ChemicalBook
Chinese Japanese Germany Korea

Tadalafil

Indications and uses Clinical Research Side effects Warnings and precautions
Tadalafil
Tadalafil structure
CAS No.
171596-29-5
Chemical Name:
Tadalafil
Synonyms
afiL;TadaL;Calai;IC 351;CIALIS;Calais;hyjskn;Adcirca;ICOS 351;TADALAFIL
CBNumber:
CB2236841
Molecular Formula:
C22H19N3O4
Formula Weight:
389.4
MOL File:
171596-29-5.mol

Tadalafil Properties

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)
Flash point:
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
InChIKey
WOXKDUGGOYFFRN-IIBYNOLFSA-N
CAS DataBase Reference
171596-29-5(CAS DataBase Reference)
FDA UNII
742SXX0ICT
NCI Dictionary of Cancer Terms
Cialis; tadalafil
NCI Drug Dictionary
Cialis
SAFETY
  • Risk and Safety Statements
Symbol(GHS) 
GHS02,GHS07
Signal word  Danger
Hazard statements  H225-H302+H312+H332-H319-H315-H335
Precautionary statements  P210-P261-P302+P352+P312-P304+P340+P312-P337+P313-P403+P235-P305+P351+P338
Hazard Codes  F,Xn
Risk Statements  11-20/21/22-36
Safety Statements  16-36/37
WGK Germany  3
RTECS  UQ4431050
HS Code  2934990002

Tadalafil price More Price(12)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich PHR1810 Tadalafil Pharmaceutical Secondary Standard; Certified Reference Material 171596-29-5 500mg $133 2021-03-22 Buy
Sigma-Aldrich T-072 Tadalafil solution 1.0?mg/mL in acetonitrile, ampule of 1?mL, certified reference material, Cerilliant? 171596-29-5 1 mL $145 2021-03-22 Buy
Sigma-Aldrich Y0001417 Tadalafil European Pharmacopoeia (EP) Reference Standard 171596-29-5 $190 2021-03-22 Buy
Sigma-Aldrich 1642879 Tadalafil United States Pharmacopeia (USP) Reference Standard 171596-29-5 200mg $492 2021-03-22 Buy
Cayman Chemical 14024 Tadalafil ≥98% 171596-29-5 10mg $35 2021-03-22 Buy

Tadalafil Chemical Properties,Uses,Production

Indications and uses

Cialis (or Tadalafil) was developed by American pharmaceutical company Lilly. It is used to treat erectile dysfunction and belongs to a second generation of PDE5 inhibitors. Studies show that Cialis works very quickly, taking effect in around 15-20 minutes, and has a prolonged effect that can last for up to 36 hours. T1/2 is 17.5h.

Clinical 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.

Side effects

No severe negative reactions. No perceived facial flushing or sight abnormalities following medication. Rare cases of headache and indigestion.

Warnings and 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.

Description

Tadalafil (market name “Cialis” or “Adcirca”) 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.

Chemical Properties

White to Off-White Cyrstalline Solid

Originator

Lilly/ICOS (US)

Uses

analgesic, norepinephrine uptake blocker, mu-opiod receptor agonist.A phosphodiesterase 5 inhibitor.Tadalafil is used for the treatment of erectile dysfunction.

Definition

ChEBI: 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

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 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. 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. Tadalafil is a potent and highly selective inhibitor of PDE5 (IC50=1 nm). It shows >10,000-fold selectivity for PDE5 versus PDE1, 2, 3, 4, 7, 8 and 9, and >700-fold selectivity versus PDE6. Typically administered at 10 and 20 mg doses, tadalafil is rapidly absorbed and has a tmax of 2 h, which is slightly longer than those of sildenafil (1 h) and vardenafil (0.75 h). Clinically, all of these agents appear to have efficacy for many men within 30–60 min. However, tadalafil distinguishes itself from other PDE5 inhibitors in terms of significantly longer duration of action. The half-life of tadalafil dosed at 20 mg is 17.5 h as compared with 3.8 h for sildenafil (100 mg) and 4.7 h for vardenafil (20 mg). In clinical studies, significant rates of response were reported up to 36 h following drug ingestion. Tadalafil is predominantly metabolized in the liver by CYP3A4 to entities that are not active against PDE5 and excreted mainly as metabolites in the feces and the urine. The pharmacokinetics of tadalafil are unaffected by factors such as intake of food and alcohol, age, the presence of diabetes, and mild or moderate hepatic insufficiency. 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. Tadalafil has a modest synergistic effect on the nitrate-induced reduction in blood pressure and, as with sildenafil and vardenafil, it is contraindicated for use in patients on nitrate therapy. In diabetic patients, improvement of erectile function by tadalafil is irrespective of the type of diabetes and the type of diabetic therapy.

Side effects

Adverse effects related to oral therapy for erectile function are primarily concerned with adverse cardiovascular effects, because PDE5 inhibitors promote vasodilation and, therefore, have an inherent potential to cause hypotension. This is a particular concern for elderly patients with a preexisting condition.

Chemical 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- β-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.

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.

Tadalafil Preparation Products And Raw materials

Raw materials

Preparation Products


Tadalafil Suppliers

Global( 595)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
Hubei XinRunde Chemical Co., Ltd.
+8615102730682
02783214688 bruce@xrdchem.cn CHINA 567 55
Xi'an Kono chem co., Ltd.,
13289246953 029-86107037
info@konochemical.com CHINA 3000 58
Shaanxi Yikanglong Biotechnology Co., Ltd.
17791478691
yklbiotech@163.com CHINA 297 58
Hebei Jimi Trading Co., Ltd.
+86 319 5273535
bestoneforyou@sina.com CHINA 292 58
Cangzhou Wanyou New Material Technology Co.,Ltd
18631714998
sales@czwytech.com CHINA 914 58
hdzhl biotechnology co., ltd
86-13032617415
sales@luchibiology.com CHINA 1275 58
Shanghai Worldyang Chemical Co.,Ltd.
+86-13651600618
CHINA 832 58
Jinan Gongchuang Pharmaceutical Technology Co., Ltd.
13287783460
3166282224@qq.com CHINA 10 58
Shanghai Longyu Biotechnology Co., Ltd.
+8615821988213
info@longyupharma.com CHINA 2462 58
Jurong Coupling Biotechnology Co., Ltd.
13656108824
coupling278191416@hotmail.com CHINA 184 58

Related articles


View Lastest Price from Tadalafil manufacturers

Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
2021-10-21 Tadalafil
171596-29-5
US $30.00 / g 1000g 99% 20ton/month Wuhan Aoliqisi New Material Technology Co., Ltd.
2021-10-21 Tadalafil
171596-29-5
US $70.00 / KG 100g 99% 10000kg Hanhong Medicine Technology (Hubei) Co., Ltd.
2021-10-20 Tadalafil
171596-29-5
US $380.00 / KG 1KG 99% 9000kg/per week Hebei Lingding Biological Technology Co., Ltd

171596-29-5(Tadalafil)Related Search:


Copyright 2017 © ChemicalBook. All rights reserved