WO1990011762A1 - 6-amino-1,2-dihydro-1-hydroxy-2-imino-4-(4-hydroxypiperidine-1-yl)-pyrimidine hydroxyminoxidile presentant une activite antifibroblastique - Google Patents

6-amino-1,2-dihydro-1-hydroxy-2-imino-4-(4-hydroxypiperidine-1-yl)-pyrimidine hydroxyminoxidile presentant une activite antifibroblastique Download PDF

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Publication number
WO1990011762A1
WO1990011762A1 PCT/EP1990/000542 EP9000542W WO9011762A1 WO 1990011762 A1 WO1990011762 A1 WO 1990011762A1 EP 9000542 W EP9000542 W EP 9000542W WO 9011762 A1 WO9011762 A1 WO 9011762A1
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WO
WIPO (PCT)
Prior art keywords
amino
activity
dihydro
hydroxy
hydroxypiperidin
Prior art date
Application number
PCT/EP1990/000542
Other languages
English (en)
Inventor
Francesco Gatti
Original Assignee
Kemios S.R.L. Bio Medical Research
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 Kemios S.R.L. Bio Medical Research filed Critical Kemios S.R.L. Bio Medical Research
Publication of WO1990011762A1 publication Critical patent/WO1990011762A1/fr

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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

Definitions

  • the present invention refers to the use of 6-a ino-l ,2-dihydro-hydroxy-2-imino-( -hydroxypiperidin-l -yDpyridine for the preparation of a medicament having antifibrotic activity useful for the treatment of proliferation conditions of the connective tissue and collagen accumulation.
  • Is is known that pathological conditions such as keloids, hypertrophic scars and fibrotic conditions such as scleroderma, are characterized by an excessive proliferation of the connective tissue, whose main component is the finrous protein known as collagen. Said abnormal growth of the connective tissue, taking place also as a consequence of phlogistic processes of various kind (fractures, contusions, distortions, traumas etc.) hinders the physiological processes of tissue repair and healing.
  • minoxidil has been studied because of its additional capacity of stimulating hair growth.
  • the main pharmacological activity of minoxidil namely the antihypertensive and vasodilating activity, may limit the topical use of the drug, both in the known and widespread treatment of alopecias and in the proposed treatment of fibrotic conditions.
  • minoxidil metabolite according to the present invention for the preparation of a medicament having antifibrotic activity is therefore more advantageous in comparison with minoxidil because of possible side-effects that the latter may induce as a consequence • of its vasodilating and antihypertensive activity.
  • SKM/101 The new pharmacological activity of the minoxidil metabolite of the invention, hereinafter referred to as SKM/101, was confirmed by inhibition tests of the enzymes prolylhydroxylase and lysylhydroxylase in human skin fibroplasts cultures, according to the method reported in Dermatologica 175(2), 12-18, 1987. A further confirmation was obtained from in vivo tests using guinea-pigs on whose back a silastic valve was implanted, SKM/101 may be formulated in topical phar ⁇ maceutical compositions, using conventional techniques and excipients. Examples of suited pharmaceutical compo- sitions are lotions, creams, ointments, sprays, gauzes, plasters, balsams and the like.
  • a particularly convenient administration form consists of lyophilized bovine native collagen, impregnated with SKM/101 or its acceptable salts.
  • the concentration of the active principle or of its salts in the above cited pharmaceutical compositions may range from 0.2 to 20% by weight.
  • the compositions may also contain other active principles having complementary or anyhow useful activity such as vitamin A or its derivatives, vitamin E or its derivatives, ascorbic acid, glutathion, antioxidants.
  • the pharmaceutical compositions of the invention may be administered one or more times a day, according to the pathology to be treated and of the kind of used formulations.
  • plasters containing SKM/101 able to release slowly and gradually the active principle are particularly useful.
  • SKM/101 may also be administered by local infiltration using known methods, in place of cortison. The following examples further illustrate the invention.
  • Vitamine A acetate g 0.20
  • Vitamine E acetate g 0.20
  • Vitamine C acetate g 0.2
  • Each gauze 10 x 10 cm is soaked at saturation with 40 g of a mixture having the following composition: SKM/101 g 2.0 Collagen g 15.0 Glycerine g 10.0
  • Vitamine E acetate g 0.2 Purified water q.s, to g 40

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Cosmetics (AREA)

Abstract

La 6-amino-1,2-dihydro-1-hydroxy-2-imino-4(4-hydroxypipéridine-1-yl)pyrimidine est dotée d'une activité antifibroplastique, et peut être utilisée pour la préparation d'un médicament utile pour le traitement d'états pathologiques caractérisés par la prolifération du tissu conjonctif.
PCT/EP1990/000542 1989-04-13 1990-04-06 6-amino-1,2-dihydro-1-hydroxy-2-imino-4-(4-hydroxypiperidine-1-yl)-pyrimidine hydroxyminoxidile presentant une activite antifibroblastique WO1990011762A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT8920126A IT1230056B (it) 1989-04-13 1989-04-13 Derivato di 4-(piperidin-1-il) piridina ad attivita' antifibroplastica.
IT20126A/89 1989-04-13

Publications (1)

Publication Number Publication Date
WO1990011762A1 true WO1990011762A1 (fr) 1990-10-18

Family

ID=11164017

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1990/000542 WO1990011762A1 (fr) 1989-04-13 1990-04-06 6-amino-1,2-dihydro-1-hydroxy-2-imino-4-(4-hydroxypiperidine-1-yl)-pyrimidine hydroxyminoxidile presentant une activite antifibroblastique

Country Status (3)

Country Link
EP (1) EP0467908A1 (fr)
IT (1) IT1230056B (fr)
WO (1) WO1990011762A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1986004231A1 (fr) * 1985-01-25 1986-07-31 The Upjohn Company Sulfates de pyrimidine favorisant la croissance des cheveux
GB2183632A (en) * 1985-12-06 1987-06-10 Kemyos Bio Medical Res Pyrimidine compounds for the growth of hair and cosmetic formulations containing such compounds
EP0242967A1 (fr) * 1986-03-14 1987-10-28 Unilever Plc Composition de traitement de la peau

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1986004231A1 (fr) * 1985-01-25 1986-07-31 The Upjohn Company Sulfates de pyrimidine favorisant la croissance des cheveux
GB2183632A (en) * 1985-12-06 1987-06-10 Kemyos Bio Medical Res Pyrimidine compounds for the growth of hair and cosmetic formulations containing such compounds
EP0242967A1 (fr) * 1986-03-14 1987-10-28 Unilever Plc Composition de traitement de la peau

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
Dermatologica 175, Suppl. 2, 1987, S. Karger AG, (Basel, CH), S.R. PINNELL et al.: "Effects of Minoxidil on Cultured Human Skin Fibroblasts", pages 12-18 *
Journal of Biological Chemistry, Volume 262, No. 25, 5 September 1987, The American Society for Biochemistry and Molecular Biology, Inc., (US), S. MURAD et al.: "Suppression of Fibroblast Proliferation and Lysyl Hydroxylase Activity by Minoxidil", pages 11973-11978 *
Journal of Pharmaceutical Sciences, Volume 64, No. 8, August 1975, R.C. THOMAS et al.: "Metabolism of Minoxidil, a New Hypotensive Agent II: Biotransformation Following Oral Administration to Rats, Dogs, and Monkeys", pages 1366-1371 *
The Merck Index, an Encyclopedia of Chemicals, Drugs, and Biologicals, Tenth Edition, 1983, Merck & Co., Inc., (Rahway, N.J., US), see Abstract No. 6069, "Minoxdil" *

Also Published As

Publication number Publication date
IT1230056B (it) 1991-09-27
EP0467908A1 (fr) 1992-01-29
IT8920126A0 (it) 1989-04-13

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