CA2885217C - Substituted alkyl diaryl derivatives, methods of preparation and uses - Google Patents
Substituted alkyl diaryl derivatives, methods of preparation and uses Download PDFInfo
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- CA2885217C CA2885217C CA2885217A CA2885217A CA2885217C CA 2885217 C CA2885217 C CA 2885217C CA 2885217 A CA2885217 A CA 2885217A CA 2885217 A CA2885217 A CA 2885217A CA 2885217 C CA2885217 C CA 2885217C
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- 238000000034 method Methods 0.000 title claims abstract description 142
- 238000002360 preparation method Methods 0.000 title description 28
- 150000001875 compounds Chemical class 0.000 claims abstract description 358
- 150000003839 salts Chemical class 0.000 claims abstract description 212
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 74
- 201000011510 cancer Diseases 0.000 claims abstract description 38
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 148
- 229920006395 saturated elastomer Polymers 0.000 claims description 105
- -1 hydroxy, carboxy Chemical group 0.000 claims description 101
- 239000011541 reaction mixture Substances 0.000 claims description 92
- 125000001424 substituent group Chemical group 0.000 claims description 79
- 125000002015 acyclic group Chemical group 0.000 claims description 75
- 229910052739 hydrogen Inorganic materials 0.000 claims description 72
- 125000004122 cyclic group Chemical group 0.000 claims description 71
- 125000004432 carbon atom Chemical group C* 0.000 claims description 52
- 229910052799 carbon Inorganic materials 0.000 claims description 48
- 125000005518 carboxamido group Chemical group 0.000 claims description 45
- 230000008569 process Effects 0.000 claims description 45
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 43
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 38
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 38
- 125000001153 fluoro group Chemical group F* 0.000 claims description 35
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 35
- 125000005239 aroylamino group Chemical group 0.000 claims description 34
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 34
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 32
- 125000001246 bromo group Chemical group Br* 0.000 claims description 31
- 125000002837 carbocyclic group Chemical group 0.000 claims description 25
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 15
- 208000032839 leukemia Diseases 0.000 claims description 14
- ORLOIZRWYPMTFC-UHFFFAOYSA-N 2-methoxy-5-[2-(2,4,6-trimethoxyphenyl)ethylsulfonylmethyl]aniline Chemical compound COC1=CC(OC)=CC(OC)=C1CCS(=O)(=O)CC1=CC=C(OC)C(N)=C1 ORLOIZRWYPMTFC-UHFFFAOYSA-N 0.000 claims description 12
- 125000004442 acylamino group Chemical group 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 125000002252 acyl group Chemical group 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 10
- 208000020816 lung neoplasm Diseases 0.000 claims description 10
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 9
- 206010006187 Breast cancer Diseases 0.000 claims description 9
- 208000026310 Breast neoplasm Diseases 0.000 claims description 9
- 206010009944 Colon cancer Diseases 0.000 claims description 9
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 9
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 9
- 206010033128 Ovarian cancer Diseases 0.000 claims description 9
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 9
- 206010060862 Prostate cancer Diseases 0.000 claims description 9
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 9
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 9
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 9
- 150000001767 cationic compounds Chemical class 0.000 claims description 9
- 229910001411 inorganic cation Inorganic materials 0.000 claims description 9
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 8
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 8
- 206010038389 Renal cancer Diseases 0.000 claims description 8
- 201000010982 kidney cancer Diseases 0.000 claims description 8
- 201000005202 lung cancer Diseases 0.000 claims description 8
- 150000002892 organic cations Chemical class 0.000 claims description 8
- 201000003120 testicular cancer Diseases 0.000 claims description 8
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 7
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 7
- 206010057644 Testis cancer Diseases 0.000 claims description 7
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 7
- 201000010881 cervical cancer Diseases 0.000 claims description 7
- 201000000849 skin cancer Diseases 0.000 claims description 7
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 6
- VVVLTGMSHYUYEA-UHFFFAOYSA-N 2-[2-methoxy-5-[2-(2,4,6-trimethoxyphenyl)ethylsulfonylmethyl]anilino]acetic acid Chemical compound COC1=CC(OC)=CC(OC)=C1CCS(=O)(=O)CC1=CC=C(OC)C(NCC(O)=O)=C1 VVVLTGMSHYUYEA-UHFFFAOYSA-N 0.000 claims description 5
- BGGSAZMFBNCKFE-UHFFFAOYSA-N 4-[2-[(4-chlorophenyl)methylsulfonyl]ethyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1CCS(=O)(=O)CC1=CC=C(Cl)C=C1 BGGSAZMFBNCKFE-UHFFFAOYSA-N 0.000 claims description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 5
- HEWJRHOJRHHIMM-UHFFFAOYSA-N 1,3,5-trimethoxy-2-[2-[(4-methoxyphenyl)methylsulfonyl]ethyl]benzene Chemical compound C1=CC(OC)=CC=C1CS(=O)(=O)CCC1=C(OC)C=C(OC)C=C1OC HEWJRHOJRHHIMM-UHFFFAOYSA-N 0.000 claims description 3
- HOKGDMRTJJNKKF-UHFFFAOYSA-N 2-[2-methoxy-5-[2-(2,4,6-trimethoxyphenyl)ethylsulfonylmethyl]anilino]-2-phenylacetic acid Chemical compound COC1=CC(OC)=CC(OC)=C1CCS(=O)(=O)CC1=CC=C(OC)C(NC(C(O)=O)C=2C=CC=CC=2)=C1 HOKGDMRTJJNKKF-UHFFFAOYSA-N 0.000 claims description 3
- AOLIEXFAJQTCRI-UHFFFAOYSA-N 2-methoxy-5-[2-(2,4,6-trimethoxyphenyl)ethylsulfonylmethyl]phenol Chemical compound COC1=CC(OC)=CC(OC)=C1CCS(=O)(=O)CC1=CC=C(OC)C(O)=C1 AOLIEXFAJQTCRI-UHFFFAOYSA-N 0.000 claims description 3
- 230000001590 oxidative effect Effects 0.000 claims description 3
- VVNSAGFVOFCHEZ-UHFFFAOYSA-N 1-[2-[(4-chlorophenyl)methylsulfonyl]ethyl]-4-fluorobenzene Chemical compound C1=CC(F)=CC=C1CCS(=O)(=O)CC1=CC=C(Cl)C=C1 VVNSAGFVOFCHEZ-UHFFFAOYSA-N 0.000 claims description 2
- ZYNDYVNREASBDG-UHFFFAOYSA-N 2-[2-methoxy-5-[2-(2,4,6-trimethoxyphenyl)ethylsulfonylmethyl]anilino]-3-phenylpropanoic acid Chemical compound COC1=CC(OC)=CC(OC)=C1CCS(=O)(=O)CC1=CC=C(OC)C(NC(CC=2C=CC=CC=2)C(O)=O)=C1 ZYNDYVNREASBDG-UHFFFAOYSA-N 0.000 claims description 2
- JDNQNGHPXHOJQU-UHFFFAOYSA-N 2-[2-methoxy-5-[2-(2,4,6-trimethoxyphenyl)ethylsulfonylmethyl]anilino]propanoic acid Chemical compound COC1=CC(OC)=CC(OC)=C1CCS(=O)(=O)CC1=CC=C(OC)C(NC(C)C(O)=O)=C1 JDNQNGHPXHOJQU-UHFFFAOYSA-N 0.000 claims description 2
- KQOJXHGFGHDDLR-UHFFFAOYSA-N methyl 2-[2-methoxy-5-[2-(2,4,6-trimethoxyphenyl)ethylsulfonylmethyl]anilino]acetate Chemical compound C1=C(OC)C(NCC(=O)OC)=CC(CS(=O)(=O)CCC=2C(=CC(OC)=CC=2OC)OC)=C1 KQOJXHGFGHDDLR-UHFFFAOYSA-N 0.000 claims description 2
- LOQFEVOQDUJSGR-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-[2-methoxy-5-[2-(2,4,6-trimethoxyphenyl)ethylsulfonylmethyl]anilino]acetic acid Chemical compound COC1=CC(OC)=CC(OC)=C1CCS(=O)(=O)CC1=CC=C(OC)C(NC(C(O)=O)C=2C=CC(Cl)=CC=2)=C1 LOQFEVOQDUJSGR-UHFFFAOYSA-N 0.000 claims 1
- ARELIXMFRBREQS-UHFFFAOYSA-N 2-(4-fluorophenyl)-2-[2-methoxy-5-[2-(2,4,6-trimethoxyphenyl)ethylsulfonylmethyl]anilino]acetic acid Chemical compound COC1=CC(OC)=CC(OC)=C1CCS(=O)(=O)CC1=CC=C(OC)C(NC(C(O)=O)C=2C=CC(F)=CC=2)=C1 ARELIXMFRBREQS-UHFFFAOYSA-N 0.000 claims 1
- REMLYGMYCSCYPB-UHFFFAOYSA-N 2-[2-methoxy-5-[2-(2,4,6-trimethoxyphenyl)ethylsulfonylmethyl]anilino]-2-(1h-pyrrol-3-yl)acetic acid Chemical compound COC1=CC(OC)=CC(OC)=C1CCS(=O)(=O)CC1=CC=C(OC)C(NC(C(O)=O)C2=CNC=C2)=C1 REMLYGMYCSCYPB-UHFFFAOYSA-N 0.000 claims 1
- DZEPLHZROPFQIZ-UHFFFAOYSA-N 2-[2-methoxy-5-[2-(2,4,6-trimethoxyphenyl)ethylsulfonylmethyl]anilino]-2-methylpropanoic acid Chemical compound COC1=CC(OC)=CC(OC)=C1CCS(=O)(=O)CC1=CC=C(OC)C(NC(C)(C)C(O)=O)=C1 DZEPLHZROPFQIZ-UHFFFAOYSA-N 0.000 claims 1
- MLVWKTZLSNWMMB-UHFFFAOYSA-N 2-cyclopropyl-2-[2-methoxy-5-[2-(2,4,6-trimethoxyphenyl)ethylsulfonylmethyl]anilino]acetic acid Chemical compound COC1=CC(OC)=CC(OC)=C1CCS(=O)(=O)CC1=CC=C(OC)C(NC(C2CC2)C(O)=O)=C1 MLVWKTZLSNWMMB-UHFFFAOYSA-N 0.000 claims 1
- QDTZXIJXCDBCNV-UHFFFAOYSA-N methyl 2-[2-methoxy-n-(2-methoxy-2-oxoethyl)-5-[2-(2,4,6-trimethoxyphenyl)ethylsulfonylmethyl]anilino]acetate Chemical compound C1=C(OC)C(N(CC(=O)OC)CC(=O)OC)=CC(CS(=O)(=O)CCC=2C(=CC(OC)=CC=2OC)OC)=C1 QDTZXIJXCDBCNV-UHFFFAOYSA-N 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 71
- 230000002062 proliferating effect Effects 0.000 abstract description 59
- 230000001413 cellular effect Effects 0.000 abstract description 44
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 114
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 111
- 238000006243 chemical reaction Methods 0.000 description 103
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 80
- 208000035475 disorder Diseases 0.000 description 68
- 239000000203 mixture Substances 0.000 description 68
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
- 239000000243 solution Substances 0.000 description 63
- 125000003118 aryl group Chemical group 0.000 description 58
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 58
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 51
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 50
- 150000001721 carbon Chemical group 0.000 description 44
- 239000007787 solid Substances 0.000 description 41
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 40
- 125000001072 heteroaryl group Chemical group 0.000 description 39
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- 238000004809 thin layer chromatography Methods 0.000 description 31
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- 238000011282 treatment Methods 0.000 description 26
- 229960000583 acetic acid Drugs 0.000 description 25
- 210000004027 cell Anatomy 0.000 description 25
- 239000000741 silica gel Substances 0.000 description 25
- 229910002027 silica gel Inorganic materials 0.000 description 25
- 239000002904 solvent Substances 0.000 description 25
- 125000003545 alkoxy group Chemical group 0.000 description 22
- 125000003107 substituted aryl group Chemical group 0.000 description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
- 235000011054 acetic acid Nutrition 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- 101150041968 CDC13 gene Proteins 0.000 description 18
- 239000002585 base Substances 0.000 description 18
- 125000000623 heterocyclic group Chemical group 0.000 description 18
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 17
- 150000001413 amino acids Chemical class 0.000 description 17
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 125000000217 alkyl group Chemical group 0.000 description 15
- 239000012298 atmosphere Substances 0.000 description 14
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- 239000005457 ice water Substances 0.000 description 14
- 229940125904 compound 1 Drugs 0.000 description 13
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- 239000012043 crude product Substances 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 13
- 238000000746 purification Methods 0.000 description 13
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 12
- 238000002425 crystallisation Methods 0.000 description 12
- 230000008025 crystallization Effects 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- 239000001632 sodium acetate Substances 0.000 description 11
- 235000017281 sodium acetate Nutrition 0.000 description 11
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 239000013543 active substance Substances 0.000 description 10
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- 229940079593 drug Drugs 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- 238000012544 monitoring process Methods 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 210000004881 tumor cell Anatomy 0.000 description 10
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- 229910052794 bromium Inorganic materials 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
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- 238000005984 hydrogenation reaction Methods 0.000 description 7
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- 238000002844 melting Methods 0.000 description 7
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 6
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000003935 benzaldehydes Chemical class 0.000 description 6
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzenecarboxaldehyde Natural products O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
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- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 6
- LTPVSOCPYWDIFU-UHFFFAOYSA-N 4-methoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1 LTPVSOCPYWDIFU-UHFFFAOYSA-N 0.000 description 5
- 208000023275 Autoimmune disease Diseases 0.000 description 5
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical class NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 5
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
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- 238000006467 substitution reaction Methods 0.000 description 5
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 4
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical group CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- CGUNKAXAEZSOFA-UHFFFAOYSA-N 2-(2,4,6-trimethoxyphenyl)ethanamine Chemical compound COC1=CC(OC)=C(CCN)C(OC)=C1 CGUNKAXAEZSOFA-UHFFFAOYSA-N 0.000 description 4
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 4
- WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical class BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 4
- DVOBBRWMQDXYPW-UHFFFAOYSA-N 3-amino-4-methoxy-n-[2-(2,4,6-trimethoxyphenyl)ethyl]benzenesulfonamide Chemical compound COC1=CC(OC)=CC(OC)=C1CCNS(=O)(=O)C1=CC=C(OC)C(N)=C1 DVOBBRWMQDXYPW-UHFFFAOYSA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- 201000009030 Carcinoma Diseases 0.000 description 4
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- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
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- 206010038934 Retinopathy proliferative Diseases 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- 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
- C07D207/30—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 two double bonds between ring members or between ring members and non-ring members
- C07D207/32—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 two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—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 two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/337—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C235/38—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/23—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atoms of the sulfonamide groups bound to acyclic carbon atoms
- C07C311/27—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atoms of the sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/04—Preparation of sulfones; Preparation of sulfoxides by reactions not involving the formation of sulfone or sulfoxide groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/02—Sulfones; Sulfoxides having sulfone or sulfoxide groups bound to acyclic carbon atoms
- C07C317/10—Sulfones; Sulfoxides having sulfone or sulfoxide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/16—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C317/18—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/24—Sulfones; Sulfoxides having sulfone or sulfoxide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/26—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C317/28—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/01—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and halogen atoms, or nitro or nitroso groups bound to the same carbon skeleton
- C07C323/02—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and halogen atoms, or nitro or nitroso groups bound to the same carbon skeleton having sulfur atoms of thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/07—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and halogen atoms, or nitro or nitroso groups bound to the same carbon skeleton having sulfur atoms of thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
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- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pyrrole Compounds (AREA)
- Epidemiology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261703368P | 2012-09-20 | 2012-09-20 | |
| US61/703,368 | 2012-09-20 | ||
| PCT/US2013/060294 WO2014047110A2 (en) | 2012-09-20 | 2013-09-18 | Substituted alkyl diaryl derivatives, methods of preparation and uses |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2885217A1 CA2885217A1 (en) | 2014-03-27 |
| CA2885217C true CA2885217C (en) | 2019-10-08 |
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|---|---|---|---|
| CA2885217A Active CA2885217C (en) | 2012-09-20 | 2013-09-18 | Substituted alkyl diaryl derivatives, methods of preparation and uses |
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| Country | Link |
|---|---|
| US (1) | US10207989B2 (enExample) |
| EP (1) | EP2897599B1 (enExample) |
| JP (1) | JP6348904B2 (enExample) |
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| ES (1) | ES2863538T3 (enExample) |
| IL (1) | IL237699B (enExample) |
| WO (1) | WO2014047110A2 (enExample) |
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| US8563573B2 (en) | 2007-11-02 | 2013-10-22 | Vertex Pharmaceuticals Incorporated | Azaindole derivatives as CFTR modulators |
| US8802868B2 (en) | 2010-03-25 | 2014-08-12 | Vertex Pharmaceuticals Incorporated | Solid forms of (R)-1(2,2-difluorobenzo[D][1,3]dioxo1-5-yl)-N-(1-(2,3-dihydroxypropyl-6-fluoro-2-(1-hydroxy-2-methylpropan2-yl)-1H-Indol-5-yl)-Cyclopropanecarboxamide |
| MX342288B (es) | 2010-04-22 | 2016-09-23 | Vertex Pharma | Proceso para producir compuestos de cicloalquilcarboxamido-indol. |
| KR102447581B1 (ko) | 2014-04-15 | 2022-09-28 | 버텍스 파마슈티칼스 인코포레이티드 | 낭포성 섬유증 막전도 조절자 매개 질환 치료용 약제학적 조성물 |
| CN105085436B (zh) | 2014-04-19 | 2019-08-16 | 广东东阳光药业有限公司 | 磺酰胺类衍生物及其在药物上的应用 |
| EP3233072A1 (en) * | 2014-12-16 | 2017-10-25 | Glucox Biotech AB | Compounds for use in the treatment of conditions associated with nadph oxidase |
| US10383831B2 (en) | 2015-08-03 | 2019-08-20 | Temple University—Of the Commonwealth System of Higher Education | 2,4,6-trialkoxystryl aryl sulfones, sulfonamides and carboxamides, and methods of preparation and use |
| US12202790B2 (en) | 2018-05-09 | 2025-01-21 | Glucox Biotech Ab | Sulfonamide derivatives having selective Nox inhibiting activity |
| CR20220316A (es) | 2019-12-06 | 2022-10-07 | Vertex Pharma | Tetrahidrofuranos sustituidos como moduladores de canales de sodio |
| CN115334959A (zh) | 2020-01-31 | 2022-11-11 | 瑞思迈传感器技术有限公司 | 用于呼吸暂停-低通气指数计算的睡眠状态检测 |
| JP2024522292A (ja) | 2021-06-04 | 2024-06-13 | バーテックス ファーマシューティカルズ インコーポレイテッド | ナトリウムチャネルのモジュレーターとしてのn-(ヒドロキシアルキル(ヘテロ)アリール)テトラヒドロフランカルボキサミド |
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| DE3000377A1 (de) * | 1980-01-07 | 1981-07-09 | Boehringer Mannheim Gmbh, 6800 Mannheim | Neue sulfonamide, verfahren zu deren herstellung sowie diese verbindungen enthaltende arzneimittel |
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| GB8311678D0 (en) * | 1983-04-28 | 1983-06-02 | Ici Plc | Phenol derivatives |
| US5070099A (en) * | 1988-10-31 | 1991-12-03 | E. R. Squibb & Sons, Inc. | Arylthioalkylphenyl carboxylic acids, derivatives thereof, compositions containing same method of use |
| JP3660395B2 (ja) | 1995-06-22 | 2005-06-15 | 大鵬薬品工業株式会社 | フェニルスルホン誘導体及びその製造方法 |
| GB9717576D0 (en) * | 1997-08-19 | 1997-10-22 | Xenova Ltd | Pharmaceutical compounds |
| ATE284386T1 (de) | 1997-10-03 | 2004-12-15 | Univ Temple | Styrolsulfone als antikrebsmittel |
| US6548553B2 (en) | 1997-10-03 | 2003-04-15 | Temple University-Of The Commonwealth System Of Higher Education | Styryl sulfone anticancer agents |
| US6201154B1 (en) | 1999-03-31 | 2001-03-13 | Temple University-Of The Commonwealth Of Higher Education | Z-styryl sulfone anticancer agents |
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| CA2375511A1 (en) | 1999-06-16 | 2000-12-21 | Temple University - Of The Commonwealth System Of Higher Education | (z)-styryl acetoxyphenyl sulfides as cyclooxygenase inhibitors |
| US6767926B1 (en) | 1999-10-12 | 2004-07-27 | Temple University - Of The Commonwealth System Of Higher Education | Method for protecting normal cells from cytotoxicity of chemotherapeutic agents |
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| US6486210B2 (en) | 2000-04-14 | 2002-11-26 | Temple University—Of the Commonwealth System of Higher Education | Substituted styryl benzylsulfones for treating proliferative disorders |
| CA2424884C (en) | 2000-10-05 | 2009-12-15 | E. Premkumar Reddy | Substituted (e)-styryl benzylsulfones for treating proliferative disorders |
| US6833480B2 (en) | 2001-02-27 | 2004-12-21 | Temple University - Of The Commonwealth System Of Higher Education | (Z)-styrylbenzylsulfones and pharmaceutical uses thereof |
| IL157540A0 (en) | 2001-02-28 | 2004-03-28 | Univ Temple | N-(aryl)-2-arylethenesulphonamides and therapeutic uses thereof |
| ATE406881T1 (de) | 2001-02-28 | 2008-09-15 | Univ Temple | Verwendung von alpha, beta ungesättigten arylsulfonen zum schutz von zellen und geweben vor toxizität ionischer strahlung |
| MXPA04008356A (es) | 2002-02-28 | 2005-09-12 | Univ Temple | (e)-2,6-dialcoxiestiril bencilsulfonas sustituidas con un grupo amino y en la posicion 4 para tratar trastornos poliferativos. |
| ATE517626T1 (de) | 2002-02-28 | 2011-08-15 | Univ Temple | Aminosubstituierte sulphonanilide und ihre derivate zur behandlung von proliferativen erkrankungen |
| NZ538663A (en) | 2002-08-29 | 2006-02-24 | Univ Temple | Aryl and heteroaryl propene amides, derivatives thereof and therapeutic uses thereof |
| EP1549614A4 (en) | 2002-10-03 | 2008-04-16 | Targegen Inc | VASCULATORY AGENTS AND METHODS FOR THEIR APPLICATION |
| HUE032523T2 (en) | 2003-11-14 | 2017-09-28 | Temple Univ - Of The Commonwealth System Of Higher Education | Alpha, beta-unsaturated sulfoxides for the treatment of proliferative disorders |
| ES2609084T3 (es) | 2004-03-16 | 2017-04-18 | Temple University - Of The Commonwealth System Of Higher Education | Derivados de fenoxi y feniltio sustituidos para tratar trastornos proliferativos |
| EP1765804A4 (en) | 2004-06-08 | 2009-11-11 | Univ Temple | HETEROARYLSULFONES AND SULFONAMIDES AND THEIR THERAPEUTIC USES |
| CA2577309C (en) | 2004-06-24 | 2013-10-22 | Temple University - Of The Commonwealth System Of Higher Education | Alpha, beta-unsaturated sulfones, sulfoxides, sulfonimides, sulfinimides, acylsulfonamides and acylsulfinamides and therapeutic uses thereof |
| AU2006204103B2 (en) | 2005-01-05 | 2011-11-24 | Temple University Of The Commonwealth System Of Higher Education | Treatment of drug-resistant proliferative disorders |
| PT1896401E (pt) * | 2005-02-25 | 2013-07-17 | Univ Temple | Síntese de sulfuretos, sulfonas, sulfóxidos e sulfonamidas não saturados |
| WO2006104668A2 (en) | 2005-03-11 | 2006-10-05 | Temple University - Of The Commonwealth System Of Higher Education | Composition and methods for the treatment of proliferative diseases |
| WO2007127366A2 (en) | 2006-04-25 | 2007-11-08 | Targegen, Inc. | Kinase inhibitors and methods of use thereof |
| JP5278968B2 (ja) | 2006-08-30 | 2013-09-04 | テンプル・ユニバーシティ−オブ・ザ・コモンウェルス・システム・オブ・ハイアー・エデュケイション | 骨髄異形性症候群及び急性骨髄性白血病の治療のための組成物及び方法 |
| CL2007003591A1 (es) | 2006-12-12 | 2008-02-29 | Wyeth Corp | Compuestos derivados de sulfonamida ciclicos, inhibidores de retoma de monoamina; procedimiento de preparacion; composicion farmaceutica; y uso para el tratamiento o prevencion de disfuncion sexual, trastorno gastrointestinal, trastorno genitourinari |
| CL2007003874A1 (es) | 2007-01-03 | 2008-05-16 | Boehringer Ingelheim Int | Compuestos derivados de benzamida; composicion farmaceutica que comprende a dichos compuestos; y su uso para tratar enfermedades cardiovasculares, hipertension, aterosclerosis, reestenosis, ictus, insuficiencia cardiaca, lesion isquemica, hipertensio |
| US8124605B2 (en) * | 2007-07-06 | 2012-02-28 | Kinex Pharmaceuticals, Llc | Compositions and methods for modulating a kinase cascade |
| AU2008345225A1 (en) | 2007-12-21 | 2009-07-09 | University Of Rochester | Method for altering the lifespan of eukaryotic organisms |
| US8686190B2 (en) * | 2008-04-10 | 2014-04-01 | The Uab Research Foundation | Bis-aromatic anticancer agents |
| MX2010014172A (es) | 2008-07-03 | 2011-02-22 | Amira Pharmaceuticals Inc | Antagonistas de receptores de prostaglandina d2. |
| EP2226329B1 (en) | 2009-03-02 | 2013-07-10 | Ruhr-Universität Bochum | Metal-containing platensimycin analogues |
| GB0908293D0 (en) | 2009-05-14 | 2009-06-24 | Syngenta Ltd | Herbicidal compounds |
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| EP2897599B1 (en) | 2020-12-30 |
| WO2014047110A2 (en) | 2014-03-27 |
| AU2013318206A1 (en) | 2015-04-30 |
| US10207989B2 (en) | 2019-02-19 |
| WO2014047110A3 (en) | 2014-06-26 |
| IL237699B (en) | 2019-12-31 |
| US20150266819A1 (en) | 2015-09-24 |
| CN104812382A (zh) | 2015-07-29 |
| KR20150059769A (ko) | 2015-06-02 |
| CN110776447A (zh) | 2020-02-11 |
| JP2015533810A (ja) | 2015-11-26 |
| IL237699A0 (en) | 2015-05-31 |
| CA2885217A1 (en) | 2014-03-27 |
| ES2863538T3 (es) | 2021-10-11 |
| JP6348904B2 (ja) | 2018-06-27 |
| KR101992929B1 (ko) | 2019-06-25 |
| AU2013318206B2 (en) | 2018-07-26 |
| EP2897599A2 (en) | 2015-07-29 |
| EP2897599A4 (en) | 2016-05-11 |
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