OA12010A - Pteridinones as kinase inhibitors. - Google Patents

Pteridinones as kinase inhibitors. Download PDF

Info

Publication number: OA12010A
Authority: OA; OAPI
Prior art keywords: amino; substituted; mono; pteridin; hydroxy
Prior art date: 1999-09-15

Application number

OA1200200058A

Other languages

English (en)

Inventor

William Alexander Denny

Ellen Myra Dobrusin

James Bernard Kramer

Dennis Joseph Mcnamara

Gordon William Rewcastle

Howard Daniel Hollis Showalter

Peter Laurence Toogood

Original Assignee

Warner Lambert Co

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.)

1999-09-15

Filing date

2000-06-21

Publication date

2006-04-19

2000-06-21 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

2006-04-19 Publication of OA12010A publication Critical patent/OA12010A/en

Links

229940043355 kinase inhibitor Drugs 0.000 title description 2
239000003757 phosphotransferase inhibitor Substances 0.000 title description 2
VWXIHLCLIOQWRA-UHFFFAOYSA-N 1h-pteridin-2-one Chemical class N1=CC=NC2=NC(O)=NC=C21 VWXIHLCLIOQWRA-UHFFFAOYSA-N 0.000 title 1
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 224
150000001875 compounds Chemical class 0.000 claims abstract description 149
125000000217 alkyl group Chemical group 0.000 claims abstract description 117
150000002367 halogens Chemical class 0.000 claims abstract description 74
229910052736 halogen Inorganic materials 0.000 claims abstract description 69
125000003545 alkoxy group Chemical group 0.000 claims abstract description 65
239000001257 hydrogen Substances 0.000 claims abstract description 52
125000002837 carbocyclic group Chemical group 0.000 claims abstract description 46
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 41
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 32
229910052760 oxygen Inorganic materials 0.000 claims abstract description 29
125000005842 heteroatom Chemical group 0.000 claims abstract description 27
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 24
239000001301 oxygen Substances 0.000 claims abstract description 24
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 21
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 20
206010028980 Neoplasm Diseases 0.000 claims abstract description 19
238000000034 method Methods 0.000 claims abstract description 19
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 18
125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 16
201000011510 cancer Diseases 0.000 claims abstract description 14
102000003903 Cyclin-dependent kinases Human genes 0.000 claims abstract description 9
108090000266 Cyclin-dependent kinases Proteins 0.000 claims abstract description 9
208000037803 restenosis Diseases 0.000 claims abstract description 8
239000003102 growth factor Substances 0.000 claims abstract description 7
230000001404 mediated effect Effects 0.000 claims abstract description 6
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 123
-1 CO2Z Chemical compound 0.000 claims description 118
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 74
125000004663 dialkyl amino group Chemical group 0.000 claims description 63
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 59
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 57
125000003118 aryl group Chemical group 0.000 claims description 55
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 39
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RGJOEKWQDUBAIZ-HDCXRZRFSA-N [[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(3s)-3-hydroxy-2,2-dimethyl-4-oxo-4-[[3-oxo-3-(2-sulfanylethylamino)propyl]amino]butyl] hydrogen phosphate Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-HDCXRZRFSA-N 0.000 claims description 34
125000000304 alkynyl group Chemical group 0.000 claims description 27
150000003839 salts Chemical class 0.000 claims description 27
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125000002431 aminoalkoxy group Chemical group 0.000 claims description 17
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
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125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
125000005236 alkanoylamino group Chemical group 0.000 claims description 14
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125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 13
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MQWJPMGOBKTYPD-UHFFFAOYSA-N 2-[4-[4-[(8-cyclopentyl-5-methyl-7-oxo-6h-pteridin-2-yl)amino]phenyl]piperazin-1-yl]acetic acid Chemical compound C12=NC(NC=3C=CC(=CC=3)N3CCN(CC(O)=O)CC3)=NC=C2N(C)CC(=O)N1C1CCCC1 MQWJPMGOBKTYPD-UHFFFAOYSA-N 0.000 claims description 3
PMVFPBHHPYGTOT-UHFFFAOYSA-N 6-(2,6-dichloro-3-hydroxyphenyl)-8-methyl-2-(4-morpholin-4-ylanilino)pteridin-7-one Chemical compound N=1C=C2N=C(C=3C(=C(O)C=CC=3Cl)Cl)C(=O)N(C)C2=NC=1NC(C=C1)=CC=C1N1CCOCC1 PMVFPBHHPYGTOT-UHFFFAOYSA-N 0.000 claims description 3
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FMCDMQJLMPRJLV-UHFFFAOYSA-N 8-cyclopentyl-5-methyl-2-(4-morpholin-4-ylanilino)-6h-pteridin-7-one Chemical compound C12=NC(NC=3C=CC(=CC=3)N3CCOCC3)=NC=C2N(C)CC(=O)N1C1CCCC1 FMCDMQJLMPRJLV-UHFFFAOYSA-N 0.000 claims description 3
208000024827 Alzheimer disease Diseases 0.000 claims description 3
101150012716 CDK1 gene Proteins 0.000 claims description 3
101100005789 Caenorhabditis elegans cdk-4 gene Proteins 0.000 claims description 3
241000450599 DNA viruses Species 0.000 claims description 3
101100059559 Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) nimX gene Proteins 0.000 claims description 3
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XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 claims description 2
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125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims 19
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101100295741 Gallus gallus COR4 gene Proteins 0.000 claims 3
YQYPLGPPOZBEJU-UHFFFAOYSA-N acetyloxycarbamic acid Chemical class CC(=O)ONC(O)=O YQYPLGPPOZBEJU-UHFFFAOYSA-N 0.000 claims 3
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125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 1
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230000000171 quenching effect Effects 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
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230000002829 reductive effect Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
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239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
230000004044 response Effects 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
229940116351 sebacate Drugs 0.000 description 1
CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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235000012239 silicon dioxide Nutrition 0.000 description 1
210000000813 small intestine Anatomy 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
206010041823 squamous cell carcinoma Diseases 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
238000003756 stirring Methods 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
238000012360 testing method Methods 0.000 description 1
210000001550 testis Anatomy 0.000 description 1
CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
208000030901 thyroid gland follicular carcinoma Diseases 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
210000002105 tongue Anatomy 0.000 description 1
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239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
231100000588 tumorigenic Toxicity 0.000 description 1
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229940070710 valerate Drugs 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
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LSGOVYNHVSXFFJ-UHFFFAOYSA-N vanadate(3-) Chemical compound [O-][V]([O-])([O-])=O LSGOVYNHVSXFFJ-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
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- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/02—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4
- C07D475/04—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4 with a nitrogen atom directly attached in position 2
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Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
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Virology (AREA)
Communicable Diseases (AREA)
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Neurosurgery (AREA)
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Urology & Nephrology (AREA)
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Obesity (AREA)
Emergency Medicine (AREA)
Hematology (AREA)
Tropical Medicine & Parasitology (AREA)
AIDS & HIV (AREA)
Heart & Thoracic Surgery (AREA)
Endocrinology (AREA)
Hospice & Palliative Care (AREA)
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OA1200200058A 1999-09-15 2000-06-21 Pteridinones as kinase inhibitors. OA12010A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US15409599P	1999-09-15	1999-09-15

Publications (1)

Publication Number	Publication Date
OA12010A true OA12010A (en)	2006-04-19

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ID=22549985

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Application Number	Title	Priority Date	Filing Date
OA1200200058A OA12010A (en)	1999-09-15	2000-06-21	Pteridinones as kinase inhibitors.

Country Status (29)

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US (2)	US7169778B2 (is)
EP (1)	EP1409487A1 (is)
JP (1)	JP2003509425A (is)
KR (1)	KR20020027649A (is)
CN (1)	CN1373763A (is)
AP (1)	AP2002002479A0 (is)
AU (1)	AU777468B2 (is)
BG (1)	BG106594A (is)
BR (1)	BR0013952A (is)
CA (1)	CA2393896A1 (is)
CR (1)	CR6586A (is)
CZ (1)	CZ2002846A3 (is)
DZ (1)	DZ3186A1 (is)
EA (1)	EA005287B1 (is)
EE (1)	EE200200140A (is)
HK (1)	HK1048992A1 (is)
HU (1)	HUP0202713A3 (is)
IL (1)	IL148614A0 (is)
IS (1)	IS6298A (is)
MA (1)	MA26819A1 (is)
MX (1)	MXPA02001108A (is)
NO (1)	NO20021239L (is)
NZ (1)	NZ516872A (is)
OA (1)	OA12010A (is)
PL (1)	PL353269A1 (is)
SK (1)	SK3542002A3 (is)
WO (1)	WO2001019825A1 (is)
YU (1)	YU18502A (is)
ZA (1)	ZA200200896B (is)

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DZ3186A1 (fr)	2001-03-22
HUP0202713A2 (hu)	2002-12-28
HUP0202713A3 (en)	2005-02-28
US20070049600A1 (en)	2007-03-01
EP1409487A1 (en)	2004-04-21
MA26819A1 (fr)	2004-12-20
NO20021239D0 (no)	2002-03-13
EE200200140A (et)	2003-04-15
IL148614A0 (en)	2002-09-12
EA200200078A1 (ru)	2002-12-26
KR20020027649A (ko)	2002-04-13
IS6298A (is)	2002-03-13
WO2001019825A1 (en)	2001-03-22
YU18502A (sh)	2004-12-31
CA2393896A1 (en)	2001-03-22
AP2002002479A0 (en)	2002-06-30
SK3542002A3 (en)	2003-04-01
NO20021239L (no)	2002-03-13
PL353269A1 (en)	2003-11-03
NZ516872A (en)	2003-10-31
EA005287B1 (ru)	2004-12-30
BR0013952A (pt)	2002-05-14
AU777468B2 (en)	2004-10-21
US20030130286A1 (en)	2003-07-10
CR6586A (es)	2004-02-02
MXPA02001108A (es)	2002-08-20
HK1048992A1 (zh)	2003-04-25
US7169778B2 (en)	2007-01-30
AU5629500A (en)	2001-04-17
JP2003509425A (ja)	2003-03-11
ZA200200896B (en)	2003-07-30
CZ2002846A3 (cs)	2003-02-12
BG106594A (en)	2002-12-29
CN1373763A (zh)	2002-10-09

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