WO2004026312A1 - Utilisation d'un derive de quinazoline pour traiter des symptomes des voies urinaires inferieures - Google Patents

Utilisation d'un derive de quinazoline pour traiter des symptomes des voies urinaires inferieures Download PDF

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Publication number
WO2004026312A1
WO2004026312A1 PCT/IB2003/003905 IB0303905W WO2004026312A1 WO 2004026312 A1 WO2004026312 A1 WO 2004026312A1 IB 0303905 W IB0303905 W IB 0303905W WO 2004026312 A1 WO2004026312 A1 WO 2004026312A1
Authority
WO
WIPO (PCT)
Prior art keywords
quinazoline
tetrahydroisoquinol
methanesulfonamido
dimethoxy
pyridyl
Prior art date
Application number
PCT/IB2003/003905
Other languages
English (en)
Inventor
Ian William Mills
Original Assignee
Pfizer Limited
Pfizer Inc.
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
Application filed by Pfizer Limited, Pfizer Inc. filed Critical Pfizer Limited
Priority to EP03797435A priority Critical patent/EP1545541A1/fr
Priority to JP2004537394A priority patent/JP2006501276A/ja
Priority to MXPA05002912A priority patent/MXPA05002912A/es
Priority to BR0314381-3A priority patent/BR0314381A/pt
Priority to CA002495311A priority patent/CA2495311A1/fr
Priority to AU2003259464A priority patent/AU2003259464A1/en
Publication of WO2004026312A1 publication Critical patent/WO2004026312A1/fr

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/08Drugs for disorders of the urinary system of the prostate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/10Drugs for disorders of the urinary system of the bladder
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives

Definitions

  • This invention relates to a new use of 4-amino-6,7-dimethoxy-2-(5- methanesulfonamido-1 ,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline (disclosed as example 19 in International Patent Application Publication No. WO 98/30560), and its pharmaceutically acceptable derivatives.
  • the mesylate salt is disclosed in International Patent Application Publication No. WO 01/64672 (e.g. Example 2). Both WO 98/30560 and WO 01/64672 are incorporated herein by reference. It is indicated in the treatment of Benign Prostatic Hyperplasia (BPH) and has the following structure:
  • Lower urinary tract symptoms comprise three groups of symptoms, which are irritative, obstructive and post micturition symptoms. Irritative symptoms comprise urgency, frequency and nocturia, which can be associated with: overactive bladder (with or without concomitant detrusor over activity); pelvic floor dysfunction; or chronic prostatitis.
  • Over Active Bladder is defined as urgency, with or without urge incontinence, usually with frequency and nocturia [Abrams et al., Neurourology and Urodynamics 21 :167-178 (2002)].
  • Prevalence of OAB in men and women is similar, with approximately 16% of the population of the USA suffering from the condition [Stewart et al, Prevalence of Overactive Bladder in the United States: Results from the NOBLE Program; Abstract Presented at the 2 nd International Consultation on Incontinence, July 2001 , Paris, France].
  • Pelvic floor dysfunction occurs when the muscles of the pelvic floor no longer relax properly during urination while the bladder contracts. The muscles may become irritated and often contract abnormally. PFD may result in irritative LUTS.
  • Chronic prostatitis is an inflammatory condition of the prostate, which may or may not be associated with uropathogenic bacteria detected by standard microbiological methodology. It is characterized by the presence of genitourinary pain or discomfort, often associated with irritative LUTS.
  • Overactive bladder may be suffered by individuals of any age, while pelvic floor dysfunction and prostatitis are conditions typically suffered by middle-aged men. Patients with any of these conditions are likely to experience irritative lower urinary tract symptoms, and often the eventual diagnosis is empirical.
  • LUTS 4- amino-6,7-dimethoxy-2-(5-methanesulfonamido-1 ,2,3,4-tetrahydroisoquinol-2-yl)- 5-(2-pyridyl)quinazoline, or a pharmaceutically acceptable derivative thereof, for the manufacture of a medicament for the treatment of LUTS associated with: OAB (with or without concomitant detrusor over activity); pelvic floor dysfunction; or chronic prostatitis.
  • OAB with or without concomitant detrusor over activity
  • pelvic floor dysfunction or chronic prostatitis.
  • the LUTS is associated with pelvic floor dysfunction.
  • the LUTS is preferably associated with chronic prostatitis.
  • the 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1 ,2,3,4- tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline is in the form of its mesylate salt.
  • the compound, or a pharmaceutically acceptable derivative thereof can be administered alone or in any convenient pharmaceutical presentation. Oral administration is preferred.
  • a suitable dosage of the compound, or of the active moiety in a pharmaceutically acceptable derivative thereof is from about 0.01 to 10.0 mg/kg of body weight, and preferably about 0.05 to 1.0 mg/kg is suitable.
  • Administration may be in single does of from 1 to 4 times daily or preferably it may be in a controlled release formulation such as is disclosed in International Application Publication No. WO 03/032956 (see in particular examples 1 to 5). Administration may be p.r.n. for occasions when the patient may have limited access to toilet facilities, e.g. during a long journey.
  • the invention further provides 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido- 1 ,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline, or a pharmaceutically acceptable derivative thereof, for use in the treatment of LUTS associated with: OAB (with or without concomitant detrusor over activity); pelvic floor dysfunction; or chronic prostatitis.
  • the invention further provides a method of treating LUTS associated with: OAB (with or without concomitant detrusor over activity); pelvic floor dysfunction; or chronic prostatitis, which comprises administering 4-amino-6,7-dimethoxy-2-(5- methanesulfonamido-1 ,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline, or a pharmaceutically acceptable derivative thereof, to a patient in need of such treatment.
  • OAB with or without concomitant detrusor over activity
  • pelvic floor dysfunction or chronic prostatitis
  • the following table shows the ingredients for preparing five tablet formulations containing, respectively, 1 , 3, 6, 9 and 12 mg of active ingredient, expressed as free base, according to International Application Publication No. WO 03/032956.
  • the adipic acid was first screened through a suitable screen (e.g. 500 micron).
  • a suitable screen e.g. 500 micron.
  • the lactose monohydrate, hydroxypropylmethyl cellulose, 4-amino-6,7-dimethoxy- 2-(5-methanesulfonamido-1 ,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline mesylate, the screened adipic acid and calcium hydrogen phosphate, anhydrous were then added to a suitable blender (e.g. a tumble mixer) and blended.
  • the blend was screened through a suitable screen (e.g. 500 micron) and reblended. About 50% of the lubricant (magnesium stearate) was screened, added to the blend and blended briefly.
  • the blend was roller compacted through a suitable roller compactor.
  • the ribbon blend was then granulated, by screening through a suitable screen (e.g. 500 micron) and reblended. The remaining lubricant was screened, added to the blend and blended briefly.
  • the granules were then tabletted using appropriate 6 mm tooling to give 6 mm standard round convex white tablets with no engraving, which were then de- dusted.
  • IPSS International Prostate Symptom Score
  • the IPSS is composed of seven questions, each with potential responses of 0-5 on a Likert scale. These questions are grouped into two validated domains: the irritative domain (urgency, frequency and nocturia) and the obstructive domain (incomplete emptying, intermittency, weak stream and straining to begin).
  • a bladder diary was completed by each subject to provide baseline incidence of individual symptoms, and subsequently to demonstrate change in incidence of these symptoms following double blind treatment.

Abstract

Utilisation de 4-amino-6,7-diméthoxy-2-(5-méthanesulfonamido-1,2,3,4-tétrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline, ou d'un de ses dérivés acceptables sue le plan pharmaceutique afin de traiter des symptômes des voies urinaires inférieures associés à : OAB (avec ou sans suractivité concomitante du détrusor), dysfonctionnement de la paroi inférieure pelvienne ou affection chronique de la prostate.
PCT/IB2003/003905 2002-09-17 2003-09-04 Utilisation d'un derive de quinazoline pour traiter des symptomes des voies urinaires inferieures WO2004026312A1 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
EP03797435A EP1545541A1 (fr) 2002-09-17 2003-09-04 Utilisation d'un derive de quinazoline pour traiter des symptomes des voies urinaires inferieures
JP2004537394A JP2006501276A (ja) 2002-09-17 2003-09-04 尿管下部兆候の治療のためのキナゾリン誘導体の使用
MXPA05002912A MXPA05002912A (es) 2002-09-17 2003-09-04 Uso de un derivado de quinazolina para tratar sintomas del tracto urinario inferior.
BR0314381-3A BR0314381A (pt) 2002-09-17 2003-09-04 Uso de um derivado da quinazolina para tratar sintomas do trato urinário inferior
CA002495311A CA2495311A1 (fr) 2002-09-17 2003-09-04 Utilisation d'un derive de quinazoline pour traiter des symptomes des voies urinaires inferieures
AU2003259464A AU2003259464A1 (en) 2002-09-17 2003-09-04 Use of a quinazoline derivative for treating lower urinary tract symptoms

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0221582.0 2002-09-17
GBGB0221582.0A GB0221582D0 (en) 2002-09-17 2002-09-17 Method of treatment

Publications (1)

Publication Number Publication Date
WO2004026312A1 true WO2004026312A1 (fr) 2004-04-01

Family

ID=9944253

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2003/003905 WO2004026312A1 (fr) 2002-09-17 2003-09-04 Utilisation d'un derive de quinazoline pour traiter des symptomes des voies urinaires inferieures

Country Status (12)

Country Link
EP (1) EP1545541A1 (fr)
JP (1) JP2006501276A (fr)
KR (1) KR20050057349A (fr)
CN (1) CN1681506A (fr)
AU (1) AU2003259464A1 (fr)
BR (1) BR0314381A (fr)
CA (1) CA2495311A1 (fr)
GB (1) GB0221582D0 (fr)
MX (1) MXPA05002912A (fr)
PL (1) PL374730A1 (fr)
TW (1) TW200409770A (fr)
WO (1) WO2004026312A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998030560A1 (fr) * 1997-01-11 1998-07-16 Pfizer Limited Composes de quinoleine et de quinazoline presentant une utilite therapeutique en particulier pour le traitement de l'hyperplasie prostatique benigne
EP1123705A1 (fr) * 2000-02-09 2001-08-16 Pfizer Products Inc. Combinaisons pharmaceutiques pour le traitement de troubles fonctionnels de l' uretère inférieur
WO2001064672A1 (fr) * 2000-03-03 2001-09-07 Pfizer Limited Mesylate de 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline et polymorphes

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998030560A1 (fr) * 1997-01-11 1998-07-16 Pfizer Limited Composes de quinoleine et de quinazoline presentant une utilite therapeutique en particulier pour le traitement de l'hyperplasie prostatique benigne
EP1123705A1 (fr) * 2000-02-09 2001-08-16 Pfizer Products Inc. Combinaisons pharmaceutiques pour le traitement de troubles fonctionnels de l' uretère inférieur
WO2001064672A1 (fr) * 2000-03-03 2001-09-07 Pfizer Limited Mesylate de 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline et polymorphes

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
HIEBLE J P ET AL: "RECENT PROGRESS IN THE PHARMACOTHERAPY OF DISEASES OF THE LOWER URINARY TRACT", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, EDITIONS SCIENTIFIQUE ELSEVIER, PARIS, FR, vol. 30, no. SUPPL, 1995, pages 269S - 298S, XP000608494, ISSN: 0223-5234 *
SERELS S ET AL: "Prospective study comparing hyoscyamine, doxazosin, and combination therapy for the treatment of urgency and frequency in women", MEDLINE, XP002169616 *
VARIOUS: "Merck manual", 1999, MERCK RESEARCH LABORATORIES, USA, XP002260525 *

Also Published As

Publication number Publication date
KR20050057349A (ko) 2005-06-16
PL374730A1 (en) 2005-10-31
GB0221582D0 (en) 2002-10-23
TW200409770A (en) 2004-06-16
BR0314381A (pt) 2005-07-19
JP2006501276A (ja) 2006-01-12
MXPA05002912A (es) 2005-09-30
AU2003259464A1 (en) 2004-04-08
CA2495311A1 (fr) 2004-04-01
EP1545541A1 (fr) 2005-06-29
CN1681506A (zh) 2005-10-12

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