WO2005074926A1 - Organic compounds - Google Patents

Organic compounds Download PDF

Info

Publication number
WO2005074926A1
WO2005074926A1 PCT/US2005/003427 US2005003427W WO2005074926A1 WO 2005074926 A1 WO2005074926 A1 WO 2005074926A1 US 2005003427 W US2005003427 W US 2005003427W WO 2005074926 A1 WO2005074926 A1 WO 2005074926A1
Authority
WO
WIPO (PCT)
Prior art keywords
lower alkyl
hydrogen
compound
treatment
halogen
Prior art date
Application number
PCT/US2005/003427
Other languages
French (fr)
Inventor
Anna Ottlecz
Rudolf Karl Andreas Giger
Carlos Alvarez
Original Assignee
Novartis Ag
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 Novartis Ag filed Critical Novartis Ag
Priority to EP05712759A priority Critical patent/EP1718302A4/en
Publication of WO2005074926A1 publication Critical patent/WO2005074926A1/en
Priority to US11/460,355 priority patent/US20060258717A1/en

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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents

Definitions

  • the present invention relates to the use of certain imidazolylalkyl-pyridines in the treatment of ocular disorders. More particularly, the present invention relates to the use of compounds of formula I,
  • Rj. is hydrogen, lower alkyl, halogen with an atomic number of 9 to 35 or amino optionally mono- or disubstituted by lower alkyl
  • R 2 . and R 3 . independently of one another are hydrogen or lower alkyl
  • R 4 . is hydrogen, hydroxy, lower alkyl, lower alkoxy or halogen with an atomic number of 9 to 35, in free base or acid addition salt form
  • the bridge between the pyridine and the imidazole, illustrated as methylene is methylene or ethylene.
  • Rj. is hydrogen, lower alkyl, halogen with an atomic number of 9 to 35 or amino optionally mono- or disubstituted by lower alkyl
  • R 2 . and R 3 . independently of one another are hydrogen or lower alkyl
  • R 4 . is hydrogen, hydroxy, lower alkyl, lower alkoxy or halogen with an atomic number of 9 to 35
  • the bridge between the pyridine and the imidazole, illustrated as methylene is methylene or ethylene.
  • a second aspect of the invention provides a use of a compound of formula (I) in the manufacture of a medicament for the treatment of ocular neovascularization, said compound of formula (I) being
  • Rj. is hydrogen, lower alkyl, halogen with an atomic number of 9 to 35 or amino optionally mono- or disubstituted by lower alkyl
  • R 2 . and R 3 . independently of one another are hydrogen or lower alkyl
  • ⁇ . is hydrogen, hydroxy, lower alkyl, lower alkoxy or halogen with an atomic number of 9 to 35
  • Figure 1 illustrates the effect of a compound of the present invention on capillary network formation in cultured human umbilical vein endothelial cells (HUVECs).
  • alkyl and alkoxy groups denote a radical having up to 7 carbon atoms, preferably up to 4 carbon atoms and more preferably up to 2 carbon atoms. Consequently, lower alkyl has especially up to 7 carbon atoms, preferably up to 4 carbon atoms, and in particular up to 2 carbon atoms and is, for example, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl, or hexyl.
  • lower alkoxy has up to 7 carbon atoms, preferably up to 4 carbon atoms, and in particular up to 2 carbon atoms and is, for example, methoxy, ethoxy, propoxy, butoxy, tert-butoxy or hexyloxy.
  • these preferably have one or two carbon atoms and especially signify methyl or methoxy.
  • the imidazolylmethyl radical is preferably in position 2 of the pyridine.
  • Rj is preferably methyl or ethyl, more preferably methyl.
  • R and R 3 are preferably each hydrogen.
  • R is preferably methyl, ethyl or hydrogen, more preferably methyl or hydrogen, and in particular hydrogen.
  • the compound A of Example 1 is strongly preferred.
  • Rj is lower alkyl
  • R 2 and R 3 independently of one another are hydrogen or lower alkyl
  • t is hydrogen, lower alkyl or halogen with an atomic number of 9 to 35.
  • Ri is methyl
  • R 2 and R 3 independently of one another are hydrogen or methyl
  • R) is hydrogen, methyl or halogen with an atomic number of 9 to 35.
  • Halogen with an atomic number of 9 to 35 denote in particular a fluorine and chlorine residue, more particularly a chlorine residue.
  • the compounds of formula (I) may be present in free base form or in the form of their acid addition salts, including, for example, hydrogen fumarate and fumarate salt forms. Acid addition salts may be produced from the free bases in known manner, and vice versa.
  • the compounds of formula (I) are known, e.g., from US 5,856,343 and US 5,635,521, which are incorporated herein by reference, or may be produced in accordance with known processes, i.e., analogously to known processes.
  • the compounds of formula I and their physiologically acceptable salts exhibit interesting pharmacological activities in the eye and may therefore be used in accordance thereto. The compounds according to the invention are therefore useful for the treatment of ocular neovascularization.
  • treatment refers to both prophylactic or preventive treatment as well as curative or disease-modifying treatment, including treatment of patients at risk of contracting the disease or suspected to have contracted the disease as well as patients who are ill or have been diagnosed as suffering from a disease or medical condition.
  • the appropriate dosage will, of course, vary depending upon, for example, the compound employed, the host, the mode of administration and the nature and severity of the condition being treated. However, in general, satisfactory results in animals are indicated to be obtained at daily dosages from about 0.05 to about 50 mg/kg animal body weight.
  • an indicated daily dosage may typically range from about 0.1 mg to about 100 mg, conveniently administered, for example, in divided doses up to four times a day.
  • the compounds according to the invention may be administered by any conventional route, in particular enterally, orally, or topically, for example in the form of tablets, capsules or eye drops, or parenterally, for example in the form of injectable solutions or suspensions.
  • the present invention furthermore provides a method of treating ocular neovascularization in a subject in need of such treatment, which comprises administering a therapeutically effective amount of a compound of formula (I).
  • Ocular neovascularization is in particular referring to a medical condition which involves corneal, iris, choroidal, or retinal neovascularization (NV), age related macular degeneration, proliferative diabetic retinopathy, retinopathy of prematurity (ROP), ischemic retinopathy, and central vein occlusion.
  • age related macular degeneration refers to both the dry and wet form of age related macular degeneration, the wet form being a preferred form. The following examples illustrate the invention.
  • Capillary network formation in cultured HUVECs Various concentrations of compound A (0.1, 1, and 10 mM) are tested to assess the quality of effect of this compound on capillary networking (tube formation) in cultured human umbilical vein endothelial cells (HUVECs) seeded on growth factor-reduced Matrigel.
  • the intensity of capillary networking is evaluated at 24 hours using a phase-contrast microscope. Images are captured and analySYS 3.2 software is used to count the number of tubes in five random fields of each well (8 wells altogether). The effect of the compound is compared to untreated cells grown in cell culture medium (control).
  • Compound A significantly decreases the number of tubes at 1 mM and 10 mM concentrations as compared to the control group ( Figure 1).
  • FIG. 1 illustrates the effect of compound A on capillary network formation in cultured HUVECs.
  • compound A and related compounds are considered useful in the treatment of various ocular diseases that result from pathological angiogenesis, also called neovascularization (NV).
  • NV neovascularization

Abstract

The present invention provides methods and uses of imidazolylalkyl-pyridines in the treatment of ocular disorders. A first aspect of the invention provides a method of treating ocular neovascularization comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound having the formula (I) in free base or physiologically acceptable acid addition salt form, wherein R1.is hydrogen, lower alkyl, halogen with an atomic number of 9 to 35 or amino optionally mono- or disubstituted by lower alkyl, R2. and R3. independently of one another are hydrogen or lower alkyl, R4. is hydrogen, hydroxy, lower alkyl, lower alkoxy or halogen with an atomic number of 9 to 35, and the bridge between the pyridine and the imidazole, illustrated as methylene, is methylene or ethylene.

Description

ORGANIC COMPOUNDS
CROSS REFERENCE TO RELATED APPLICATIONS The current application claims the benefit of co-pending United Kingdom Patent Application No. GB 0402100.2, filed 30 January 2004, which is hereby incorporated herein by reference.
BACKGROUND OF THE INVENTION The present invention relates to the use of certain imidazolylalkyl-pyridines in the treatment of ocular disorders. More particularly, the present invention relates to the use of compounds of formula I,
Figure imgf000002_0001
wherein Rj. is hydrogen, lower alkyl, halogen with an atomic number of 9 to 35 or amino optionally mono- or disubstituted by lower alkyl, R2. and R3. independently of one another are hydrogen or lower alkyl, R4. is hydrogen, hydroxy, lower alkyl, lower alkoxy or halogen with an atomic number of 9 to 35, in free base or acid addition salt form, and the bridge between the pyridine and the imidazole, illustrated as methylene, is methylene or ethylene. SUMMARY OF THE INVENTION The present invention provides methods and uses of imidazolylalkyl-pyri dines in the treatment of ocular disorders. A first aspect of the invention provides a method of treating ocular neovascularization comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound having the formula (I) in free base or physiologically acceptable acid addition salt form,
Figure imgf000003_0001
wherein Rj. is hydrogen, lower alkyl, halogen with an atomic number of 9 to 35 or amino optionally mono- or disubstituted by lower alkyl, R2. and R3. independently of one another are hydrogen or lower alkyl, R4. is hydrogen, hydroxy, lower alkyl, lower alkoxy or halogen with an atomic number of 9 to 35, and the bridge between the pyridine and the imidazole, illustrated as methylene, is methylene or ethylene. A second aspect of the invention provides a use of a compound of formula (I) in the manufacture of a medicament for the treatment of ocular neovascularization, said compound of formula (I) being
Figure imgf000003_0002
wherein Rj. is hydrogen, lower alkyl, halogen with an atomic number of 9 to 35 or amino optionally mono- or disubstituted by lower alkyl, R2. and R3. independently of one another are hydrogen or lower alkyl, ^. is hydrogen, hydroxy, lower alkyl, lower alkoxy or halogen with an atomic number of 9 to 35, and the bridge between the pyridine and the imidazole, illustrated as methylene, is methylene or ethylene.
BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 illustrates the effect of a compound of the present invention on capillary network formation in cultured human umbilical vein endothelial cells (HUVECs).
DETAILD DESCRIPTION OF THE INVENTION As used herein lower in the context with alkyl and alkoxy groups denote a radical having up to 7 carbon atoms, preferably up to 4 carbon atoms and more preferably up to 2 carbon atoms. Consequently, lower alkyl has especially up to 7 carbon atoms, preferably up to 4 carbon atoms, and in particular up to 2 carbon atoms and is, for example, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl, or hexyl. Accordingly, lower alkoxy has up to 7 carbon atoms, preferably up to 4 carbon atoms, and in particular up to 2 carbon atoms and is, for example, methoxy, ethoxy, propoxy, butoxy, tert-butoxy or hexyloxy. Insofar as above-defined lower alkyl or lower alkoxy groups are present in the compounds of formula (I), these preferably have one or two carbon atoms and especially signify methyl or methoxy. The imidazolylmethyl radical is preferably in position 2 of the pyridine. Rj is preferably methyl or ethyl, more preferably methyl. R and R3 are preferably each hydrogen. R» is preferably methyl, ethyl or hydrogen, more preferably methyl or hydrogen, and in particular hydrogen. The compound A of Example 1 is strongly preferred. In a particular group of compounds of formula (I), Rj is lower alkyl, R2 and R3 independently of one another are hydrogen or lower alkyl, and t is hydrogen, lower alkyl or halogen with an atomic number of 9 to 35. In a further particular group of compounds of formula (I), Ri is methyl, R2 and R3 independently of one another are hydrogen or methyl, and R) is hydrogen, methyl or halogen with an atomic number of 9 to 35. Halogen with an atomic number of 9 to 35 denote in particular a fluorine and chlorine residue, more particularly a chlorine residue. The compounds of formula (I) may be present in free base form or in the form of their acid addition salts, including, for example, hydrogen fumarate and fumarate salt forms. Acid addition salts may be produced from the free bases in known manner, and vice versa. The compounds of formula (I) are known, e.g., from US 5,856,343 and US 5,635,521, which are incorporated herein by reference, or may be produced in accordance with known processes, i.e., analogously to known processes. The compounds of formula I and their physiologically acceptable salts exhibit interesting pharmacological activities in the eye and may therefore be used in accordance thereto. The compounds according to the invention are therefore useful for the treatment of ocular neovascularization. As used herein the terms "treatment" or "treat" refer to both prophylactic or preventive treatment as well as curative or disease-modifying treatment, including treatment of patients at risk of contracting the disease or suspected to have contracted the disease as well as patients who are ill or have been diagnosed as suffering from a disease or medical condition. For the indications as described herein, the appropriate dosage will, of course, vary depending upon, for example, the compound employed, the host, the mode of administration and the nature and severity of the condition being treated. However, in general, satisfactory results in animals are indicated to be obtained at daily dosages from about 0.05 to about 50 mg/kg animal body weight. In larger mammals, for example humans, an indicated daily dosage may typically range from about 0.1 mg to about 100 mg, conveniently administered, for example, in divided doses up to four times a day. The compounds according to the invention may be administered by any conventional route, in particular enterally, orally, or topically, for example in the form of tablets, capsules or eye drops, or parenterally, for example in the form of injectable solutions or suspensions. The present invention furthermore provides a method of treating ocular neovascularization in a subject in need of such treatment, which comprises administering a therapeutically effective amount of a compound of formula (I). Ocular neovascularization is in particular referring to a medical condition which involves corneal, iris, choroidal, or retinal neovascularization (NV), age related macular degeneration, proliferative diabetic retinopathy, retinopathy of prematurity (ROP), ischemic retinopathy, and central vein occlusion. As used herein age related macular degeneration refers to both the dry and wet form of age related macular degeneration, the wet form being a preferred form. The following examples illustrate the invention.
Example 1
Compound A: [2-(2-methylimidazol-l-yl)methyl]pyridine (See, e.g., US 5,856,343)
9.7 g (75 mM) of 2-(chloromethyl)pyridine and 42 g (512 mM) of 2- methyl-imidazole are suspended in 40 ml dimethylformamide, then stirred for 3 hours at 105 °C. The dimethylformamide is distilled off and the crystalline residue is diluted with ethyl acetate and a little hexane. Following filtration, the mother solution is concentrated by evaporation and the dimethylformamide distilled off, and then shaken out several times between water and methylene chloride. 10.3 g of the oily title compound are obtained. Capillary network formation in cultured HUVECs Various concentrations of compound A (0.1, 1, and 10 mM) are tested to assess the quality of effect of this compound on capillary networking (tube formation) in cultured human umbilical vein endothelial cells (HUVECs) seeded on growth factor-reduced Matrigel. The intensity of capillary networking is evaluated at 24 hours using a phase-contrast microscope. Images are captured and analySYS 3.2 software is used to count the number of tubes in five random fields of each well (8 wells altogether). The effect of the compound is compared to untreated cells grown in cell culture medium (control). Compound A significantly decreases the number of tubes at 1 mM and 10 mM concentrations as compared to the control group (Figure 1). The inhibitory effect of this compound is not related to cell toxicity as this is excluded by an additional study using ToxiLight kit (Cambrex), which is a very sensitive assay based on ATP release from damaged cells. Figure 1 illustrates the effect of compound A on capillary network formation in cultured HUVECs. In this figure the bars represent mean ± SD of the number of tubes per group; wells per group, n=8; *P<0.001, **P<0.0001 versus control. Based on the above finding, compound A and related compounds are considered useful in the treatment of various ocular diseases that result from pathological angiogenesis, also called neovascularization (NV).

Claims

CLAIMS 1. A method of treating ocular neovascularization comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound having the formula (I) in free base or physiologically acceptable acid addition salt form,
Figure imgf000008_0001
wherein Rj. is hydrogen, lower alkyl, halogen with an atomic number of 9 to 35 or amino optionally mono- or disubstituted by lower alkyl; R2. and R3. independently of one another are hydrogen or lower alkyl; Rt. is hydrogen, hydroxy, lower alkyl, lower alkoxy or halogen with an atomic number of 9 to 35; and the bridge between the pyridine and the imidazole, illustrated as methylene, is methylene or ethylene.
2. The method of claim 1 which comprises administering the compound of Formula (I) wherein Rj is lower alkyl, halogen with an atomic number of 9 to 35 or amino optionally mono- or disubstituted by lower alkyl and the bridge between the pyridine and the imidazole is methylene.
3. The method of claim 2 wherein the compound administered is the compound of Formula (I) wherein Rj is methyl.
4. The method of claim 1 wherein the compound administered is in free base, hydrogen fumarate, or fumarate salt form.
5. The method of claim 1 wherein the compound administered is [2-(2-methylimidazol- l-yl-)methyl]pyridine, in free base or physiologically acceptable acid addition salt form.
6. The method of claim 5 wherein the compound administered is [2-(2-methylimidazol- l-yl)methyl]pyridine in free base, hydrogen fumarate, or fumarate salt form.
7. The method of claim 5 wherein the compound administered is [2-(2-methylimidazol- 1 -yl)methyl]pyridine fumarate.
8. The method of claim 1, wherein said ocular neovascularization is at least one of choroidal and retinal neovascularization.
9. The method of claim 1, wherein said ocular neovascularization is age related macular degeneration.
10. The method of claim 1, wherein said ocular neovascularization is proliferative diabetic retinopathy.
11. The method of claim 1 , wherein said ocular neovascularization is ischemic retinopathy.
12. The method of claim 1 wherein said method is for treating human or a mammal.
13. Use of a compound of Formula (I) in the manufacture of a medicament for the treatment of ocular neovascularization, said compound of formula (I) being
Figure imgf000010_0001
wherein Rj. is hydrogen, lower alkyl, halogen with an atomic number of 9 to 35 or amino optionally mono- or disubstituted by lower alkyl; R2. and R3. independently of one another are hydrogen or lower alkyl; Rt. is hydrogen, hydroxy, lower alkyl, lower alkoxy or halogen with an atomic number of 9 to 35; and the bridge between the pyridine and the imidazole, illustrated as methylene, is methylene or ethylene.
14. A method or use according to any of the preceding claims wherein said treatment is both prophylactic or preventive treatment as well as curative or disease-modifying treatment, including treatment of patients at risk of contracting the disease or suspected to have contracted the disease as well as patients who are ill or have been diagnosed as suffering from a disease or medical condition.
PCT/US2005/003427 2004-01-30 2005-01-28 Organic compounds WO2005074926A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP05712759A EP1718302A4 (en) 2004-01-30 2005-01-28 Organic compounds
US11/460,355 US20060258717A1 (en) 2004-01-30 2006-07-27 Organic compounds

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0402100.2A GB0402100D0 (en) 2004-01-30 2004-01-30 Organic compounds
GB0402100.2 2004-01-30

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US11/460,355 Continuation US20060258717A1 (en) 2004-01-30 2006-07-27 Organic compounds

Publications (1)

Publication Number Publication Date
WO2005074926A1 true WO2005074926A1 (en) 2005-08-18

Family

ID=31971769

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2005/003427 WO2005074926A1 (en) 2004-01-30 2005-01-28 Organic compounds

Country Status (3)

Country Link
EP (1) EP1718302A4 (en)
GB (1) GB0402100D0 (en)
WO (1) WO2005074926A1 (en)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5635521A (en) * 1991-09-23 1997-06-03 Sandoz Ltd. Imidazolylmethyl-pyridines

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU7985698A (en) * 1997-06-19 1999-01-04 Johns Hopkins University, The Methods for treatment of ocular neovascularization
AU771920B2 (en) * 1999-03-05 2004-04-08 Daiichi Suntory Pharma Co., Ltd Heterocyclic compounds having effect of activating nicotinic acetylcholine alpha4beta2 receptor
ES2289004T3 (en) * 2000-11-20 2008-02-01 Smithkline Beecham Corporation NEW COMPOUNDS.
EP1401480B1 (en) * 2001-02-22 2012-11-28 Novartis AG Viral vectors encoding endostatin in the treatment of ocular neovascularization

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5635521A (en) * 1991-09-23 1997-06-03 Sandoz Ltd. Imidazolylmethyl-pyridines

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP1718302A4 *

Also Published As

Publication number Publication date
EP1718302A4 (en) 2010-04-28
EP1718302A1 (en) 2006-11-08
GB0402100D0 (en) 2004-03-03

Similar Documents

Publication Publication Date Title
DE69631134T2 (en) METHOD FOR CONTROLLING INFECTIOUS DISEASES USING DICATIONIC BIS-BENZIMIDAZOLES
RU2414904C2 (en) PROTECTIVE MEDICIATION FOR RETINA NEURON WHICH CONTAINS AS ACTIVE COMPONETS PROSTAGLANDIN F2α DERIVATIVE
US20200129423A1 (en) Donepezil pamoate, preparation methode and its use
KR20150119037A (en) Crystalline form having specific crystal habit and pharmaceutical composition containing this crystalline form as active ingredient
US20080146663A1 (en) Compositions and Methods for the Treatment of Renal and Cardiovascular Disease
CN111655669A (en) Compositions and methods for treating neurological disorders including motor neuron diseases
US6225327B1 (en) Compounds which inhibit human conjunctival mast cell degranulation for treating ocular allergic-type complications
JP5204484B2 (en) Lidocaine-derived compounds, pharmaceutical compositions, methods of use, and methods of treatment, prevention or suppression of diseases
JP5328244B2 (en) A therapeutic agent for amyotrophic lateral sclerosis
TW202317518A (en) Compound as potassium channel regulator, and preparation and use thereof
WO2016171152A1 (en) Therapeutic agent, improving agent, and preventative agent for corneal disorders
WO2019225741A1 (en) Indole compound-containing nephrotic syndrome therapeutic or prophylactic agent
EP1718302A1 (en) Organic compounds
US20060258717A1 (en) Organic compounds
JP2012006918A (en) Preventive or therapeutic agent of retinochoroidal degeneration disorder containing isoquinolinesulfonyl derivative as effective ingredient
EP2589593B1 (en) (2e)-3-phenyl-n-[2,2,2-trifluoro-1-[[(8-quinolineamino)thiomethyl]amino]ethyl]-2-acrylamide and pharmaceutical uses thereof
US10537563B2 (en) Methods for treating ocular disease using inhibitors of CSF-1R
KR20000035869A (en) Preventives/remedies for muscle tissue degenerations
US20090221610A1 (en) Compositions and Methods for Treating Cognitive Disorders
EP0759756A1 (en) Pharmaceutical composition for treating glaucoma containing terazosin
JP7093489B2 (en) Treatment for cerebral infarction
US8242152B2 (en) Use of 4-[(4-thiazolyl)phenoxy]alkoxy-benzamidine derivatives for the prophylaxis and treatment of osteoporosis
KR20030087074A (en) Novel Use of Arylethenesulfonamide Derivative
US6248759B1 (en) Method for treatment of light-injured retinal degeneration disease
DE102012103717A1 (en) Use of phosphonoformic acid or its hydrate, ester and/or salt for treating tumor diseases and/or age-related macular degeneration, where tumor diseases are fibroblast growth factor-2 overexpressing tumors consisting of e.g. melanoma

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 11460355

Country of ref document: US

NENP Non-entry into the national phase

Ref country code: DE

WWW Wipo information: withdrawn in national office

Country of ref document: DE

WWE Wipo information: entry into national phase

Ref document number: 2005712759

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2005712759

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 11460355

Country of ref document: US