mol |
| Chemical Properties | Back Directory | [Appearance]
White to Off-White Cyrstalline Solid | [Melting point ]
298-300°C | [alpha ]
D20 +71.0° | [Boiling point ]
679.1±55.0 °C(Predicted) | [density ]
1.51±0.1 g/cm3(Predicted) | [Fp ]
2℃ | [storage temp. ]
Sealed in dry,2-8°C | [solubility ]
DMSO: soluble20mg/mL, clear | [form ]
powder | [pka]
16.68±0.40(Predicted) | [color ]
white to beige | [optical activity]
[α]/D +68 to +78°, c = 1 in chloroform-d | [Usage]
Used for the treatment of erectile dysfunction. A phosphodiesterase 5 inhibitor | [BCS Class]
4 | [Stability:]
Unstable in Methanol | [InChI]
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 | [InChIKey]
WOXKDUGGOYFFRN-IIBYNOLFSA-N | [SMILES]
N1C2=C(C=CC=C2)C2C[C@]3([H])C(=O)N(C)CC(=O)N3[C@H](C3=CC=C4OCOC4=C3)C1=2 | [CAS DataBase Reference]
171596-29-5(CAS DataBase Reference) |
| Questions and Answers (Q&A) | Back Directory | [Description]
Tadalafil (market name “Cialis” or “Adcirca” or 171596-29-5) is a kind of PDE5 inhibitor used for the treatment of erectile dysfunction, benign prostatic hypertrophy and pulmonary arterial hypertension. The effect of Tadalafil is relaxing the blood vessels muscles and increasing the blood flow into the corpus cavernosum. The mechanism of action of tadalafil is through inhibiting the activity of the cGMP specific phosphodiesterase type 5 (PDE5). PDE5 degrades cGMP in the corpus cavernosum located around the penis. Therefore, tadalafi leads to the increased concentration of cGMP which further causes the smooth muscle relaxation and increased blood flow into the corpus cavernosum. Some clinical studies also implied that tadalafil could improve endothelia function in men with increased cardiovascular risk and lower the urinary tract symptoms secondary to benign prostatic hyperplasia.
| [References]
https://www.drugs.com/tadalafil.html
https://www.drugbank.ca/drugs/DB00820
Roehrborn, C. G., et al. "Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a dose finding study." Journal of Urology 180.4(2008):1228.
Rosano, Giuseppe M. C., et al. "Chronic Treatment with Tadalafil Improves Endothelial Function in Men with Increased Cardiovascular Risk." European Urology 47.2(2005):214-222.
|
| Hazard Information | Back Directory | [Chemical Properties]
White to Off-White Cyrstalline Solid | [Originator]
Lilly/ICOS (US) | [Uses]
Tadalafil is used for the treatment of erectile dysfunction. A phosphodiesterase 5 inhibitor. | [Definition]
ChEBI: Tadalafil(171596-29-5) is a pyrazinopyridoindole that is 2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione substituted at position 2 by a methyl group and at position 6 by a 1,3-benzodioxol-5-yl group (the 6R,12aR-diastereomer). A phosphodiesterase V inhibitor inhibitor, currently marketed in pill form for treating erectile dysfunction under the name Cialis; and under the name Adcirca for the treatment of pulmonary arterial hypertension. It has a role as an EC 3.1.4.35 (3',5'-cyclic-GMP phosphodiesterase) inhibitor and a vasodilator agent. It is a pyrazinopyridoindole and a member of benzodioxoles. | [Preparation]
Tadalafil is synthesized in three steps starting from D-tryptophan methyl ester, by first condensing with piperonal in a Pictet-Spengler cyclization reaction to form the tetrahydro-β-carboline derivative, which is followed by chloroacetylation of the piperidine ring nitrogen and cyclization with methylamine. | [Brand name]
Cialis (Lilly). | [General Description]
Tadalafil, (6R-trans)-6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methyl-pyrazino[1＇, 2＇ :1,6]pyrido[3,4-b]indole-1,4-dione (Cialis), is a potent PDE5 inhibitor.It received FDA approval for the treatment of erectiledysfunction in December 2003. Because of its half-life of17.5 hours, it is marketed as a 36-hour treatment. Tadalafil ispredominantly metabolized by hepatic enzymes, includingCYP3A4. The concomitant use of CYP3A4 inhibitors suchas ritonavir, indinavir, ketoconazole, as well as moderateCYP3A inhibitors such as erythromycin have been shown toresult in significant increases in tadalafil plasma levels.Much like sildenafil, tadalafil is under clinical investigationfor managing PAH. | [Mechanism of action]
Tadalafil was the last agent to be released and can be taken on a full stomach without slowing the onset. It has a much longer duration of action, lasting up to 48 hours, compared with sildenafil and vardenafil, which last for approximately 4 hours. The longer half-life of tadalafil results in a lengthened period of responsiveness as compared to sildenafil and vardenafil. This longer therapeutic window requires fewer time constraints for the effectiveness of tadalafil and has been interpreted as being advantageous through providing the option for more spontaneous sexual activity. Because of its long half-life, however, tadalafil, has been detected in plasma even 5 days after oral administration. This suggests the possibility of accumulation if taken regularly and in short intervals, which may result in an increased risk of side effects with the excessive use of this PDE5 inhibitor. The 3,4-methylenedioxy substitution on the phenyl ring was significant for increasing its potency as PDE5 inhibitor. Optimization of the chain on the piperazinedione ring resulted in no significant change in IC50s. Tadalafil is a highly potent PDE5 inhibitor (IC50, 5 nM), with high selectivity for PDE5 versus PDE1 through PDE4. The PDE5/PDE6 selectivity ratio is 85. | [Pharmacokinetics]
Tadalafil is different in structure from both sildenafil and vardenafil. It is rapidly absorbed and peaks in concentration (378 μg/L after a
20-mg dose) after 2 hours, displaying a long half-life of 17.5 hours. It also is metabolized by the liver (CYP3A4). Notably, its
pharmacokinetics is not clinically influenced by alcohol or food intake or by factors such as diabetes or impaired hepatic or renal
function. | [Clinical Use]
Tadalafil(171596-29-5) is one of the two new PDE5 inhibitors launched for the oral treatment of male erectile dysfunction. Tadalafil is a b-carboline derivative and it is structurally distinct from vardenafil (Levitraw) and sildenafil (Viagraw), both of which are PDE5 inhibitors based on a fused pyrimidine core structure. | [Side effects]
The most common drug-related adverse events are headache, back pain, dyspepsia, and myalgia. At 10 and 20 mg doses, Tadalafil does not have a significant effect on blood pressure and heart rate and does not result in increased instances of myocardial infarction. Rare reports of prolonged erections greater than 4 h and priapism have been noted with the use of tadalafil. Priapism, if not treated properly, can result in irreversible damage to the erectile tissue. Patients who have an erection lasting greater than 4 h are advised to seek emergency medical attention. | [Synthesis]
D-(-)-Tryptophan methyl ester (175) and 1,3-
benzodioxole-5-carboxaldehyde (176) were subjected to a
modified Pictet-Spengler reaction to form cis- and transtetrahydro-
|?-carboline tricyclic compounds. The ciscompound
177 was isolated as a white solid in 42% yield.
The basic nitrogen in the piperidine ring of 177 was acylated
with chloroacetyl chloride (179) to give compound 180 in
93% yield. Finally, the diketonepiperazine ring was formed
by adding 180 to 33% methylamine in ethanol under
refluxing conditions and yielded tadalafil (XXII) in 77% as
a white solid.
| [Drug interactions]
Potentially hazardous interactions with other drugs
Alpha-blockers: enhanced hypotensive effect - avoid
concomitant use.
Antibacterials: concentration possibly increased by
clarithromycin and erythromycin; concentration
reduced by rifampicin - avoid.
Antifungals: concentration increased by ketoconazole
- avoid; concentration possibly increased by
itraconazole.
Antivirals: concentration possibly increased by
fosamprenavir and indinavir; increased by ritonavir -
avoid; increased risk of ventricular arrhythmias with
saquinavir - avoid; avoid high doses of tadalafil with
telaprevir.
Cobicistat: concentration of tadalafil possibly
increased - reduce dose of tadalafil.
Nicorandil: possibly enhanced hypotensive effect -
avoid concomitant use.
Nitrates: enhanced hypotensive effect - avoid
concomitant use.
Riociguat: enhanced hypotensive effect - avoid
concomitant use. | [Metabolism]
Tadalafil is metabolised in the liver mainly by the cytochrome
P450 isoenzyme CYP3A4. The major metabolite, the
methylcatechol glucuronide, is inactive. Tadalafil is excreted,
mainly as metabolites, in the faeces (61% of the dose), and to
a lesser extent the urine (36% of the dose). | [storage]
Store at -20°C | [Clinical claims and research]
In a study of 348 cases of mild to severe erectile dysfunction, patients were randomly given 20mg of Cialis or a placebo. Results showed that in comparison to the placebo group, patients who took Cialis experienced improved intercourse success in the 24-36 hours following medication, with many patients achieving successful sexual intercourse twice in 36 hours. Side effect rate and severity were also no different from those of the placebo group. Over 5% of patients in the Cialis group experienced headaches and indigestion. | [Precautions]
Patients currently taking nitrates, experiencing angina pectoris, suffering from heart disease, patients who have unregulated hypertension or hypotension, or patients who have had a stroke in the past 6 months should not take Cialis. |
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