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WO2003020720A1 - Maleate de sildenafil - Google Patents

Maleate de sildenafil Download PDF

Info

Publication number
WO2003020720A1
WO2003020720A1 PCT/EC2002/000003 EC0200003W WO03020720A1 WO 2003020720 A1 WO2003020720 A1 WO 2003020720A1 EC 0200003 W EC0200003 W EC 0200003W WO 03020720 A1 WO03020720 A1 WO 03020720A1
Authority
WO
WIPO (PCT)
Prior art keywords
ethoxy
methyl
methylpiperazine
dihydro
propyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EC2002/000003
Other languages
English (en)
Spanish (es)
Inventor
Manuel Del Valle
Rafael Llano
Eduardo Llano
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=40091701&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2003020720(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Individual filed Critical Individual
Priority to MXPA04002149A priority Critical patent/MXPA04002149A/es
Priority to KR10-2004-7003315A priority patent/KR20040071117A/ko
Publication of WO2003020720A1 publication Critical patent/WO2003020720A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • C07D487/04—Ortho-condensed systems
    • 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
    • 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

Definitions

  • the present invention relates to a pharmaceutical compound for the treatment of male sexual dysfunction.
  • the invention also relates to a process for its preparation.
  • EP-A-046375 and EP-A-0812845 Published in Europe describes the preparation of 5- [2-ethoxy-5- (4 ⁇ methylpiperazine-1- iisuifoni penHl-l-methyl-Sn ⁇ ropil -l. ⁇ ⁇ lihydro-TH-pyrazolo ⁇ .ad ⁇ irimidirra -? - one of formula (1)
  • This compound has a great systematic vasodilator activity, however we have found that compound (1) has side effects such as serious heart problems Due to the excesses of NO in the blood system, in order to eliminate the risks we have prepared the compound which makes it especially useful for the preparation of pharmaceutical products.These products would show less toxic effects as well as increase the effectiveness time.
  • the subject of the present invention is a compound 5- [2-ethoxy-5- (4- methylpiperazine-1-ylsulfonyl) penJI3-1-methyl-3-n-propiM, 6-dihydro-7H-pyrazolo [4,3 -d] pyrimine-7-one MALÉATE of formula I
  • Nitric oxide nitric oxide
  • guanylate cyclase guanylate cyclase
  • phosphodiesterase type 5 phosphodiesterase type 5
  • the subject of the present invention is also a process for the preparation of 5- [2-ethoxy-5- (4-met] lpiperaz ⁇ na-1-ylsulfonyl) penyl3-1-methyl-3-n-propyl-1, 6-dihydro- 7H-pira ⁇ do [4 ⁇ ⁇ 3piripidinar7-one
  • the layers are shaken together in a funnel separating thorium and the organic layer containing purified 5- [2-ethoxy-5- (4- methylpiperazine-1-ylsulfonyl) penyl] -1-methyl-3-n-propyl-1 , 6-dihydro-7H-pyrazolo ⁇ 4,3-d] pyrimidiná-7-one removed.
  • the product is isolated with evaporation to the dry state.
  • the invention consists of the compound 5- ⁇ 2-ethoxy ⁇ 5- (4-methylpiperazine * 1 -
  • the suspension obtained in the first step (1) is heated to 50-60 degrees Celslus and stirred using a hot iron with a magnetic stirrer. Stirring constantly drops the solution obtained in step (2) into the separatory funnel until all 5-t2-ethoxy-5- (4-methylpiperazine-1-ylsulfonyl) penyl] -1- methyl-3- disappears n-propyl-1, 6-dihydro-7H-pyrazolo [4,3-djpyrimidine-7-one suspension.
  • 40-45 DEG C. is gradually added by the syringe pump 5 ml of 8.03 M methylamino in ethanol which is further diluted to a total volume of 25 ml; The addition occurred in 12 hours.
  • the reaction is followed by the appearance of the product according to TLC 70/30/1 v / v / v toluene / methanol / triéthylamine.
  • the solvent is removed and the crude mixture is dissolved in 100 ml Of. 1: 1 v / v 85% phosphoric acid and water.
  • 100 ml of methylene chloride is added and " with stirring 1.5 g (0.01 mol) of sodium iodide is added.
  • the reaction mixture was obtained in Example A after the termination of the reaction is heated to 20-25 ° C and is gradually stirring over 12 hours treated with 4.0 ml (0.032 mol) Of. 33% methylamine in ethanol that is diluted to a total volume of 25 ml with ethanol.
  • 4.0 ml (0.032 mol) Of. 33% methylamine in ethanol that is diluted to a total volume of 25 ml with ethanol.
  • 100 ml of the water is added to the reaction flask and to the pH of the aqueous phase adjusted using 50% aqueous sodium hydroxide at 8.0-8.5. The aqueous phase is cut and discarded.

Landscapes

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Health & Medical Sciences (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

Le maléate de sildenafil et un nouveau composé destiné au traitement de la dysfonction sexuelle masculine. L'invention concerne un nouveau procédé de préparation de maléate de sildenafil possédant une grande activité vasodilatatrice systémique.
PCT/EC2002/000003 2001-09-05 2002-07-16 Maleate de sildenafil Ceased WO2003020720A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
MXPA04002149A MXPA04002149A (es) 2001-09-05 2002-07-16 Maleato de sildenafil.
KR10-2004-7003315A KR20040071117A (ko) 2001-09-05 2002-07-16 실데나필 말리에이트

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SV2001000624A SV2002000624A (es) 2001-09-05 2001-09-05 Maleato de sildenafil
SV012001000624 2001-09-05

Publications (1)

Publication Number Publication Date
WO2003020720A1 true WO2003020720A1 (fr) 2003-03-13

Family

ID=40091701

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EC2002/000003 Ceased WO2003020720A1 (fr) 2001-09-05 2002-07-16 Maleate de sildenafil

Country Status (8)

Country Link
KR (1) KR20040071117A (fr)
AR (1) AR037811A1 (fr)
GT (1) GT200200177A (fr)
MX (1) MXPA04002149A (fr)
PA (1) PA8553601A1 (fr)
SV (1) SV2002000624A (fr)
UY (1) UY27426A1 (fr)
WO (1) WO2003020720A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111491630A (zh) * 2017-12-19 2020-08-04 马莱西尔研究与技术有限责任公司 糖尿病足溃疡的治疗方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000000199A1 (fr) * 1998-06-26 2000-01-06 Nastech Pharmaceutical Company, Inc. Administration intranasale de citrate de sildenafil
WO2001005386A2 (fr) * 1999-07-15 2001-01-25 Shmuel Simon Composition pharmaceutique utile dans le traitement de bourdonnement d'oreilles et de surdite
WO2001019827A1 (fr) * 1999-09-13 2001-03-22 Cipla Ltd. Nouveau procede de synthese du citrate de sildefanile

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000000199A1 (fr) * 1998-06-26 2000-01-06 Nastech Pharmaceutical Company, Inc. Administration intranasale de citrate de sildenafil
WO2001005386A2 (fr) * 1999-07-15 2001-01-25 Shmuel Simon Composition pharmaceutique utile dans le traitement de bourdonnement d'oreilles et de surdite
WO2001019827A1 (fr) * 1999-09-13 2001-03-22 Cipla Ltd. Nouveau procede de synthese du citrate de sildefanile

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111491630A (zh) * 2017-12-19 2020-08-04 马莱西尔研究与技术有限责任公司 糖尿病足溃疡的治疗方法

Also Published As

Publication number Publication date
KR20040071117A (ko) 2004-08-11
AR037811A1 (es) 2004-12-09
PA8553601A1 (es) 2003-05-14
GT200200177A (es) 2003-06-05
UY27426A1 (es) 2003-04-30
SV2002000624A (es) 2002-09-12
MXPA04002149A (es) 2005-03-07

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