UA75084C2 - Pyrimidine derivatives - Google Patents

Pyrimidine derivatives Download PDF

Info

Publication number: UA75084C2
Authority: UA; Ukraine
Prior art keywords: sulfamoyl; alkyl; cyano; group; pyrimidine
Prior art date: 2000-07-11

Application number

UA2003021194A

Other languages

English (en)

Ukrainian (uk)

Inventor

Nicolas John Newcome

David William Haton

Original Assignee

Astrazeneca Ab

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.)

2000-07-11

Filing date

2001-06-07

Publication date

2006-03-15

2001-06-07 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2006-03-15 Publication of UA75084C2 publication Critical patent/UA75084C2/uk

Links

150000003230 pyrimidines Chemical class 0.000 title description 7
229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 194
238000000034 method Methods 0.000 claims abstract description 159
150000002148 esters Chemical class 0.000 claims abstract description 58
150000003839 salts Chemical class 0.000 claims abstract description 58
241001465754 Metazoa Species 0.000 claims abstract description 32
230000002401 inhibitory effect Effects 0.000 claims abstract description 19
230000022131 cell cycle Effects 0.000 claims abstract description 18
-1 nitro, cyano, hydroxy, amino, carboxy, carbamoyl Chemical group 0.000 claims description 204
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 175
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 131
125000000217 alkyl group Chemical group 0.000 claims description 113
125000000623 heterocyclic group Chemical group 0.000 claims description 74
229910052757 nitrogen Inorganic materials 0.000 claims description 61
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 55
229910052799 carbon Inorganic materials 0.000 claims description 54
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 44
125000004433 nitrogen atom Chemical group N* 0.000 claims description 44
150000001721 carbon Chemical group 0.000 claims description 43
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 39
238000011282 treatment Methods 0.000 claims description 34
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 30
206010028980 Neoplasm Diseases 0.000 claims description 27
229910052736 halogen Inorganic materials 0.000 claims description 26
150000002367 halogens Chemical class 0.000 claims description 26
239000001257 hydrogen Substances 0.000 claims description 26
229910052739 hydrogen Inorganic materials 0.000 claims description 26
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 23
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
241000282414 Homo sapiens Species 0.000 claims description 17
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
125000004429 atom Chemical group 0.000 claims description 15
230000004663 cell proliferation Effects 0.000 claims description 13
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
201000011510 cancer Diseases 0.000 claims description 11
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 11
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
125000006125 ethylsulfonyl group Chemical group 0.000 claims description 10
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 10
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 10
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 9
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 9
230000005764 inhibitory process Effects 0.000 claims description 9
238000004519 manufacturing process Methods 0.000 claims description 9
239000008194 pharmaceutical composition Substances 0.000 claims description 9
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
239000003085 diluting agent Substances 0.000 claims description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
150000002431 hydrogen Chemical class 0.000 claims description 7
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
125000003277 amino group Chemical group 0.000 claims description 6
125000000753 cycloalkyl group Chemical group 0.000 claims description 6
229940126601 medicinal product Drugs 0.000 claims description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 5
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
230000035407 negative regulation of cell proliferation Effects 0.000 claims description 4
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 4
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 3
125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 3
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 3
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 2
XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 claims 1
ZHMMEIFAGDPKQU-UHFFFAOYSA-N 4-(cyclopropylamino)-2-(4-methylsulfonylanilino)pyrimidine-5-carbonitrile Chemical compound C1=CC(S(=O)(=O)C)=CC=C1NC1=NC=C(C#N)C(NC2CC2)=N1 ZHMMEIFAGDPKQU-UHFFFAOYSA-N 0.000 claims 1
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
230000000694 effects Effects 0.000 abstract description 23
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238000005481 NMR spectroscopy Methods 0.000 description 29
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 26
239000000126 substance Substances 0.000 description 20
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 20
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 19
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VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
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YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
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102000003909 Cyclin E Human genes 0.000 description 10
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230000001154 acute effect Effects 0.000 description 10
150000001412 amines Chemical class 0.000 description 10
208000035475 disorder Diseases 0.000 description 10
238000010561 standard procedure Methods 0.000 description 10
239000003039 volatile agent Substances 0.000 description 10
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
125000002252 acyl group Chemical group 0.000 description 9
238000001914 filtration Methods 0.000 description 9
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125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 8
125000001424 substituent group Chemical group 0.000 description 8
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102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 7
239000002253 acid Substances 0.000 description 7
239000003054 catalyst Substances 0.000 description 7
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 7
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208000032839 leukemia Diseases 0.000 description 7
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 7
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239000000377 silicon dioxide Substances 0.000 description 7
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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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- 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
- A61P35/00—Antineoplastic agents
- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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UA2003021194A 2000-07-11 2001-06-07 Pyrimidine derivatives UA75084C2 (en)

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2000
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Also Published As

Publication number	Publication date
DK1303496T3 (da)	2007-12-27
IL153754A (en)	2008-04-13
ES2292599T3 (es)	2008-03-16
AR031251A1 (es)	2003-09-17
IL153754A0 (en)	2003-07-06
NZ523357A (en)	2004-07-30
KR20030020925A (ko)	2003-03-10
AU6931701A (en)	2002-01-21
WO2002004429A1 (en)	2002-01-17
US6908920B2 (en)	2005-06-21
RU2299201C2 (ru)	2007-05-20
PL360385A1 (en)	2004-09-06
ATE372988T1 (de)	2007-09-15
HK1054940A1 (en)	2003-12-19
BG107451A (bg)	2003-09-30
IS6672A (is)	2003-01-08
NO20030146D0 (no)	2003-01-10
EE200300020A (et)	2004-10-15
IS2521B (is)	2009-07-15
GB0016877D0 (en)	2000-08-30
MXPA03000254A (es)	2004-12-13
CZ200376A3 (cs)	2003-04-16
KR100783447B1 (ko)	2007-12-07
CA2415486C (en)	2009-12-08
DE60130463D1 (de)	2007-10-25
CA2415486A1 (en)	2002-01-17
CN1196685C (zh)	2005-04-13
EP1303496A1 (en)	2003-04-23
TWI221470B (en)	2004-10-01
DE60130463T2 (de)	2008-06-05
NO325280B1 (no)	2008-03-17
EP1303496B1 (en)	2007-09-12
NO20030146L (no)	2003-01-10
EP1303496B9 (en)	2008-03-19
CY1107807T1 (el)	2013-06-19
AU2001269317B2 (en)	2006-08-31
JP2004502763A (ja)	2004-01-29
ZA200300079B (en)	2004-05-05
SK282003A3 (en)	2003-07-01
PT1303496E (pt)	2007-11-28
BR0112420A (pt)	2003-06-24
CN1454210A (zh)	2003-11-05
US20030216406A1 (en)	2003-11-20
HUP0301722A2 (hu)	2003-12-29
HUP0301722A3 (en)	2004-03-29

Publication	Publication Date	Title
UA75084C2 (en)	2006-03-15	Pyrimidine derivatives
RU2248976C2 (ru)	2005-03-27	Имидазо[1,2-а]пиридиновые и пиразол[2,3-а]пиридиновые производные
DE60217118T2 (de)	2007-06-28	2-anilino-pyrimidin-derivate als cyclin-abhängige kinase hemmer
DE60202844T2 (de)	2006-01-12	Pyrimidinderivate zum inhibieren der zellproliferation
DE60128343T2 (de)	2008-01-17	Pyrimidine verbindungen
DE60103935T2 (de)	2005-07-21	Imidazol-5-yl-2-anilino-pyrimidine als inhibitoren der zellproliferation
ZA200206957B (en)	2003-12-01	4-amino-5-cyano-2-anilino-pyrimidine derivatives and their use as inhibitors of cell-cycle kinases.
US20100063049A1 (en)	2010-03-11	2-carbocycloamino-4-imidazolylpyrimidines as agents for the inhbition of cell proliferation
UA78292C2 (en)	2007-03-15	Cdk-inhibiting derivatives of 4-(imidasol-5-yl)-2-(4-sulfoanilino)pyrimidine
US7485638B2 (en)	2009-02-03	Pyrimidine compounds
JP2005524672A (ja)	2005-08-18	Ｃｄｋ阻害活性を有するイミダゾリル置換ピリミジン誘導体
US7446105B2 (en)	2008-11-04	Pyrimidine compounds
AU2002302769A1 (en)	2002-12-09	2-anilino-pyrimidine derivatives as cyclin dependent kinase inhibitors