EP0690849A1 - Derives d'amidine contenant des heterocycles, leur preparation et leur utilisation - Google Patents

Derives d'amidine contenant des heterocycles, leur preparation et leur utilisation

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Publication number
EP0690849A1
EP0690849A1 EP94911191A EP94911191A EP0690849A1 EP 0690849 A1 EP0690849 A1 EP 0690849A1 EP 94911191 A EP94911191 A EP 94911191A EP 94911191 A EP94911191 A EP 94911191A EP 0690849 A1 EP0690849 A1 EP 0690849A1
Authority
EP
European Patent Office
Prior art keywords
alkyl
formula
alkoxy
compounds
phenyl
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
EP94911191A
Other languages
German (de)
English (en)
Inventor
Ernst-Otto Renth
Kurt Schromm
Ralf Anderskewitz
Franz Birke
Armin Fügner
Hubert Heuer
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.)
CH Boehringer Sohn AG and Co KG
Boehringer Ingelheim GmbH
Original Assignee
CH Boehringer Sohn AG and Co KG
Boehringer Ingelheim GmbH
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 CH Boehringer Sohn AG and Co KG, Boehringer Ingelheim GmbH filed Critical CH Boehringer Sohn AG and Co KG
Publication of EP0690849A1 publication Critical patent/EP0690849A1/fr
Ceased legal-status Critical Current

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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/08—Bronchodilators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
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    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/84—Sulfur atoms
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    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
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    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
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    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
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    • C07D239/72—Quinazolines; Hydrogenated quinazolines
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    • C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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    • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
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    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
    • C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
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    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
    • C07D271/113—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
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    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/08—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D277/12—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/38—Nitrogen atoms
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    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
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    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C07D277/70—Sulfur atoms
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    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
    • C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
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    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
    • C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
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    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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    • C07D513/04—Ortho-condensed systems

Definitions

  • the invention relates to new, heterocycle-containing amidine derivatives, their preparation by conventional methods and their use as active ingredients in
  • a 1 is a straight-chain or branched double-bonded aliphatic C 2 -C 6 group, which can also contain a double or triple bond, or one of the groups
  • X 1 for O, S, SO, SO 2 , CH 2 , NH or
  • Chiral compounds of the formula I can be in the form of racemates, in enantiomerically pure or enriched form and in each case as a base or as salts with inorganic or organic, in particular physiologically
  • R 1 and R 2 which are the same or different
  • C 1 -C 4 alkyl can be substituted for halogen, OH, CF 3 , R 5 , OR 6 , COR 6 ,
  • R 5 represents a heterocyclic five-membered ring with 1 to 3 heteroatoms and the formula
  • D, E and G which may be the same or different, are CH, N, C- (C 1 -C 4 alkyl) or
  • C is phenyl and L is Ooer S
  • R 4 for H, halogen, NH 2 , NH- (C 1 -C 4 alkyl), C 1 -C 4 alkyl, N (C 1 -C 4 alkyl) 2 , OH, C 1 -C 4 - Alkoxy, phenyl,
  • R 5 is H, C 1 -C 12 alkyl, pydridyl, phenyl, optionally by halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy
  • R 6 for C 1 -C 12 alkyl, phenyl or optionally
  • R 7 is H or C 1 -C 12 alkyl
  • R 8 , R 9 (which may be the same or different)
  • R 10 is H or C 1 -C 4 alkyl
  • R 11 , R 12 which can be the same or different
  • R 13 , R 14 which may be the same or different,
  • radicals from the group fluorine, chlorine, bromine, C 1 -C 4 alkyl, C 1 -C 4 alkoxy or pseudohalogens such as CN, CF 3 may be substituted, or for pyridyl.
  • a 1 contains a double or triple bond, this is generally not a hetero atom
  • R 3 generally means hydrogen only if at least one of the radicals R 1 , R 2 is not hydrogen.
  • a 1 ' (CH 2 ) 2-6 , CH 2 -C 6 H 4 -CH 2 ,
  • CH 2 -C C-CH 2 ;
  • X 1 ' O, S;
  • Het ' a group of the above formulas a, b, e, f, g, k, n, where R 1 , R 2 , R 3 , the may be the same or different, mean H, R 5 , OR 5 or COR 5 and
  • R 1 and R 2 together also one
  • condensed ring can mean.
  • Ammonia in an alcohol such as methanol, ethanol, n-propanol, i-propanol, or in an inert solvent, such as dichloromethane,
  • Tetrahydrofuran, dioxane at temperatures between about 0 and 50 ° C, preferably at about 20 ° C. 2. Reduction of an amidoxime of the formula
  • Het, R 4 , A and B have the above meaning
  • a catalyst such as Raney nickel, palladium or platinum.
  • O or S can also be according to the scheme
  • Metal hydroxides, metal hydrides at temperatures between about 0 and 140 ° C or the boiling point of the reaction mixture.
  • the phenols or thiophenols can also be used in the form of salts, for example the alkali salts.
  • Suitable as a nucleofugic leaving group eg halogens, such as Br, Cl or residues of
  • Sulfonic acids such as methanesulfonic acid
  • the starting materials X and XI are preferably from the corresponding nitriles of the formula
  • the further synthetic route consists in the reaction of the corresponding nitriles with HCl via the stage of the imide chlorides or the direct reaction with eg
  • reaction can also be carried out with a trialkyloxonium salt such as
  • nitriles XVI can be reacted with hydroxylamine in alcohols, for example methanol, ethanol, Propanol, isopropanol, the corresponding amidoximes of the formula XI obtained.
  • the starting materials of the formulas XII, XIII, XIV and XV can also be prepared by conventional processes.
  • the compounds according to the invention can be used therapeutically, in particular because of their
  • LTB 4 -antagonistic effect are therefore particularly suitable for use in those diseases in which inflammatory and / or allergic processes play a role, for example IBD (inflammatory bowel diseases), allergic rhinitis; ARDS (adult respiratory distress syndron), asthma, colitis
  • IBD inflammatory bowel diseases
  • ARDS adult respiratory distress syndron
  • asthma chronic respiratory distress syndron
  • ulcerative pain, psoriasis also used to treat gastropathy induced by nonsteroidal anti-inflammatory drugs (NSAID).
  • NSAID nonsteroidal anti-inflammatory drugs
  • the new compounds can also be used in combination with other active ingredients, e.g. B. with antiallergics, secretolytics,
  • Antihistamines and / or PAF antagonists are included in the composition.
  • Administration can be topical, oral, transdermal, nasal, parenteral or inhalative.
  • the therapeutic or prophylactic dose is - apart from the potency of the individual compounds and the body weight of the patient - dependent on the nature and seriousness of the
  • the new compounds can be administered topically, orally,
  • compositions consisting essentially of an inert pharmaceutical carrier and a
  • an effective dose of the active ingredient e.g. Tablets, coated tablets, capsules, wafers, powders, solutions, suspensions, inhalation aerosols, ointments, emulsions, syrups, suppositories, etc.
  • An effective dose of the compounds according to the invention is oral
  • Inhalation should be used in powders or solutions containing 0.5% to 5% active ingredient, with each dose containing approximately 2 to 20 mg active ingredient.
  • the new compounds can be combined, inter alia, with antiallergics, secretolytics, ⁇ 2 -adrenergics, inhalable steroids or antihistamines.
  • Active ingredient according to the invention 20 parts by weight
  • the ingredients are processed in the usual way to tablets of 500 mg weight.
  • the active ingredient content can be increased or decreased and the amount of glucose reduced or increased accordingly.
  • Active ingredient according to the invention 100 parts by weight
  • the ingredients are processed in the usual way into suppositories weighing 1.7 g.
  • Micronized active ingredient powder (compound of formula I; particle size approx. 0.5 to 7 ⁇ m) is added in an amount of 5 mg, optionally with the addition of micronized lactose
  • Bottled hard gelatin capsules The powder is inhaled from conventional inhalation devices, for example according to DE-A 3 345 722.
  • the compounds of the invention were examined, inter alia, for their action in the tests below. a) LTB 4 receptor connection test
  • U937 cells differentiated, human monocytic cell line with naturally expressed
  • Concentration of the test substance is dose-dependent inhibited (incubation 2 h at 0 ° C).

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pulmonology (AREA)
  • Immunology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

On peut préparer par des procédés classiques des composés ayant la formule (I), dont la signification est expliquée plus en détail dans la description, et les utiliser dans des compositions galéniques thérapeutiques.
EP94911191A 1993-03-23 1994-03-18 Derives d'amidine contenant des heterocycles, leur preparation et leur utilisation Ceased EP0690849A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE4309285A DE4309285A1 (de) 1993-03-23 1993-03-23 Heterocyclen enthaltende Amidinderivate, ihre Herstellung und Verwendung
DE4309285 1993-03-23
PCT/EP1994/000856 WO1994021616A1 (fr) 1993-03-23 1994-03-18 Derives d'amidine contenant des heterocycles, leur preparation et leur utilisation

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EP0690849A1 true EP0690849A1 (fr) 1996-01-10

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JP (1) JPH08508467A (fr)
KR (1) KR960701026A (fr)
CN (1) CN1124486A (fr)
AU (1) AU6378094A (fr)
BG (1) BG100069A (fr)
CA (1) CA2158994A1 (fr)
CZ (1) CZ246695A3 (fr)
DE (1) DE4309285A1 (fr)
FI (1) FI954491A (fr)
HU (1) HUT73968A (fr)
IL (1) IL109073A0 (fr)
LV (1) LV11465B (fr)
NO (1) NO953763L (fr)
PL (1) PL310806A1 (fr)
SK (1) SK117495A3 (fr)
WO (1) WO1994021616A1 (fr)
ZA (1) ZA941993B (fr)

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US11891366B1 (en) 2023-10-12 2024-02-06 King Faisal University 4-methoxy-n′-(2-(5-phenyl-1,3,4-oxadiazol-2-ylthio)acetoxy)benzimidamide as an antimicrobial compound
US11897850B1 (en) 2023-10-11 2024-02-13 King Faisal University N′-(2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)acetoxy)-4-methoxybenzimidamide as an antimicrobial compound
US11905263B1 (en) 2023-10-13 2024-02-20 King Faisal University 4-nitro-N′-(2-(5-phenyl-1,3,4-oxadiazol-2-ylthio)acetoxy)benzimidamide as an antimicrobial compound
US11912675B1 (en) 2023-10-11 2024-02-27 King Faisal University N'-(2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)acetoxy)-3,4-dimethoxybenzimidamide as an antimicrobial compound
US11919872B1 (en) 2023-10-11 2024-03-05 King Faisal University N′-(2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)acetoxy)benzimidamide as an antimicrobial compound
US11932632B1 (en) 2023-10-13 2024-03-19 King Faisal University N'-(2-(5-phenyl-1,3,4-oxadiazol-2-ylthio)acetoxy)benzo[d][1,3]dioxole-5 carboximidamide as an antimicrobial compound
US11976050B1 (en) 2023-10-11 2024-05-07 King Faisal University N′-(2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)acetoxy)-1-naphthimidamide as an antimicrobial compound
US11999706B1 (en) 2023-10-13 2024-06-04 King Faisal University 4-chloro-N′-(2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)acetoxy)benzimidamide as an antimicrobial compound

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ID24720A (id) 1997-12-12 2000-08-03 Novartis Ag Senyawa amidino tersubstitusi dalam perawatan penyakit gangguan paru-paru kronis
KR100682199B1 (ko) * 2004-07-05 2007-02-12 동화약품공업주식회사 알러지성 염증 질환의 예방 및 치료용 조성물
KR20060017929A (ko) 2004-08-04 2006-02-28 동화약품공업주식회사 티아졸 유도체가 치환된 신규한 벤즈아미딘 유도체, 그의제조방법 및 이를 유효성분으로 하는 약학 조성물
BRPI0620292B1 (pt) 2005-12-21 2021-08-24 Janssen Pharmaceutica N. V. Compostos de triazolopiridazinas como moduladores da cinase, composição, uso, combinação e processo de preparo do referido composto
WO2008021781A1 (fr) 2006-08-07 2008-02-21 Incyte Corporation Utilisation de triazolotriazines en tant qu'inhibiteurs des kinases
AU2007323725B2 (en) 2006-11-22 2014-02-20 Incyte Holdings Corporation Imidazotriazines and imidazopyrimidines as kinase inhibitors
MY187131A (en) 2008-05-21 2021-09-02 Incyte Corp Salts of 2-fluoro-n-methyl-4-[7-(quinolin-6-yl-methyl)-imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide and processes related to preparing the same
US8487096B2 (en) 2010-02-03 2013-07-16 Incyte Corporation Imidazo[1,2-B][1,2,4]triazines as C-MET inhibitors
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US11897850B1 (en) 2023-10-11 2024-02-13 King Faisal University N′-(2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)acetoxy)-4-methoxybenzimidamide as an antimicrobial compound
US11912675B1 (en) 2023-10-11 2024-02-27 King Faisal University N'-(2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)acetoxy)-3,4-dimethoxybenzimidamide as an antimicrobial compound
US11919872B1 (en) 2023-10-11 2024-03-05 King Faisal University N′-(2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)acetoxy)benzimidamide as an antimicrobial compound
US11976050B1 (en) 2023-10-11 2024-05-07 King Faisal University N′-(2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)acetoxy)-1-naphthimidamide as an antimicrobial compound
US11999707B1 (en) 2023-10-11 2024-06-04 King Faisal University N′-(2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)acetoxy)-1-naphthimidamide as an antimicrobial compound
US11891366B1 (en) 2023-10-12 2024-02-06 King Faisal University 4-methoxy-n′-(2-(5-phenyl-1,3,4-oxadiazol-2-ylthio)acetoxy)benzimidamide as an antimicrobial compound
US11905263B1 (en) 2023-10-13 2024-02-20 King Faisal University 4-nitro-N′-(2-(5-phenyl-1,3,4-oxadiazol-2-ylthio)acetoxy)benzimidamide as an antimicrobial compound
US11932632B1 (en) 2023-10-13 2024-03-19 King Faisal University N'-(2-(5-phenyl-1,3,4-oxadiazol-2-ylthio)acetoxy)benzo[d][1,3]dioxole-5 carboximidamide as an antimicrobial compound
US11999706B1 (en) 2023-10-13 2024-06-04 King Faisal University 4-chloro-N′-(2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)acetoxy)benzimidamide as an antimicrobial compound
US11999705B1 (en) 2023-10-13 2024-06-04 King Faisal University 4-chloro-N′-(2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)acetoxy)benzimidamide as an antimicrobial compound
US12012388B1 (en) 2023-10-13 2024-06-18 King Faisal University 4-chloro-n'-(2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)acetoxy)benzimidamide as an antimicrobial compound

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JPH08508467A (ja) 1996-09-10
NO953763L (no) 1995-09-25
KR960701026A (ko) 1996-02-24
SK117495A3 (en) 1996-01-10
LV11465B (en) 1996-12-20
CA2158994A1 (fr) 1994-09-29
HU9502778D0 (en) 1995-11-28
FI954491A0 (fi) 1995-09-22
CN1124486A (zh) 1996-06-12
CZ246695A3 (en) 1996-02-14
IL109073A0 (en) 1994-06-24
HUT73968A (en) 1996-10-28
PL310806A1 (en) 1996-01-08
BG100069A (en) 1996-04-30
WO1994021616A1 (fr) 1994-09-29
NO953763D0 (no) 1995-09-22
DE4309285A1 (de) 1994-09-29
FI954491A (fi) 1995-09-22
LV11465A (lv) 1996-08-20
ZA941993B (en) 1994-09-23
AU6378094A (en) 1994-10-11

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