CA2594477C - Pharmaceutical compounds - Google Patents
Pharmaceutical compounds Download PDFInfo
- Publication number
- CA2594477C CA2594477C CA2594477A CA2594477A CA2594477C CA 2594477 C CA2594477 C CA 2594477C CA 2594477 A CA2594477 A CA 2594477A CA 2594477 A CA2594477 A CA 2594477A CA 2594477 C CA2594477 C CA 2594477C
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- Canada
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- groups
- carbocyclic
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- 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.)
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 260
- -1 fluorine) Chemical class 0.000 claims abstract description 230
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 184
- 150000003839 salts Chemical class 0.000 claims abstract description 176
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract description 157
- 125000001424 substituent group Chemical group 0.000 claims abstract description 146
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 126
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 120
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 111
- 239000001257 hydrogen Substances 0.000 claims abstract description 111
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 92
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 81
- 239000011737 fluorine Substances 0.000 claims abstract description 79
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 79
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 79
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 70
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 63
- 150000002367 halogens Chemical class 0.000 claims abstract description 62
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 57
- 229940088597 hormone Drugs 0.000 claims abstract description 54
- 239000005556 hormone Substances 0.000 claims abstract description 54
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 52
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 50
- 239000012453 solvate Substances 0.000 claims abstract description 46
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 34
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 34
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 28
- 125000004429 atom Chemical group 0.000 claims abstract description 26
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 22
- 229940100198 alkylating agent Drugs 0.000 claims abstract description 20
- 239000002168 alkylating agent Substances 0.000 claims abstract description 20
- 239000000556 agonist Substances 0.000 claims abstract description 18
- 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 claims abstract description 18
- 239000003667 hormone antagonist Substances 0.000 claims abstract description 14
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 13
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims abstract description 12
- 239000002875 cyclin dependent kinase inhibitor Substances 0.000 claims abstract description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 92
- 238000000034 method Methods 0.000 claims description 86
- 125000001072 heteroaryl group Chemical group 0.000 claims description 84
- 125000005842 heteroatom Chemical group 0.000 claims description 71
- 238000011282 treatment Methods 0.000 claims description 61
- 102000003903 Cyclin-dependent kinases Human genes 0.000 claims description 59
- 108090000266 Cyclin-dependent kinases Proteins 0.000 claims description 59
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 59
- 201000011510 cancer Diseases 0.000 claims description 54
- 230000000694 effects Effects 0.000 claims description 54
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 52
- 239000002253 acid Substances 0.000 claims description 51
- 229910052757 nitrogen Inorganic materials 0.000 claims description 49
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 43
- 239000000460 chlorine Substances 0.000 claims description 42
- 229910052801 chlorine Inorganic materials 0.000 claims description 41
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 38
- 125000003545 alkoxy group Chemical group 0.000 claims description 38
- 125000002950 monocyclic group Chemical group 0.000 claims description 38
- 201000010099 disease Diseases 0.000 claims description 37
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 34
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 claims description 31
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 30
- 239000003814 drug Substances 0.000 claims description 30
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 27
- 125000002619 bicyclic group Chemical group 0.000 claims description 25
- 125000001153 fluoro group Chemical group F* 0.000 claims description 25
- OVPNQJVDAFNBDN-UHFFFAOYSA-N 4-(2,6-dichlorobenzamido)-N-(piperidin-4-yl)-pyrazole-3-carboxamide Chemical compound ClC1=CC=CC(Cl)=C1C(=O)NC1=CNN=C1C(=O)NC1CCNCC1 OVPNQJVDAFNBDN-UHFFFAOYSA-N 0.000 claims description 23
- 108091007914 CDKs Proteins 0.000 claims description 23
- 238000004519 manufacturing process Methods 0.000 claims description 23
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 21
- 125000003282 alkyl amino group Chemical group 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 239000003112 inhibitor Substances 0.000 claims description 17
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 17
- 230000004044 response Effects 0.000 claims description 17
- 241000124008 Mammalia Species 0.000 claims description 16
- 239000000051 antiandrogen Substances 0.000 claims description 16
- 230000002401 inhibitory effect Effects 0.000 claims description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 125000004043 oxo group Chemical group O=* 0.000 claims description 16
- 230000002280 anti-androgenic effect Effects 0.000 claims description 15
- 239000000328 estrogen antagonist Substances 0.000 claims description 15
- 229960001603 tamoxifen Drugs 0.000 claims description 15
- 238000002648 combination therapy Methods 0.000 claims description 14
- 239000000262 estrogen Substances 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
- 238000011321 prophylaxis Methods 0.000 claims description 12
- BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 11
- 230000012010 growth Effects 0.000 claims description 11
- HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 claims description 11
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
- VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 claims description 10
- ROBVIMPUHSLWNV-UHFFFAOYSA-N aminoglutethimide Chemical compound C=1C=C(N)C=CC=1C1(CC)CCC(=O)NC1=O ROBVIMPUHSLWNV-UHFFFAOYSA-N 0.000 claims description 10
- 229960003437 aminoglutethimide Drugs 0.000 claims description 10
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 claims description 10
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 claims description 10
- 229960002932 anastrozole Drugs 0.000 claims description 9
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 229960000255 exemestane Drugs 0.000 claims description 9
- 229960002258 fulvestrant Drugs 0.000 claims description 9
- 229960003881 letrozole Drugs 0.000 claims description 9
- 229960004622 raloxifene Drugs 0.000 claims description 9
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 claims description 9
- 229960005026 toremifene Drugs 0.000 claims description 9
- 230000004614 tumor growth Effects 0.000 claims description 9
- 210000000481 breast Anatomy 0.000 claims description 8
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 claims description 8
- 210000004881 tumor cell Anatomy 0.000 claims description 8
- 101100243950 Arabidopsis thaliana PIE1 gene Chemical group 0.000 claims description 7
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
- 239000003886 aromatase inhibitor Substances 0.000 claims description 7
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 claims description 7
- AQYSYJUIMQTRMV-UHFFFAOYSA-N hypofluorous acid Chemical compound FO AQYSYJUIMQTRMV-UHFFFAOYSA-N 0.000 claims description 7
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
- 208000003950 B-cell lymphoma Diseases 0.000 claims description 6
- ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 claims description 6
- 241001465754 Metazoa Species 0.000 claims description 6
- 229940046836 anti-estrogen Drugs 0.000 claims description 6
- 230000001833 anti-estrogenic effect Effects 0.000 claims description 6
- 229950004203 droloxifene Drugs 0.000 claims description 6
- 208000032839 leukemia Diseases 0.000 claims description 6
- 210000001685 thyroid gland Anatomy 0.000 claims description 6
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 claims description 5
- 101100509371 Arabidopsis thaliana CHR11 gene Proteins 0.000 claims description 5
- 229960000997 bicalutamide Drugs 0.000 claims description 5
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 5
- 239000002552 dosage form Substances 0.000 claims description 5
- 230000003394 haemopoietic effect Effects 0.000 claims description 5
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims description 4
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 4
- 229940079156 Proteasome inhibitor Drugs 0.000 claims description 4
- BIIVYFLTOXDAOV-YVEFUNNKSA-N alvocidib Chemical compound O[C@@H]1CN(C)CC[C@@H]1C1=C(O)C=C(O)C2=C1OC(C=1C(=CC=CC=1)Cl)=CC2=O BIIVYFLTOXDAOV-YVEFUNNKSA-N 0.000 claims description 4
- 229950010817 alvocidib Drugs 0.000 claims description 4
- 238000011319 anticancer therapy Methods 0.000 claims description 4
- 210000003169 central nervous system Anatomy 0.000 claims description 4
- 229940111134 coxibs Drugs 0.000 claims description 4
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000002708 enhancing effect Effects 0.000 claims description 4
- 230000003325 follicular Effects 0.000 claims description 4
- 239000003276 histone deacetylase inhibitor Substances 0.000 claims description 4
- 210000004185 liver Anatomy 0.000 claims description 4
- 210000001672 ovary Anatomy 0.000 claims description 4
- 230000003389 potentiating effect Effects 0.000 claims description 4
- 239000003207 proteasome inhibitor Substances 0.000 claims description 4
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 3
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 3
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 3
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
- 201000009030 Carcinoma Diseases 0.000 claims description 3
- 108010000817 Leuprolide Proteins 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 210000001072 colon Anatomy 0.000 claims description 3
- 238000003745 diagnosis Methods 0.000 claims description 3
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 claims description 3
- 229960004338 leuprorelin Drugs 0.000 claims description 3
- 201000008968 osteosarcoma Diseases 0.000 claims description 3
- 210000002307 prostate Anatomy 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
- CXBHMSHVCKEEGW-UHFFFAOYSA-N 4-(2,6-difluorobenzamido)-N-(piperidin-4-yl)-1H-pyrazole-3-carboxamide Chemical compound FC1=CC=CC(F)=C1C(=O)NC1=CNN=C1C(=O)NC1CCNCC1 CXBHMSHVCKEEGW-UHFFFAOYSA-N 0.000 claims description 2
- NPPBDFFMJNUJRY-UHFFFAOYSA-N 4-[(2-fluoro-6-methoxybenzoyl)amino]-n-piperidin-4-yl-1h-pyrazole-5-carboxamide Chemical compound COC1=CC=CC(F)=C1C(=O)NC1=CNN=C1C(=O)NC1CCNCC1 NPPBDFFMJNUJRY-UHFFFAOYSA-N 0.000 claims description 2
- 229940122815 Aromatase inhibitor Drugs 0.000 claims description 2
- 101100240520 Caenorhabditis elegans nhr-14 gene Chemical group 0.000 claims description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 2
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 2
- 108060004795 Methyltransferase Proteins 0.000 claims description 2
- 102000016397 Methyltransferase Human genes 0.000 claims description 2
- 101710160107 Outer membrane protein A Proteins 0.000 claims description 2
- 201000010208 Seminoma Diseases 0.000 claims description 2
- 201000006083 Xeroderma Pigmentosum Diseases 0.000 claims description 2
- 230000001093 anti-cancer Effects 0.000 claims description 2
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 claims description 2
- 150000001541 aziridines Chemical class 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- 230000001588 bifunctional effect Effects 0.000 claims description 2
- 210000003679 cervix uteri Anatomy 0.000 claims description 2
- 229960004630 chlorambucil Drugs 0.000 claims description 2
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 2
- 229960004397 cyclophosphamide Drugs 0.000 claims description 2
- 210000002615 epidermis Anatomy 0.000 claims description 2
- 210000000232 gallbladder Anatomy 0.000 claims description 2
- 125000005059 halophenyl group Chemical group 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 210000004072 lung Anatomy 0.000 claims description 2
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 claims description 2
- 229960004961 mechlorethamine Drugs 0.000 claims description 2
- 229960004296 megestrol acetate Drugs 0.000 claims description 2
- 201000001441 melanoma Diseases 0.000 claims description 2
- 229960004857 mitomycin Drugs 0.000 claims description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
- 238000011275 oncology therapy Methods 0.000 claims description 2
- 210000000496 pancreas Anatomy 0.000 claims description 2
- 210000001428 peripheral nervous system Anatomy 0.000 claims description 2
- 238000012216 screening Methods 0.000 claims description 2
- BTIHMVBBUGXLCJ-OAHLLOKOSA-N seliciclib Chemical compound C=12N=CN(C(C)C)C2=NC(N[C@@H](CO)CC)=NC=1NCC1=CC=CC=C1 BTIHMVBBUGXLCJ-OAHLLOKOSA-N 0.000 claims description 2
- 210000003491 skin Anatomy 0.000 claims description 2
- 210000002784 stomach Anatomy 0.000 claims description 2
- 208000001608 teratocarcinoma Diseases 0.000 claims description 2
- 208000010570 urinary bladder carcinoma Diseases 0.000 claims description 2
- KDKUVYLMPJIGKA-UHFFFAOYSA-N 4-[[5-amino-1-[(2,6-difluorophenyl)-oxomethyl]-1,2,4-triazol-3-yl]amino]benzenesulfonamide Chemical compound N=1N(C(=O)C=2C(=CC=CC=2F)F)C(N)=NC=1NC1=CC=C(S(N)(=O)=O)C=C1 KDKUVYLMPJIGKA-UHFFFAOYSA-N 0.000 claims 3
- 150000002431 hydrogen Chemical group 0.000 claims 3
- WJRRGYBTGDJBFX-UHFFFAOYSA-N 4-(2-methyl-3-propan-2-yl-4-imidazolyl)-N-(4-methylsulfonylphenyl)-2-pyrimidinamine Chemical compound CC(C)N1C(C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(C)(=O)=O)=N1 WJRRGYBTGDJBFX-UHFFFAOYSA-N 0.000 claims 2
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims 2
- OUSFTKFNBAZUKL-UHFFFAOYSA-N N-(5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-1,3-thiazol-2-yl)piperidine-4-carboxamide Chemical compound O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)C1CCNCC1 OUSFTKFNBAZUKL-UHFFFAOYSA-N 0.000 claims 2
- 229960002092 busulfan Drugs 0.000 claims 2
- BWDQBBCUWLSASG-MDZDMXLPSA-N (e)-n-hydroxy-3-[4-[[2-hydroxyethyl-[2-(1h-indol-3-yl)ethyl]amino]methyl]phenyl]prop-2-enamide Chemical compound C=1NC2=CC=CC=C2C=1CCN(CCO)CC1=CC=C(\C=C\C(=O)NO)C=C1 BWDQBBCUWLSASG-MDZDMXLPSA-N 0.000 claims 1
- GDKWIFWOHXMZBS-UHFFFAOYSA-N 4-[(2,6-difluorobenzoyl)amino]-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C1=NNC=C1NC(=O)C1=C(F)C=CC=C1F GDKWIFWOHXMZBS-UHFFFAOYSA-N 0.000 claims 1
- PBCZSGKMGDDXIJ-UHFFFAOYSA-N 7beta-hydroxystaurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3C(O)NC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 PBCZSGKMGDDXIJ-UHFFFAOYSA-N 0.000 claims 1
- 102100038080 B-cell receptor CD22 Human genes 0.000 claims 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims 1
- 102000013135 CD52 Antigen Human genes 0.000 claims 1
- 108010065524 CD52 Antigen Proteins 0.000 claims 1
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical group ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims 1
- 230000007067 DNA methylation Effects 0.000 claims 1
- NMJREATYWWNIKX-UHFFFAOYSA-N GnRH Chemical group C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CC(C)C)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 NMJREATYWWNIKX-UHFFFAOYSA-N 0.000 claims 1
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 claims 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims 1
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 claims 1
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 claims 1
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims 1
- HRNLUBSXIHFDHP-UHFFFAOYSA-N N-(2-aminophenyl)-4-[[[4-(3-pyridinyl)-2-pyrimidinyl]amino]methyl]benzamide Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CNC1=NC=CC(C=2C=NC=CC=2)=N1 HRNLUBSXIHFDHP-UHFFFAOYSA-N 0.000 claims 1
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical group O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 claims 1
- NCNRHFGMJRPRSK-MDZDMXLPSA-N belinostat Chemical compound ONC(=O)\C=C\C1=CC=CC(S(=O)(=O)NC=2C=CC=CC=2)=C1 NCNRHFGMJRPRSK-MDZDMXLPSA-N 0.000 claims 1
- 229960005243 carmustine Drugs 0.000 claims 1
- 229960000590 celecoxib Drugs 0.000 claims 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 claims 1
- 229960000578 gemtuzumab Drugs 0.000 claims 1
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Classifications
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- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
- A61K31/5685—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone having an oxo group in position 17, e.g. androsterone
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- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
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Landscapes
- Health & Medical Sciences (AREA)
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| TW200533657A (en) | 2004-02-17 | 2005-10-16 | Esteve Labor Dr | Substituted pyrazoline compounds, their preparation and use as medicaments |
| KR101345002B1 (ko) * | 2005-01-21 | 2013-12-31 | 아스텍스 테라퓨틱스 리미티드 | 제약 화합물 |
| AR054425A1 (es) * | 2005-01-21 | 2007-06-27 | Astex Therapeutics Ltd | Sales de adicion de piperidin 4-il- amida de acido 4-(2,6-dicloro-benzoilamino) 1h-pirazol-3-carboxilico. |
| US20080139620A1 (en) * | 2005-01-21 | 2008-06-12 | Astex Therapeutics Limited | Pyrazole Derivatives For The Inhibition Of Cdk's And Gsk's |
| WO2008007113A2 (en) * | 2006-07-14 | 2008-01-17 | Astex Therapeutics Limited | Pharmaceutical combinations |
| AR052660A1 (es) * | 2005-01-21 | 2007-03-28 | Astex Therapeutics Ltd | Derivados de pirazol para inhibir la cdk's y gsk's |
| US8404718B2 (en) | 2005-01-21 | 2013-03-26 | Astex Therapeutics Limited | Combinations of pyrazole kinase inhibitors |
| NZ589276A (en) | 2005-02-03 | 2012-06-29 | Topotarget Uk Ltd | Combination therapies using hdac inhibitors and erlotinib (tarceva) |
| EP1862478B1 (en) * | 2005-03-03 | 2012-01-25 | Mitsubishi Rayon Co., Ltd. | Polymer particle, resin composition containing same, and molded body |
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| EP2361619A1 (en) | 2005-11-10 | 2011-08-31 | TopoTarget UK Limited | Histone deacetylase (hdac) inhibitors (pxd-101) alone for the treatment of hematological cancer |
| AU2007246895A1 (en) * | 2006-05-05 | 2007-11-15 | Astex Therapeutics Limited | 4- (2,6-dichloro-benzoylamino) -1H-pyrazole-3-carboxylic acid (1-methanesulphonyl-piperidin-4-yl) -amide for the treatment of cancer |
| WO2007129062A1 (en) * | 2006-05-08 | 2007-11-15 | Astex Therapeutics Limited | Pharmaceutical combinations of diazole derivatives for cancer treatment |
| EP2049516A2 (en) * | 2006-07-14 | 2009-04-22 | Astex Therapeutics Limited | Pharmaceutical compounds |
| CL2008000119A1 (es) | 2007-01-16 | 2008-05-16 | Wyeth Corp | Compuestos derivados de pirazol, antagonistas del receptor nicotinico de acetilcolina; composicion farmaceutica; y uso en el tratamiento de enfermedades tales como demencia senil, alzheimer y esquizofrenia. |
| MX2010003230A (es) * | 2007-09-25 | 2010-04-07 | Topotarget Uk Ltd | Metodos para la sintesis de ciertos compuestos de acido hidroxamico. |
| EP2070916A1 (de) | 2007-12-10 | 2009-06-17 | Bayer Schering Pharma Aktiengesellschaft | 2-Aryl-thiazol-4-carbonsäureamid-Derivate, deren Herstellung und Verwendung als Arzneimittel |
| EP2070925A1 (de) | 2007-12-10 | 2009-06-17 | Bayer Schering Pharma Aktiengesellschaft | Neue 2-substituierte Tiazol-4-carbonsäureamid-Derivative deren Herstellung und Verwendung als Arzneimittel |
| EP2070924A1 (de) | 2007-12-10 | 2009-06-17 | Bayer Schering Pharma Aktiengesellschaft | Neue 2-Hetarylthiazol-4-carbonsäureamid-Derivative, deren Herstellung und Verwendung als Arzneimittel |
| MX2010006457A (es) | 2007-12-19 | 2010-07-05 | Amgen Inc | Compuestos fusionados de piridina, pirimidina y triazina como inhibidores de ciclo celular. |
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| ES2552338T3 (es) | 2015-11-27 |
| WO2006077428A1 (en) | 2006-07-27 |
| MX2007008781A (es) | 2007-09-11 |
| BRPI0606455A (pt) | 2008-03-11 |
| EP1845973B1 (en) | 2015-08-12 |
| US20090036435A1 (en) | 2009-02-05 |
| KR101346886B1 (ko) | 2014-01-02 |
| JP5475235B2 (ja) | 2014-04-16 |
| EP1845973A1 (en) | 2007-10-24 |
| KR20070107045A (ko) | 2007-11-06 |
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