CA3188320A1 - Azole dione compounds with anti-cancer activity - Google Patents
Azole dione compounds with anti-cancer activityInfo
- Publication number
- CA3188320A1 CA3188320A1 CA3188320A CA3188320A CA3188320A1 CA 3188320 A1 CA3188320 A1 CA 3188320A1 CA 3188320 A CA3188320 A CA 3188320A CA 3188320 A CA3188320 A CA 3188320A CA 3188320 A1 CA3188320 A1 CA 3188320A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- dione
- trifluoromethyl
- chloro
- salt
- 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.)
- Pending
Links
- WIFCKLPZYYALGY-UHFFFAOYSA-N 1h-pyrrole-2,3-dione Chemical class O=C1NC=CC1=O WIFCKLPZYYALGY-UHFFFAOYSA-N 0.000 title abstract description 9
- 230000001093 anti-cancer Effects 0.000 title abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 664
- 238000000034 method Methods 0.000 claims abstract description 204
- 238000011282 treatment Methods 0.000 claims abstract description 128
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 116
- 201000011510 cancer Diseases 0.000 claims abstract description 91
- 208000035269 cancer or benign tumor Diseases 0.000 claims abstract description 40
- 238000011394 anticancer treatment Methods 0.000 claims abstract description 35
- 150000003839 salts Chemical class 0.000 claims description 198
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 123
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 115
- -1 amino, carboxyl Chemical group 0.000 claims description 89
- 125000000217 alkyl group Chemical group 0.000 claims description 51
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 51
- 125000003118 aryl group Chemical group 0.000 claims description 46
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 36
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 claims description 29
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 29
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 27
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 25
- 125000002252 acyl group Chemical group 0.000 claims description 24
- 125000003107 substituted aryl group Chemical group 0.000 claims description 21
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 19
- 239000012623 DNA damaging agent Substances 0.000 claims description 17
- 125000004414 alkyl thio group Chemical group 0.000 claims description 17
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 16
- 125000004104 aryloxy group Chemical group 0.000 claims description 15
- 238000000338 in vitro Methods 0.000 claims description 15
- 125000005110 aryl thio group Chemical group 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 claims description 14
- 125000004193 piperazinyl group Chemical group 0.000 claims description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 13
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 claims description 12
- AZRRZGIBBLWSSQ-UHFFFAOYSA-N 4-ethyl-7-phenyl-3,5-diazabicyclo[2.2.2]octane-2,6-dione Chemical compound N1C(=O)C2C(=O)NC1(CC)CC2C1=CC=CC=C1 AZRRZGIBBLWSSQ-UHFFFAOYSA-N 0.000 claims description 11
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 10
- 208000032839 leukemia Diseases 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000004122 cyclic group Chemical group 0.000 claims description 9
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 claims description 9
- 206010025323 Lymphomas Diseases 0.000 claims description 8
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 8
- 238000006467 substitution reaction Methods 0.000 claims description 8
- 150000001555 benzenes Chemical group 0.000 claims description 7
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- XVMCKKVXRWMBKJ-UHFFFAOYSA-N 1-[(4-bromonaphthalen-1-yl)amino]-3,4-dimethylpyrrole-2,5-dione Chemical compound O=C1C(C)=C(C)C(=O)N1NC1=CC=C(Br)C2=CC=CC=C12 XVMCKKVXRWMBKJ-UHFFFAOYSA-N 0.000 claims description 5
- ZTWMBHJPUJJJME-UHFFFAOYSA-N 3,4-dimethylpyrrole-2,5-dione Chemical compound CC1=C(C)C(=O)NC1=O ZTWMBHJPUJJJME-UHFFFAOYSA-N 0.000 claims description 5
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 claims description 5
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- FNDXSFNNTIJBJR-UHFFFAOYSA-N 1-[[6-chloro-5-(trifluoromethyl)pyridin-2-yl]amino]-3-methyl-4-(3-methylbutoxymethyl)pyrrole-2,5-dione Chemical compound O=C1C(COCCC(C)C)=C(C)C(=O)N1NC1=CC=C(C(F)(F)F)C(Cl)=N1 FNDXSFNNTIJBJR-UHFFFAOYSA-N 0.000 claims description 4
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 3
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 3
- 125000004423 acyloxy group Chemical group 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- KEWLEGQSHLOJIA-UHFFFAOYSA-N 1-[(4-chloro-6-methylquinolin-2-yl)amino]-3,4-dimethylpyrrole-2,5-dione Chemical compound O=C1C(C)=C(C)C(=O)N1NC1=CC(Cl)=C(C=C(C)C=C2)C2=N1 KEWLEGQSHLOJIA-UHFFFAOYSA-N 0.000 claims 4
- HXDAXUIQFVRGRG-UHFFFAOYSA-N 1-[[6-chloro-5-(trifluoromethyl)pyridin-2-yl]amino]-3-(hydroxymethyl)-4-methylpyrrole-2,5-dione Chemical compound O=C1C(C)=C(CO)C(=O)N1NC1=CC=C(C(F)(F)F)C(Cl)=N1 HXDAXUIQFVRGRG-UHFFFAOYSA-N 0.000 claims 4
- STQBWQZUNHRYCH-UHFFFAOYSA-N 1-[[6-chloro-5-(trifluoromethyl)pyridin-2-yl]amino]-3-methyl-4-(2-propoxyethyl)pyrrole-2,5-dione Chemical compound O=C1C(CCOCCC)=C(C)C(=O)N1NC1=CC=C(C(F)(F)F)C(Cl)=N1 STQBWQZUNHRYCH-UHFFFAOYSA-N 0.000 claims 4
- HDFGOPSGAURCEO-UHFFFAOYSA-N N-ethylmaleimide Chemical compound CCN1C(=O)C=CC1=O HDFGOPSGAURCEO-UHFFFAOYSA-N 0.000 claims 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 4
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 3
- 125000001331 3-methylbutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 claims 3
- UDZLNHDKHSJBID-UHFFFAOYSA-N 1-[(4-chloro-8-methylquinolin-2-yl)amino]-3,4-dimethylpyrrole-2,5-dione Chemical compound O=C1C(C)=C(C)C(=O)N1NC1=CC(Cl)=C(C=CC=C2C)C2=N1 UDZLNHDKHSJBID-UHFFFAOYSA-N 0.000 claims 2
- ARWPFGOBKTVBHB-UHFFFAOYSA-N 1-[(7-bromo-4-chloroquinolin-2-yl)amino]-3,4-dimethylpyrrole-2,5-dione Chemical compound O=C1C(C)=C(C)C(=O)N1NC1=CC(Cl)=C(C=CC(Br)=C2)C2=N1 ARWPFGOBKTVBHB-UHFFFAOYSA-N 0.000 claims 2
- PADWTOLAUDXONP-UHFFFAOYSA-N 1-[[6-(4-chlorophenyl)-5-(trifluoromethyl)pyridin-2-yl]amino]-3,4-dimethylpyrrole-2,5-dione Chemical compound O=C1C(C)=C(C)C(=O)N1NC1=CC=C(C(F)(F)F)C(C=2C=CC(Cl)=CC=2)=N1 PADWTOLAUDXONP-UHFFFAOYSA-N 0.000 claims 2
- IWHJJPLWVDUNKA-UHFFFAOYSA-N 1-[[6-chloro-4-(trifluoromethyl)pyridin-2-yl]amino]-3,4-dimethylpyrrole-2,5-dione Chemical compound O=C1C(C)=C(C)C(=O)N1NC1=CC(C(F)(F)F)=CC(Cl)=N1 IWHJJPLWVDUNKA-UHFFFAOYSA-N 0.000 claims 2
- VHQLAASPWVWVAE-UHFFFAOYSA-N 1-[[6-chloro-5-(trifluoromethyl)pyridin-2-yl]amino]-3-(2,2-dimethylpropoxymethyl)-4-methylpyrrole-2,5-dione Chemical compound O=C1C(C)=C(COCC(C)(C)C)C(=O)N1NC1=CC=C(C(F)(F)F)C(Cl)=N1 VHQLAASPWVWVAE-UHFFFAOYSA-N 0.000 claims 2
- WDYKXAZSSZAMDL-UHFFFAOYSA-N 1-[[7-bromo-4-(hydroxymethyl)quinolin-2-yl]amino]-3,4-dimethylpyrrole-2,5-dione Chemical compound O=C1C(C)=C(C)C(=O)N1NC1=CC(CO)=C(C=CC(Br)=C2)C2=N1 WDYKXAZSSZAMDL-UHFFFAOYSA-N 0.000 claims 2
- GGZMTTCIDWSCQV-UHFFFAOYSA-N 2-[[6-chloro-5-(trifluoromethyl)pyridin-2-yl]amino]-4,5,6,7-tetrahydroisoindole-1,3-dione Chemical compound N1=C(Cl)C(C(F)(F)F)=CC=C1NN1C(=O)C(CCCC2)=C2C1=O GGZMTTCIDWSCQV-UHFFFAOYSA-N 0.000 claims 2
- NCHWAOFXSKUWFY-UHFFFAOYSA-N 3-(butoxymethyl)-1-[[6-chloro-5-(trifluoromethyl)pyridin-2-yl]amino]-4-methylpyrrole-2,5-dione Chemical compound O=C1C(COCCCC)=C(C)C(=O)N1NC1=CC=C(C(F)(F)F)C(Cl)=N1 NCHWAOFXSKUWFY-UHFFFAOYSA-N 0.000 claims 2
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 2
- BHEPCUXRKMFLBW-UHFFFAOYSA-N 1-[[6-bromo-5-(trifluoromethyl)pyridin-2-yl]amino]-3,4-dimethylpyrrole-2,5-dione Chemical compound O=C1C(C)=C(C)C(=O)N1NC1=CC=C(C(F)(F)F)C(Br)=N1 BHEPCUXRKMFLBW-UHFFFAOYSA-N 0.000 claims 1
- JMIDKKZEZVZPIE-UHFFFAOYSA-N 1-[[6-bromo-5-(trifluoromethyl)pyridin-2-yl]methylamino]-3,4-dimethylpyrrole-2,5-dione Chemical compound O=C1C(C)=C(C)C(=O)N1NCC1=CC=C(C(F)(F)F)C(Br)=N1 JMIDKKZEZVZPIE-UHFFFAOYSA-N 0.000 claims 1
- AJJLKXUFMLSMAK-UHFFFAOYSA-N 1-[[6-chloro-5-(trifluoromethyl)pyridin-2-yl]amino]-3-methyl-4-(3-methylbutyl)pyrrole-2,5-dione Chemical compound O=C1C(CCC(C)C)=C(C)C(=O)N1NC1=CC=C(C(F)(F)F)C(Cl)=N1 AJJLKXUFMLSMAK-UHFFFAOYSA-N 0.000 claims 1
- HQEVBMMZKMQNSO-UHFFFAOYSA-N 1-[[6-chloro-5-(trifluoromethyl)pyridin-2-yl]methylamino]-3,4-dimethylpyrrole-2,5-dione Chemical compound O=C1C(C)=C(C)C(=O)N1NCC1=CC=C(C(F)(F)F)C(Cl)=N1 HQEVBMMZKMQNSO-UHFFFAOYSA-N 0.000 claims 1
- ZEVUABRZOIAEMG-UHFFFAOYSA-N 1-[[6-chloro-5-(trifluoromethyl)pyridin-2-yl]methylamino]-3-(methoxymethyl)-4-methylpyrrole-2,5-dione Chemical compound O=C1C(COC)=C(C)C(=O)N1NCC1=CC=C(C(F)(F)F)C(Cl)=N1 ZEVUABRZOIAEMG-UHFFFAOYSA-N 0.000 claims 1
- HYAYPDUDDXSFBY-UHFFFAOYSA-N 1-amino-3,4-dimethylpyrrole-2,5-dione Chemical compound CC1=C(C)C(=O)N(N)C1=O HYAYPDUDDXSFBY-UHFFFAOYSA-N 0.000 claims 1
- ZJOUWIDFMYAYBJ-UHFFFAOYSA-N 3,4-dimethyl-1-[[6-(4-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]amino]pyrrole-2,5-dione Chemical compound O=C1C(C)=C(C)C(=O)N1NC1=CC=C(C(F)(F)F)C(C=2C=CC(C)=CC=2)=N1 ZJOUWIDFMYAYBJ-UHFFFAOYSA-N 0.000 claims 1
- GGVYZOXFFBXEOJ-UHFFFAOYSA-N 3-(methoxymethyl)-4-methylpyrrole-2,5-dione Chemical compound COCC1=C(C)C(=O)NC1=O GGVYZOXFFBXEOJ-UHFFFAOYSA-N 0.000 claims 1
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- LMTGCJANOQOGPI-UHFFFAOYSA-N n-methyl-n-phenylacetamide Chemical compound CC(=O)N(C)C1=CC=CC=C1 LMTGCJANOQOGPI-UHFFFAOYSA-N 0.000 claims 1
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- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A—HUMAN NECESSITIES
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- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/44—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members
- C07D207/444—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5
- C07D207/448—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. maleimide
- C07D207/452—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. maleimide with hydrocarbon radicals, substituted by hetero atoms, directly attached to the ring nitrogen atom
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- C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
- C07D207/50—Nitrogen atoms
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- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| CN105175394B (zh) * | 2007-04-11 | 2018-06-08 | 三井有限公司 | 具有抗癌活性的化合物 |
| WO2010006291A1 (en) | 2008-07-10 | 2010-01-14 | Nodality, Inc. | Methods for diagnosis, prognosis and treatment |
| EP3620154A1 (en) * | 2009-02-06 | 2020-03-11 | University Of Southern California | Therapeutic compositions comprising monoterpenes |
| US20100215644A1 (en) * | 2009-02-25 | 2010-08-26 | Nodality, Inc. A Delaware Corporation | Analysis of nodes in cellular pathways |
| EP2542082B8 (en) | 2010-03-03 | 2020-06-17 | Neonc Technologies Inc. | PHARMACEUTICAL COMPOSITIONS COMPRISING (S)-perillyl alcohol |
| US20160038600A1 (en) | 2012-08-03 | 2016-02-11 | Neonc Technologies Inc. | Pharmaceutical compositions comprising poh derivatives |
| CN105078973B (zh) | 2010-08-27 | 2020-10-09 | 尼昂克技术公司 | 包含poh衍生物的药物组合物 |
| EP2651864B1 (en) | 2010-12-17 | 2016-07-13 | Neonc Technologies Inc. | Methods and devices for using isoperillyl alcohol |
| WO2013020024A2 (en) * | 2011-08-03 | 2013-02-07 | Karyopharm Therapeutics, Inc. | Maleimide compounds and methods of treatment |
| US9814693B2 (en) | 2012-05-09 | 2017-11-14 | Delmar Pharmaceuticals, Inc. | Veterinary use of dianhydrogalactitol, diacetyldianhydrogalactitol, and dibromodulcitol to treat malignancies |
| CN104781257A (zh) | 2012-06-14 | 2015-07-15 | 第一三共株式会社 | 哌啶基吡唑并吡啶衍生物 |
| JP2016506921A (ja) * | 2013-01-30 | 2016-03-07 | バイエル ファーマ アクチエンゲゼルシャフト | アミノ置換イソチアゾール |
| WO2016090355A2 (en) * | 2014-12-05 | 2016-06-09 | Massachusetts Institute Of Technology | Catechol-rich polymers from n-substituted maleimides |
| CA2970954C (en) | 2015-01-26 | 2023-10-31 | Ottawa Hospital Research Institute | Compositions and methods for viral sensitization |
| JP6674957B2 (ja) | 2015-02-12 | 2020-04-01 | ネオンク テクノロジーズ インク． | ペリリルアルコール誘導体を含む医薬組成物 |
| US20190053492A1 (en) | 2016-03-16 | 2019-02-21 | Bayer Cropscience Aktiengesellschaft | Substituted pyridine compounds as pesticides |
| USD801721S1 (en) | 2016-03-31 | 2017-11-07 | Patricia Grayson Briden | Spooled item holding device |
| USD915100S1 (en) | 2016-03-31 | 2021-04-06 | Ocean 22, Llc | Spooled item holding device |
| TW201811766A (zh) | 2016-08-29 | 2018-04-01 | 瑞士商諾華公司 | N-(吡啶-2-基)吡啶-磺醯胺衍生物及其用於疾病治療之用途 |
| EP3746065A4 (en) | 2018-01-29 | 2022-02-16 | Cognos Therapeutics Inc. | INTRATUMORAL ADMINISTRATION OF BORTEZOMIB |
| CN111655700B (zh) | 2018-02-02 | 2023-07-18 | 勃林格殷格翰国际有限公司 | 作为饥饿素o-酰基转移酶(goat)抑制剂的噁二唑并吡啶衍生物 |
| JP7083397B2 (ja) | 2018-02-02 | 2022-06-10 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | グレリンｏ－アシルトランスフェラーゼ（ｇｏａｔ）阻害剤として使用するためのトリアゾロピリミジン誘導体 |
| WO2019157195A1 (en) | 2018-02-08 | 2019-08-15 | Neonc Technologies, Inc | Methods of permeabilizing the blood brain barrier |
| CN115916789B (zh) | 2020-05-22 | 2025-06-27 | 勃林格殷格翰国际有限公司 | 制备烷基7-氨基-5-甲基-[1,2,5]噁二唑并[3,4-b]吡啶羧酸酯的连续方法 |
| ES2984466T3 (es) | 2020-05-22 | 2024-10-29 | Boehringer Ingelheim Int | Procedimiento de fabricación de 7-amino-5-metil-[1,2,5]oxadiazolo[3,4-b]piridín-carboxilato de alquilo |
| US20250017889A1 (en) * | 2021-10-15 | 2025-01-16 | The Curators Of The University Of Missouri | Inhibitors of p1b-type atpases |
| CN114425054A (zh) * | 2022-01-20 | 2022-05-03 | 中国人民解放军军事科学院军事医学研究院 | 一种蛋白酶体抑制剂Bortezomib在抗辐射损伤中的用途 |
| CN120247782B (zh) * | 2025-06-04 | 2025-08-19 | 北京颖泰嘉和生物科技股份有限公司 | 氟吡菌酰胺类化合物及其制备方法 |
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| JPS5564557A (en) * | 1978-11-08 | 1980-05-15 | Mitsui Toatsu Chem Inc | Diphenyl ether compound and herbicide containing the same |
| IL81307A0 (en) * | 1986-01-23 | 1987-08-31 | Union Carbide Agricult | Method for reducing moisture loss from plants and increasing crop yield utilizing nitrogen containing heterocyclic compounds and some novel polysubstituted pyridine derivatives |
| US5635966A (en) * | 1994-01-11 | 1997-06-03 | Hewlett-Packard Company | Edge feed ink delivery thermal inkjet printhead structure and method of fabrication |
| JPH07224032A (ja) | 1994-02-09 | 1995-08-22 | Mitsui Petrochem Ind Ltd | Ｎ−アリールオキシフタルイミド誘導体、その製造方 法及びそれを有効成分として含有する除草剤 |
| JPH07244032A (ja) * | 1994-03-01 | 1995-09-19 | Ishikawajima Harima Heavy Ind Co Ltd | 溶接部検査装置 |
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| US5935966A (en) * | 1995-09-01 | 1999-08-10 | Signal Pharmaceuticals, Inc. | Pyrimidine carboxylates and related compounds and methods for treating inflammatory conditions |
| CA2245029A1 (en) * | 1998-03-13 | 1999-09-13 | University Of British Columbia | Granulatimide compounds as g2 checkpoint inhibitors |
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| CA2385257A1 (en) | 1999-09-22 | 2001-03-29 | Canbas Co., Ltd. | Compositions and methods for inhibiting g2 cell cycle arrest and sensitizing cells to dna damaging agents |
| CA2400224A1 (en) * | 2000-02-26 | 2001-08-30 | Basf Aktiengesellschaft | Fungicidal agents containing pyrrolidones as their active agents and use thereof for treating plants |
| JP2002318434A (ja) * | 2001-04-23 | 2002-10-31 | Konica Corp | ハロゲン化銀写真感光材料、処理方法、および画像形成方法 |
| FR2826653B1 (fr) * | 2001-06-29 | 2005-10-14 | Servier Lab | Nouveaux derives de pyrido-pyrido-pyrrolo[3,2-g]pyrrolo [3,4-e]-indole et pyrido-pyrrolo[2,3-a]pyrrolo[3,4-c] carbazole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| ES2369534T3 (es) * | 2002-06-06 | 2011-12-01 | Canbas Co. Ltd. | Compuestos que anulan el punto de control g2 del ciclo celular inducido por daños en el adn y/o que incrementan la actividad anticancerosa de los tratamientos que dañan el adn. |
| WO2005024755A2 (en) * | 2002-12-31 | 2005-03-17 | Deciphera Pharmaceuticals, Llc. | Medicaments for the treatment of neurodegenerative disorders or diabetes |
| WO2005011573A2 (en) * | 2003-08-01 | 2005-02-10 | Auspex Pharmaceuticals, Inc. | Novel therapeutic agents for the treatment of cancer, metabolic diseases and skin disorders |
| CA2558600C (en) * | 2004-03-10 | 2013-07-09 | Kureha Corporation | A substituted-trialkyl amine compound with anti-viral activity based on antagonism against a chemokine receptor cxcr4 |
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| EP1851203A2 (en) | 2005-02-08 | 2007-11-07 | Merck & Co., Inc. | Inhibitors of checkpoint kinases |
| CN101287727A (zh) * | 2005-08-17 | 2008-10-15 | 先灵公司 | 新的高亲和力喹啉基激酶配体 |
| CA2627910A1 (en) * | 2005-11-01 | 2007-05-10 | Janssen Pharmaceutica N.V. | Substituted cycloalkylpyrrolones as allosteric modulators of glucokinase |
| WO2007114338A1 (ja) * | 2006-03-31 | 2007-10-11 | Takeda Pharmaceutical Company Limited | 酸分泌抑制薬 |
| WO2008110891A2 (en) * | 2007-03-09 | 2008-09-18 | Orchid Research Laboratories Limited, | New heterocyclic compounds |
| CN105175394B (zh) | 2007-04-11 | 2018-06-08 | 三井有限公司 | 具有抗癌活性的化合物 |
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