TWI259085B - Piperazine derivatives having SST1 antagonistic activity - Google Patents
Piperazine derivatives having SST1 antagonistic activity Download PDFInfo
- Publication number
- TWI259085B TWI259085B TW091132777A TW91132777A TWI259085B TW I259085 B TWI259085 B TW I259085B TW 091132777 A TW091132777 A TW 091132777A TW 91132777 A TW91132777 A TW 91132777A TW I259085 B TWI259085 B TW I259085B
- Authority
- TW
- Taiwan
- Prior art keywords
- compound
- formula
- patent application
- free base
- acid addition
- Prior art date
Links
- 230000003042 antagnostic effect Effects 0.000 title description 2
- 102100029563 Somatostatin Human genes 0.000 title 1
- 150000004885 piperazines Chemical class 0.000 title 1
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 43
- 239000003814 drug Substances 0.000 claims abstract description 14
- 150000003839 salts Chemical class 0.000 claims description 22
- 238000011282 treatment Methods 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 18
- 239000012458 free base Substances 0.000 claims description 18
- 208000019901 Anxiety disease Diseases 0.000 claims description 13
- 230000036506 anxiety Effects 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 239000005557 antagonist Substances 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 208000020401 Depressive disease Diseases 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 claims 2
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims 1
- 102000000393 Ghrelin Receptors Human genes 0.000 claims 1
- 108010016122 Ghrelin Receptors Proteins 0.000 claims 1
- 150000003573 thiols Chemical class 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 29
- 239000003795 chemical substances by application Substances 0.000 description 25
- 239000000203 mixture Substances 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- 235000019439 ethyl acetate Nutrition 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- -1 for example Inorganic materials 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 238000012360 testing method Methods 0.000 description 8
- 239000003921 oil Substances 0.000 description 7
- 239000000018 receptor agonist Substances 0.000 description 7
- 229940044601 receptor agonist Drugs 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 239000002464 receptor antagonist Substances 0.000 description 6
- 229940044551 receptor antagonist Drugs 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 201000000980 schizophrenia Diseases 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000003542 behavioural effect Effects 0.000 description 4
- 229910000420 cerium oxide Inorganic materials 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- BMMGVYCKOGBVEV-UHFFFAOYSA-N oxo(oxoceriooxy)cerium Chemical compound [Ce]=O.O=[Ce]=O BMMGVYCKOGBVEV-UHFFFAOYSA-N 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000003039 volatile agent Substances 0.000 description 4
- 206010012289 Dementia Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 208000019022 Mood disease Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 3
- 229960004170 clozapine Drugs 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 229940126062 Compound A Drugs 0.000 description 2
- 108010056643 Corticotropin-Releasing Hormone Receptors Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 208000026139 Memory disease Diseases 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 108050001286 Somatostatin Receptor Proteins 0.000 description 2
- 102000011096 Somatostatin receptor Human genes 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000003693 atypical antipsychotic agent Substances 0.000 description 2
- 229940049706 benzodiazepine Drugs 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 2
- 229960000623 carbamazepine Drugs 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 239000000544 cholinesterase inhibitor Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000003775 serotonin noradrenalin reuptake inhibitor Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 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 description 2
- VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- VRVIKRZIQWEYFB-UHFFFAOYSA-N 1-(3,4-difluorophenyl)piperazine Chemical compound C1=C(F)C(F)=CC=C1N1CCNCC1 VRVIKRZIQWEYFB-UHFFFAOYSA-N 0.000 description 1
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- WBWAHPQXFIMEOA-UHFFFAOYSA-N 2-(9h-xanthen-9-yl)acetic acid Chemical compound C1=CC=C2C(CC(=O)O)C3=CC=CC=C3OC2=C1 WBWAHPQXFIMEOA-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 108091005436 5-HT7 receptors Proteins 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Natural products CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
- 206010001488 Aggression Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 206010002869 Anxiety symptoms Diseases 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 208000011597 CGF1 Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 206010054089 Depressive symptom Diseases 0.000 description 1
- 208000027534 Emotional disease Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- 208000020358 Learning disease Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010026749 Mania Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- YGDPMZUVLNLWSP-UHFFFAOYSA-N N1N=NC=C1.C1(C=CC(C=C1)=O)=O Chemical compound N1N=NC=C1.C1(C=CC(C=C1)=O)=O YGDPMZUVLNLWSP-UHFFFAOYSA-N 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-O Piperidinium(1+) Chemical compound C1CC[NH2+]CC1 NQRYJNQNLNOLGT-UHFFFAOYSA-O 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 208000010340 Sleep Deprivation Diseases 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 102000005157 Somatostatin Human genes 0.000 description 1
- 108010056088 Somatostatin Proteins 0.000 description 1
- 102000004136 Vasopressin Receptors Human genes 0.000 description 1
- 108090000643 Vasopressin Receptors Proteins 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 1
- 208000012761 aggressive behavior Diseases 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 230000036626 alertness Effects 0.000 description 1
- QWCKQJZIFLGMSD-UHFFFAOYSA-N alpha-aminobutyric acid Chemical compound CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000002539 anti-aggressive effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 229940127236 atypical antipsychotics Drugs 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000006612 decyloxy group Chemical group 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000021824 exploration behavior Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 238000002309 gasification Methods 0.000 description 1
- 208000037870 generalized anxiety Diseases 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 201000003723 learning disability Diseases 0.000 description 1
- 230000007786 learning performance Effects 0.000 description 1
- 239000010985 leather Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 230000007334 memory performance Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000006996 mental state Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229960004136 rivastigmine Drugs 0.000 description 1
- 238000003572 second messenger assay Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 230000004039 social cognition Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 229960000553 somatostatin Drugs 0.000 description 1
- 108010082379 somatostatin receptor type 1 Proteins 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 229910052712 strontium Inorganic materials 0.000 description 1
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- JOUDBUYBGJYFFP-FOCLMDBBSA-N thioindigo Chemical compound S\1C2=CC=CC=C2C(=O)C/1=C1/C(=O)C2=CC=CC=C2S1 JOUDBUYBGJYFFP-FOCLMDBBSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 229940102566 valproate Drugs 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 239000002536 vasopressin receptor antagonist Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- 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
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- 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
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
- C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
- C07D311/82—Xanthenes
- C07D311/90—Xanthenes with hydrocarbon radicals, substituted by amino radicals, directly attached in position 9
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
- C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D335/10—Dibenzothiopyrans; Hydrogenated dibenzothiopyrans
- C07D335/12—Thioxanthenes
- C07D335/20—Thioxanthenes with hydrocarbon radicals, substituted by amino radicals, directly attached in position 9
-
- C—CHEMISTRY; METALLURGY
- 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
- C07D405/02—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 two hetero rings
- C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D487/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyrane Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0127008.1A GB0127008D0 (en) | 2001-11-09 | 2001-11-09 | Organic compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW200300088A TW200300088A (en) | 2003-05-16 |
| TWI259085B true TWI259085B (en) | 2006-08-01 |
Family
ID=9925528
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW091132777A TWI259085B (en) | 2001-11-09 | 2002-11-07 | Piperazine derivatives having SST1 antagonistic activity |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US7271168B2 (enExample) |
| EP (1) | EP1446399B1 (enExample) |
| JP (1) | JP4199668B2 (enExample) |
| CN (1) | CN1269811C (enExample) |
| AR (1) | AR037521A1 (enExample) |
| AT (1) | ATE294787T1 (enExample) |
| BR (1) | BR0213990A (enExample) |
| CA (1) | CA2465680A1 (enExample) |
| DE (1) | DE60204044T2 (enExample) |
| ES (1) | ES2240830T3 (enExample) |
| GB (1) | GB0127008D0 (enExample) |
| MY (1) | MY136297A (enExample) |
| PE (1) | PE20030539A1 (enExample) |
| PT (1) | PT1446399E (enExample) |
| TW (1) | TWI259085B (enExample) |
| WO (1) | WO2003040125A1 (enExample) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7390813B1 (en) | 2001-12-21 | 2008-06-24 | Xenon Pharmaceuticals Inc. | Pyridylpiperazines and aminonicotinamides and their use as therapeutic agents |
| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| BRPI0515477A (pt) | 2004-09-20 | 2008-07-22 | Xenon Pharmaceuticals Inc | derivados heterocìclicos bicìclicos e o uso dos mesmos como inibidores de estaroil-coa-desaturase (scd) |
| AU2005286846A1 (en) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as therapeutic agents |
| WO2006101521A2 (en) | 2004-09-20 | 2006-09-28 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-coa desaturase inhibitors |
| US7951805B2 (en) | 2004-09-20 | 2011-05-31 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as mediators of stearoyl-CoA desaturase |
| US8071603B2 (en) | 2004-09-20 | 2011-12-06 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-CoA desaturase inhibitors |
| AU2005286647A1 (en) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-CoA desaturase inhibitors |
| AR051026A1 (es) | 2004-09-20 | 2006-12-13 | Xenon Pharmaceuticals Inc | Derivados heterociclicos y su uso como inhibidores de la estearoil-coa desaturasa |
| EP2316458A1 (en) | 2004-09-20 | 2011-05-04 | Xenon Pharmaceuticals Inc. | Pyridazine derivatives for inhibiting human stearoyl-coa-desaturase |
| JP2009513563A (ja) | 2005-06-03 | 2009-04-02 | ゼノン・ファーマシューティカルズ・インコーポレイテッド | ヒトのステアロイル−ＣｏＡデサチュラーゼ阻害剤としてのアミノチアゾール誘導体 |
| GB0514615D0 (en) | 2005-07-15 | 2005-08-24 | Novartis Ag | Organic compounds |
| ES2541528T3 (es) | 2008-11-19 | 2015-07-21 | Forum Pharmaceuticals Inc. | Tratamiento de trastornos cognitivos con (R)-7-cloro-N-(quinuclidin-3-il)benzo[b]tiofeno-2-carboxamida y sales farmacéuticamente aceptables de la misma |
| JP5749797B2 (ja) | 2010-05-17 | 2015-07-15 | フォルム ファーマシューティカルズ、インコーポレイテッド | （ｒ）−７−クロロ−ｎ−（キヌクリジン−３−イル）ベンゾ［ｂ］チオフェン−２−カルボキサミド塩酸塩一水和物の結晶形 |
| CA2872005A1 (en) | 2012-05-08 | 2013-11-14 | Forum Pharmaceuticals, Inc. | Methods of maintaining, treating or improving cognitive function |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5495047A (en) | 1991-07-10 | 1996-02-27 | Merck, Sharp & Dohme (Ltd.) | Fused tricyclic compounds, pharmaceutical compositions containing them and their use in therapy |
-
2001
- 2001-11-09 GB GBGB0127008.1A patent/GB0127008D0/en not_active Ceased
-
2002
- 2002-11-07 PE PE2002001085A patent/PE20030539A1/es not_active Application Discontinuation
- 2002-11-07 TW TW091132777A patent/TWI259085B/zh not_active IP Right Cessation
- 2002-11-07 AR ARP020104273A patent/AR037521A1/es not_active Application Discontinuation
- 2002-11-08 ES ES02787612T patent/ES2240830T3/es not_active Expired - Lifetime
- 2002-11-08 JP JP2003542171A patent/JP4199668B2/ja not_active Expired - Fee Related
- 2002-11-08 DE DE60204044T patent/DE60204044T2/de not_active Expired - Lifetime
- 2002-11-08 WO PCT/EP2002/012514 patent/WO2003040125A1/en not_active Ceased
- 2002-11-08 AT AT02787612T patent/ATE294787T1/de not_active IP Right Cessation
- 2002-11-08 EP EP02787612A patent/EP1446399B1/en not_active Expired - Lifetime
- 2002-11-08 CA CA002465680A patent/CA2465680A1/en not_active Abandoned
- 2002-11-08 PT PT02787612T patent/PT1446399E/pt unknown
- 2002-11-08 US US10/494,898 patent/US7271168B2/en not_active Expired - Fee Related
- 2002-11-08 BR BR0213990-1A patent/BR0213990A/pt not_active Application Discontinuation
- 2002-11-08 CN CNB028236912A patent/CN1269811C/zh not_active Expired - Fee Related
- 2002-11-08 MY MYPI20024185A patent/MY136297A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP1446399B1 (en) | 2005-05-04 |
| ES2240830T3 (es) | 2005-10-16 |
| US7271168B2 (en) | 2007-09-18 |
| JP2005516898A (ja) | 2005-06-09 |
| CA2465680A1 (en) | 2003-05-15 |
| BR0213990A (pt) | 2004-08-31 |
| HK1068338A1 (en) | 2005-04-29 |
| JP4199668B2 (ja) | 2008-12-17 |
| DE60204044D1 (de) | 2005-06-09 |
| AR037521A1 (es) | 2004-11-17 |
| CN1596251A (zh) | 2005-03-16 |
| US20060079527A1 (en) | 2006-04-13 |
| TW200300088A (en) | 2003-05-16 |
| WO2003040125A1 (en) | 2003-05-15 |
| EP1446399A1 (en) | 2004-08-18 |
| GB0127008D0 (en) | 2002-01-02 |
| CN1269811C (zh) | 2006-08-16 |
| PT1446399E (pt) | 2005-09-30 |
| ATE294787T1 (de) | 2005-05-15 |
| PE20030539A1 (es) | 2003-08-13 |
| MY136297A (en) | 2008-09-30 |
| DE60204044T2 (de) | 2006-01-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN115197225B (zh) | 一种五元杂环并喹唑啉酮类化合物及其制备方法 | |
| Zhang et al. | Discovery of a new class of PROTAC BRD4 degraders based on a dihydroquinazolinone derivative and lenalidomide/pomalidomide | |
| TWI259085B (en) | Piperazine derivatives having SST1 antagonistic activity | |
| US5159083A (en) | Certain aminomethyl phenylimidazole derivatives; a class of dopamine receptor subtype specific ligands | |
| CN102448951B (zh) | 丙酮酸激酶m2调节剂、治疗组合物和相关使用方法 | |
| US5760234A (en) | Certain 1-substituted aminomethyl imidazole and pyrrole derivatives: novel dopamine receptor subtype specific ligands | |
| JP5764555B2 (ja) | 治療組成物および関連する使用方法 | |
| BG65104B1 (bg) | Изотиазолови производни, метод за получаването им, фармацевтичен състав и използването им като противоракови средства | |
| KR19990028757A (ko) | 벤조[ｇ]퀴놀린 유도체 | |
| JP5778297B2 (ja) | 癌治療用のｈｄａｃ阻害剤としての新規４−アミノ−ｎ−ヒドロキシ−ベンズアミド | |
| JP2018513219A (ja) | 縮合環ピリミジンアミノ誘導体、その製造方法、中間体、薬学的組成物及び応用 | |
| US6391891B1 (en) | Bicyclic compounds as ligands for 5-HT1 receptors | |
| WO2022179584A1 (zh) | 新型ezh2抑制剂及其用途 | |
| RU2727194C2 (ru) | Гетероциклические соединения для лечения заболевания | |
| CN102249981A (zh) | N-芳基磺酰基-3-氨基烷氧基吲哚 | |
| US20050222418A1 (en) | Novel tyloindicines and related processes, pharmaceutical compositions and methods | |
| FR2960876A1 (fr) | Derives de 3,4-dihydropyrrolo[1,2-a]pyrazine-2,8(1h)-dicarboxamide leur preparation et leur application en therapeutique. | |
| CN115974855A (zh) | Ezh2和hdac双靶点抑制剂、其药物组合物及其制备方法和用途 | |
| FR2758329A1 (fr) | Derives d'imidazole-4-butane boronique, leur preparation et leur utilisation en therapeutique | |
| JP2007504263A (ja) | オキシトシン作働薬としてのピペラジン類 | |
| US20060264431A1 (en) | P38 inhibitors and methods of use thereof | |
| JPH0733743A (ja) | ２−アリール−４−キノリノール誘導体 | |
| US6002005A (en) | Certain 1-substituted aminomethyl imidazole and pyrrole derivatives: novel dopamine receptor subtype specific ligands | |
| TWI261590B (en) | C-6 ring-substituted pyrido [1,2-a]benzimidazole derivatives useful in treating central nervous system disorders | |
| JPWO2001000588A1 (ja) | ベンズイミダゾール化合物及びこれを含む医薬 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Annulment or lapse of patent due to non-payment of fees |