WO1997049397A1 - Nouvelles compositions medicinales d'hydropyridines - Google Patents

Nouvelles compositions medicinales d'hydropyridines Download PDF

Info

Publication number
WO1997049397A1
WO1997049397A1 PCT/JP1997/002173 JP9702173W WO9749397A1 WO 1997049397 A1 WO1997049397 A1 WO 1997049397A1 JP 9702173 W JP9702173 W JP 9702173W WO 9749397 A1 WO9749397 A1 WO 9749397A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
substituted
alkoxy
substituent
pyridin
Prior art date
Application number
PCT/JP1997/002173
Other languages
English (en)
Japanese (ja)
Inventor
Fumitoshi Asai
Taketoshi Ogawa
Teruhiko Inoue
Original Assignee
Sankyo Company, Limited
Ube Industries, Ltd.
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 Sankyo Company, Limited, Ube Industries, Ltd. filed Critical Sankyo Company, Limited
Priority to AU31915/97A priority Critical patent/AU3191597A/en
Publication of WO1997049397A1 publication Critical patent/WO1997049397A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems

Definitions

  • the present invention relates to the treatment or prevention of arteriosclerosis containing 4,5,6,7-tetrahydrothienoeno [3,2-c] pyridines or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present inventors have studied the pharmacological action of a tetrahydrocheno [3,2-c] pyridine derivative for many years. As a result, they found that certain tetrahydrohydro [3,2-c] pyridines have an excellent inhibitory effect on the progression of arteriosclerosis and are useful as a therapeutic or prophylactic agent for arteriosclerosis. It was completed.
  • the present invention relates to a method for treating or preventing arteriosclerosis containing 4,5,6,7-tetrahydrocheno [3,2-c] pyridine or a pharmacologically acceptable salt thereof as an active ingredient.
  • Composition for producing a medicament for treating or preventing arteriosclerosis, 4,5,6,7-tetrahydrocheno [3,2-c] pyridines or a medicament thereof Use of a physiologically acceptable salt or a pharmacologically effective amount of 4,5,6,7-tetrahydrodrocheno [3,2-1c] pyridines or a pharmaceutically acceptable salt thereof in warm-blooded animals.
  • a method for treating or preventing arteriosclerosis to be administered is provided.
  • the active ingredient of the therapeutic or prophylactic agent for arteriosclerosis of the present invention has the general formula
  • R ′ is a phenyl group which may be substituted (the substituent may be d—C, an alkyl group, a halogen atom, a full-substituted C—, C 4 alkyl group, C, 1 C 4 An alkoxy group, a fluoro-substituted C, an alkoxy group, a cyano group or a double-hole group).
  • R 2 represents a hydrogen atom, a carboxy group, a C, -C 6 alkoxycarbonyl group or an optionally substituted C, -CT aliphatic acryl group (the substituent is a halogen atom, a hydroxyl group, a C, A C 4 alkoxy group or a cyano group.
  • R 3 represents an optionally substituted 4, 5, 6, 7-tetrahydrocheno [3, 21 c] pyridine-5-yl group (the substituent is a hydroxyl group, a C, —C 4 alkoxy group, C, -C 4 alkoxy or C, -C 6 alkanol substituted with C, -C 6 alkoxy, C 7 -C 14 aralkyloxy, d — C 1 B alkanoyloxy, 1 C, cycloalphaalkyl carbonyl O alkoxy group, C fi -. showing the C, a 4 ⁇ Lal kill O alkoxycarbonyl O alkoxy group) - Ariru carbonyl O alkoxy group, C, one C 4 alkoxycarbonyl O alkoxy group or a C 7..
  • Each of the above substituents of the optionally substituted phenyl group for R ′ is, for a C 1 -C 4 alkyl group, for example, methyl, ethyl, propyl, isopropyl, butyl, s-butyl, t-butyl, isobutyl.
  • a halogen atom may be, for example, a fluorine, chlorine, bromine or iodine atom; a fluoro-substituted 1 C, alkyl group
  • linear or branched such as fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2-fluoropropyl, 3-fluoropropyl, 2-fluorobutyl, 3-fluorobutyl, and 4-fluorobutyl.
  • Carbon number It can be 1 to 4 fluoro-substituted alkyl groups; for C, 1C 4 alkoxy groups, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, s-butoxy, t-butoxy, isobutoxy
  • C, 1C 4 alkoxy groups for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, s-butoxy, t-butoxy, isobutoxy
  • Such a straight-chain or branched alkoxy group having 1 to 4 carbon atoms may be used.
  • fluoro-substituted mono-C, -C 4 alkoxy group for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2- — Linear or branched C1-C4 such as fluorethoxy, 2-fluoropropoxy, 3-fluoropropoxy, 2-fluorisopropoxy, 4-fluorobutoxy; It may be a fluoro-substituted alkoxy group.
  • the substituent of the optionally substituted phenyl group represented by R 1 is preferably a methyl group, an ethyl group, an octogen atom, a fluoro-substituted-methyl group, a methoxy group, an ethoxy group, a fluoro-substituted methyl group A xy, cyano or nitro group;
  • they are a fluorine atom, a chlorine atom, a bromine atom, a trifluoromethyl group, a difluoromethoxy group, a trifluoromethoxy group, a cyano group or a nitro group, and particularly preferably a fluorine atom or a chlorine atom. is there.
  • the number of the substituents is preferably 1 to 3, and more preferably 1 or 2. Further, the substitution position is preferably 2, 4 or 6, and particularly preferably ortho.
  • the R 2 C, - C 6 alkoxycarbonyl group for example, main Bok Kishikaruboni ⁇ , ethoxycarbonyl, propoxycarbonyl, iso-Bo, butoxycarbonyl, Ibb Bok alkoxycarbonyl, t one-butoxycarbonyl, pentyl O alkoxycarbonyl, It may be a hexyloxycarbonyl group, preferably a d-C 4 alkoxycarbonyl group, more preferably a C, —C 2 alkoxycarbonyl group, and particularly preferably a methoxycarbonyl group. Group.
  • the aliphatic acetyl group of the optionally substituted C, -C 7 aliphatic acetyl group of R 2 includes, for example, formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, bivaloyl, and hexanoyl groups.
  • the halogen atom and the C, —C 4 alkoxy group of the substituent of the aliphatic acryl group have the same meanings as those defined for the substituent of the fuunyl group, and the substituent of the aliphatic acryl group is preferably Is a fluorine atom, a chlorine atom, a hydroxyl group, a methoxy group, an ethoxy group or a cyano group, more preferably a fluorine atom or a chlorine atom, and particularly preferably a fluorine atom.
  • substituted aliphatic acyl group examples include, for example, fluoroacetyl, difluoroacetyl, trifluoroacetyl, chloroacetyl, trichloroacetyl, bromoacetyl, iodoacetyl, 3-fluoropropionyl, and 3-chloropropionyl.
  • fluoroacetyl More preferably, fluoroacetyl, difluoroacetyl, trifluoroacetyl, chloroacetyl, 3-fluoropropionyl, 2-fluorocyclopropylcarbonyl, 2-chlorocyclopropylcarbonyl or 2-fluorocyclobutylcarbonyl Group,
  • R 3 It may be substituted for R 3 4, 5, 6, 7- te Bok Rahi Dorocheno in substituents of 5-I group, an unsubstituted or substituted C, - - [3, 2 - c] pyridine C 4 ⁇ C, -C, alkoxy moiety of alkoxy group and d—C 4 alkoxycarbonyloxy group, C, -C 6 alkanoyl moiety of C,-Ce alkanoyloxy group,
  • C - C of C cycloalkylcarbonyl O carboxymethyl group - C cycloalkyl Cal Boniru moiety is the same as defined in R 1 or R 2 described above.
  • C 7 of C 4 ⁇ Lal Kill O alkoxycarbonyl O alkoxy group - - C 7 one C 14 Ararukiru old alkoxy group and a C 7 C 14 Ararukiru moiety, C described above, to be described later to one C 4 alkyl group
  • C R —C 10 aryls are substituted, for example benzyl, naphthylmethyl, diphenylmethyl, phenethyl, 3-phenylpropyl, 4-phenylphenyl, preferably benzyl or It is a phenethyl group, particularly preferably a benzyl group.
  • C one C 4 Al kill group, C, alkoxy group or a halogen atom (preferably, a methyl group, main Bok alkoxy group, a fluorine atom or a chlorine atom) with a Is also good.
  • C one C 4 Al kill group, C, alkoxy group or a halogen atom (preferably, a methyl group, main Bok alkoxy group, a fluorine atom or a chlorine atom) with a Is also good.
  • the C 1B alkanol moiety of the C, — C, a alkanoyloxy group is, for example, C, -C E alkanol, heptanyl, octanoyl, nonanoyl, decanol, lauroyl, myristoyl, palmitolyl in R 2 described above.
  • a stearolyl preferably a C 1, 1C 12 alkanoyl, more preferably a C 2 -C 10 alkanoyl group, particularly preferably a .1 alkanoyl group.
  • C 6 one C,. C 6 — C, in the arylcarbonyl group.
  • the aryl moiety may be, for example, a phenyl or naphthyl group, preferably a phenyl group.
  • a C, monoalkyl group, a C, — alkoxy group or a halogen atom (preferably a methyl group, a methoxy group, a fluorine atom or a chlorine atom) may be present as a substituent. Alright.
  • Arca noisy Ruo alkoxy group, or - a C 4 alkoxycarbonyl old alkoxy group, particularly preferably a hydroxyl group, is pivaloyl old Kishime butoxy group, C 2 -C 6 ⁇ Rukanoiruokishi group or Ct -C 4 alkoxycarbonyl O alkoxy group .
  • the substitution position is preferably the 2-position of the tetrahydrochenobiridyl ring.
  • keto-enol type tautomers exist in the tetrahydrochenobiridyl compound substituted at the 2-position with a hydroxyl group, and isomers and mixtures thereof are also included in the compounds of the present invention.
  • the compound represented by the general formula (I) when the carbon atom or the like to which R 1 is bonded is an asymmetric carbon atom, optical isomers based on the asymmetric carbon atom exist, but the isomer and Mixtures thereof are also included in the compounds of the present invention.
  • Compound (I) is easily converted to a pharmacologically acceptable salt.
  • salts include salts with inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, and phosphoric acid, acetic acid, oxalic acid, drip acid, benzoic acid, oxalic acid, malonic acid, succinic acid, and maleic acid.
  • a salt with an organic acid such as fumaric acid, tartaric acid, citric acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid can be mentioned.
  • hydrochloride, sulfate, Nitrate, oxalate, succinate, fumarate or methanesulfonate Preferably, hydrochloride, sulfate, Nitrate, oxalate, succinate, fumarate or methanesulfonate. Further, hydrates of compound (I) or a salt thereof are also included in the present invention.
  • R 1 -substituted phenyl group (the substituent is a methyl group, an ethyl group, a halogen atom, a fluoro-substituted methyl group, a methoxy group, an ethoxy group, a fluoro-substituted methoxy group, a cyano group or A compound which is a nitro group.
  • R 1 Force Substituted Funinyl Group (The substituents are a fluorine atom, a chlorine atom, a bromine atom, a trifluoromethyl group, a difluoromethoxy group, a trifluoromethoxy group, a cyano group or a nitro group.)
  • R ′ is a substituted phenyl group (the substituent is a fluorine atom or a chlorine atom);
  • a compound wherein the substituted position of the substituted phenyl group of R 1 is 2, 4 or 6.
  • R 2 force hydrogen atom, carboxy group, C, -C 4 alkoxycarbonyl group or C 2 -alkanol group or C 3 -C 6 cycloalkylcarbonyl group which may be substituted (the substituent is , A fluorine atom, a chlorine atom, a hydroxyl group, a methoxy group, an ethoxy group or a cyano group.
  • R 2 force A compound which may be substituted with a fluorine atom, which is an acetyl, propionyl, isobutyryl, cyclopropylcarbonyl or cyclobutylcarbonyl group,
  • R 2 force a compound which is a propionyl or cyclobutylpyrcarbonyl group which may be substituted by a fluorine atom,
  • R 3 force an optionally substituted 4,5,6,7-tetrahydrothieno [3,2-c] pyridine-5-yl group (the substituent is a hydroxyl group, C> ⁇ alkoxy group, C, one C 4 Arukokishime butoxy group, C, - C 5 alkanoyloxy Noi Ruo carboxymethyl main Bok carboxymethyl group, methyl, main Bok alkoxy, Yoibe Njiruokishi group optionally substituted by Furuoro or black hole, C, — C 1B alkanoyloxy, C 3 -C 6 cycloalkylcarbonyloxy, benzoyloxy optionally substituted with methyl, methoxy, fluoro or chloro, C, -C, alkoxycarbonyloxy Benzyloxy, which may be substituted with a group or methyl, methoxy, fluoro or It is a bonyloxy group.
  • R 3 force 4,5,6,7-tetrahydrothieno [3,2-c] pyridin-5-yl group which may be substituted at the 2-position (the substituent may be a hydroxyl group, a bivaloyl oxime A compound which is a methoxy group, C 2 —C, an alkanoyloxy group or a C, alkoxy group.
  • R 3 force 4,5,6,7-tetrahydrocheno [3,2-c] pyridine-5-yl group substituted at the 2-position (the substituent is a hydroxyl group, bivaloyloxymethylene) A xy group, a C 2 -C 6 alkanoyloxy group or a C, -C, alkoxycarbonyloxy group.
  • R 1 is a substituted phenyl group (the substituent is a methyl group, an ethyl group, a halogen atom, a fluoro-substituted monomethyl group, a methoxy group, an ethoxy group, a fluoro-substituted methoxy group)
  • R 2 is a hydrogen atom, a carboxy group, a d-alkoxycarbonyl group or an optionally substituted C 2 —C 4 alkanoyl group or C 3 —C 6 is a cycloalkylcarbonyl group (the substituent is a fluorine atom, a chlorine atom, a hydroxyl group, a methoxy group, an ethoxy group or a cyano group), and R 3 may be substituted at the 2nd position.
  • R 1 force A substituted phenyl group (the substituent is a fluorine atom, a chlorine atom, a bromine atom, a trifluoromethyl group, a difluoromethoxy group, a trifluoromethoxy group, a cyano group or a nitro group).
  • R 2 a hydrogen atom, a carboxy group, a C 2 -C 4 alkoxycarbonyl group or an optionally substituted C 2 -C 4 alkanol group or a C 3 -C B cycloalkylcarbonyl group (the substituent is , A fluorine atom, a chlorine atom, a hydroxyl group, a methoxy group, an ethoxyquin group, or a cyano group.), R 3 force, and 4,5-, 6-, 7-tetrahydroche which may be substituted at the 2-position [3,2-c] pyridine-5-yl group (the substituents are hydroxyl group, C, alkoxy group, C, —C 4 alkoxymethoxy group, C, -C 5 alkanoyloxymethoxy group) Group, methyl, methoxy, fluoro Or black hole which may be substituted with Ben Jiruokishi group, C, one C 18 alk noisy Ruo alkoxy group, C
  • R ′ is a substituted phenyl group (the substituent is a fluorine atom or a chlorine atom), and R 2 is a C, 1C 2 alkoxycarbonyl group or an optionally substituted group; (I) a C 4 alkanol group or a C 3 -C R cycloalkylcarbonyl group (the substituent is a fluorine atom or a chlorine atom), and the R 3 and 2-positions may be substituted; 5,6,7-tetrahydrocheno [3,2-c] pyridin-5-yl group (the substituents are a hydroxyl group, a methoxy group, an ethoxy group, a t-butoxy group, a methoxy methoxy group, C, — C 5 alkanoyloxymethoxy, benzyloxy, — C 12 alkanoyloxy, C 3 -C 6 cycloalkylcarbonyloxy, benzoyloxy, C, 1 C 4
  • R 2 is a C, -C 2 alkoxycarbonyl group or an optionally substituted C-C, ⁇ A lucanyl group or a C 3 -Cs cycloalkylcarbonyl group (the substituent is a fluorine atom or a chlorine atom), and the R 3 position may be substituted at the second position 4, 5, 6, 7— tetrahydronaphthalene Choi Bruno [3, 2-c] pyridine one 5- I le group ( ⁇ substituent is a hydroxyl group, main butoxy group, an ethoxy group, t-butoxy group, main Tokishime butoxy group, C, one C 5 Arukanoi Ruokishime Bok alkoxy group, Benjiruokishi group, C, - C 12 alk noisy Ruo alkoxy group, C 3 - C 6 cycloalkylcarbonyl O alkoxy group, benzo I
  • R 1 The number of substituents of the substituted phenyl group of R 1 is 1 to 2, and R 2 may be substituted with a fluorine atom, acetyl, propionyl, isoptyryl, cyclopropylcarbonyl or cyclobutyl A 4,5,6,7-tetrahydrothithieno [3,2-c] pyridin-5-yl group which is a carbonyl group and may be substituted at the R 3 position 2 position (the substituent is . hydroxyl, Viva Roy Ruo Kishime Bok alkoxy group, C 2 one C, alk Noi Ruo alkoxy group or a C, -. C, alkoxycarbonyl O alkoxy Ru group der) compounds wherein,
  • the substituent position of the substituted phenyl group of R 1 is para or ortho;
  • R 2 is ; a propionyl or cyclopropylcarbonyl group which may be substituted by a fluorine atom; 3 force substituted in position 2 4, 5.6, 7-Te Bok Rahi Dorocheno [3, 2-c] pyridine one 5- I le group (said substituent represents a hydroxyl group, Pibaro Iruokishime butoxy group, z - C 6 is an alkanoyloxy group or a C, -C, alkoxycarbonyloxy group.
  • Illustrative Compound No. 4 2—acetate 5— ( ⁇ —cyclopropylcarbonyl — 2 — Fluorobenzyl) 1, 4, 5, 6, 7 — Tetrahidrothieno [3, 2-c] pyridin,
  • Exemplified Compound No. 28 5-( ⁇ -propionyl 2- 2 -fluorobenzyl) 1 2 -oxo _ 2, 4,5,6,7,7 a —Hexahidrothieno [3,2-c] pyridine
  • Illustrative Compound No. 29 5- ( ⁇ -cyclopropylcarbinyl 2 —fluoropentyl) 1-2 —oxo-1,2,4,5.6,7,7 a—Hexahi-drocheno [3,2-c] The pyridine,
  • Illustrative Compound No. 40 2—acetoxy-5— ( ⁇ -cyclopropylcarboxyl-2-cyclochlorobenzyl) 1-4,5,6,7—tetrahydrodreno [3,2-c ] Pyridine,
  • Illustrative Compound No. 5 1 2 — Hydroxy 5 — ( ⁇ — 2 — Fluorocyclopropylcarbonyl 2 — Fluorobenzyl) 1-4, ⁇ , 6, 7 — Tetrahidrocheno [3, 2-c] gin,
  • Illustrative compound number 5 3 2 —acetoxy 5 — ( ⁇ — 2 —fluorocyclopropylcarbonyl-2 —fluorobenzyl) 1-4,5,6,7 —tetrahydrodreno [3,2-c] Pyridine,
  • Illustrative Compound No. 1 8 8 2 —Acetoxy 5 — ( ⁇ -Methoxyxycarbonyl 2 —Fusoleo benzyl) 1-4,5,6,7—Tetrahydrochroeno [3,2-c] Plastic,
  • Illustrative Compound No. 2 7 7 5-( ⁇ -methoxycarbonyl 2-black benzene 4, 5, 6, 7-tetrahydrothiotheno [3,2-c] pyridine
  • Illustrative Compound No. 2 7 8 5-( ⁇ -Methoxyxycarbonyl 2 —fluorobenzil) _ 4,5,6,7 Tetrahydrodrocheno [3,2—c] pyridine
  • Illustrative Compound No. 29 7 5 ( ⁇ -cyclopropylcarbonyl 2- 2-chlorobenzyl) 1,4,5,67 7 —tetrahydrothiotheno [3,2-c] pyridine
  • the compound having the general formula (I) of the present invention is disclosed in JP-A-50-46688, JP-A-58-10583, JP-A-59-27895, JP-A-6-411139 It is easily manufactured according to a method described in a gazette or a method similar thereto.
  • Compound (I) and its pharmacologically acceptable salts have an excellent inhibitory effect on atherosclerosis progression and have low toxicity, so that they are useful as therapeutic or preventive agents (preferably, therapeutic agents) for arteriosclerosis. It is.
  • the compound (I) and a pharmacologically acceptable salt thereof are used as a therapeutic or prophylactic agent for arteriosclerosis
  • the compound itself or a pharmacologically acceptable excipient or diluent as such is used.
  • excipients eg, lactose, sucrose, glucose, sugar derivatives such as mannitol, sorbitol; corn starch, potato starch, ⁇ -starch, dextrin, carboxy.
  • Starch derivatives such as methyl starch; crystalline cellulose, low-substituted hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxymethylcellulose scalpium, internal crosslinkability propyloxymethylcellulose sodium Cell mouth derivatives such as Pum; Arabic gum; Dextran; Pullulan; Silicates such as light anhydrous silicic acid, synthetic aluminum silicate, magnesium metasilicate aluminum; phosphoric acid Phosphates such as calcium; carbonates such as carbonated calcium Sulphate such as sulfated calcium), binders (eg, the above-mentioned excipients; gelatin; polyvinylpyrrolidone; magnum gall, etc.); disintegrants (eg, the above-mentioned excipients
  • the dosage varies depending on symptoms, age, etc., but for oral administration, the lower limit is 1 mg (preferably 10 mg) and the upper limit is 200 mg (preferably 50 mg) per dose.
  • a lower limit of 0.5 mg (preferably 5 mg) and an upper limit of 500 mg (preferably 200 mg) should be administered to adults. It is desirable to administer 1 to 6 times a day depending on the symptoms.
  • the aorta is incised, and the luminal lesion is examined by Xerographic method [Hata et al., Acerosclerosis, Vol. 29, No. 251-285, pp. 1978; Hata et al. al .. Atherosclerosis, 29, 251-258 (1978)]
  • the area of the lesion was measured using an image analyzer (Image Command 5098, manufactured by Olympus).
  • the lesion area was expressed as a percentage (%) of the aortic area. Tables 2 and 3 show the results.
  • the powder of the above formulation is mixed and passed through a 60-mesh sieve, and this powder is placed in a 25 Omg No. 3 gelatin capsule to prepare a capsule.
  • the powder of the above formulation is mixed and tableted with a tableting machine to make a tablet of 20 Omg per tablet.
  • the tablets can be sugar-coated as needed.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

On décrit des compositions qui contiennent comme ingrédient actif des 4,5,6,7-tétrahydrothiéno[3,2-c]pyridines représentées par la formule (I): R?1-CH(R2)-R3¿, ou bien leurs sels pharmacologiquement acceptables. Ces compositions ont pour effet d'inhiber la progression de l'artériosclérose, elles présentent une faible toxicité et par conséquent elles sont extrêmement utiles en tant que remèdes thérapeutiques ou prophylactiques contre l'artériosclérose. Dand la formule R1 représente phényle facultativement substitué; R2 représente H, alcoxycarbonyle ou acyle aliphatique facultativement substitué; et R3 représente 4,5,6,7-tétrahydrothiéno[3,2-c]pyridin-5-yl facultativement substitué.
PCT/JP1997/002173 1996-06-26 1997-06-24 Nouvelles compositions medicinales d'hydropyridines WO1997049397A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU31915/97A AU3191597A (en) 1996-06-26 1997-06-24 Novel medicinal compositions of hydropyridines

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP16612696 1996-06-26
JP8/166126 1996-06-26
JP9/54587 1997-03-10
JP5458797 1997-03-10

Publications (1)

Publication Number Publication Date
WO1997049397A1 true WO1997049397A1 (fr) 1997-12-31

Family

ID=26395359

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1997/002173 WO1997049397A1 (fr) 1996-06-26 1997-06-24 Nouvelles compositions medicinales d'hydropyridines

Country Status (2)

Country Link
AU (1) AU3191597A (fr)
WO (1) WO1997049397A1 (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004098713A2 (fr) * 2003-05-05 2004-11-18 Eli Lilly And Company Methode de traitement de maladies cardio-vasculaires
WO2007024472A3 (fr) * 2005-08-19 2007-06-07 Lilly Co Eli Procede pour le traitement de maladies vasculaires
WO2011042918A3 (fr) * 2009-10-07 2011-06-03 Msn Laboratories Limited Procedes perfectionnes et nouveaux de preparation de prasugrel, de ses intermediaires et de sels de qualite pharmaceutique
WO2011095049A1 (fr) 2010-02-02 2011-08-11 江苏威凯尔医药科技有限公司 Dérivés de 2-hydroxytétrahydrothiénopyridine optiquement actifs, leur procédé de préparation et utilisation dans fabrication de médicament
RU2478385C2 (ru) * 2007-05-22 2013-04-10 Новартис Аг Соединения триазола для лечения образования биопленок
CN103923101A (zh) * 2014-04-29 2014-07-16 湖南方盛制药股份有限公司 普拉格雷的合成方法
US9321785B2 (en) 2010-08-26 2016-04-26 Ipca Laboratories Limited Methods for the treatment or prophylaxis of thrombosis or embolism
US11130766B2 (en) 2015-06-23 2021-09-28 Jiangsu Tasly Diyi Pharmaceutical Co., Ltd. Deuterated thienopiperidine derivatives, manufacturing method, and application thereof
CN115260086A (zh) * 2022-09-28 2022-11-01 吉林大学 一种氟代内标物及其应用和制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5486626A (en) * 1977-12-22 1979-07-10 Dai Ichi Seiyaku Co Ltd Remedy for peripheral artery obstruction
JPH03130289A (ja) * 1989-10-02 1991-06-04 Sanofi Sa 窒素含有環縮合チオフェンおよびフラン誘導体
JPH0641139A (ja) * 1991-09-09 1994-02-15 Sankyo Co Ltd ヒドロピリジン誘導体

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5486626A (en) * 1977-12-22 1979-07-10 Dai Ichi Seiyaku Co Ltd Remedy for peripheral artery obstruction
JPH03130289A (ja) * 1989-10-02 1991-06-04 Sanofi Sa 窒素含有環縮合チオフェンおよびフラン誘導体
JPH0641139A (ja) * 1991-09-09 1994-02-15 Sankyo Co Ltd ヒドロピリジン誘導体

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KYORIN IGAKKAI ZASSHI, 1985, Vol. 16, TANAKA et al., "Study of Platelet Aggregation Test. V. Effect of Antiplatelet Agents on Platelet Aggregation in Arteriosclerotic Disease", pages 513-519. *
THROMBOSIS RESEARCH, 1992, Vol. 65, DEMBINSKA-KIEC et al., "Ticlopidine and Platelet Function in Healthy Volunteers", pages 559-570. *

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004098713A3 (fr) * 2003-05-05 2004-12-29 Lilly Co Eli Methode de traitement de maladies cardio-vasculaires
JP2006525328A (ja) * 2003-05-05 2006-11-09 イーライ リリー アンド カンパニー 心疾患の治療方法
WO2004098713A2 (fr) * 2003-05-05 2004-11-18 Eli Lilly And Company Methode de traitement de maladies cardio-vasculaires
WO2007024472A3 (fr) * 2005-08-19 2007-06-07 Lilly Co Eli Procede pour le traitement de maladies vasculaires
RU2478385C2 (ru) * 2007-05-22 2013-04-10 Новартис Аг Соединения триазола для лечения образования биопленок
WO2011042918A3 (fr) * 2009-10-07 2011-06-03 Msn Laboratories Limited Procedes perfectionnes et nouveaux de preparation de prasugrel, de ses intermediaires et de sels de qualite pharmaceutique
US8772489B2 (en) 2010-02-02 2014-07-08 Jiangsu Vcare PharmaTech Co. Ltd. Optically active 2-hydroxy tetrahydrothienopyridine derivatives, preparation method and use in manufacture of medicament thereof
CN102863457A (zh) * 2010-02-02 2013-01-09 江苏威凯尔医药科技有限公司 光学活性2-羟基四氢噻吩并吡啶衍生物及其制备方法与在制药中的用途
WO2011095049A1 (fr) 2010-02-02 2011-08-11 江苏威凯尔医药科技有限公司 Dérivés de 2-hydroxytétrahydrothiénopyridine optiquement actifs, leur procédé de préparation et utilisation dans fabrication de médicament
US20170121341A1 (en) * 2010-02-02 2017-05-04 Jiangsu Vcare Pharmatech Co., Ltd. Optically active 2-hydroxy tetrahydrothienopyridine derivatives, preparation method and use in manufacture of medicament thereof
EP3290423A1 (fr) 2010-02-02 2018-03-07 Jiangsu Vcare Pharmatech Co., Ltd Dérivés de 2-hydroxytétrahydrothiénopyridine optiquement actifs, leur procédé de préparation et utilisation dans la fabrication de médicament
US10000506B2 (en) 2010-02-02 2018-06-19 Jiangsu Vcare Pharmatech Co., Ltd. Optically active 2-hydroxy tetrahydrothienopyridine derivatives, preparation method and use in manufacture of medicament thereof
US20190055260A1 (en) * 2010-02-02 2019-02-21 Jiangsu Vcare Pharmatech Co., Ltd. Optically active 2-hydroxy tetrahydrothienopyridine derivatives, preparation method and use in manufacture of medicament thereof
US9321785B2 (en) 2010-08-26 2016-04-26 Ipca Laboratories Limited Methods for the treatment or prophylaxis of thrombosis or embolism
CN103923101A (zh) * 2014-04-29 2014-07-16 湖南方盛制药股份有限公司 普拉格雷的合成方法
CN103923101B (zh) * 2014-04-29 2017-05-03 湖南方盛制药股份有限公司 普拉格雷的合成方法
US11130766B2 (en) 2015-06-23 2021-09-28 Jiangsu Tasly Diyi Pharmaceutical Co., Ltd. Deuterated thienopiperidine derivatives, manufacturing method, and application thereof
CN115260086A (zh) * 2022-09-28 2022-11-01 吉林大学 一种氟代内标物及其应用和制备方法

Also Published As

Publication number Publication date
AU3191597A (en) 1998-01-14

Similar Documents

Publication Publication Date Title
US20240336624A1 (en) Parp inhibitor containing piperazine structure, preparation method therefor and pharmaceutical use thereof
US11427539B2 (en) Beta-hydroxy heterocyclic amines and their use in the treatment of hyperglycaemia
US9556149B2 (en) Processes for the preparation of pyrazole derivatives useful as modulators of the 5-HT2A serotonin receptor
WO1998024768A1 (fr) Nouveaux derives d'uree
JP2002047288A (ja) 置換チアゾリジンジオン誘導体
EP3992183A1 (fr) Procédé de traitement de la fibrose pulmonaire idiopathique
US20140039007A1 (en) Compositions and methods for modulating farnesoid x receptors
JP2019524747A (ja) 痛風または高尿酸血症に関連する症状を処置または予防するための化合物、組成物、および方法
JP2008521934A (ja) Ｕｇｔ１ａ１によって代謝される薬物の薬物動態を改善するためのアタザナビルの使用
TWI848911B (zh) 以三唑并吡啶治療rbp4相關疾病之方法
WO1997049397A1 (fr) Nouvelles compositions medicinales d'hydropyridines
JP2022525795A (ja) 高血糖症の治療に有用なヘテロシクロリル（フェニル）メタノール化合物
US11793774B2 (en) Chiral beta-hydroxyethylamines and their use in the treatment of hyperglycemia
KR20210137086A (ko) 지방간 질환 및/또는 지방간염의 치료 방법
WO1998025908A1 (fr) Nouveaux derives d'aminopyrazole
JP2022525948A (ja) 高血糖症の治療に有用なヘテロアリール（ヘテロシクリル）メタノール化合物
TWI841532B (zh) 以稠合雙環吡唑治療代謝疾病之方法
JP2017533237A (ja) 強力なγ−セクレターゼモジュレータ
CN116368141A (zh) 噻二唑酮衍生物及其作为ampk激动剂用于治疗糖尿病和相关疾病的用途
JPH10310586A (ja) ヒドロピリジン類の新規医薬用途
US20210387939A1 (en) Monomethyl fumarate precursor drug compounds and pharmaceutical compositions thereof
JP2022541178A (ja) （ｓ）－３－アミノ－６－メトキシ－ｎ－（３，３，３－トリフルオロ－２－ヒドロキシ－２－メチルプロピル）－５－（トリフルオロメチル）ピコリンアミド製剤
EP0103897B1 (fr) Composition pharmaceutique utile pour l'amélioration ou le traitement des symptômes mentaux causés par des désordres organiques dans le cerveau
TWI852999B (zh) 治療脂肪性肝病及/或脂肪性肝炎的方法
WO2011058943A1 (fr) Composition pharmaceutique formée par combinaison d'un composé ayant une activité antagoniste de mchr1 et un composé ayant une activité antagoniste de npy y5

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU CA CN CZ HU KR MX NO NZ RU US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: CA