CA2014457A1 - Pyrimidine derivatives - Google Patents

Pyrimidine derivatives

Info

Publication number
CA2014457A1
CA2014457A1 CA2014457A CA2014457A CA2014457A1 CA 2014457 A1 CA2014457 A1 CA 2014457A1 CA 2014457 A CA2014457 A CA 2014457A CA 2014457 A CA2014457 A CA 2014457A CA 2014457 A1 CA2014457 A1 CA 2014457A1
Authority
CA
Canada
Prior art keywords
alkyl
cycloalkyl
alkenyl
carbon atoms
group
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.)
Granted
Application number
CA2014457A
Other languages
French (fr)
Other versions
CA2014457C (en
Inventor
Rodney Brian Hargreaves
Paul William Marshall
Bernard Joseph Mcloughlin
Stuart Dennett Mills
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.)
Syngenta Ltd
Original Assignee
Imperial Chemical 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
Priority claimed from GB898909054A external-priority patent/GB8909054D0/en
Priority claimed from GB898910548A external-priority patent/GB8910548D0/en
Application filed by Imperial Chemical Industries Ltd filed Critical Imperial Chemical Industries Ltd
Publication of CA2014457A1 publication Critical patent/CA2014457A1/en
Application granted granted Critical
Publication of CA2014457C publication Critical patent/CA2014457C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48—Two nitrogen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • 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
    • 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
    • A61P9/06—Antiarrhythmics
    • 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
    • A61P9/08—Vasodilators for multiple indications
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D403/04—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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—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
    • 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
    • C07D471/04—Ortho-condensed systems

Abstract

This invention concerns novel aminopyrimidinium salts of the formula I: <IMAGE> in which R1 is alkyl, alkenyl, cycloalkyl, phenyl, phenylalkyl or cycloalkyl-alkyl; one of R2 and R6 is a basic group selected from amino, alkylamino, dialkylamino of up to eight carbon atoms, pyrrolidino, piperidino and morpholino; and the other of R2 and R6 is hydrogen, alkyl, alkenyl, alkoxyalkyl, phenyl, phenylalkyl, cycloalkyl or cycloalkyl-alkyl; or both of R2 and R6 are basic groups as mentioned above; and R5 is hydrogen, (1-4C)alkyl or (3-6C)alkenyl; or R2 is a basic group as mentioned above, and R5 and R6 together form alkylene or, together with the appendant carbon atoms of the pyrimidine ring, complete a benzene ring; R4 is hydrogen, alkyl, cycloalkyl-alkyl, alkenyl, alkynyl or phenylalkyl; or R4 is an optionally substitutued alkylene or alkenylene linked to the nitrogen atom of the group Q.A.N-, either of which linking groups may thereby completing a ring including two adjacent carbon atoms of Q, the carbon atoms of A and the adjacent nitrogen atom of the group -A.N-; A is a direct bond to the the group -N(R4)- or is alkylene or oxyalkylene; Q is a pyridyl, furyl, thienyl or phenyl moiety; and Y is a physiologically acceptable anion; but excluding a number of compounds specified hereinafter. The invention also includes certain closely related anhydro-base derivatives which, like the formula I compounds, possess beneficial effects on the cardiovascular system (and in particular beneficial effects modulated via the sino-atrial node). Also included are pharmaceutical compositions containing the formula I compound (or a related anhydro-base) as active ingredient, and processes for the manufacture of the various novel compounds.
CA002014457A 1989-04-21 1990-04-12 Pyrimidine derivatives Expired - Fee Related CA2014457C (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB8909054.2 1989-04-21
GB898909054A GB8909054D0 (en) 1989-04-21 1989-04-21 Amino heterocycles
GB898910548A GB8910548D0 (en) 1989-05-08 1989-05-08 Heterocyclic compounds
GB8910548.0 1989-05-08

Publications (2)

Publication Number Publication Date
CA2014457A1 true CA2014457A1 (en) 1990-10-21
CA2014457C CA2014457C (en) 1999-09-28

Family

ID=26295250

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002014457A Expired - Fee Related CA2014457C (en) 1989-04-21 1990-04-12 Pyrimidine derivatives

Country Status (28)

Country Link
US (1) US5223505A (en)
EP (1) EP0422178B1 (en)
JP (1) JP2528218B2 (en)
KR (1) KR920700203A (en)
CN (1) CN1024793C (en)
AT (1) ATE112561T1 (en)
AU (1) AU635260B2 (en)
CA (1) CA2014457C (en)
DE (1) DE69013112T2 (en)
DK (1) DK0422178T3 (en)
ES (1) ES2064727T3 (en)
FI (1) FI95377C (en)
GB (1) GB2230527B (en)
GR (1) GR1000371B (en)
HR (1) HRP930793A2 (en)
HU (1) HU209586B (en)
IE (1) IE63502B1 (en)
IL (1) IL94062A (en)
MW (1) MW9090A1 (en)
MY (1) MY105637A (en)
NO (1) NO177054C (en)
NZ (1) NZ233292A (en)
PL (2) PL165502B1 (en)
PT (1) PT93823B (en)
RU (1) RU2108329C1 (en)
SI (1) SI9010799A (en)
WO (1) WO1990012790A1 (en)
YU (1) YU79990A (en)

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9012592D0 (en) * 1990-06-06 1990-07-25 Smithkline Beecham Intercredit Compounds
GB9022644D0 (en) * 1990-10-18 1990-11-28 Ici Plc Heterocyclic compounds
US5952331A (en) * 1996-05-23 1999-09-14 Syntex (Usa) Inc. Aryl pyrimidine derivatives
US5958934A (en) * 1996-05-23 1999-09-28 Syntex (U.S.A.) Inc. Aryl pyrimidine derivatives and uses thereof
TW440563B (en) * 1996-05-23 2001-06-16 Hoffmann La Roche Aryl pyrimidine derivatives and a pharmaceutical composition thereof
DE69909756D1 (en) 1998-02-17 2003-08-28 Tularik Inc ANTIVIRAL PYRIMIDINE DERIVATIVES
DE69943247D1 (en) 1998-03-27 2011-04-14 Janssen Pharmaceutica Nv HIV-inhibiting pyrimidine derivatives
DE19851421A1 (en) * 1998-11-07 2000-05-11 Boehringer Ingelheim Pharma New pyrimidines, their production and use
KR100820605B1 (en) 1999-09-24 2008-04-08 얀센 파마슈티카 엔.브이. Antiviral compositions
US6410726B1 (en) 2000-01-12 2002-06-25 Tularik Inc. Arylsulfonic acid salts of pyrimidine-based antiviral
WO2002092090A1 (en) * 2001-05-14 2002-11-21 Bristol-Myers Squibb Pharma Company Substituted pyrazinones, pyridines and pyrimidines as corticotropin releasing factor ligands
TWI329105B (en) 2002-02-01 2010-08-21 Rigel Pharmaceuticals Inc 2,4-pyrimidinediamine compounds and their uses
ES2337782T3 (en) 2002-07-29 2010-04-29 Rigel Pharmaceuticals, Inc. METHODS TO TREAT OR PREVENT AUTOIMMUNITY DISEASES WITH 2,4-PYRIMIDINDIAMINE COMPOUNDS.
US20040242568A1 (en) 2003-03-25 2004-12-02 Syrrx, Inc. Dipeptidyl peptidase inhibitors
US8309562B2 (en) 2003-07-03 2012-11-13 Myrexis, Inc. Compounds and therapeutical use thereof
EP1660092A2 (en) * 2003-07-03 2006-05-31 Myriad Genetics, Inc. 4-arylamino-quinazolines as activators of caspases and inducers of apoptosis
NZ545270A (en) * 2003-07-30 2010-04-30 Rigel Pharmaceuticals Inc 2,4-Pyrimidinediamine compounds for use in the treatment or prevention of autoimmune diseases
BRPI0413452A (en) 2003-08-13 2006-10-17 Takeda Pharmaceutical compound, pharmaceutical composition, kit, article of manufacture, and methods of inhibiting dpp-iv, therapeutic, and treating a disease state, cancer, autoimmune disorders, a condition and HIV infection
WO2005026148A1 (en) 2003-09-08 2005-03-24 Takeda San Diego, Inc. Dipeptidyl peptidase inhibitors
CN102134231B (en) 2004-03-15 2020-08-04 武田药品工业株式会社 Dipeptidyl peptidase inhibitors
ES2380550T3 (en) 2004-11-24 2012-05-16 Rigel Pharmaceuticals, Inc. Spiro-2,4-pyrimidinediamine compounds and their uses
JP2008524331A (en) 2004-12-21 2008-07-10 武田薬品工業株式会社 Dipeptidyl peptidase inhibitor
US8258145B2 (en) 2005-01-03 2012-09-04 Myrexis, Inc. Method of treating brain cancer
CA2592900A1 (en) 2005-01-03 2006-07-13 Myriad Genetics Inc. Nitrogen containing bicyclic compounds and therapeutical use thereof
KR101278397B1 (en) 2005-01-19 2013-06-25 리겔 파마슈티칼스, 인크. Prodrugs of 2,4-pyrimidinediamine compounds and their uses
WO2007027238A2 (en) * 2005-05-03 2007-03-08 Rigel Pharmaceuticals, Inc. Jak kinase inhibitors and their uses
CN101248051B (en) 2005-05-26 2013-07-17 泰博特克药品有限公司 Process for preparing 4-[(1,6-dihydro-6-oxo-2-pyrimidinyl)amino benzonitrile
PL1942898T5 (en) 2005-09-14 2014-10-31 Takeda Pharmaceuticals Co Dipeptidyl peptidase inhibitors for treating diabetes
US8222411B2 (en) 2005-09-16 2012-07-17 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
US20090221610A1 (en) * 2006-01-31 2009-09-03 Yale University Compositions and Methods for Treating Cognitive Disorders
US8324383B2 (en) 2006-09-13 2012-12-04 Takeda Pharmaceutical Company Limited Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile
TW200838536A (en) 2006-11-29 2008-10-01 Takeda Pharmaceutical Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor
US20080217501A1 (en) * 2007-02-14 2008-09-11 Chad Jensen Power a-frame
CL2008000467A1 (en) * 2007-02-14 2008-08-22 Janssen Pharmaceutica Nv COMPOUNDS DERIVED FROM 2-AMINOPIRIMIDINE, HISTAMINE RECEIVER MODULATORS H4; YOUR PREPARATION PROCEDURE; PHARMACEUTICAL COMPOSITION THAT INCLUDES SUCH COMPOUNDS; AND ITS USE TO TREAT A SELECTED INFLAMMATORY DISORDER OF ALEGIA, ASMA
US8093236B2 (en) 2007-03-13 2012-01-10 Takeda Pharmaceuticals Company Limited Weekly administration of dipeptidyl peptidase inhibitors
TWI401023B (en) * 2008-02-06 2013-07-11 Du Pont Mesoionic pesticides
US9616064B2 (en) 2011-03-30 2017-04-11 H. Lee Moffitt Cancer Center And Research Institute, Inc. Rho kinase inhibitors and methods of use
WO2018187652A1 (en) 2017-04-06 2018-10-11 Janssen Pharmaceutica Nv 2,4-diaminopyrimidine derivatives as histamine h4 modulators
AU2018352695A1 (en) 2017-10-19 2020-05-28 Effector Therapeutics, Inc. Benzimidazole-indole inhibitors of Mnk1 and Mnk2

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB815833A (en) * 1956-09-26 1959-07-01 Boots Pure Drug Co Ltd Phenanthridine compounds
BE492034A (en) * 1948-11-05
US2784124A (en) * 1953-07-01 1957-03-05 Howard R Moore Method of coating ferrous metal surface and composition therefor
US2748124A (en) * 1954-05-06 1956-05-29 Searle & Co 1-(4-anilino-2-pyrimidino)-3-alkylureas
US2845425A (en) * 1956-10-04 1958-07-29 Lilly Co Eli Substituted aminopyrimidines
DE1241832B (en) * 1963-02-23 1967-06-08 Hoechst Ag Process for the preparation of pyrimidinium compounds
DE1445740A1 (en) * 1963-09-04 1968-11-28 Bayer Ag Process for the preparation of bispyrimidinium compounds
GB1229413A (en) * 1967-06-14 1971-04-21
IN142539B (en) * 1974-05-10 1977-07-23 Ciba Geigy India Ltd
US4339453A (en) * 1979-07-23 1982-07-13 Merck & Co., Inc. Antimicrobial aminopyrimidinium salts
GR80171B (en) * 1983-08-29 1985-01-02 Ciba Geigy Ag N-(2-nitrophenyl)-4-aminopyrimidine derivatives process for the preparation thereof and use
US4725600A (en) * 1984-07-13 1988-02-16 Fujisawa Pharmaceutical Co., Ltd. Pyrimidine compounds having activity as a cardiotonic anti-hypertensive cerebrovascular vasodilator and anti-platelet aggregation agent
DE3717480A1 (en) * 1987-05-23 1988-12-01 Shell Agrar Gmbh & Co Kg Novel herbicidal and microbicidal 2,6-diaminopyrimidines
IL88507A (en) * 1987-12-03 1993-02-21 Smithkline Beckman Intercredit 2,4-diaminoquinazolines, process for their preparation and pharmaceutical compositions comprising them

Also Published As

Publication number Publication date
PL165917B1 (en) 1995-03-31
SI9010799A (en) 1995-08-31
HU903555D0 (en) 1991-05-28
HUT56080A (en) 1991-07-29
US5223505A (en) 1993-06-29
KR920700203A (en) 1992-02-19
IL94062A (en) 1995-11-27
HU209586B (en) 1994-08-29
PL165502B1 (en) 1994-12-30
GB2230527A (en) 1990-10-24
GR900100304A (en) 1991-09-27
CN1024793C (en) 1994-06-01
CA2014457C (en) 1999-09-28
JP2528218B2 (en) 1996-08-28
DE69013112D1 (en) 1994-11-10
NO177054C (en) 1995-07-12
CN1047080A (en) 1990-11-21
AU635260B2 (en) 1993-03-18
NO905519L (en) 1991-02-20
NO905519D0 (en) 1990-12-20
FI906307A0 (en) 1990-12-20
IL94062A0 (en) 1991-01-31
GB2230527B (en) 1993-05-05
EP0422178B1 (en) 1994-10-05
GR1000371B (en) 1992-06-30
MW9090A1 (en) 1991-11-13
ATE112561T1 (en) 1994-10-15
NO177054B (en) 1995-04-03
WO1990012790A1 (en) 1990-11-01
EP0422178A1 (en) 1991-04-17
GB9007964D0 (en) 1990-06-06
JPH03505741A (en) 1991-12-12
IE901258L (en) 1990-10-21
PT93823A (en) 1990-11-20
FI95377C (en) 1996-01-25
NZ233292A (en) 1992-05-26
YU79990A (en) 1991-10-31
RU2108329C1 (en) 1998-04-10
AU5435490A (en) 1990-11-16
HRP930793A2 (en) 1996-08-31
MY105637A (en) 1994-11-30
DE69013112T2 (en) 1995-01-26
PT93823B (en) 1996-09-30
FI95377B (en) 1995-10-13
IE63502B1 (en) 1995-05-03
DK0422178T3 (en) 1994-12-19
ES2064727T3 (en) 1995-02-01

Similar Documents

Publication Publication Date Title
CA2014457A1 (en) Pyrimidine derivatives
AU642482B2 (en) 4-aminopyridinium derivatives
MY106091A (en) Heterocyclic compounds.
AU639154B2 (en) New imidazole compounds, a process for the preparation thereof, and pharmaceutical compositions containing them
JO1631B1 (en) Pyrimidine derivatives

Legal Events

Date Code Title Description
EEER Examination request
MKLA Lapsed