CIALIS;IC 351;
(6R,12AR)-6-(benzo[d][1,3]dioxol-5-yl)-2-methyl-2,3,12,12a-tetrahydropyrazino[1',2':1,6]pyrido;
GF 196960;ICOS 351;
Tildenafil;
UK 336017
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Tadalafil, with the molecular formula C22H19N3O4 and molecular weight 389.4, which has been widely used to treat erectile dysfunction in men since 2003 under the trade name Cialis. In 2008, Eli Lilly Company sold the commercial development rights for PAH treatment to United Therapeutics. In June 2009, the FDA approved Tadafil for the treatment of patients with pulmonary arterial hypertension (PAH) in the United States under the trade name Adcirca. Tadafil was developed in 2003 as a drug for treatment of ED, and the effect was effective 30min after administration, but the best effect was 2h after administration, and the effect could last for 36h, and the effect was not affected by food. The dosage of tadafil is 10 or 20mg, the recommended initial dose is 10mg, depending on the patient's reaction and adverse reactions. Pre-market studies showed that after 12 weeks of oral administration of 10 or 20mg of tadafil, the response rates were 67% and 81%, respectively. Many studies have shown that tadafil has better efficacy in treating ED.
Erectile dysfunction: Tadanafil and sildenafil belong to the same selective phosphodiesterase type 5 (PDE5), but their structure is different from that of the latter, and high-fat diet does not interfere with their absorption. Under sexual stimulation, nitric oxide synthase (NOS) in penile nerve endings and vascular endothelial cells catalyzes the synthesis of nitric oxide (NO) from the substrate L-arginine. NO activates the guanylate cyclase, which converts guanosine triphosphate to cyclic guanosine phosphate (cGMP), thereby activating cyclic guanosine phospho-dependent protein kinase, resulting in a decrease in intracellular calcium concentration of smooth muscle, resulting in relaxation of the smooth muscle of the penile sponge and erection. Phosphodiesterase type 5 (PDE5) degrades cGMP into inactive products, causing penile weakness. By inhibiting the degradation of PDE5, tardanafil leads to the accumulation of cGMP, which relaxes the smooth muscle of the corpus cavernosum of the penis and leads to penile erection. Since nitrate esters are NO donors, their combination with tadanafil can significantly increase cGMP level and lead to severe hypotension, therefore, clinical contraindications of both are contraindicated.
Tardanafil affects this by inhibiting PDES. GMP degradation, so when used in combination with nitric acid and vinegar may cause an extreme drop in blood pressure and increase the risk of syncope. CY3PA4 induction agent can reduce the abiotic availability of tadana, and the combination with rifampicin, cimetidine, erythromycin, clarithromycin, itraconwa, ketoconwa and HVI protease inhibitors may increase the blood concentration of this product. Attention should be paid to adjusting the dose. So far, there has been no report on the pharmacokinetic parameters of this product affected by diet and alcohol.
Using D-tryptophan as raw material, the first methyl ester reaction, the resulting D-tryptophan methyl ester hydrochloride in isopropyl alcohol and piperaldehyde Pictet-spengler reaction to get cis-tetra hydrocarboline compound, and then reaction with chloroacetyl chloride and methylamine, the total yield is 56%, after screening, Glacial acetic acid was further purified as a recrystallization solvent. The specific reaction equation is as follows:
Cialis is Tadalafil, an oral drug developed by Eli Lilly Pharmaceutical Company for the treatment of erectile dysfunction in men. It is a second-generation phosphodiesterase 5 inhibitor. Research reports show that compared with sildenafil, Cialis takes effect very quickly, about 15 to 20 minutes, and the effect lasts for up to 36 hours. T1/2 is 17.5 hours. In a study of 348 men with mild to severe erectile dysfunction who were randomized to take tadalafil 20mg or a placebo, both 24 and 36 hours after taking the drug improved sexual success compared to placebo, with most men successfully having sex twice at 36 hours. There was no difference in the incidence and severity of adverse drug reactions compared with placebo. More than 5% of men in the Tadalafil group had headaches and indigestion. [Adverse reactions] No serious adverse reactions were observed, such as flushing and visual abnormalities. Occasionally headache, dyspepsia. [Precautions] Patients who are taking nitrates, angina pectoris, heart disease, uncontrolled hypertension or hypotension, and patients who have had a stroke in the last 6 months should not be allowed.
Phosphodiesterase 5 inhibitors are used to treat erectile dysfunction in men. The second generation phosphodiesterase 5 inhibitors are used to treat to erectile dysfunction in men.
