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WO1980000444A1 - Derives de l'acide hydroxamique - Google Patents

Derives de l'acide hydroxamique Download PDF

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Publication number
WO1980000444A1
WO1980000444A1 PCT/JP1979/000217 JP7900217W WO8000444A1 WO 1980000444 A1 WO1980000444 A1 WO 1980000444A1 JP 7900217 W JP7900217 W JP 7900217W WO 8000444 A1 WO8000444 A1 WO 8000444A1
Authority
WO
WIPO (PCT)
Prior art keywords
methyl
acid
hydrogen
compound according
compound
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
PCT/JP1979/000217
Other languages
English (en)
Japanese (ja)
Inventor
A Tsuda
T Munakata
T Oe
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.)
Tanabe Pharma Corp
Original Assignee
Yoshitomi Pharmaceutical 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 Yoshitomi Pharmaceutical Industries Ltd filed Critical Yoshitomi Pharmaceutical Industries Ltd
Publication of WO1980000444A1 publication Critical patent/WO1980000444A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D277/04—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D277/06—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members 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

Definitions

  • the present invention relates to a smid acid derivative in ⁇ which is therapeutically useful as an antihypertensive agent.
  • an acyl is, for example, an acetyl, a phenyl, a tylyl or a penile.
  • a low-grade cow is, for example, a methyl, an ethyl, a ° ⁇ j, an isola ⁇ pill, a ⁇ chill, an ⁇ ⁇ chill or a pli j j That is.
  • Preferred of the samric acid derivatives in the dro dro of the general formula (I) are compounds wherein? Is hydrogen and i- 1 is methyl.
  • the compound of the general formula (I) can be produced by the following methods 1 to]. Method I This method is also applied for producing a compound of the general formula (I) wherein ⁇ is other than hydrogen. ]), (I) General formula.
  • the reactive derivative of the carboxylic acid of the general formula ( ⁇ ) or (5) is, for example, an acid chloride, an acid bromide, an acid anhydride, a compound of the general formula ( ⁇ ) or ( ⁇ ⁇ Polyacid and beef carbonate (for example, chlorocarbonate or chlorocarbonate), and sulfonate sulfide (for example, For example, it is always used with methacrylic acid chloride or toluene chloride or inorganic acid chloride (for example, chlorinated chloride, chlorobenzene chloride or trichloride).
  • Mixed acid anhydrides or active esters formed by the process for example, — nitrophenyl esters or polyclonal phenyl esters) ).
  • ⁇ wipo The a-reaction is usually performed in advance with methylene chloride, black hologram, ether, tetradrofl, ⁇ ⁇ ⁇ , ⁇ : /, ⁇ General formula ( ⁇ ) or (R), a reactive derivative of R 2 / acid dissolved in methyl holamide, etc., and water, methanol , Ethanol, ⁇ otisa, tetrad, ⁇ methyl-methyl-ad, etc.
  • triethyla5 ⁇ methylanilyl, pyrin, sodium bicarbonate, sodium acid carbonate, potassium carbonate
  • a deoxidizing agent such as aluminum, sodium hydroxide or potassium hydroxide
  • the temperature is between 50 and 100 ° C, preferably between 20 and 10 ° C. To react with Is done.
  • the reaction is usually carried out with water, methanol, ethanol, lanthanum, detraridero, toluene or a mixture thereof.
  • A. WlPO In an inert solvent of the compound, preferably, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium beef
  • the reaction is carried out at 0 to 100 ° C. in the presence of a basic condensing agent such as sodium, sodium hydride or sodium hydrogen.
  • the reaction may be performed in a stream of inert gas (eg, nitrogen, argon, or helium).
  • inert gas eg, nitrogen, argon, or helium.
  • Hydrolysis involves essentially similar reactions such as analysis, t-dra ⁇ 2 / decomposition, and ester exchange.
  • Basic substances such as realm, potassium carbonate, methyl benzene, ethyl) reamy, perfluorocarbon / acid, acidic substances such as hydrochloric acid, sulfuric acid, and borohydride
  • a basic reducing agent such as sodium or a mixture thereof, preferably in water, methanol, ethanol or a mixture of these solvents. It is carried out at room temperature or under heating or cooling.
  • the reaction is an inert gas (eg, nitrogen, al: pentane or helium)
  • the succinic acid derivative in the t-mouth of the present invention exists as an optical isomer, a stereoisomer and a mixture of these isomers. All of these are included within the scope of the present invention. Mixtures of isomers can be separated into individual isomers, if desired], or by conventional methods such as fractional crystallization or chromatography. When the optical isomer of the compound of the general formula (3 ⁇ 4) or (V) is used, the compound of the general formula (I) can be stereoselectively produced.
  • the present invention relates to a compound represented by the general formula (I), wherein the succinic acid derivative in I: dro is a potent antioxidant having an inhibitory activity on angiotensin. It has been completed based on the finding that it is useful for treating malignant hypertension and essential hypertension.
  • the compounds of the present invention have an activity of inhibiting the pressor response in rats and an activity of inhibiting contractile responses to rat and ileum-excised ileum; It shows the antihypertensive activity in blood pressure rats and renal hypertension rats.
  • compound (I) has side effects such as zinc- and copper-deficiency-associated concomitant symptoms, increased tachycardiagenin edema formation, and an increase in the 7 la ⁇ f2 induced pain response in rats. Yes !? Low and very low acute toxicity in rats and mice.
  • the compounds of the invention of the general formula (I) can be obtained in the form of pharmaceutical preparations with suitable and customary pharmaceutically acceptable excipients. It is safely administered for the treatment of hypertension without giving side effects to the breather.
  • compositions are in the form of tablets, caramels, granules, powders, injections, and other common forms! ) sell.
  • Formulation examples of pharmaceutical preparations for administering the compound of the present invention for pharmaceutical purposes are as follows.
  • the daily adult dose of Compound (I) for oral administration is usually about 30 ⁇ to about 150 ⁇ .]) These are administered once or in several divided doses. Age, weight, and Z or severity of the condition to be treated and response to therapy]?

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Pyrrole Compounds (AREA)

Abstract

Derives de l'acide hydroxamique representes par la formule suivante: (FORMULE) dans laquelle R represente l'hydrogene, un groupe acyle, (R4) (R5)-NCO-, (R4) (R5) NCS- ou R6OCO- (ou R4 et R5 represente chacun l'hydrogene ou un groupe alkyle inferieur), R1 represente l'hydrogene ou un groupe alkyle inferieur, R2 et R3 represente chacun l'hydrogene un groupe alkyle inferieur ou phenyle et X represente CH2-ou-5-. Ces derives sont utilisables en tant qu'hypotenseurs. Les procedes de preparation sont les suivants: 1) Lorsque R represente un substituant autre que l'hydrogene: (FORMULE) 2) Lorsque R represente l'hydrogene: (FORMULE) (dans laquelle R7 represente un groupe alkyle inferieur et R8 est le meme que R (l'hydrogene etant exclus). ii) L'hydrolyse de composes de formule (1) dans laquelle R represente un substituant autre que l'hydrogene.
PCT/JP1979/000217 1978-08-24 1979-08-16 Derives de l'acide hydroxamique Ceased WO1980000444A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP10351778A JPS5531022A (en) 1978-08-24 1978-08-24 Hydroxamic acid derivative and its preparation
JP78/103517 1978-08-24

Publications (1)

Publication Number Publication Date
WO1980000444A1 true WO1980000444A1 (fr) 1980-03-20

Family

ID=14356131

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1979/000217 Ceased WO1980000444A1 (fr) 1978-08-24 1979-08-16 Derives de l'acide hydroxamique

Country Status (5)

Country Link
JP (1) JPS5531022A (fr)
ES (1) ES8101046A1 (fr)
FR (1) FR2434150A1 (fr)
IT (1) IT1118846B (fr)
WO (1) WO1980000444A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4745124A (en) * 1978-09-11 1988-05-17 University Of Miami Orally effective anti-hypertensive agents

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5683483A (en) * 1979-12-13 1981-07-08 Santen Pharmaceut Co Ltd Thiazolidine compound
JPS57112381A (en) * 1980-12-29 1982-07-13 Santen Pharmaceut Co Ltd Five-membered heterocyclic compound
EP0640594A1 (fr) 1993-08-23 1995-03-01 Fujirebio Inc. Dérivé de hydantoine comme inhibiteur de métalloprotease
AU4249700A (en) * 1999-04-19 2000-11-02 Sumitomo Pharmaceuticals Company, Limited Hydroxamic acid derivative
US6713477B1 (en) 2000-04-19 2004-03-30 Sumitomo Pharmaceuticals Company, Limited Hydroxamic acid derivatives

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS52100461A (en) * 1976-02-13 1977-08-23 Squibb & Sons Inc Ploline related compound and production thereof
US4046889A (en) * 1976-02-13 1977-09-06 E. R. Squibb & Sons, Inc. Azetidine-2-carboxylic acid derivatives
JPS5382778A (en) * 1976-12-03 1978-07-21 Squibb & Sons Inc Thiazolidinecarboxylate derivative and related compounds thereof process for preparing same and application thereof
JPS53112810A (en) * 1977-03-11 1978-10-02 Squibb & Sons Inc Thiopropanoylamino acid derivative and process for preparing same
JPS54103867A (en) * 1978-01-06 1979-08-15 Science Union & Cie Novel thiobutylamides and their manufacture

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2404635A1 (fr) * 1977-09-28 1979-04-27 Science Union & Cie Nouveaux thioproprionylamides, leurs procedures d'obtention et leur emploi en therapeutique

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS52100461A (en) * 1976-02-13 1977-08-23 Squibb & Sons Inc Ploline related compound and production thereof
US4046889A (en) * 1976-02-13 1977-09-06 E. R. Squibb & Sons, Inc. Azetidine-2-carboxylic acid derivatives
JPS5382778A (en) * 1976-12-03 1978-07-21 Squibb & Sons Inc Thiazolidinecarboxylate derivative and related compounds thereof process for preparing same and application thereof
JPS53112810A (en) * 1977-03-11 1978-10-02 Squibb & Sons Inc Thiopropanoylamino acid derivative and process for preparing same
JPS54103867A (en) * 1978-01-06 1979-08-15 Science Union & Cie Novel thiobutylamides and their manufacture

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4745124A (en) * 1978-09-11 1988-05-17 University Of Miami Orally effective anti-hypertensive agents

Also Published As

Publication number Publication date
IT7968693A0 (it) 1979-08-20
ES483583A0 (es) 1980-04-16
ES8101046A1 (es) 1980-04-16
FR2434150A1 (fr) 1980-03-21
JPS5531022A (en) 1980-03-05
IT1118846B (it) 1986-03-03

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