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EP1235806A1 - Nouveaux derives de 5-pyrimidinecarboxamide et compositions pharmaceutiques renfermant ces derives - Google Patents

Nouveaux derives de 5-pyrimidinecarboxamide et compositions pharmaceutiques renfermant ces derives

Info

Publication number
EP1235806A1
EP1235806A1 EP00981886A EP00981886A EP1235806A1 EP 1235806 A1 EP1235806 A1 EP 1235806A1 EP 00981886 A EP00981886 A EP 00981886A EP 00981886 A EP00981886 A EP 00981886A EP 1235806 A1 EP1235806 A1 EP 1235806A1
Authority
EP
European Patent Office
Prior art keywords
formula
derivatives
straight
group
compounds
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.)
Withdrawn
Application number
EP00981886A
Other languages
German (de)
English (en)
Other versions
EP1235806A4 (fr
Inventor
Sung June Yoon
Sang Wook Lee
Nam Doo Kim
Yong Kyun 103-1804 Seohae Apt. Park
Geun Hyung Lee
Jong Woo Kim
Sang Jin Park
Hee Jeoung Park
Hwan Bong Jang
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.)
Dong Wha Pharm Co Ltd
Original Assignee
Dong Wha Pharm Ind Co 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
Priority claimed from KR1019990053294A external-priority patent/KR100566188B1/ko
Priority claimed from KR1019990064403A external-priority patent/KR100566194B1/ko
Application filed by Dong Wha Pharm Ind Co Ltd filed Critical Dong Wha Pharm Ind Co Ltd
Publication of EP1235806A1 publication Critical patent/EP1235806A1/fr
Publication of EP1235806A4 publication Critical patent/EP1235806A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics

Definitions

  • the present invention relates to novel
  • compositions containing said derivatives More specifically,
  • the present invention relates to novel 5-pyr ⁇ m ⁇ d ⁇ necarboxam ⁇ de
  • the present invention also relates to
  • Ri is H, hydroxy, straight or branched al yl group with C ⁇ C 5 , straight or branched alkoxy group with C ⁇ C 5 , straight
  • N selected from N, 0, and S, which may be unsubstituted or
  • Ri may or may not contain
  • R 2 is H or Straight or branched alkyl group with C ⁇ C 4 ;
  • both R x and R 2 consist of 5 or 6 membered saturated
  • n is an integer between 0 and 4;
  • R 3 is mdazol-5-yl , or indazol- ⁇ -yl .
  • HBV Hepatitis B virus
  • liver cirrhosis causes acute or chronic hepatitis, which may progress to liver cirrhosis and liver cancer. It is estimated that three hundred
  • HBV genome consists of genes for polymerase (P) , surface
  • pre-Sl pre-S2 and S
  • core protein pre-C and C
  • polymerase, surface protein, and core protein are structural
  • the gene for HBV polymerase comprises 80% of the whole
  • This polypeptide includes sequences responsible for
  • HBV enters liver when antigenic protein on vi ⁇ on surface
  • liver cell DNAs are synthesized by HBV polymerase action
  • nucleic acids which is responsible for facile encapsidation .
  • nucleoside compounds such as lamivudme and
  • AIDS is a disease inducing dramatic decrease in immune
  • HIV Human immunodeficiency virus
  • HIV HIV
  • attack helper T cells which is one of the T cells with regulatory
  • helper T cells When helper T cells are infected
  • HIV have been most widely used for the treatment of AIDS.
  • the present invention provides novel
  • compositions containing said derivatives More specifically,
  • the present invention provides 5-pyr ⁇ m ⁇ dmecarboxam ⁇ de
  • invention provides novel 5-pyr ⁇ m ⁇ dmecarboxam ⁇ de derivatives
  • Ri is H, hydroxy, straight or branched alkyl group with
  • N selected from N, 0, and S, which may be unsubstituted or
  • Ri may or may not contain
  • R 2 is H or straight or branched alkyl group with C ⁇ "-C 4 ;
  • Ri and R 2 consist of 5 or 6 membered saturated
  • R 3 is indazol-5-yl or indazol-6-yl ;
  • n is an integer between 0 and .
  • Rx and R 2 are represented as a 5 or 6 membered
  • heterocyclic compounds with 1 to 3 heteroatoms selected from
  • This heterocyclic ring may be
  • Both inorganic and organic acids may be used as free acids in
  • hydrobromic acid, sulfuric acid, and phosphoric acid may be used.
  • organic acids citric acid, acetic acid, lactic acid,
  • glutamic acid and aspartic acid may be used.
  • the present invention provides a process for preparing 5-pyrimidinecarboxamide derivatives represented
  • Ri, R 2 , R 3 and n are as defined in formula 1.
  • present invention comprises two steps as in the following:
  • step 1 condition at an appropriate temperature
  • step 1 with amme compound of formula 7 in an appropriate solvent
  • organic compound may be used as a base .
  • tertiary amine such as triethylamine
  • Preferable reaction temperature is20 ⁇ 40 ° C andpreferable
  • reaction time is 1 ⁇ 6 hrs.
  • Preferable is a single solvent or a mixture of solvents
  • alcohol selected from alcohol such as methanol and ethanol, chloroform,
  • formula 7 may be carried out using one of two methods.
  • step 2-A an appropriate amine compound of formula
  • propanolamine are used all of which are commercially available.
  • organic base such as used in preparing compounds
  • a solvent a single or a mixture of solvents selected
  • alcohol such as H 2 0, methanol, ethanol, and isopropanol
  • the reaction temperature is preferably 25 ⁇ 60 ° C and may
  • step 2-B alkali compound used for the reaction in step 2-B
  • hydrolyzmg the compound of formula 6 is preferably sodium
  • hydroxide potassium hydroxide, sodium carbonate, or potassium
  • alcohol such as methanol or ethanol is preferably used.
  • Preferable reaction temperature and time are 30 — 60 ° C and
  • chloroform methylene chloride, acetonitrile
  • the present invention provides the
  • the present invention also provides the pharmaceutical
  • formula 1 as effective ingredients to prevent and treat AIDS.
  • compositions of the present invention compounds of formula 1
  • Effective dosage for compounds of formula 1 is generally
  • reaction mixture was slowly added H 2 0 (100 ml), stirred at
  • peroxidase enzyme recognize the polymerized substrates.
  • test compound 20 ⁇ l (added to 1, 0.1, and 0.01 .g/m-?) were added and allowed to react at
  • HBV polymerase catalyzes
  • nucleosides andmay be appliedtogether with nucleoside compounds
  • HBV and proliferation of HBV and may be useful as therapeutics for
  • the cell concentration was adjusted to 1> ⁇ 10 5 cells/m?
  • PCR was performed using genetic sequence of HBV core protein as a matrix. PCR reaction was carried out by adding 1 unit of
  • the present invention on the reduction of HBV proliferation.
  • invention being non-nucleosides, may not have problems such
  • control HBV proliferation and may be useful as therapeutics for
  • reaction mixture containing matrix-primer hybrid 20 ⁇ of reaction mixture containing matrix-primer hybrid
  • TTP were added to wells coated with streptavidm. Test compounds were also added at the final concentrations of 0.1 and 1 g/ml'
  • HIV reverse transcriptase was calculated using the group without
  • test compound as control and the results are represented m Table TABLE 5 Inhibitory effect on the activities of HIV reverse
  • transcriptase having more than 80%, up to max. 89% reduction
  • nucleoside compounds may be used together with nucleoside compounds since the former
  • control HIV proliferation and may be useful as therapeutics for

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Communicable Diseases (AREA)
  • Oncology (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)

Abstract

Cette invention concerne de nouveaux dérivés de 5-pyrimidinecarboxamide et des compositions pharmaceutiques les renfermant, plus précisément des dérivés de 5-pyrimidinecarboxamide et des sels de ces dérivés pharmaceutiquement acceptables. L'invention concerne également le procédé de fabrication de ces dérivés et des compositions qui les renferment comme ingrédients actifs. En particulier, lesdits dérivés de 5-pyrimidinecarboxamide peuvent être utilisés, compte tenu de leur action inhibitrice sur la prolifération du virus de l'immunodéficience humaine (VIH) et du virus de l'hépatite B (VHB), pour le traitement et la prévention de l'hépatite B et du syndrome d'immunodéficience acquise (SIDA).
EP00981886A 1999-11-27 2000-11-27 Nouveaux derives de 5-pyrimidinecarboxamide et compositions pharmaceutiques renfermant ces derives Withdrawn EP1235806A4 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
KR1019990053294A KR100566188B1 (ko) 1999-11-27 1999-11-27 신규의 5-피리미딘카르복스아미드 유도체 및 그를포함하는 약학적 조성물
KR9953294 1999-11-27
KR1019990064403A KR100566194B1 (ko) 1999-12-29 1999-12-29 신규의 3-니트로피리딘 유도체 및 그를 포함하는 약학적조성물
KR9964403 1999-12-29
PCT/KR2000/001364 WO2001038308A1 (fr) 1999-11-27 2000-11-27 Nouveaux derives de 5-pyrimidinecarboxamide et compositions pharmaceutiques renfermant ces derives

Publications (2)

Publication Number Publication Date
EP1235806A1 true EP1235806A1 (fr) 2002-09-04
EP1235806A4 EP1235806A4 (fr) 2004-02-04

Family

ID=26636372

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00981886A Withdrawn EP1235806A4 (fr) 1999-11-27 2000-11-27 Nouveaux derives de 5-pyrimidinecarboxamide et compositions pharmaceutiques renfermant ces derives

Country Status (3)

Country Link
EP (1) EP1235806A4 (fr)
AU (1) AU1899401A (fr)
WO (1) WO2001038308A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7135575B2 (en) 2003-03-03 2006-11-14 Array Biopharma, Inc. P38 inhibitors and methods of use thereof

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4210942A1 (de) * 1992-04-02 1993-10-07 Bayer Ag 7-Oxo-7H-pyrido[1,2,3-d,e][1,4]benzoxacin-6-carbonsäuren und -ester
KR200162458Y1 (ko) * 1996-12-31 1999-12-15 정몽규 차량의 에어 배출 그릴 개. 폐구조

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
No further relevant documents disclosed *
See also references of WO0138308A1 *

Also Published As

Publication number Publication date
AU1899401A (en) 2001-06-04
WO2001038308A1 (fr) 2001-05-31
EP1235806A4 (fr) 2004-02-04

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