ZA200603938B - Pyrazole derivatives as inhibitors of receptor tyroyne kinases - Google Patents

Pyrazole derivatives as inhibitors of receptor tyroyne kinases Download PDF

Info

Publication number: ZA200603938B
Authority: ZA; South Africa
Prior art keywords: amino; optionally substituted; alkyl; methyl; formula
Prior art date: 2003-11-17

Application number

ZA200603938A

Other languages

English (en)

Inventor

Block Michael Howard

Josey John Anthony

Scott David

Wang Haixia

Yu Dingwei

Han Yongxin

John W Lee

Wang Bin

Wang Tao

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.)

2003-11-17

Filing date

2006-05-16

Publication date

2007-11-28

2006-05-16 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2007-11-28 Publication of ZA200603938B publication Critical patent/ZA200603938B/en

Links

239000003112 inhibitor Substances 0.000 title description 8
150000003217 pyrazoles Chemical class 0.000 title description 8
108091000080 Phosphotransferase Proteins 0.000 title description 4
102000020233 phosphotransferase Human genes 0.000 title description 4
-1 nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl Chemical group 0.000 claims description 97
125000000217 alkyl group Chemical group 0.000 claims description 69
125000000623 heterocyclic group Chemical group 0.000 claims description 41
150000001875 compounds Chemical class 0.000 claims description 39
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 38
150000003839 salts Chemical class 0.000 claims description 30
229910052757 nitrogen Inorganic materials 0.000 claims description 29
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 29
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 28
229910052799 carbon Inorganic materials 0.000 claims description 28
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
125000005843 halogen group Chemical group 0.000 claims description 22
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 19
125000004452 carbocyclyl group Chemical group 0.000 claims description 17
229910052739 hydrogen Inorganic materials 0.000 claims description 17
206010028980 Neoplasm Diseases 0.000 claims description 15
239000001257 hydrogen Substances 0.000 claims description 14
125000003545 alkoxy group Chemical group 0.000 claims description 11
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
238000004519 manufacturing process Methods 0.000 claims description 11
238000000034 method Methods 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
125000004423 acyloxy group Chemical group 0.000 claims description 9
150000002431 hydrogen Chemical class 0.000 claims description 9
238000011282 treatment Methods 0.000 claims description 9
208000000236 Prostatic Neoplasms Diseases 0.000 claims description 8
125000002619 bicyclic group Chemical group 0.000 claims description 8
201000011510 cancer Diseases 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
206010060862 Prostate cancer Diseases 0.000 claims description 7
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 7
125000001589 carboacyl group Chemical group 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 7
239000008194 pharmaceutical composition Substances 0.000 claims description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 5
206010041067 Small cell lung cancer Diseases 0.000 claims description 5
125000003342 alkenyl group Chemical group 0.000 claims description 5
230000001028 anti-proliverative effect Effects 0.000 claims description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
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208000000587 small cell lung carcinoma Diseases 0.000 claims description 5
208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 5
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208000001333 Colorectal Neoplasms Diseases 0.000 claims description 4
206010033128 Ovarian cancer Diseases 0.000 claims description 4
206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
230000000694 effects 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
238000011321 prophylaxis Methods 0.000 claims description 4
125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 3
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 3
206010006187 Breast cancer Diseases 0.000 claims description 3
208000026310 Breast neoplasm Diseases 0.000 claims description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
208000007766 Kaposi sarcoma Diseases 0.000 claims description 3
206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
241001465754 Metazoa Species 0.000 claims description 3
125000002837 carbocyclic group Chemical group 0.000 claims description 3
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
208000032839 leukemia Diseases 0.000 claims description 3
201000005202 lung cancer Diseases 0.000 claims description 3
208000020816 lung neoplasm Diseases 0.000 claims description 3
201000001441 melanoma Diseases 0.000 claims description 3
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 3
125000001424 substituent group Chemical group 0.000 claims description 3
125000001054 5 membered carbocyclic group Chemical group 0.000 claims description 2
206010005003 Bladder cancer Diseases 0.000 claims description 2
206010008342 Cervix carcinoma Diseases 0.000 claims description 2
208000006168 Ewing Sarcoma Diseases 0.000 claims description 2
208000008839 Kidney Neoplasms Diseases 0.000 claims description 2
206010025323 Lymphomas Diseases 0.000 claims description 2
206010029260 Neuroblastoma Diseases 0.000 claims description 2
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206010035226 Plasma cell myeloma Diseases 0.000 claims description 2
206010038389 Renal cancer Diseases 0.000 claims description 2
208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 2
125000002947 alkylene group Chemical group 0.000 claims description 2
201000010881 cervical cancer Diseases 0.000 claims description 2
206010017758 gastric cancer Diseases 0.000 claims description 2
201000010536 head and neck cancer Diseases 0.000 claims description 2
208000014829 head and neck neoplasm Diseases 0.000 claims description 2
201000010982 kidney cancer Diseases 0.000 claims description 2
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
201000000050 myeloid neoplasm Diseases 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
201000011549 stomach cancer Diseases 0.000 claims description 2
201000005112 urinary bladder cancer Diseases 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims 5
125000004193 piperazinyl group Chemical group 0.000 claims 5
239000003085 diluting agent Substances 0.000 claims 4
239000003937 drug carrier Substances 0.000 claims 4
239000000546 pharmaceutical excipient Substances 0.000 claims 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
230000005764 inhibitory process Effects 0.000 claims 3
125000000714 pyrimidinyl group Chemical group 0.000 claims 3
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 2
125000002373 5 membered heterocyclic group Chemical group 0.000 claims 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
239000000203 mixture Substances 0.000 claims 2
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
YPFDHNVEDLHUCE-UHFFFAOYSA-N propane-1,3-diol Chemical compound OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 claims 2
125000004076 pyridyl group Chemical group 0.000 claims 2
125000000719 pyrrolidinyl group Chemical group 0.000 claims 2
125000000335 thiazolyl group Chemical group 0.000 claims 2
125000001544 thienyl group Chemical group 0.000 claims 2
MAYHUFQBMJUHBX-HNNXBMFYSA-N (2r)-2-[[4-[(5-cyclopropyl-1h-pyrazol-3-yl)amino]-5-fluoropyrimidin-2-yl]amino]-2-(4-fluorophenyl)ethanol Chemical compound N([C@@H](CO)C=1C=CC(F)=CC=1)C(N=1)=NC=C(F)C=1NC(=NN1)C=C1C1CC1 MAYHUFQBMJUHBX-HNNXBMFYSA-N 0.000 claims 1
ODABQTDWBANHOR-IBGZPJMESA-N (2r)-2-[[4-[(5-cyclopropyl-1h-pyrazol-3-yl)amino]-7-fluoroquinazolin-2-yl]amino]-2-(4-fluorophenyl)ethanol Chemical compound N([C@@H](CO)C=1C=CC(F)=CC=1)C(N=C1C=C(F)C=CC1=1)=NC=1NC(=NN1)C=C1C1CC1 ODABQTDWBANHOR-IBGZPJMESA-N 0.000 claims 1
FXSOVNSBVDXYOV-HNNXBMFYSA-N (2r)-2-[[5-chloro-4-[(5-cyclopropyl-1h-pyrazol-3-yl)amino]pyrimidin-2-yl]amino]-2-(4-fluorophenyl)ethanol Chemical compound N([C@@H](CO)C=1C=CC(F)=CC=1)C(N=1)=NC=C(Cl)C=1NC(NN=1)=CC=1C1CC1 FXSOVNSBVDXYOV-HNNXBMFYSA-N 0.000 claims 1
ILROLYQPRYHHFG-UHFFFAOYSA-N 1-$l^{1}-oxidanylprop-2-en-1-one Chemical group [O]C(=O)C=C ILROLYQPRYHHFG-UHFFFAOYSA-N 0.000 claims 1
125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims 1
XFGQQCZWCNSYOC-LBPRGKRZSA-N 2-[[5-chloro-2-[[(1s)-1-(4-fluorophenyl)ethyl]amino]-6-[(3-propan-2-yloxy-1h-pyrazol-5-yl)amino]pyrimidin-4-yl]amino]propane-1,3-diol Chemical compound N1C(OC(C)C)=CC(NC=2C(=C(NC(CO)CO)N=C(N[C@@H](C)C=3C=CC(F)=CC=3)N=2)Cl)=N1 XFGQQCZWCNSYOC-LBPRGKRZSA-N 0.000 claims 1
SWQAOASNZJKPPA-INIZCTEOSA-N 2-[[5-chloro-6-[(5-cyclopropyl-1h-pyrazol-3-yl)amino]-2-[[(1r)-1-(4-fluorophenyl)-2-hydroxyethyl]amino]pyrimidin-4-yl]amino]propane-1,3-diol Chemical compound C1([C@H](CO)NC=2N=C(C(=C(NC3=NNC(=C3)C3CC3)N=2)Cl)NC(CO)CO)=CC=C(F)C=C1 SWQAOASNZJKPPA-INIZCTEOSA-N 0.000 claims 1
125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims 1
GMMWNTHAIOJBSD-UHFFFAOYSA-N 6-chloro-4-n-(2,3-dimethylphenyl)-2-n,2-n-dimethylpyrimidine-2,4-diamine Chemical compound CN(C)C1=NC(Cl)=CC(NC=2C(=C(C)C=CC=2)C)=N1 GMMWNTHAIOJBSD-UHFFFAOYSA-N 0.000 claims 1
201000008808 Fibrosarcoma Diseases 0.000 claims 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 1
125000004744 butyloxycarbonyl group Chemical group 0.000 claims 1
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims 1
210000003169 central nervous system Anatomy 0.000 claims 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 1
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims 1
125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims 1
201000008968 osteosarcoma Diseases 0.000 claims 1
210000001428 peripheral nervous system Anatomy 0.000 claims 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 1
125000006239 protecting group Chemical group 0.000 claims 1
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims 1
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125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
108010025020 Nerve Growth Factor Proteins 0.000 description 7
102000007072 Nerve Growth Factors Human genes 0.000 description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
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GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
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VVVPGLRKXQSQSZ-UHFFFAOYSA-N indolo[3,2-c]carbazole Chemical class C1=CC=CC2=NC3=C4C5=CC=CC=C5N=C4C=CC3=C21 VVVPGLRKXQSQSZ-UHFFFAOYSA-N 0.000 description 1
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NFVJNJQRWPQVOA-UHFFFAOYSA-N n-[2-chloro-5-(trifluoromethyl)phenyl]-2-[3-(4-ethyl-5-ethylsulfanyl-1,2,4-triazol-3-yl)piperidin-1-yl]acetamide Chemical compound CCN1C(SCC)=NN=C1C1CN(CC(=O)NC=2C(=CC=C(C=2)C(F)(F)F)Cl)CCC1 NFVJNJQRWPQVOA-UHFFFAOYSA-N 0.000 description 1
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125000004095 oxindolyl group Chemical class N1(C(CC2=CC=CC=C12)=O)* 0.000 description 1
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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

ZA200603938A 2003-11-17 2006-05-16 Pyrazole derivatives as inhibitors of receptor tyroyne kinases ZA200603938B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US52058103P	2003-11-17	2003-11-17

Publications (1)

Publication Number	Publication Date
ZA200603938B true ZA200603938B (en)	2007-11-28

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ID=37674889

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200603938A ZA200603938B (en)	2003-11-17	2006-05-16	Pyrazole derivatives as inhibitors of receptor tyroyne kinases

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CN (1)	CN1905884A (ru)
UA (1)	UA90254C2 (ru)
ZA (1)	ZA200603938B (ru)

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN103242341B (zh) *	2013-04-19	2015-12-09	中国科学院广州生物医药与健康研究院	噻吩并2，4取代嘧啶类化合物及其药物组合物与应用
CN116023380B (zh) *	2021-10-26	2024-01-23	沈阳药科大学	一类吡唑并嘧啶衍生物及制备方法和应用

2004
- 2004-11-15 CN CN 200480040487 patent/CN1905884A/zh active Pending
- 2004-11-15 UA UAA200606736A patent/UA90254C2/ru unknown
2006
- 2006-05-16 ZA ZA200603938A patent/ZA200603938B/en unknown

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Publication number	Publication date
UA90254C2 (ru)	2010-04-26
CN1905884A (zh)	2007-01-31

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