WO2001047895A1 - Nouveaux composes comprenant des cycles heteroaromatiques a cinq chainons - Google Patents

Nouveaux composes comprenant des cycles heteroaromatiques a cinq chainons Download PDF

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Publication number
WO2001047895A1
WO2001047895A1 PCT/JP2000/009172 JP0009172W WO0147895A1 WO 2001047895 A1 WO2001047895 A1 WO 2001047895A1 JP 0009172 W JP0009172 W JP 0009172W WO 0147895 A1 WO0147895 A1 WO 0147895A1
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WIPO (PCT)
Prior art keywords
group
substituted
optionally substituted
formula
alkyl group
Prior art date
Application number
PCT/JP2000/009172
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English (en)
Japanese (ja)
Inventor
Masashi Nakatsuka
Katsunori Tsuboi
Shoji Watanabe
Original Assignee
Sumitomo Pharmaceuticals Company, Limited
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 Sumitomo Pharmaceuticals Company, Limited filed Critical Sumitomo Pharmaceuticals Company, Limited
Publication of WO2001047895A1 publication Critical patent/WO2001047895A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • 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
    • C07D263/48—Nitrogen atoms not forming part of a nitro radical
    • 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
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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

Definitions

  • acidic non-steroidal anti-inflammatory drugs or steroid drugs have been used as therapeutic agents for inflammatory diseases, but their use is limited due to side effects.
  • these treatments belong to symptomatic treatment and do not have the effect of improving the underlying causes of the disease.
  • drugs that improve the disease state by acting on the immune system such as gold preparations and D-jesilamine, have attracted attention as causative therapies. However, it is not necessarily in a satisfactory state due to side effects and lack of sustained effects. Disclosure of the invention
  • R 45 and R 48 are as shown in the following (al) or (bl), and R 46 and R 47 are as described in the above (a) or the following (cl).
  • R 45 and R 47 independently represent a hydrogen atom, an acyl group, a protecting group for an NH group, a linear or branched alkyl group having 1 to 10 carbon atoms (a linear or branched alkyl group having 1 to 10 carbon atoms) Examples of the group include a nitro group, a cyano group, an optionally substituted amino group, a hydroxyl group, an alkoxy group, an acyl group, a carboxy group, an optionally substituted sorbamoyl group, an optionally substituted sulfamoyl group, a mercapto group, S (0) r- R 32 ( r and R 32 are as defined above.), _C0 2 R 32 ( R 32 has the same meaning as defined above) 1 to 4 substituents selected arbitrarily from the group consisting of May be substituted with a group). (3 1) R 45 and R 46 represent said (bl).
  • each group in this group includes, for example, a parogen atom, a nitro group, a cyano group, a mercapto group, an oxo group, a thioxo group, a lower alkyl group, a lower haloalkyl group, a substituted or unsubstituted amino group, a hydroxyl group, and a lower alkoxy group.
  • substituent in the substituted alkyl group or the substituted lower alkyl group include, for example, any group contained in each of the following groups a) to d), and these groups may be arbitrarily substituted one or more times.
  • alkynyloxy group refers to an oxy group to which an alkynyl group is bonded.
  • a lower alkyl-oxy group refers to an oxy group to which a lower alkyl group is bonded.
  • preferred L includes a group represented by the formula (4) and the formula (9).
  • R 5 ° and R 51 are as defined above. However, when M or M 1 is a single bond or 10—, both R 5 ° and R 51 do not represent a hydrogen atom. ],
  • R 112 , R 113 or R m is a protecting group for an NH group in the compound of the formula 4-3
  • deprotection can be carried out in the same manner as described above.
  • a known method for example, TW Greene and PGM Wuts, "Protective Groups in Organic Synthesis", 2nd Ed., John Wiley and Sons, inc., P. 379-385 (1991)
  • Examples of the acid include hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, Lewis acid, and the like, and preferably, hydrochloric acid, sulfuric acid, and the like.
  • Examples of the base include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and the like.
  • Preferred solvents include, for example, water, alcoholic solvents such as methanol and ethanol, ethereal solvents such as tetrahydrofuran and 1,4-dioxane, dimethylformamide, acetate ditrinole, or methylene chloride, chlorophonolem, Examples of the solvent include a halogenated hydrocarbon solvent such as dichloroethane and benzene, and a mixed solvent thereof.
  • the solvent examples include alcohol solvents such as acetone, water, methanol, and ethanol; ether solvents such as tetrahydrofuran and 1,4-dioxane; and methylene chloride, chlorophonolem, 1,2-dichloroethane, and benzene.
  • alcohol solvents such as acetone, water, methanol, and ethanol
  • ether solvents such as tetrahydrofuran and 1,4-dioxane
  • methylene chloride, chlorophonolem, 1,2-dichloroethane, and benzene examples include halogenated hydrocarbon solvents and mixed solvents thereof. More preferably, acetone, water, and alcohol solvents are used.
  • the raw material compounds represented by Formula 1-1, Formula 2-4, Formula 5-1, Formula 5-2, Formula 5-4, Formula 5-5, and Formula 6-1 in the above production method are known compounds per se. Or a compound that can be produced by a known method. For example, it can be produced by the following method.
  • the compound represented by the formula 5-4 can be obtained by converting a carboxylic acid of the formula 8-1 into an acid chloride according to a known method (for example, A. Wissner, J. Org. Chera., 44, 4617 (1979)). , Tris
  • the target product (3.42 g) was obtained from the compound (3.0 g) obtained in Reference Example 44 and 2-methoxyethanolanol in the same manner as in Example 30.
  • the target product (2.72 g) was obtained from the compound (3.0 g) obtained in Reference Example 45 and N, N 5 -dimethyl-1,3-diaminopropane in the same manner as in Example 60 described later.
  • the desired product was obtained by the same operation as in Reference Example 1 using the same.
  • Thioamide compound which is a known compound: N- ⁇ 4- [1- (2-fluoro [1,1, -biphenyl] -4-yl) ethynole] -1,3_thiazole-2-ynole) thiopere ( Acetone (300 ml) and potassium carbonate (29.2 g ) were added to 58.0 g ) (JP-A-63-152368), and methyl iodide (25.3 g ) was added dropwise to this mixture over 30 minutes under ice-cooling. The mixture was stirred at room temperature for 2 hours.
  • the target compound (9.82 g) was obtained from the compound (lOg) obtained in Reference Example 4 by the same operation as in Reference Example 41.

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

Abstract

On décrit des composés comportant des cycles hétéroaromatiques à cinq chaînons tels que ceux représentés par la formule (1). Dans la formule (1), l'anneau A est sélectionné entre thiazole, oxazole et imidazole; E représente éventuellement aryle fusionné; G représente un groupe de liaison; et L représente une amidine. Un exemple caractéristique de ces composés est un composé représenté par la formule (2), qui est utile dans le traitement des maladies immunes et l'inflammation chronique. Formules (1) et (2)
PCT/JP2000/009172 1999-12-28 2000-12-25 Nouveaux composes comprenant des cycles heteroaromatiques a cinq chainons WO2001047895A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP11/374203 1999-12-28
JP37420399 1999-12-28

Publications (1)

Publication Number Publication Date
WO2001047895A1 true WO2001047895A1 (fr) 2001-07-05

Family

ID=18503442

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2000/009172 WO2001047895A1 (fr) 1999-12-28 2000-12-25 Nouveaux composes comprenant des cycles heteroaromatiques a cinq chainons

Country Status (1)

Country Link
WO (1) WO2001047895A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1587798A2 (fr) * 2003-01-14 2005-10-26 Merck & Co., Inc. Derives de nsaid a disubstitution geminale servant d'agents reducteurs de abeta 42

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0248399A1 (fr) * 1986-06-03 1987-12-09 Sumitomo Pharmaceuticals Company, Limited Dérivés d'aminoazoles, leur production et leur utilisation
EP0449211A1 (fr) * 1990-03-27 1991-10-02 Warner-Lambert Company 3,5-ditertiarybutyl-4-hydroxyphényl, 1,3,4-thiadiazoles et oxazoles liés par des résidues de carbone, d'oxygène et de soufre
JPH0959258A (ja) * 1995-08-11 1997-03-04 Ono Pharmaceut Co Ltd グアニジル誘導体
WO1998047880A1 (fr) * 1997-04-21 1998-10-29 Sumitomo Pharmaceuticals Company, Limited Derives d'isoxazole
WO2001005774A1 (fr) * 1999-07-15 2001-01-25 Sumitomo Pharmaceuticals Co., Ltd. Composes de cycles heteroaromatiques

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0248399A1 (fr) * 1986-06-03 1987-12-09 Sumitomo Pharmaceuticals Company, Limited Dérivés d'aminoazoles, leur production et leur utilisation
EP0449211A1 (fr) * 1990-03-27 1991-10-02 Warner-Lambert Company 3,5-ditertiarybutyl-4-hydroxyphényl, 1,3,4-thiadiazoles et oxazoles liés par des résidues de carbone, d'oxygène et de soufre
JPH0959258A (ja) * 1995-08-11 1997-03-04 Ono Pharmaceut Co Ltd グアニジル誘導体
WO1998047880A1 (fr) * 1997-04-21 1998-10-29 Sumitomo Pharmaceuticals Company, Limited Derives d'isoxazole
WO2001005774A1 (fr) * 1999-07-15 2001-01-25 Sumitomo Pharmaceuticals Co., Ltd. Composes de cycles heteroaromatiques

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1587798A2 (fr) * 2003-01-14 2005-10-26 Merck & Co., Inc. Derives de nsaid a disubstitution geminale servant d'agents reducteurs de abeta 42
JP2006517925A (ja) * 2003-01-14 2006-08-03 メルク　エンド　カムパニー　インコーポレーテッド Ａβ４２低下薬としてのジェミナル二置換ＮＳＡＩＤ誘導体
EP1587798A4 (fr) * 2003-01-14 2007-06-27 Merck & Co Inc Derives de nsaid a disubstitution geminale servant d'agents reducteurs de abeta 42
US7332516B2 (en) 2003-01-14 2008-02-19 Merck + Co., Inc. Geminally di-substituted NSAID derivatives as Aβ42 lowering agents

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