ME01934B - Derives de pyrazole servant de modulateurs de proteine kinase - Google Patents

Derives de pyrazole servant de modulateurs de proteine kinase

Info

Publication number: ME01934B
Authority: ME; Montenegro
Prior art keywords: phenyl; group; pyrazol; chloro; methyl
Prior art date: 2003-12-23

Application number

MEP-2010-532A

Other languages

English (en)

Unknown language (me)

Inventor

Valerio Berdini

Hannah Fiona Sore

David Winter Walker

Ian Collins

Robert Downham

Robin Arthur Ellis Carr

Marinus Leendert Verdonk

Steven John Woodhead

Paul Graham Wyatt

Robert George Boyle

Gordon Saxty

Original Assignee

Gordon Saxty

The Institute Of Cancer Res Royal Cancer Hospital

Cancer Research Tech 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.)

2003-12-23

Filing date

2004-12-23

Publication date

2011-06-30

2004-12-23 Application filed by Gordon Saxty, The Institute Of Cancer Res Royal Cancer Hospital, Cancer Research Tech Ltd filed Critical Gordon Saxty

2004-12-23 Priority claimed from EP04806258A external-priority patent/EP1706385B1/fr

2011-06-30 Publication of ME01934B publication Critical patent/ME01934B/fr

Links

102000001253 Protein Kinase Human genes 0.000 title description 8
108060006633 protein kinase Proteins 0.000 title description 8
150000003217 pyrazoles Chemical class 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims description 439
238000000034 method Methods 0.000 claims description 193
-1 pyrrolidinocarbonyl Chemical group 0.000 claims description 188
125000001183 hydrocarbyl group Chemical group 0.000 claims description 96
125000001424 substituent group Chemical group 0.000 claims description 88
108091008611 Protein Kinase B Proteins 0.000 claims description 78
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 76
229910052757 nitrogen Inorganic materials 0.000 claims description 70
125000005647 linker group Chemical group 0.000 claims description 69
229910052739 hydrogen Inorganic materials 0.000 claims description 67
239000001257 hydrogen Substances 0.000 claims description 66
LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 65
229910052760 oxygen Inorganic materials 0.000 claims description 64
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 62
125000004432 carbon atom Chemical group C* 0.000 claims description 56
102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 claims description 55
108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 claims description 55
125000000623 heterocyclic group Chemical group 0.000 claims description 54
238000011282 treatment Methods 0.000 claims description 54
201000010099 disease Diseases 0.000 claims description 53
125000004429 atom Chemical group 0.000 claims description 51
229910052799 carbon Inorganic materials 0.000 claims description 46
125000001072 heteroaryl group Chemical group 0.000 claims description 45
125000005842 heteroatom Chemical group 0.000 claims description 45
239000002253 acid Substances 0.000 claims description 42
125000003118 aryl group Chemical group 0.000 claims description 42
125000004093 cyano group Chemical group *C#N 0.000 claims description 42
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 42
206010028980 Neoplasm Diseases 0.000 claims description 41
238000006243 chemical reaction Methods 0.000 claims description 41
125000002837 carbocyclic group Chemical group 0.000 claims description 39
150000002431 hydrogen Chemical class 0.000 claims description 38
229910052731 fluorine Inorganic materials 0.000 claims description 37
229910052736 halogen Inorganic materials 0.000 claims description 37
125000004433 nitrogen atom Chemical group N* 0.000 claims description 37
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
150000003839 salts Chemical class 0.000 claims description 36
239000011737 fluorine Substances 0.000 claims description 33
229910052717 sulfur Inorganic materials 0.000 claims description 31
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 31
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 30
150000002367 halogens Chemical class 0.000 claims description 30
125000002950 monocyclic group Chemical group 0.000 claims description 30
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 29
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 29
229910052801 chlorine Inorganic materials 0.000 claims description 28
239000000460 chlorine Substances 0.000 claims description 27
230000002265 prevention Effects 0.000 claims description 25
239000003814 drug Substances 0.000 claims description 24
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 23
125000003545 alkoxy group Chemical group 0.000 claims description 23
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 23
125000004122 cyclic group Chemical group 0.000 claims description 23
150000002148 esters Chemical class 0.000 claims description 23
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
229910052794 bromium Inorganic materials 0.000 claims description 21
201000011510 cancer Diseases 0.000 claims description 21
125000004043 oxo group Chemical group O=* 0.000 claims description 21
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 20
230000001404 mediated effect Effects 0.000 claims description 20
150000001204 N-oxides Chemical class 0.000 claims description 17
239000002585 base Substances 0.000 claims description 16
125000002619 bicyclic group Chemical group 0.000 claims description 16
125000001153 fluoro group Chemical group F* 0.000 claims description 16
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 15
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
125000003226 pyrazolyl group Chemical group 0.000 claims description 15
125000004423 acyloxy group Chemical group 0.000 claims description 14
230000010261 cell growth Effects 0.000 claims description 14
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 14
125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 14
239000008194 pharmaceutical composition Substances 0.000 claims description 14
229920006395 saturated elastomer Polymers 0.000 claims description 14
230000002159 abnormal effect Effects 0.000 claims description 13
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 13
230000006907 apoptotic process Effects 0.000 claims description 12
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
239000012453 solvate Substances 0.000 claims description 12
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 11
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 11
239000003054 catalyst Substances 0.000 claims description 11
239000001301 oxygen Substances 0.000 claims description 11
238000002360 preparation method Methods 0.000 claims description 11
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
IVDLDHJBOWQROZ-UHFFFAOYSA-N 2-(4-chlorophenyl)-n-methyl-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CNC)C1=CC=C(Cl)C=C1 IVDLDHJBOWQROZ-UHFFFAOYSA-N 0.000 claims description 10
125000002252 acyl group Chemical group 0.000 claims description 10
238000004519 manufacturing process Methods 0.000 claims description 10
206010006187 Breast cancer Diseases 0.000 claims description 9
208000026310 Breast neoplasm Diseases 0.000 claims description 9
239000003638 chemical reducing agent Substances 0.000 claims description 9
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
208000035475 disorder Diseases 0.000 claims description 9
229940079593 drug Drugs 0.000 claims description 9
230000008569 process Effects 0.000 claims description 9
HWVGILTYGZFGLR-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CN)C1=CC=C(Cl)C=C1 HWVGILTYGZFGLR-UHFFFAOYSA-N 0.000 claims description 8
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 8
208000000236 Prostatic Neoplasms Diseases 0.000 claims description 8
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 8
229930195734 saturated hydrocarbon Natural products 0.000 claims description 8
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 7
206010061535 Ovarian neoplasm Diseases 0.000 claims description 7
206010060862 Prostate cancer Diseases 0.000 claims description 7
125000002527 bicyclic carbocyclic group Chemical group 0.000 claims description 7
125000001246 bromo group Chemical group Br* 0.000 claims description 7
229910002091 carbon monoxide Inorganic materials 0.000 claims description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
125000001309 chloro group Chemical group Cl* 0.000 claims description 7
125000002883 imidazolyl group Chemical group 0.000 claims description 7
229910052740 iodine Inorganic materials 0.000 claims description 7
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
230000035755 proliferation Effects 0.000 claims description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 6
210000000481 breast Anatomy 0.000 claims description 6
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
206010033128 Ovarian cancer Diseases 0.000 claims description 5
230000004069 differentiation Effects 0.000 claims description 5
239000011630 iodine Chemical group 0.000 claims description 5
229910052763 palladium Inorganic materials 0.000 claims description 5
210000002307 prostate Anatomy 0.000 claims description 5
210000001685 thyroid gland Anatomy 0.000 claims description 5
SSRZUATVJOAMJJ-UHFFFAOYSA-N 1-[(3,4-dichlorophenyl)-[4-(1h-pyrazol-4-yl)phenyl]methyl]piperazine Chemical compound C1=C(Cl)C(Cl)=CC=C1C(C=1C=CC(=CC=1)C1=CNN=C1)N1CCNCC1 SSRZUATVJOAMJJ-UHFFFAOYSA-N 0.000 claims description 4
MGYPCCQLBPTNML-UHFFFAOYSA-N 1-[(4-chlorophenyl)-[4-(1h-pyrazol-4-yl)phenyl]methyl]piperazine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(=CC=1)C1=CNN=C1)N1CCNCC1 MGYPCCQLBPTNML-UHFFFAOYSA-N 0.000 claims description 4
IIRWNGPLJQXWFJ-UHFFFAOYSA-N 2-amino-1-(4-chlorophenyl)-1-[4-(1h-pyrazol-4-yl)phenyl]ethanol Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(O)(CN)C1=CC=C(Cl)C=C1 IIRWNGPLJQXWFJ-UHFFFAOYSA-N 0.000 claims description 4
PMSURQYNKZJHOA-UHFFFAOYSA-N 3-(4-chlorophenyl)-3-[4-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CCN)C1=CC=C(Cl)C=C1 PMSURQYNKZJHOA-UHFFFAOYSA-N 0.000 claims description 4
WZTPTWWAPVMONU-UHFFFAOYSA-N 4-[4-(2-methoxyethoxy)phenyl]-4-[4-(1h-pyrazol-4-yl)phenyl]piperidine Chemical compound C1=CC(OCCOC)=CC=C1C1(C=2C=CC(=CC=2)C2=CNN=C2)CCNCC1 WZTPTWWAPVMONU-UHFFFAOYSA-N 0.000 claims description 4
208000029742 colonic neoplasm Diseases 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
230000003325 follicular Effects 0.000 claims description 4
208000019691 hematopoietic and lymphoid cell neoplasm Diseases 0.000 claims description 4
125000005553 heteroaryloxy group Chemical group 0.000 claims description 4
125000001624 naphthyl group Chemical group 0.000 claims description 4
238000006268 reductive amination reaction Methods 0.000 claims description 4
229930192474 thiophene Natural products 0.000 claims description 4
BSDJRCSCDXPNOO-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-(methylamino)-1-[4-(1h-pyrazol-4-yl)phenyl]ethanol Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(O)(CNC)C1=CC=C(Cl)C=C1 BSDJRCSCDXPNOO-UHFFFAOYSA-N 0.000 claims description 3
KAPLTLJNVKHMLV-UHFFFAOYSA-N 2-(4-chlorophenyl)-n,n-dimethyl-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CN(C)C)C1=CC=C(Cl)C=C1 KAPLTLJNVKHMLV-UHFFFAOYSA-N 0.000 claims description 3
GCIJUVFCSAIPKY-UHFFFAOYSA-N 3-(3,4-dichlorophenyl)-3-[4-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(CCN)C(C=C1)=CC=C1C=1C=NNC=1 GCIJUVFCSAIPKY-UHFFFAOYSA-N 0.000 claims description 3
MLWHKTLBRHPGGV-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-methyl-3-[4-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CCNC)C1=CC=C(Cl)C=C1 MLWHKTLBRHPGGV-UHFFFAOYSA-N 0.000 claims description 3
SAJGJQMGFRPHDO-UHFFFAOYSA-N 3-(4-phenoxyphenyl)-3-[4-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CCN)C(C=C1)=CC=C1OC1=CC=CC=C1 SAJGJQMGFRPHDO-UHFFFAOYSA-N 0.000 claims description 3
GNOJHSRNZXLFFX-UHFFFAOYSA-N 3-phenyl-2-[4-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CN)CC1=CC=CC=C1 GNOJHSRNZXLFFX-UHFFFAOYSA-N 0.000 claims description 3
LQLAOBTZZLDUJD-UHFFFAOYSA-N 4-(3-chloro-4-methoxyphenyl)-4-[4-(1h-pyrazol-4-yl)phenyl]piperidine Chemical compound C1=C(Cl)C(OC)=CC=C1C1(C=2C=CC(=CC=2)C2=CNN=C2)CCNCC1 LQLAOBTZZLDUJD-UHFFFAOYSA-N 0.000 claims description 3
LZMOSYUFVYJEPY-UHFFFAOYSA-N AT7867 Chemical compound C1=CC(Cl)=CC=C1C1(C=2C=CC(=CC=2)C2=CNN=C2)CCNCC1 LZMOSYUFVYJEPY-UHFFFAOYSA-N 0.000 claims description 3
206010009944 Colon cancer Diseases 0.000 claims description 3
125000004442 acylamino group Chemical group 0.000 claims description 3
125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
201000001441 melanoma Diseases 0.000 claims description 3
125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 3
AVMYSWGHPQZPKK-UHFFFAOYSA-N n-methyl-2-(4-pyrazin-2-yloxyphenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CNC)C(C=C1)=CC=C1OC1=CN=CC=N1 AVMYSWGHPQZPKK-UHFFFAOYSA-N 0.000 claims description 3
210000002784 stomach Anatomy 0.000 claims description 3
125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 2
YPAHULZLTKIWQR-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethyl]imidazole Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(=CC=1)C1=CNN=C1)CN1C=NC=C1 YPAHULZLTKIWQR-UHFFFAOYSA-N 0.000 claims description 2
HLVUQRHDBODCFJ-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethyl]piperazine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(=CC=1)C1=CNN=C1)CN1CCNCC1 HLVUQRHDBODCFJ-UHFFFAOYSA-N 0.000 claims description 2
XGMBCVUAPHUSMA-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethyl]piperidine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(=CC=1)C1=CNN=C1)CN1CCCCC1 XGMBCVUAPHUSMA-UHFFFAOYSA-N 0.000 claims description 2
FVHKVHULVJSUGS-UHFFFAOYSA-N 1-[3-(4-chlorophenyl)-3-[4-(1h-pyrazol-4-yl)phenyl]propyl]imidazole Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(=CC=1)C1=CNN=C1)CCN1C=NC=C1 FVHKVHULVJSUGS-UHFFFAOYSA-N 0.000 claims description 2
YMOIUHMRAZGIKG-UHFFFAOYSA-N 1-[3-phenoxy-3-[4-(1h-pyrazol-4-yl)phenyl]propyl]imidazole Chemical compound C=1C=CC=CC=1OC(C=1C=CC(=CC=1)C1=CNN=C1)CCN1C=CN=C1 YMOIUHMRAZGIKG-UHFFFAOYSA-N 0.000 claims description 2
YHDRFTQLBPOIDN-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(CN)C(C=C1)=CC=C1C=1C=NNC=1 YHDRFTQLBPOIDN-UHFFFAOYSA-N 0.000 claims description 2
KTCZKWVYZSCJKV-UHFFFAOYSA-N 2-(3-chloro-4-methoxyphenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C1=C(Cl)C(OC)=CC=C1C(CN)C1=CC=C(C2=CNN=C2)C=C1 KTCZKWVYZSCJKV-UHFFFAOYSA-N 0.000 claims description 2
YVVUEDSXVDPICU-UHFFFAOYSA-N 2-(3-chloro-4-methoxyphenyl)-n-methyl-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(OC)C(Cl)=CC=1C(CNC)C(C=C1)=CC=C1C=1C=NNC=1 YVVUEDSXVDPICU-UHFFFAOYSA-N 0.000 claims description 2
JQAPAUAVUKTZPG-UHFFFAOYSA-N 2-(3-chlorophenyl)-n-methyl-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=CC(Cl)=CC=1C(CNC)C(C=C1)=CC=C1C=1C=NNC=1 JQAPAUAVUKTZPG-UHFFFAOYSA-N 0.000 claims description 2
FSSABRHCBJFDJH-UHFFFAOYSA-N 2-(4-chloro-3-fluorophenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(Cl)C(F)=CC=1C(CN)C(C=C1)=CC=C1C=1C=NNC=1 FSSABRHCBJFDJH-UHFFFAOYSA-N 0.000 claims description 2
OQPBTDKODFFOER-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]morpholine Chemical compound C1=CC(Cl)=CC=C1C1(C=2C=CC(=CC=2)C2=CNN=C2)OCCNC1 OQPBTDKODFFOER-UHFFFAOYSA-N 0.000 claims description 2
WJIBOVOTOYHIAY-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-fluoro-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(F)(CN)C1=CC=C(Cl)C=C1 WJIBOVOTOYHIAY-UHFFFAOYSA-N 0.000 claims description 2
HGJXGKHMXZTCMI-UHFFFAOYSA-N 2-(4-chlorophenyl)-n-(cyclopropylmethyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(=CC=1)C1=CNN=C1)CNCC1CC1 HGJXGKHMXZTCMI-UHFFFAOYSA-N 0.000 claims description 2
HBXOAWAFHYIFMJ-UHFFFAOYSA-N 2-(4-chlorophenyl)-n-ethyl-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CNCC)C1=CC=C(Cl)C=C1 HBXOAWAFHYIFMJ-UHFFFAOYSA-N 0.000 claims description 2
UAALBJPKYVOYRB-UHFFFAOYSA-N 2-(4-chlorophenyl)-n-methyl-2-[4-(1h-pyrazol-4-yl)phenyl]acetamide Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(C(=O)NC)C1=CC=C(Cl)C=C1 UAALBJPKYVOYRB-UHFFFAOYSA-N 0.000 claims description 2
YMBOWJASIPJHPL-UHFFFAOYSA-N 2-(4-chlorophenyl)-n-methyl-2-[4-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(C)(CNC)C1=CC=C(Cl)C=C1 YMBOWJASIPJHPL-UHFFFAOYSA-N 0.000 claims description 2
RQEUDJXTUCAVAA-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-methyl-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CNC)C1=CC=C(F)C=C1 RQEUDJXTUCAVAA-UHFFFAOYSA-N 0.000 claims description 2
HNVSGFVICJTHBH-UHFFFAOYSA-N 2-(4-methoxyphenyl)-n-methyl-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CNC)C1=CC=C(OC)C=C1 HNVSGFVICJTHBH-UHFFFAOYSA-N 0.000 claims description 2
XNIAUSRAGOBQDX-UHFFFAOYSA-N 2-[(4-chlorophenyl)-[4-(1h-pyrazol-4-yl)phenyl]methoxy]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(OCCN)C1=CC=C(Cl)C=C1 XNIAUSRAGOBQDX-UHFFFAOYSA-N 0.000 claims description 2
NQEBEJVATHZQHM-UHFFFAOYSA-N 2-[3-(3,5-dimethyl-1h-pyrazol-4-yl)phenyl]-1-phenylethanamine Chemical compound CC1=NNC(C)=C1C1=CC=CC(CC(N)C=2C=CC=CC=2)=C1 NQEBEJVATHZQHM-UHFFFAOYSA-N 0.000 claims description 2
QBUGJWXOVSASPH-UHFFFAOYSA-N 2-[4-(3,5-dimethyl-1h-pyrazol-4-yl)phenyl]-2-phenylethanamine Chemical compound CC1=NNC(C)=C1C1=CC=C(C(CN)C=2C=CC=CC=2)C=C1 QBUGJWXOVSASPH-UHFFFAOYSA-N 0.000 claims description 2
PEVARZMNCRMKAQ-UHFFFAOYSA-N 2-[4-[2-(methylamino)-1-[4-(1h-pyrazol-4-yl)phenyl]ethyl]phenoxy]pyridine-4-carboxamide Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CNC)C(C=C1)=CC=C1OC1=CC(C(N)=O)=CC=N1 PEVARZMNCRMKAQ-UHFFFAOYSA-N 0.000 claims description 2
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DFTKQDLKQXTTKT-UHFFFAOYSA-N tert-butyl n-[2-(4-bromophenyl)-2-hydroxyethyl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)CC(O)C1=CC=C(Br)C=C1 DFTKQDLKQXTTKT-UHFFFAOYSA-N 0.000 description 1
CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
238000012360 testing method Methods 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
150000003536 tetrazoles Chemical group 0.000 description 1
CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
150000007970 thio esters Chemical class 0.000 description 1
150000003556 thioamides Chemical class 0.000 description 1
125000003396 thiol group Chemical group [H]S* 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
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
230000002103 transcriptional effect Effects 0.000 description 1
238000013519 translation Methods 0.000 description 1
230000014616 translation Effects 0.000 description 1
108091008578 transmembrane receptors Proteins 0.000 description 1
102000027257 transmembrane receptors Human genes 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
YOIAWAIKYVEKMF-UHFFFAOYSA-N trifluoromethanesulfonic acid Chemical group OS(=O)(=O)C(F)(F)F.OS(=O)(=O)C(F)(F)F YOIAWAIKYVEKMF-UHFFFAOYSA-N 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
235000019798 tripotassium phosphate Nutrition 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
239000000225 tumor suppressor protein Substances 0.000 description 1
208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
241000701161 unidentified adenovirus Species 0.000 description 1
241001529453 unidentified herpesvirus Species 0.000 description 1
208000011479 upper respiratory tract disease Diseases 0.000 description 1
150000003672 ureas Chemical class 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
125000005500 uronium group Chemical group 0.000 description 1
235000016788 valerian Nutrition 0.000 description 1
239000002966 varnish Substances 0.000 description 1
230000002792 vascular Effects 0.000 description 1
210000003556 vascular endothelial cell Anatomy 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
238000010792 warming Methods 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
238000001262 western blot Methods 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

MEP-2010-532A 2003-12-23 2004-12-23 Derives de pyrazole servant de modulateurs de proteine kinase ME01934B (fr)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
US53219903P	2003-12-23	2003-12-23
GB0329617A GB0329617D0 (en)	2003-12-23	2003-12-23	Pharmaceutical compounds
US57784304P	2004-06-08	2004-06-08
EP04806258A EP1706385B1 (fr)	2003-12-23	2004-12-23	Derives de pyrazole servant de modulateurs de proteine kinase
PCT/GB2004/005464 WO2005061463A1 (fr)	2003-12-23	2004-12-23	Derives de pyrazole servant de modulateurs de proteine kinase

Publications (1)

Publication Number	Publication Date
ME01934B true ME01934B (fr)	2011-06-30

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ID=30776233

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
MEP-2010-532A ME01934B (fr)	2003-12-23	2004-12-23	Derives de pyrazole servant de modulateurs de proteine kinase

Country Status (11)

Country	Link
CN (1)	CN1922148B (fr)
AT (1)	ATE483689T1 (fr)
DE (1)	DE602004029501D1 (fr)
DK (1)	DK1706385T3 (fr)
GB (1)	GB0329617D0 (fr)
ME (1)	ME01934B (fr)
PT (1)	PT1706385E (fr)
RS (1)	RS51546B (fr)
SI (1)	SI1706385T1 (fr)
UA (1)	UA90461C2 (fr)
ZA (1)	ZA200605127B (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB0704932D0 (en) *	2007-03-14	2007-04-25	Astex Therapeutics Ltd	Pharmaceutical compounds
CN108339121A (zh) *	2017-01-25	2018-07-31	苏州大学	蛋白激酶a抑制剂在制备治疗血小板数量增多相关疾病药物中的用途
CN111056990B (zh) *	2019-12-16	2022-06-17	爱斯特（成都）生物制药股份有限公司	一种合成1-叔丁氧羰基-4-(4-羧基苯基)哌啶的制备方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9804734D0 (en) *	1998-03-05	1998-04-29	Pfizer Ltd	Compounds
AU6388900A (en) *	1999-07-30	2001-02-19	Abbott Gmbh & Co. Kg	2-pyrazolin-5-ones

2003
- 2003-12-23 GB GB0329617A patent/GB0329617D0/en not_active Ceased
2004
- 2004-12-23 RS RSP-2010/0532A patent/RS51546B/sr unknown
- 2004-12-23 SI SI200431571T patent/SI1706385T1/sl unknown
- 2004-12-23 UA UAA200608166A patent/UA90461C2/ru unknown
- 2004-12-23 DK DK04806258.2T patent/DK1706385T3/da active
- 2004-12-23 AT AT04806258T patent/ATE483689T1/de active
- 2004-12-23 ME MEP-2010-532A patent/ME01934B/fr unknown
- 2004-12-23 PT PT04806258T patent/PT1706385E/pt unknown
- 2004-12-23 DE DE602004029501T patent/DE602004029501D1/de not_active Expired - Lifetime
- 2004-12-23 CN CN2004800420375A patent/CN1922148B/zh not_active Expired - Fee Related
2006
- 2006-06-21 ZA ZA200605127A patent/ZA200605127B/xx unknown

Also Published As

Publication number	Publication date
CN1922148A (zh)	2007-02-28
DK1706385T3 (da)	2011-01-10
DE602004029501D1 (de)	2010-11-18
PT1706385E (pt)	2010-12-22
SI1706385T1 (sl)	2011-01-31
GB0329617D0 (en)	2004-01-28
ATE483689T1 (de)	2010-10-15
ZA200605127B (en)	2010-07-28
RS51546B (sr)	2011-06-30
CN1922148B (zh)	2012-03-21
UA90461C2 (en)	2010-05-11

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US8343953B2 (en)	2013-01-01	Pharmaceutical compounds
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US20100210617A1 (en)	2010-08-19	Aryl-Alkylamines And Heteroaryl-Alkylamines As Protein Kinase Inhibitors
WO2006136823A1 (fr)	2006-12-28	Amine contenant des heterocycliques comme inhibiteurs des kinases b
JP2008543919A (ja)	2008-12-04	医薬化合物
US20080275029A1 (en)	2008-11-06	Compounds for Treating Protein-Kinase Mediated Disorders
ME01934B (fr)	2011-06-30	Derives de pyrazole servant de modulateurs de proteine kinase
GB2427406A (en)	2006-12-27	Silicon-containing PKB/PKA kinase inhibitors
ES2354162T3 (es)	2011-03-10	Derivados de pirazol como modulares de proteína quinasas.
HK1097543B (en)	2010-12-24	Pyrazole derivatives as protein kinase modulators
TWI363622B (en)	2012-05-11	Pharmaceutical compounds
CN101563345A (zh)	2009-10-21	药物化合物
HK1134488A (en)	2010-04-30	Pharmaceutical compounds