OA11749A - Tricyclic inhibitors of poly(adp-ribose)polymerases. - Google Patents

Tricyclic inhibitors of poly(adp-ribose)polymerases. Download PDF

Info

Publication number: OA11749A
Authority: OA; OAPI
Prior art keywords: mmol; compound; tetrahydro; alkyl; azepino
Prior art date: 1999-01-11

Application number

OA1200100183A

Other languages

English (en)

Inventor

Stacie S Canan-Koch

Lars Henrik Thoresen

Jayashree Girish Tikhe

Stephen Evan Webber

Original Assignee

Agouron Pharma

Cancer Res Campaign Tech

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.)

1999-01-11

Filing date

2000-01-10

Publication date

2005-07-19

2000-01-10 Application filed by Agouron Pharma, Cancer Res Campaign Tech filed Critical Agouron Pharma

2005-07-19 Publication of OA11749A publication Critical patent/OA11749A/en

Links

229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 title claims abstract description 66
102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 title claims description 62
108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 title claims description 62
239000003112 inhibitor Substances 0.000 title abstract description 17
150000001875 compounds Chemical class 0.000 claims abstract description 130
230000000694 effects Effects 0.000 claims abstract description 25
-1 < Ikynyl Chemical group 0.000 claims description 66
125000003118 aryl group Chemical group 0.000 claims description 54
125000000217 alkyl group Chemical group 0.000 claims description 48
238000000034 method Methods 0.000 claims description 42
229940002612 prodrug Drugs 0.000 claims description 40
239000000651 prodrug Substances 0.000 claims description 40
229910052736 halogen Inorganic materials 0.000 claims description 35
150000002367 halogens Chemical class 0.000 claims description 35
230000002401 inhibitory effect Effects 0.000 claims description 33
230000005764 inhibitory process Effects 0.000 claims description 30
125000003342 alkenyl group Chemical group 0.000 claims description 29
239000003795 chemical substances by application Substances 0.000 claims description 29
229910052760 oxygen Inorganic materials 0.000 claims description 28
125000000304 alkynyl group Chemical group 0.000 claims description 27
125000000753 cycloalkyl group Chemical group 0.000 claims description 27
125000001424 substituent group Chemical group 0.000 claims description 27
102000004190 Enzymes Human genes 0.000 claims description 26
108090000790 Enzymes Proteins 0.000 claims description 26
241000124008 Mammalia Species 0.000 claims description 20
231100000135 cytotoxicity Toxicity 0.000 claims description 19
230000003013 cytotoxicity Effects 0.000 claims description 19
125000001072 heteroaryl group Chemical group 0.000 claims description 19
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 18
101710179684 Poly [ADP-ribose] polymerase Proteins 0.000 claims description 15
102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 claims description 15
125000000547 substituted alkyl group Chemical group 0.000 claims description 15
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
238000003556 assay Methods 0.000 claims description 10
229910052717 sulfur Inorganic materials 0.000 claims description 10
239000008194 pharmaceutical composition Substances 0.000 claims description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
125000004093 cyano group Chemical group *C#N 0.000 claims description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
125000002252 acyl group Chemical group 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 4
108010017601 Tankyrases Proteins 0.000 claims description 3
HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 claims description 2
PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 claims description 2
HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 claims description 2
102100037664 Poly [ADP-ribose] polymerase tankyrase-1 Human genes 0.000 claims 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
AOFUBOWZWQFQJU-SNOJBQEQSA-N (2r,3s,4s,5r)-2,5-bis(hydroxymethyl)oxolane-2,3,4-triol;(2s,3r,4s,5s,6r)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O.OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O AOFUBOWZWQFQJU-SNOJBQEQSA-N 0.000 claims 1
238000011282 treatment Methods 0.000 abstract description 18
206010019196 Head injury Diseases 0.000 abstract description 9
230000004770 neurodegeneration Effects 0.000 abstract description 9
208000006011 Stroke Diseases 0.000 abstract description 8
229940127089 cytotoxic agent Drugs 0.000 abstract description 8
239000002254 cytotoxic agent Substances 0.000 abstract description 8
208000015122 neurodegenerative disease Diseases 0.000 abstract description 8
239000003814 drug Substances 0.000 abstract description 7
206010028980 Neoplasm Diseases 0.000 abstract description 4
102000004357 Transferases Human genes 0.000 abstract description 2
108090000992 Transferases Proteins 0.000 abstract description 2
239000012830 cancer therapeutic Substances 0.000 abstract description 2
231100000599 cytotoxic agent Toxicity 0.000 abstract description 2
230000005855 radiation Effects 0.000 abstract description 2
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 284
239000007787 solid Substances 0.000 description 138
238000005481 NMR spectroscopy Methods 0.000 description 116
JBXRLVPILRXPNH-UHFFFAOYSA-N indol-6-one Chemical compound O=C1C=CC2=CC=NC2=C1 JBXRLVPILRXPNH-UHFFFAOYSA-N 0.000 description 111
239000000243 solution Substances 0.000 description 97
229910052739 hydrogen Inorganic materials 0.000 description 95
229910052757 nitrogen Inorganic materials 0.000 description 93
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 89
229910052799 carbon Inorganic materials 0.000 description 84
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 69
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 56
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 46
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 46
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 38
GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 37
229940125797 compound 12 Drugs 0.000 description 37
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 30
238000006243 chemical reaction Methods 0.000 description 28
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
239000000203 mixture Substances 0.000 description 25
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
239000010410 layer Substances 0.000 description 23
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 22
235000019439 ethyl acetate Nutrition 0.000 description 22
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
HCUARRIEZVDMPT-UHFFFAOYSA-N indolyl-2-carboxylic acid Natural products C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 19
239000000543 intermediate Substances 0.000 description 19
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
239000012267 brine Substances 0.000 description 18
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
239000002253 acid Substances 0.000 description 16
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 15
229910052786 argon Inorganic materials 0.000 description 15
238000004587 chromatography analysis Methods 0.000 description 15
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
239000011541 reaction mixture Substances 0.000 description 15
150000003839 salts Chemical class 0.000 description 15
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
239000012043 crude product Substances 0.000 description 14
239000011734 sodium Substances 0.000 description 14
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 13
210000004027 cell Anatomy 0.000 description 13
239000012044 organic layer Substances 0.000 description 13
239000000725 suspension Substances 0.000 description 13
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 12
239000012661 PARP inhibitor Substances 0.000 description 12
229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 description 12
WEAXQUBYRSEBJD-UHFFFAOYSA-N methyl 1h-indole-4-carboxylate Chemical compound COC(=O)C1=CC=CC2=C1C=CN2 WEAXQUBYRSEBJD-UHFFFAOYSA-N 0.000 description 12
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 12
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 11
MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 10
239000007864 aqueous solution Substances 0.000 description 10
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
230000001225 therapeutic effect Effects 0.000 description 10
235000005074 zinc chloride Nutrition 0.000 description 10
239000011592 zinc chloride Substances 0.000 description 10
229960001939 zinc chloride Drugs 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
201000010099 disease Diseases 0.000 description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
125000004356 hydroxy functional group Chemical group O* 0.000 description 9
239000003921 oil Substances 0.000 description 9
235000019198 oils Nutrition 0.000 description 9
239000000047 product Substances 0.000 description 9
238000010992 reflux Methods 0.000 description 9
229920006395 saturated elastomer Polymers 0.000 description 9
235000017550 sodium carbonate Nutrition 0.000 description 9
229910000029 sodium carbonate Inorganic materials 0.000 description 9
DKFFSRBSODVODR-UHFFFAOYSA-N 6-oxo-3,4,5 ,6-tetrahydro-1h-azepino[5,4,3-cd]indole-2-carboxylic acid Chemical compound O=C1NCCC2=C(C(=O)O)NC3=CC=CC1=C32 DKFFSRBSODVODR-UHFFFAOYSA-N 0.000 description 8
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
239000007832 Na2SO4 Substances 0.000 description 8
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
238000003818 flash chromatography Methods 0.000 description 8
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
238000001953 recrystallisation Methods 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
235000011152 sodium sulphate Nutrition 0.000 description 8
238000012360 testing method Methods 0.000 description 8
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 7
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 7
108091026813 Poly(ADPribose) Proteins 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
235000019341 magnesium sulphate Nutrition 0.000 description 7
230000003389 potentiating effect Effects 0.000 description 7
239000002904 solvent Substances 0.000 description 7
238000003756 stirring Methods 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 6
WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 6
0 *C(CC1)=CC=C1c([n]c1ccc2)c(CCN3)c1c2C3=O Chemical compound *C(CC1)=CC=C1c([n]c1ccc2)c(CCN3)c1c2C3=O 0.000 description 6
DGHHQBMTXTWTJV-BQAIUKQQSA-N 119413-54-6 Chemical compound Cl.C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 DGHHQBMTXTWTJV-BQAIUKQQSA-N 0.000 description 6
ZRRIVOUCCUFNDH-UHFFFAOYSA-N 2-bromo-3,4,5,6-tetrahydro-azepino[5,4,3-cd]indol-6-one Chemical compound O=C1NCCC2=C(Br)NC3=CC=CC1=C32 ZRRIVOUCCUFNDH-UHFFFAOYSA-N 0.000 description 6
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 6
229940126208 compound 22 Drugs 0.000 description 6
125000005842 heteroatom Chemical group 0.000 description 6
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 6
125000003367 polycyclic group Chemical group 0.000 description 6
230000002829 reductive effect Effects 0.000 description 6
229960000303 topotecan Drugs 0.000 description 6
AGPZUEDYVLUKMF-UHFFFAOYSA-N 1,3,4,5-tetrahydro-6h-azepino[5,4,3-cd]indol-6-one Chemical compound O=C1NCCC2=CNC3=CC=CC1=C23 AGPZUEDYVLUKMF-UHFFFAOYSA-N 0.000 description 5
108020004414 DNA Proteins 0.000 description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
102000003960 Ligases Human genes 0.000 description 5
108090000364 Ligases Proteins 0.000 description 5
206010029350 Neurotoxicity Diseases 0.000 description 5
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
206010044221 Toxic encephalopathy Diseases 0.000 description 5
235000011054 acetic acid Nutrition 0.000 description 5
229960000583 acetic acid Drugs 0.000 description 5
125000004432 carbon atom Chemical group C* 0.000 description 5
239000003054 catalyst Substances 0.000 description 5
NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 5
230000006378 damage Effects 0.000 description 5
125000002950 monocyclic group Chemical group 0.000 description 5
230000007135 neurotoxicity Effects 0.000 description 5
231100000228 neurotoxicity Toxicity 0.000 description 5
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 5
229940001593 sodium carbonate Drugs 0.000 description 5
VXWBQOJISHAKKM-UHFFFAOYSA-N (4-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(C=O)C=C1 VXWBQOJISHAKKM-UHFFFAOYSA-N 0.000 description 4
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
BAWFJGJZGIEFAR-NNYOXOHSSA-O NAD(+) Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-O 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
208000027418 Wounds and injury Diseases 0.000 description 4
230000004913 activation Effects 0.000 description 4
125000003545 alkoxy group Chemical group 0.000 description 4
230000001093 anti-cancer Effects 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
238000001914 filtration Methods 0.000 description 4
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 4
239000007789 gas Substances 0.000 description 4
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GQJAIMWFRALLSJ-UHFFFAOYSA-N methyl 1-formylindole-4-carboxylate Chemical compound COC(=O)C1=CC=CC2=C1C=CN2C=O GQJAIMWFRALLSJ-UHFFFAOYSA-N 0.000 description 1
HVQOOSBDNRKUDW-UHFFFAOYSA-N methyl 1-methylindole-4-carboxylate Chemical compound COC(=O)C1=CC=CC2=C1C=CN2C HVQOOSBDNRKUDW-UHFFFAOYSA-N 0.000 description 1
CQLFDVCJDZOXBA-UHFFFAOYSA-N methyl 2-(4-chlorophenyl)-1h-indole-4-carboxylate Chemical compound C=1C=2C(C(=O)OC)=CC=CC=2NC=1C1=CC=C(Cl)C=C1 CQLFDVCJDZOXBA-UHFFFAOYSA-N 0.000 description 1
CRZGFIMLHZTLGT-UHFFFAOYSA-N methyl 2-methyl-3-nitrobenzoate Chemical compound COC(=O)C1=CC=CC([N+]([O-])=O)=C1C CRZGFIMLHZTLGT-UHFFFAOYSA-N 0.000 description 1
ROCKVCIOLGFBLP-UHFFFAOYSA-N methyl 3-(2-nitroethyl)-1h-indole-4-carboxylate Chemical compound COC(=O)C1=CC=CC2=C1C(CC[N+]([O-])=O)=CN2 ROCKVCIOLGFBLP-UHFFFAOYSA-N 0.000 description 1
SSLYFBZNBJBYDE-UHFFFAOYSA-N methyl 3-(3-phenylpropanoyl)-1h-indole-4-carboxylate Chemical compound C1=2C(C(=O)OC)=CC=CC=2NC=C1C(=O)CCC1=CC=CC=C1 SSLYFBZNBJBYDE-UHFFFAOYSA-N 0.000 description 1
NDSPWJRSUXVPSQ-UHFFFAOYSA-N methyl 3-amino-2-iodobenzoate Chemical compound COC(=O)C1=CC=CC(N)=C1I NDSPWJRSUXVPSQ-UHFFFAOYSA-N 0.000 description 1
HWQJAOMFBDZMPB-UHFFFAOYSA-N methyl 3-formyl-1h-indole-4-carboxylate Chemical compound COC(=O)C1=CC=CC2=C1C(C=O)=CN2 HWQJAOMFBDZMPB-UHFFFAOYSA-N 0.000 description 1
WZGHZPDXAXEVOC-UHFFFAOYSA-N methyl 3-phenacyl-1h-indole-4-carboxylate Chemical compound C1=2C(C(=O)OC)=CC=CC=2NC=C1CC(=O)C1=CC=CC=C1 WZGHZPDXAXEVOC-UHFFFAOYSA-N 0.000 description 1
QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical class COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
230000001035 methylating effect Effects 0.000 description 1
238000001471 micro-filtration Methods 0.000 description 1
238000004452 microanalysis Methods 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000000116 mitigating effect Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000000329 molecular dynamics simulation Methods 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
208000031225 myocardial ischemia Diseases 0.000 description 1
TVMXDCGIABBOFY-UHFFFAOYSA-N n-Octanol Natural products CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
IFYDWYVPVAMGRO-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]tetradecanamide Chemical compound CCCCCCCCCCCCCC(=O)NCCCN(C)C IFYDWYVPVAMGRO-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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229950006238 nadide Drugs 0.000 description 1
HUMMCEUVDBVXTQ-UHFFFAOYSA-N naphthalen-1-ylboronic acid Chemical compound C1=CC=C2C(B(O)O)=CC=CC2=C1 HUMMCEUVDBVXTQ-UHFFFAOYSA-N 0.000 description 1
KPTRDYONBVUWPD-UHFFFAOYSA-N naphthalen-2-ylboronic acid Chemical compound C1=CC=CC2=CC(B(O)O)=CC=C21 KPTRDYONBVUWPD-UHFFFAOYSA-N 0.000 description 1
KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
210000005036 nerve Anatomy 0.000 description 1
230000001537 neural effect Effects 0.000 description 1
239000004090 neuroprotective agent Substances 0.000 description 1
229960003966 nicotinamide Drugs 0.000 description 1
235000005152 nicotinamide Nutrition 0.000 description 1
239000011570 nicotinamide Substances 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
125000004971 nitroalkyl group Chemical group 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
229910000069 nitrogen hydride Inorganic materials 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
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239000002674 ointment Substances 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
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150000007524 organic acids Chemical class 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
150000003891 oxalate salts Chemical class 0.000 description 1
229940116315 oxalic acid Drugs 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical class CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
125000005498 phthalate group Chemical class 0.000 description 1
IVXQBCUBSIPQGU-UHFFFAOYSA-N piperazine-1-carboxamide Chemical compound NC(=O)N1CCNCC1 IVXQBCUBSIPQGU-UHFFFAOYSA-N 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
229910003446 platinum oxide Inorganic materials 0.000 description 1
230000005731 poly ADP ribosylation Effects 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
XUWVIABDWDTJRZ-UHFFFAOYSA-N propan-2-ylazanide Chemical compound CC(C)[NH-] XUWVIABDWDTJRZ-UHFFFAOYSA-N 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical class OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
150000003246 quinazolines Chemical class 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
230000008439 repair process Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
230000028617 response to DNA damage stimulus Effects 0.000 description 1
230000000979 retarding effect Effects 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
239000012723 sample buffer Substances 0.000 description 1
230000007017 scission Effects 0.000 description 1
CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical class OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
230000011664 signaling Effects 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
229930188929 simonin Natural products 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
238000003797 solvolysis reaction Methods 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
235000011150 stannous chloride Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical class OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 1
239000000758 substrate Substances 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
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229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
125000003396 thiol group Chemical class [H]S* 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 1
QNMBSXGYAQZCTN-UHFFFAOYSA-N thiophen-3-ylboronic acid Chemical compound OB(O)C=1C=CSC=1 QNMBSXGYAQZCTN-UHFFFAOYSA-N 0.000 description 1
210000001541 thymus gland Anatomy 0.000 description 1
AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
PYMPTRMDPJYTDF-UHFFFAOYSA-N tributyl(2-phenylethynyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C#CC1=CC=CC=C1 PYMPTRMDPJYTDF-UHFFFAOYSA-N 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
239000011534 wash buffer Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/06—Peri-condensed systems
- 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
- A61K31/275—Nitriles; Isonitriles
- A61K31/277—Nitriles; Isonitriles having a ring, e.g. verapamil
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/06—Peri-condensed systems

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Engineering & Computer Science (AREA)
Epidemiology (AREA)
Diabetes (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Obesity (AREA)
Hematology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Endocrinology (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Emergency Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

OA1200100183A 1999-01-11 2000-01-10 Tricyclic inhibitors of poly(adp-ribose)polymerases. OA11749A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US11543199P	1999-01-11	1999-01-11

Publications (1)

Publication Number	Publication Date
OA11749A true OA11749A (en)	2005-07-19

Family

ID=22361361

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
OA1200100183A OA11749A (en)	1999-01-11	2000-01-10	Tricyclic inhibitors of poly(adp-ribose)polymerases.
OA1200200262A OA12185A (en)	1999-01-11	2002-08-28	Tricyclic inhibitors of poly(adp-ribose)polymerases.

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
OA1200200262A OA12185A (en)	1999-01-11	2002-08-28	Tricyclic inhibitors of poly(adp-ribose)polymerases.

Country Status (39)

Country	Link
US (4)	US6495541B1 (de)
EP (1)	EP1140936B1 (de)
JP (1)	JP4093448B2 (de)
KR (1)	KR100632079B1 (de)
CN (1)	CN100418967C (de)
AP (1)	AP1538A (de)
AT (1)	ATE261963T1 (de)
AU (1)	AU781711B2 (de)
BG (1)	BG65210B1 (de)
BR (1)	BRPI0008614B8 (de)
CA (1)	CA2360003C (de)
CZ (1)	CZ302941B6 (de)
DE (1)	DE60009033T2 (de)
DK (1)	DK1140936T3 (de)
EA (1)	EA004989B1 (de)
EE (1)	EE05006B1 (de)
ES (1)	ES2218110T3 (de)
GE (1)	GEP20033055B (de)
HR (1)	HRP20010573B1 (de)
HU (1)	HU229875B1 (de)
ID (1)	ID30138A (de)
IL (2)	IL144112A0 (de)
IS (1)	IS5995A (de)
LT (1)	LT4936B (de)
LV (1)	LV12770B (de)
MX (1)	MXPA01007001A (de)
NO (1)	NO320343B1 (de)
NZ (1)	NZ512731A (de)
OA (2)	OA11749A (de)
PL (1)	PL210415B1 (de)
PT (1)	PT1140936E (de)
RO (1)	RO121778B1 (de)
RS (1)	RS50031B (de)
SI (1)	SI20691B (de)
SK (1)	SK287338B6 (de)
TR (1)	TR200102005T2 (de)
UA (1)	UA75034C2 (de)
WO (1)	WO2000042040A1 (de)
ZA (1)	ZA200105399B (de)

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2000
- 2000-01-10 EP EP00902358A patent/EP1140936B1/de not_active Expired - Lifetime
- 2000-01-10 DE DE60009033T patent/DE60009033T2/de not_active Expired - Lifetime
- 2000-01-10 BR BRPI0008614A patent/BRPI0008614B8/pt not_active IP Right Cessation
- 2000-01-10 EA EA200100764A patent/EA004989B1/ru not_active IP Right Cessation
- 2000-01-10 EE EEP200100364A patent/EE05006B1/xx unknown
- 2000-01-10 RS YUP-490/01A patent/RS50031B/sr unknown
- 2000-01-10 AP APAP/P/2001/002211A patent/AP1538A/en active
- 2000-01-10 TR TR2001/02005T patent/TR200102005T2/xx unknown
- 2000-01-10 US US09/479,896 patent/US6495541B1/en not_active Expired - Lifetime
- 2000-01-10 RO ROA200100795A patent/RO121778B1/ro unknown
- 2000-01-10 NZ NZ512731A patent/NZ512731A/xx not_active IP Right Cessation
- 2000-01-10 HR HR20010573A patent/HRP20010573B1/xx not_active IP Right Cessation
- 2000-01-10 SK SK966-2001A patent/SK287338B6/sk not_active IP Right Cessation
- 2000-01-10 OA OA1200100183A patent/OA11749A/en unknown
- 2000-01-10 AT AT00902358T patent/ATE261963T1/de active
- 2000-01-10 HU HU0105414A patent/HU229875B1/hu unknown
- 2000-01-10 KR KR1020017008709A patent/KR100632079B1/ko not_active Expired - Lifetime
- 2000-01-10 JP JP2000593608A patent/JP4093448B2/ja not_active Expired - Lifetime
- 2000-01-10 WO PCT/US2000/000411 patent/WO2000042040A1/en not_active Ceased
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- 2000-01-10 DK DK00902358T patent/DK1140936T3/da active
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- 2000-01-10 ES ES00902358T patent/ES2218110T3/es not_active Expired - Lifetime
- 2000-01-10 SI SI200020013A patent/SI20691B/sl active Search and Examination
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- 2000-01-19 ID IDW00200101726A patent/ID30138A/id unknown
- 2000-10-01 UA UA2001074881A patent/UA75034C2/uk unknown
2001
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2002
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- 2002-10-02 US US10/264,018 patent/US20030078254A1/en not_active Abandoned
2004
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Also Published As

Publication number	Publication date
LV12770B (lv)	2002-05-20
PL210415B1 (pl)	2012-01-31
AP2001002211A0 (en)	2001-09-30
YU49001A (sh)	2005-11-28
EP1140936A1 (de)	2001-10-10
US20060009517A1 (en)	2006-01-12
NO20013313D0 (no)	2001-07-04
ZA200105399B (en)	2002-07-01
WO2000042040A1 (en)	2000-07-20
UA75034C2 (en)	2006-03-15
EE200100364A (et)	2002-10-15
IL144112A0 (en)	2002-05-23
KR100632079B1 (ko)	2006-10-04
RS50031B (sr)	2008-11-28
CN100418967C (zh)	2008-09-17
BG65210B1 (bg)	2007-07-31
HRP20010573A2 (en)	2005-02-28
LV12770A (en)	2001-12-20
PT1140936E (pt)	2004-06-30
MXPA01007001A (es)	2002-07-30
HUP0105414A2 (hu)	2002-05-29
ID30138A (id)	2001-11-08
US6977298B2 (en)	2005-12-20
RO121778B1 (ro)	2008-04-30
HU229875B1 (en)	2014-11-28
HK1040992A1 (en)	2002-06-28
AU2408800A (en)	2000-08-01
LT2001083A (en)	2002-03-25
SI20691A (sl)	2002-04-30
TR200102005T2 (tr)	2001-12-21
BRPI0008614B8 (pt)	2021-05-25
IS5995A (is)	2001-07-10
AU781711B2 (en)	2005-06-09
HUP0105414A3 (en)	2003-04-28
JP2002534523A (ja)	2002-10-15
EP1140936B1 (de)	2004-03-17
BR0008614A (pt)	2001-10-16
SK9662001A3 (en)	2002-04-04
BR0008614B1 (pt)	2014-11-25
CA2360003C (en)	2012-07-10
CZ302941B6 (cs)	2012-01-25
GEP20033055B (en)	2003-08-25
ATE261963T1 (de)	2004-04-15
IL144112A (en)	2006-07-05
LT4936B (lt)	2002-07-25
NZ512731A (en)	2004-01-30
JP4093448B2 (ja)	2008-06-04
EA004989B1 (ru)	2004-10-28
US20030078254A1 (en)	2003-04-24
NO20013313L (no)	2001-09-10
CZ20012443A3 (cs)	2002-02-13
EA200100764A1 (ru)	2002-06-27
PL357049A1 (en)	2004-07-12
ES2218110T3 (es)	2004-11-16
HRP20010573B1 (en)	2006-04-30
EE05006B1 (et)	2008-04-15
DE60009033D1 (de)	2004-04-22
DK1140936T3 (da)	2004-06-21
CA2360003A1 (en)	2000-07-20
OA12185A (en)	2006-05-09
SI20691B (sl)	2008-10-31
CN1342161A (zh)	2002-03-27
AP1538A (en)	2006-01-10
BG105811A (en)	2002-05-31
US7429578B2 (en)	2008-09-30
NO320343B1 (no)	2005-11-28
SK287338B6 (sk)	2010-07-07
DE60009033T2 (de)	2004-08-05
KR20020008112A (ko)	2002-01-29
US20050085460A1 (en)	2005-04-21
US6495541B1 (en)	2002-12-17

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EP1208104B1 (de)	2005-01-19	Trizyklische inhibitoren von poly(adp-ribose) polymerasen
CA2762226C (en)	2017-12-05	Isoquinolin-1 (2h) -one derivatives as parp-1 inhibitors
WO2003106430A1 (en)	2003-12-24	Benzimidazole inhibitors of poly(adp-ribosyl) polymerase
JP2015523352A (ja)	2015-08-13	Ｋａｔｉｉ阻害剤としての三環式化合物
HK1040992B (en)	2004-09-10	Tricyclic inhibitors of poly(adp-ribose) polymerases