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 PDFInfo
- 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
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- 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
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
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)
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 |
-
2002
- 2002-09-17 GB GBGB0221582.0A patent/GB0221582D0/en not_active Ceased
-
2003
- 2003-09-04 AU AU2003259464A patent/AU2003259464A1/en not_active Abandoned
- 2003-09-04 PL PL03374730A patent/PL374730A1/xx not_active Application Discontinuation
- 2003-09-04 WO PCT/IB2003/003905 patent/WO2004026312A1/fr not_active Application Discontinuation
- 2003-09-04 CA CA002495311A patent/CA2495311A1/fr not_active Abandoned
- 2003-09-04 JP JP2004537394A patent/JP2006501276A/ja active Pending
- 2003-09-04 MX MXPA05002912A patent/MXPA05002912A/es unknown
- 2003-09-04 CN CNA038219786A patent/CN1681506A/zh active Pending
- 2003-09-04 BR BR0314381-3A patent/BR0314381A/pt not_active IP Right Cessation
- 2003-09-04 EP EP03797435A patent/EP1545541A1/fr not_active Withdrawn
- 2003-09-04 KR KR1020057004463A patent/KR20050057349A/ko not_active Application Discontinuation
- 2003-09-15 TW TW092125390A patent/TW200409770A/zh unknown
Patent Citations (3)
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)
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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