KR20040071117A - Sildenafil maleate - Google Patents

Sildenafil maleate Download PDF

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KR20040071117A
KR20040071117A KR10-2004-7003315A KR20047003315A KR20040071117A KR 20040071117 A KR20040071117 A KR 20040071117A KR 20047003315 A KR20047003315 A KR 20047003315A KR 20040071117 A KR20040071117 A KR 20040071117A
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methyl
ylsulfonyl
methylpiperazin
ethoxy
propyl
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델발레마누엘
라노라파엘
라노에두아르도
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팔라시오 바베란 존 루이스
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications

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Abstract

본 발명의 남성의 성기능 장애를 치료하기 위한 새로운 화합물로서, 높은 조직적 혈관확장 활동력을 가진 실데나필 말리에이트의 새로운 조제법에 관한 것이다.A novel compound for treating sexual dysfunction in men of the present invention relates to a new preparation of sildenafil maleate with high systemic vasodilation activity.

Description

실데나필 말리에이트{SILDENAFIL MALEATE}Sildenafil Maleate {SILDENAFIL MALEATE}

유럽특허 EP-A-046375 및 EP-A-0812845에는 화학식(1)의 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d] 피리미디나-7-오나 조제법이 기술되어 있다. 이 화합물은 높은 조직적 혈관확장 활동력을 가지고 있다. 단, 상기 화합물은 혈관조직에 있는 NO의 과다로 인해 심장에 심각한 문제가 발생되는 등의 부작용이 있었다.EP-A-046375 and EP-A-0812845 disclose 5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3 of formula (1). A preparation method for -n-propyl-1,6-dihydro-7H-pyrazolo [4,3-d] pyrimidina-7-ona is described. This compound has high systemic vasodilation activity. However, the compound had side effects such as serious problems in the heart due to the excess of NO in the vascular tissue.

본 발명은 남성의 성기능 장애를 치료하기 위한 약학적 화합물 및 그 조제법에 관한 것이다.The present invention relates to pharmaceutical compounds and their preparation for treating sexual dysfunction in men.

도 1은, 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d] 피리미디나-7-오나를 나타낸 것이다.1 is 5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-dihydro-7H-pyra Solo [4,3-d] pyrimidin-7-one.

도 2는, 사과산 C4H4O4 나타낸 것이다.2 shows malic acid C4H4O4.

도 3은, 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d] 피리미디나-7-오나 말리에이트를 나타낸 것이다.Figure 3 is 5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-dihydro-7H-pyra Solo [4,3-d] pyrimidina-7-one or maleate.

본 발명은, 상기와 같은 문제점을 해결하기 위하여, 약품 제조에 특별히 유용한 화합물을 만든 것으로, 중독효과를 덜 나타내고 약효시간을 증대시킨다. 본 발명의 대상으로는 화학식Ⅰ의 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d] 피리미디나-7-오나 말리에이트 화합물이 있다.The present invention, in order to solve the above problems, to make a compound that is particularly useful for the manufacture of drugs, less toxic effect and increase the drug time. Subject of the invention are 5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-di of Formula I Hydro-7H-pyrazolo [4,3-d] pyrimidina-7-one or maleate compounds.

음경 발기의 심리적 메카니즘은 성적자극을 하는 동안 해면체에 산화질소 (NO)를 송출시킨다. 그러면 질산(NA)은 구아닐고리화 효소를 활동시키게 되고 고리화 구아노신일 인산의 수준이 증가되며 해면체에 부드러운 이완이 생기게 한다. 이로써 혈류가 가능해지고 해면체에 고리화 구아노신일 인산의 저하를 일으키는 포스포디에스테아라사 5형의 억제로 산화질소 효과가 증대된다.The psychological mechanism of penile erection releases nitric oxide (NO) to the cavernous body during sexual stimulation. The nitric acid (NA) then activates the guanylcyclic enzyme, increases the level of cyclized guanosynyl phosphate and causes gentle relaxation in the cavernous body. As a result, the nitric oxide effect is enhanced by the inhibition of phosphodiesterarasa type 5, which enables blood flow and lowers cyclized guanosynyl phosphate in the cavernous body.

성적자극이 산화질소를 발생시킬 때 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d] 피리미디나-7-오나에 의한 포스포디에스테아라사 5형의 억제는 해면체 내에 고리화 구아노신일 인산을 증가시킨다. 이로써 부드러운 근육이완이 생기고 해면체에 혈류가 발생한다. 적정 복용량의 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d] 피리미디나-7-오나는 성적자극이 없는 경우에는 효과가 없다.5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-di when sexual stimulation causes nitric oxide Inhibition of phosphodiesterarasa type 5 by hydro-7H-pyrazolo [4,3-d] pyrimidina-7-ona increases the cyclized guanosynyl phosphoric acid in the cavernous body. This results in smooth muscle relaxation and blood flow to the cavernous body. Appropriate dose of 5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo [4,3-d] pyrimidina-7-ona has no effect in the absence of sexual stimulation.

5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d] 피리미디나-7-오나 말리에이트의 분자 화학검사에서 그 분자량은 다른 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d]피리미디나-7-오나 염의 분자량보다 적게 관찰된다.5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo [4, 3-d] In the molecular chemistry of pyrimidina-7-ona maleate, the molecular weight differs from that of other 5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1- Less than the molecular weight of the methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo [4,3-d] pyrimidina-7-one salt is observed.

따라서 신속히 동화되어 속효성작용을 가져온다. 또한 사과산은 디카르복시산이므로 NO의 생성은 다른 산에 의한 생성보다 더 느리고 균일하다. 이로써 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d]피리미디나-7-오나의 분해시간이 느려지고 심각한 심혈관 사고 위험을 감소시킨다.Therefore, it is quickly assimilated and brings a quick-acting effect. In addition, since malic acid is a dicarboxylic acid, NO production is slower and more uniform than that produced by other acids. This gives 5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo [4 , 3-d] Pyrimidina-7-one slows down the degradation and reduces the risk of serious cardiovascular events.

상기에서 관찰된 바에 의하면 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d]피리미디나-7-오나 말리에이트는 독성이 덜한 것으로 보인다.As observed above, 5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-dihydro-7H Pyrazolo [4,3-d] pyrimidin-7-ona maleate appears to be less toxic.

또한 본 발명의 대상으로 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d]피리미디나-7-오나 말리에이트의 조제법이 있다. 이는 용해수 속의 사과산으로 화학식(1)의 화합물을 처리하여 상응하는 첨가염을 제공한다.Also subject to the invention 5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-dihydro-7H There is a preparation method of -pyrazolo [4,3-d] pyrimidina-7-one or maleate. This treats the compound of formula (1) with malic acid in dissolved water to give the corresponding addition salt.

수막에 나타나 있는 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d]피리미디나-7-오나 염기와 50% 나트륨 수산화물 첨가로 8.0－8.5에 맞춘 pH에 의한 것이다. 수막들은 분별깔때기에서 함께 흔들리며, 유기막은 흔들린 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d] 피리미디나-7-오나를 함유하고 있다. 제품은 건조상태로 증발시킴으로써 고립된다.5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-dihydro-7H-pyra as seen in the water film The pH is adjusted to 8.0-8.5 by addition of the solo [4,3-d] pyrimidina-7-ona base and 50% sodium hydroxide. The aqueous membranes are shaken together in the separatory funnel, and the organic membranes are shaken with 5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6 -Dihydro-7H-pyrazolo [4,3-d] pyrimidin-7-one. The product is isolated by evaporation to dryness.

본 발명은 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d] 피리미디나-7-오나 말리에이트 화합물에 관한 것으로 그 조제법은 다음과 같다.The present invention relates to 5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo It relates to a [4,3-d] pyrimidin-7-one or maleate compound, the preparation method of which is as follows.

1. 2리터 비커에 앞서 언급한 방법들 중 하나를 사용하여 얻은 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필 -1,6-디히드로-7H-피라졸로[4,3-d] 피리미디나-7-오나 474.6그램(1몰)을 넣는다. 그리고 700밀리리터(67.8%의 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d]피리미디나-7-오나 서스펜션)에 달할 때까지 물을 첨가한다.1. 5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n obtained using one of the aforementioned methods in a 2 liter beaker Add 474.6 grams (1 mole) of -propyl-1,6-dihydro-7H-pyrazolo [4,3-d] pyrimidin-7-one. And 700 milliliters (67.8% of 5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-dihydro- Water is added until 7H-pyrazolo [4,3-d] pyrimidina-7-ona suspension is reached.

2. 500 밀리리터 비커에 사과산(C4H4O4) 116.07그램(1몰)을 넣고 250밀리리터(46.3%의 사과산 용액)에 달할 때까지 물을 첨가한다. 분별깔때기에 사과산 용액을 넣는다. 용액의 온도는 섭씨 25－30도 사이로 유지한다.2. Add 116.07 grams (1 mole) of malic acid (C4H4O4) to a 500 milliliter beaker and add water until it reaches 250 milliliters (46.3% solution of malic acid). Add the malic acid solution to the separatory funnel. The temperature of the solution is kept between 25-30 degrees Celsius.

3. 섭씨 50－60도의 (1)단계에서 얻은 서스펜션에 열을 가하고 자석젓개로 열판을 이용해서 휘젓는다. 계속 휘저음으로써 서스펜션의 모든 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d] 피리미디나-7-오나가 사라질 때까지 (2)단계에서 얻은 용액이 분별깔때기에방울방울 떨어지게 한다.3. Heat the suspension obtained in step (1) of 50-60 degrees Celsius and stir with a hot plate with a magnetic spoon. Stirring continued to remove all 5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-dihydro- in the suspension. Allow the solution obtained in step (2) to drop onto the separatory funnel until 7H-pyrazolo [4,3-d] pyrimidin-7-ona is disappeared.

4. 앞서 얻은 용액은 섭씨 50－55도의 온도로 진공회전증발기에서 농축된다. 무게 590그램에 섭씨 150도 용해점을 가진 엷은 노란색의 고체가 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d] 피리미디나-7-오나 말리에이트이다.4. The previously obtained solution is concentrated in a vacuum evaporator to a temperature of 50-55 degrees Celsius. Pale yellow solid with a melting point of 150 degrees Celsius at 590 grams of 5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n- Propyl-1,6-dihydro-7H-pyrazolo [4,3-d] pyrimidin-7-one or maleate.

6.36그램의 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d] 피리미디나-7-오나는 에탄올 50밀리리터 속에서 용해된다. 40－45 DEG C. 사이의 이 용액에 에탄올에 있는 5밀리리터의 8.03 M 메틸라민을 주사기 펌프를 통해 점차적으로 첨가시키는데, 총체적 25밀리리터에서 더 잘 용해된다. 첨가는 약 12시간 행해진다. 반응에 뒤따르는 것은 TLC 70/30/1 v/v/v 톨루엔/메탄올/트리에틸라민에 의한 제품의 양상이다. 반응의 종결단계에 용해제는 제거되고 조혼합물은 100밀리리터의 1:1 v/v 85% 인산과 물 속에서 용해된다. 100밀리리터의 염화메틸을 첨가하고 1.5그램(0.01몰)의 요드나트륨을 흔들어 첨가한다. 고체는 용해되고 두 액상을 같이 힘차게 흔든다. 수상이 분리되고 염화메틸은 무수황산 마그네슘으로 건조된다. 하이드로요드 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d] 피리미디나-7-오나는 염화메틸에 있다. 10밀리리터의 메탄올을 첨가하고 50% 나트륨 수산화물을 첨가하여 하이드로요드를 중화시킨다. 요드나트륨과 물 흔적을 없애기 위해 용액을 여과시킨다. 정화된 증발제품이 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d] 피리미디나-7-오나이다.6.36 grams of 5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo [4,3-d] pyrimidin-7-one dissolves in 50 milliliters of ethanol. To this solution between 40-45 DEG C., 5 milliliters of 8.03 M methylamine in ethanol are added gradually through a syringe pump, better dissolved at a total volume of 25 milliliters. The addition is carried out for about 12 hours. Following the reaction is the aspect of the product with TLC 70/30/1 v / v / v toluene / methanol / triethylamine. At the end of the reaction, the solubilizer is removed and the crude mixture is dissolved in 100 milliliters of 1: 1 v / v 85% phosphoric acid and water. Add 100 milliliters of methyl chloride and shake 1.5 grams (0.01 mole) of sodium iodine. The solids dissolve and shake the two liquids vigorously together. The aqueous phase is separated and the methyl chloride is dried over anhydrous magnesium sulfate. Hydroiod 5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo [ 4,3-d] Pyrimidina-7-one is in methyl chloride. 10 milliliters of methanol is added and 50% sodium hydroxide is added to neutralize the hydroiod. The solution is filtered to remove traces of sodium iodine and water. The purified evaporated product was 5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-dihydro-7H- Pyrazolo [4,3-d] pyrimidin-7-ona.

예 A에서 얻은 반응 혼합물은 반응의 종결 후 20－25 DEG C.로 열을 가하고, 에탄올에 있는 4.0밀리리터(0.032몰)의 33% 메틸라민으로 약 12시간 서서히 회전시키는데 총체적 25밀리리터에서 에탄올로 용해된다. TLC[톨루엔/메탄올/에틸라민 70/30/1 v/v/v 실리카 겔]로 증명된 바에 따라 제품이 형성된 경우에는 8.0－8.5의 50% 나트륨 수산화물을 사용하여 조절한 수상 pH와 반응 플라스크에 100밀리리터의 물을 첨가한다. 수상은 절단하여 버린다. 제품이 함유하고 있는 염화메틸 막에 100밀리리터의 물을 첨가하고, 수막의 pH는 계속적인 회전으로 메탄술폰산을 조심스럽게 첨가하여 pH 1.7－2.7에 맞춘다. 염화메틸 상을 분리시킨다. 염화메틸의 두번째 추출은 pH 1.7－2.7에서 행하고 염화메틸 90밀리리터와 메탄올 10밀리리터를 첨가한다.The reaction mixture obtained in Example A was heated to 20-25 DEG C. after completion of the reaction and slowly rotated for about 12 hours to 4.0 milliliters (0.032 mol) of 33% methylamine in ethanol and dissolved in ethanol at a total volume of 25 milliliters. do. If the product was formed as evidenced by TLC [toluene / methanol / ethylamine 70/30/1 v / v / v silica gel], the reaction flask was adjusted to an aqueous phase pH and a reaction flask controlled using 50% sodium hydroxide of 8.0-8.5. Add 100 milliliters of water. The water phase is cut off. 100 milliliters of water is added to the methyl chloride membrane contained in the product, and the pH of the aqueous membrane is adjusted to pH 1.7-2.7 by careful addition of methanesulfonic acid with continuous rotation. The methyl chloride phase is separated. The second extraction of methyl chloride is carried out at pH 1.7-2.7 and 90 milliliters of methyl chloride and 10 milliliters of methanol are added.

높은 조직적 혈관확장 활동력으로 남성의 성기능 장애 치료에 이용될 것이다.Its high systemic vasodilation activity will be used to treat male sexual dysfunction.

Claims (4)

5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d] 피리미디나-7-오나 말리에이트의 화합물.5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo [4, 3-d] Compound of pyrimidina-7-ona maleate. 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d] 피리미디나-7-오나 말리에이트로 이루어진 첨가염을 제공하기에 적합한 용해제 속에서 사과산으로 공식(1)의 화합물을 처리하는 것을 특징으로 하는 실데나필 말리에이트의 조제법.5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo [4, 3-d] A process for preparing sildenafil maleate, characterized by treating the compound of formula (1) with malic acid in a solvent suitable for providing an addition salt consisting of pyrimidina-7-one maleate. 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d]피리미디나-7-오나 말레아토의 조제법은 5-[2-에톡시-5-(4-메틸피페라진-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d] 피리미딘-7-오나로 이루어진 것을 특징으로 하는 실데나필 말리에이트.5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo [4, Preparation of 3-d] pyrimidina-7-ona maleato is 5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl Sildenafil maleate, consisting of -1,6-dihydro-7H-pyrazolo [4,3-d] pyrimidine-7-one. 약학적으로 수용할 만한 부형제와 함께 5-[2-에톡시-5-(4-메틸피페라지나-1-일술포닐)페닐]-1-메틸-3-n-프로필-1,6-디히드로-7H-피라졸로[4,3-d] 피리미디나-7-오나 말리에이트의 유효량을 포함하고 있는 것을 특징으로 하는 발기불능 치료를 위한 약학적 화합물.5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-di with pharmaceutically acceptable excipients A pharmaceutical compound for treating impotence, comprising an effective amount of hydro-7H-pyrazolo [4,3-d] pyrimidina-7-one or maleate.
KR10-2004-7003315A 2001-09-05 2002-07-16 Sildenafil maleate KR20040071117A (en)

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