UA77526C2 - Substituted derivatives of 1-piperazineacylpiperidine, a method for the preparation thereof and their use in therapy - Google Patents

Substituted derivatives of 1-piperazineacylpiperidine, a method for the preparation thereof and their use in therapy Download PDF

Info

Publication number: UA77526C2
Authority: UA; Ukraine
Prior art keywords: formula; compound; methyl; trifluoromethyl; phenyl
Prior art date: 2002-06-07

Application number

UA20041210010A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Sanofi Aventis

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2002-06-07

Filing date

2003-05-06

Publication date

2006-12-15

2003-05-06 Application filed by Sanofi Aventis filed Critical Sanofi Aventis

2006-12-15 Publication of UA77526C2 publication Critical patent/UA77526C2/uk

Links

238000000034 method Methods 0.000 title claims abstract description 66
238000002360 preparation method Methods 0.000 title claims description 150
238000002560 therapeutic procedure Methods 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 423
-1 trifluoromethoxy radical Chemical class 0.000 claims abstract description 117
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 31
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims abstract description 27
WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 claims abstract description 22
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 22
125000005843 halogen group Chemical group 0.000 claims abstract description 22
229910052799 carbon Inorganic materials 0.000 claims abstract description 21
125000003118 aryl group Chemical group 0.000 claims abstract description 7
239000001257 hydrogen Substances 0.000 claims abstract description 5
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
125000001424 substituent group Chemical group 0.000 claims abstract description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 124
125000000217 alkyl group Chemical group 0.000 claims description 45
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
150000003839 salts Chemical group 0.000 claims description 28
239000002253 acid Substances 0.000 claims description 24
229910052801 chlorine Inorganic materials 0.000 claims description 22
239000012453 solvate Substances 0.000 claims description 19
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 18
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 12
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 12
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 12
125000001309 chloro group Chemical group Cl* 0.000 claims description 12
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
239000000460 chlorine Substances 0.000 claims description 11
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 10
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 10
229910052794 bromium Inorganic materials 0.000 claims description 10
125000003386 piperidinyl group Chemical group 0.000 claims description 10
229910052700 potassium Inorganic materials 0.000 claims description 10
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 10
150000001412 amines Chemical group 0.000 claims description 9
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
229910052757 nitrogen Inorganic materials 0.000 claims description 8
125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 7
230000006378 damage Effects 0.000 claims description 7
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 6
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 6
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 6
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
230000006870 function Effects 0.000 claims description 5
230000002265 prevention Effects 0.000 claims description 5
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 4
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 4
206010028980 Neoplasm Diseases 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
125000000623 heterocyclic group Chemical group 0.000 claims description 4
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims description 4
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 4
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
201000001320 Atherosclerosis Diseases 0.000 claims description 3
208000027418 Wounds and injury Diseases 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 3
125000004093 cyano group Chemical group *C#N 0.000 claims description 3
208000014674 injury Diseases 0.000 claims description 3
201000006417 multiple sclerosis Diseases 0.000 claims description 3
230000002093 peripheral effect Effects 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 3
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
201000004384 Alopecia Diseases 0.000 claims description 2
208000023275 Autoimmune disease Diseases 0.000 claims description 2
208000010392 Bone Fractures Diseases 0.000 claims description 2
208000020084 Bone disease Diseases 0.000 claims description 2
206010065390 Inflammatory pain Diseases 0.000 claims description 2
206010027476 Metastases Diseases 0.000 claims description 2
208000031481 Pathologic Constriction Diseases 0.000 claims description 2
125000004429 atom Chemical group 0.000 claims description 2
230000001684 chronic effect Effects 0.000 claims description 2
230000002526 effect on cardiovascular system Effects 0.000 claims description 2
208000032839 leukemia Diseases 0.000 claims description 2
208000004296 neuralgia Diseases 0.000 claims description 2
230000004770 neurodegeneration Effects 0.000 claims description 2
208000015122 neurodegenerative disease Diseases 0.000 claims description 2
230000002981 neuropathic effect Effects 0.000 claims description 2
208000021722 neuropathic pain Diseases 0.000 claims description 2
210000001328 optic nerve Anatomy 0.000 claims description 2
208000027232 peripheral nervous system disease Diseases 0.000 claims description 2
208000033808 peripheral neuropathy Diseases 0.000 claims description 2
210000001525 retina Anatomy 0.000 claims description 2
208000020431 spinal cord injury Diseases 0.000 claims description 2
230000036262 stenosis Effects 0.000 claims description 2
208000037804 stenosis Diseases 0.000 claims description 2
229940079593 drug Drugs 0.000 claims 2
AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical compound OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 claims 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
230000003676 hair loss Effects 0.000 claims 1
125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
125000004453 alkoxycarbonyl group Chemical group 0.000 abstract description 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 2
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 2
230000001225 therapeutic effect Effects 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 186
239000000203 mixture Substances 0.000 description 163
239000000047 product Substances 0.000 description 141
239000002904 solvent Substances 0.000 description 111
239000000243 solution Substances 0.000 description 98
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 98
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 93
238000003756 stirring Methods 0.000 description 78
239000012074 organic phase Substances 0.000 description 73
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 72
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 66
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 47
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
239000003480 eluent Substances 0.000 description 42
239000000741 silica gel Substances 0.000 description 42
229910002027 silica gel Inorganic materials 0.000 description 42
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 39
239000011541 reaction mixture Substances 0.000 description 39
WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 39
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 36
238000006243 chemical reaction Methods 0.000 description 31
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
239000000706 filtrate Substances 0.000 description 29
239000003054 catalyst Substances 0.000 description 28
239000012047 saturated solution Substances 0.000 description 27
239000011734 sodium Substances 0.000 description 26
VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 22
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 22
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 22
239000002244 precipitate Substances 0.000 description 22
238000010992 reflux Methods 0.000 description 22
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
239000002585 base Substances 0.000 description 19
102000005962 receptors Human genes 0.000 description 18
108020003175 receptors Proteins 0.000 description 18
238000001953 recrystallisation Methods 0.000 description 17
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 17
102100036220 PC4 and SFRS1-interacting protein Human genes 0.000 description 16
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 15
238000001819 mass spectrum Methods 0.000 description 15
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
230000006907 apoptotic process Effects 0.000 description 14
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
210000004027 cell Anatomy 0.000 description 12
HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 12
239000000543 intermediate Substances 0.000 description 12
GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 12
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 12
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 11
239000003921 oil Substances 0.000 description 10
235000019198 oils Nutrition 0.000 description 10
239000011780 sodium chloride Substances 0.000 description 10
ZJRWDIJRKKXMNW-UHFFFAOYSA-N carbonic acid;cobalt Chemical compound [Co].OC(O)=O ZJRWDIJRKKXMNW-UHFFFAOYSA-N 0.000 description 9
229910000001 cobalt(II) carbonate Inorganic materials 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
KKCBUQHMOMHUOY-UHFFFAOYSA-N Na2O Inorganic materials [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 8
230000027455 binding Effects 0.000 description 8
238000007796 conventional method Methods 0.000 description 8
SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 8
239000000725 suspension Substances 0.000 description 8
SJZKULRDWHPHGG-UHFFFAOYSA-N 1-benzylpiperidin-4-one Chemical compound C1CC(=O)CCN1CC1=CC=CC=C1 SJZKULRDWHPHGG-UHFFFAOYSA-N 0.000 description 7
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 7
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 7
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 7
108010025020 Nerve Growth Factor Proteins 0.000 description 7
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
229960000583 acetic acid Drugs 0.000 description 7
235000011054 acetic acid Nutrition 0.000 description 7
239000008346 aqueous phase Substances 0.000 description 7
238000001816 cooling Methods 0.000 description 7
229910052759 nickel Inorganic materials 0.000 description 7
229910000027 potassium carbonate Inorganic materials 0.000 description 7
229920006395 saturated elastomer Polymers 0.000 description 7
239000012312 sodium hydride Substances 0.000 description 7
229910000104 sodium hydride Inorganic materials 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 6
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
102000007072 Nerve Growth Factors Human genes 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
239000011777 magnesium Substances 0.000 description 6
229910052749 magnesium Inorganic materials 0.000 description 6
235000006408 oxalic acid Nutrition 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
206010062717 Increased upper airway secretion Diseases 0.000 description 5
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000002609 medium Substances 0.000 description 5
239000012071 phase Substances 0.000 description 5
208000026435 phlegm Diseases 0.000 description 5
235000011181 potassium carbonates Nutrition 0.000 description 5
239000012321 sodium triacetoxyborohydride Substances 0.000 description 5
CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 5
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
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 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
230000030833 cell death Effects 0.000 description 4
239000013078 crystal Substances 0.000 description 4
239000012458 free base Substances 0.000 description 4
239000008187 granular material Substances 0.000 description 4
230000008569 process Effects 0.000 description 4
102000004169 proteins and genes Human genes 0.000 description 4
108090000623 proteins and genes Proteins 0.000 description 4
230000008929 regeneration Effects 0.000 description 4
238000011069 regeneration method Methods 0.000 description 4
DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
208000024827 Alzheimer disease Diseases 0.000 description 3
241000282412 Homo Species 0.000 description 3
108010083674 Myelin Proteins Proteins 0.000 description 3
102000006386 Myelin Proteins Human genes 0.000 description 3
206010029260 Neuroblastoma Diseases 0.000 description 3
208000024777 Prion disease Diseases 0.000 description 3
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
229910000288 alkali metal carbonate Inorganic materials 0.000 description 3
150000008041 alkali metal carbonates Chemical class 0.000 description 3
150000008044 alkali metal hydroxides Chemical class 0.000 description 3
229910001516 alkali metal iodide Inorganic materials 0.000 description 3
210000003050 axon Anatomy 0.000 description 3
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
239000012141 concentrate Substances 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
235000019439 ethyl acetate Nutrition 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
150000004677 hydrates Chemical class 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
239000011630 iodine Substances 0.000 description 3
208000028867 ischemia Diseases 0.000 description 3
210000002569 neuron Anatomy 0.000 description 3
230000007170 pathology Effects 0.000 description 3
108090000765 processed proteins & peptides Proteins 0.000 description 3
230000009467 reduction Effects 0.000 description 3
SETMGIIITGNLAS-UHFFFAOYSA-N spizofurone Chemical compound O=C1C2=CC(C(=O)C)=CC=C2OC21CC2 SETMGIIITGNLAS-UHFFFAOYSA-N 0.000 description 3
229950001870 spizofurone Drugs 0.000 description 3
239000000126 substance Substances 0.000 description 3
FQZLNQAUUMSUHT-UHFFFAOYSA-N tert-butyl n,n-bis(2-chloroethyl)carbamate Chemical compound CC(C)(C)OC(=O)N(CCCl)CCCl FQZLNQAUUMSUHT-UHFFFAOYSA-N 0.000 description 3
230000000699 topical effect Effects 0.000 description 3
XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 2
IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 description 2
BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical compound ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 2
PFIZGLUIYAZQFU-UHFFFAOYSA-N 2-chloro-6-piperazin-1-ylpyrazine;hydron;chloride Chemical compound Cl.ClC1=CN=CC(N2CCNCC2)=N1 PFIZGLUIYAZQFU-UHFFFAOYSA-N 0.000 description 2
SFWWGMKXCYLZEG-UHFFFAOYSA-N 3-methylmorpholine Chemical compound CC1COCCN1 SFWWGMKXCYLZEG-UHFFFAOYSA-N 0.000 description 2
VGRLNUVAXJAWDT-UHFFFAOYSA-N 3-piperazin-1-ylpyridazine;trihydrochloride Chemical compound Cl.Cl.Cl.C1CNCCN1C1=CC=CN=N1 VGRLNUVAXJAWDT-UHFFFAOYSA-N 0.000 description 2
VJWXIRQLLGYIDI-UHFFFAOYSA-N 4,5-dichloro-1h-pyridazin-6-one Chemical compound OC1=NN=CC(Cl)=C1Cl VJWXIRQLLGYIDI-UHFFFAOYSA-N 0.000 description 2
MEPSZTLGVPLPCD-UHFFFAOYSA-N 4-(3-chlorophenyl)piperidine-4-carbonitrile;hydrochloride Chemical compound Cl.ClC1=CC=CC(C2(CCNCC2)C#N)=C1 MEPSZTLGVPLPCD-UHFFFAOYSA-N 0.000 description 2
ILBKGTFODUPWDB-UHFFFAOYSA-N 4-(3-methoxyphenyl)piperidine-4-carbonitrile;hydrochloride Chemical compound Cl.COC1=CC=CC(C2(CCNCC2)C#N)=C1 ILBKGTFODUPWDB-UHFFFAOYSA-N 0.000 description 2
DDGOHIWHCKUFKW-UHFFFAOYSA-N 4-(3-methylphenyl)piperidin-4-ol Chemical compound CC1=CC=CC(C2(O)CCNCC2)=C1 DDGOHIWHCKUFKW-UHFFFAOYSA-N 0.000 description 2
TWXSQWIBFLBSNW-UHFFFAOYSA-N 4-(4-benzylpiperazin-1-yl)-5-chloro-1h-pyridazin-6-one Chemical compound C1=NNC(=O)C(Cl)=C1N1CCN(CC=2C=CC=CC=2)CC1 TWXSQWIBFLBSNW-UHFFFAOYSA-N 0.000 description 2
WIBNKOGGSUSKRF-UHFFFAOYSA-N 4-(4-chlorophenyl)piperidine-4-carbonitrile;hydrochloride Chemical compound Cl.C1=CC(Cl)=CC=C1C1(C#N)CCNCC1 WIBNKOGGSUSKRF-UHFFFAOYSA-N 0.000 description 2
VBVIHVWFUKMIGL-UHFFFAOYSA-N 4-chloro-2-piperazin-1-ylpyrimidine;hydrochloride Chemical compound Cl.ClC1=CC=NC(N2CCNCC2)=N1 VBVIHVWFUKMIGL-UHFFFAOYSA-N 0.000 description 2
JLZJWSWUUOLXCR-UHFFFAOYSA-N 4-piperazin-1-ylpyridazine Chemical compound C1CNCCN1C1=CC=NN=C1 JLZJWSWUUOLXCR-UHFFFAOYSA-N 0.000 description 2
ZGDACUKNZMMEQF-UHFFFAOYSA-N 5-piperazin-1-yl-1h-pyridazin-6-one;hydrochloride Chemical compound Cl.O=C1NN=CC=C1N1CCNCC1 ZGDACUKNZMMEQF-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 2
229930182566 Gentamicin Natural products 0.000 description 2
208000023105 Huntington disease Diseases 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
108010032605 Nerve Growth Factor Receptors Proteins 0.000 description 2
102000007339 Nerve Growth Factor Receptors Human genes 0.000 description 2
102100033857 Neurotrophin-4 Human genes 0.000 description 2
108090000099 Neurotrophin-4 Proteins 0.000 description 2
102000005781 Nogo Receptor Human genes 0.000 description 2
108020003872 Nogo receptor Proteins 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
108091000054 Prion Proteins 0.000 description 2
102000029797 Prion 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
230000010933 acylation Effects 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
150000001299 aldehydes Chemical class 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
150000001340 alkali metals Chemical class 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
229910052782 aluminium Inorganic materials 0.000 description 2
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
235000019270 ammonium chloride Nutrition 0.000 description 2
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
230000003143 atherosclerotic effect Effects 0.000 description 2
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
239000007853 buffer solution Substances 0.000 description 2
230000001413 cellular effect Effects 0.000 description 2
210000003169 central nervous system Anatomy 0.000 description 2
206010008118 cerebral infarction Diseases 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
201000010099 disease Diseases 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
239000000945 filler Substances 0.000 description 2
WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
239000007789 gas Substances 0.000 description 2
229960002518 gentamicin Drugs 0.000 description 2
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
239000003102 growth factor Substances 0.000 description 2
235000011167 hydrochloric acid Nutrition 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
230000003993 interaction Effects 0.000 description 2
238000007918 intramuscular administration Methods 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
230000003902 lesion Effects 0.000 description 2
239000012280 lithium aluminium hydride Substances 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
239000012528 membrane Substances 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
210000005012 myelin Anatomy 0.000 description 2
210000005036 nerve Anatomy 0.000 description 2
230000016273 neuron death Effects 0.000 description 2
230000009871 nonspecific binding Effects 0.000 description 2
210000004248 oligodendroglia Anatomy 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
125000002734 organomagnesium group Chemical group 0.000 description 2
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
XAMUDJHXFNRLCY-UHFFFAOYSA-N phenthoate Chemical compound CCOC(=O)C(SP(=S)(OC)OC)C1=CC=CC=C1 XAMUDJHXFNRLCY-UHFFFAOYSA-N 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
230000000704 physical effect Effects 0.000 description 2
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 2
235000015320 potassium carbonate Nutrition 0.000 description 2
230000000861 pro-apoptotic effect Effects 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
239000012429 reaction media Substances 0.000 description 2
229910052703 rhodium Inorganic materials 0.000 description 2
239000010948 rhodium Substances 0.000 description 2
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 2
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Inorganic materials [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 2
229940054269 sodium pyruvate Drugs 0.000 description 2
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
239000007787 solid Substances 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
239000003826 tablet Substances 0.000 description 2
GZYDEJABHMSOIM-UHFFFAOYSA-N tert-butyl 4-(2-chloropyrimidin-4-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=NC(Cl)=N1 GZYDEJABHMSOIM-UHFFFAOYSA-N 0.000 description 2
BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 2
238000001665 trituration Methods 0.000 description 2
102000003390 tumor necrosis factor Human genes 0.000 description 2
MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 1
QOOQLKSEGVNYLA-UHFFFAOYSA-N 1-$l^{1}-oxidanylbutane Chemical compound CCCC[O] QOOQLKSEGVNYLA-UHFFFAOYSA-N 0.000 description 1
MRBFGEHILMYPTF-UHFFFAOYSA-N 1-(2-Pyrimidyl)piperazine Chemical compound C1CNCCN1C1=NC=CC=N1 MRBFGEHILMYPTF-UHFFFAOYSA-N 0.000 description 1
WVLLWVAPEYSZNO-UHFFFAOYSA-N 1-(4-pyrazin-2-ylpiperazin-1-yl)ethanone Chemical compound C1CN(C(=O)C)CCN1C1=CN=CC=N1 WVLLWVAPEYSZNO-UHFFFAOYSA-N 0.000 description 1
UYMKVWIIAQEYEC-UHFFFAOYSA-N 1-benzyl-4-(3-methoxyphenyl)piperidin-4-ol Chemical compound COC1=CC=CC(C2(O)CCN(CC=3C=CC=CC=3)CC2)=C1 UYMKVWIIAQEYEC-UHFFFAOYSA-N 0.000 description 1
QFFVUVNTDUIAQB-UHFFFAOYSA-N 1-benzyl-4-(3-methylphenyl)piperidin-4-ol Chemical compound CC1=CC=CC(C2(O)CCN(CC=3C=CC=CC=3)CC2)=C1 QFFVUVNTDUIAQB-UHFFFAOYSA-N 0.000 description 1
WVUDHWBCPSXAFN-UHFFFAOYSA-N 1-bromo-3-(trifluoromethoxy)benzene Chemical compound FC(F)(F)OC1=CC=CC(Br)=C1 WVUDHWBCPSXAFN-UHFFFAOYSA-N 0.000 description 1
NNMBNYHMJRJUBC-UHFFFAOYSA-N 1-bromo-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(Br)=C1 NNMBNYHMJRJUBC-UHFFFAOYSA-N 0.000 description 1
PLDWAJLZAAHOGG-UHFFFAOYSA-N 1-bromo-3-methoxybenzene Chemical compound COC1=CC=CC(Br)=C1 PLDWAJLZAAHOGG-UHFFFAOYSA-N 0.000 description 1
LZOGPVCTSDAYIP-UHFFFAOYSA-N 1-pyrimidin-2-yl-1,4-diazepane Chemical compound C1CCNCCN1C1=NC=CC=N1 LZOGPVCTSDAYIP-UHFFFAOYSA-N 0.000 description 1
LSEAAPGIZCDEEH-UHFFFAOYSA-N 2,6-dichloropyrazine Chemical compound ClC1=CN=CC(Cl)=N1 LSEAAPGIZCDEEH-UHFFFAOYSA-N 0.000 description 1
GTIKLPYCSAMPNG-UHFFFAOYSA-N 2-(3-chlorophenyl)acetonitrile Chemical compound ClC1=CC=CC(CC#N)=C1 GTIKLPYCSAMPNG-UHFFFAOYSA-N 0.000 description 1
LXKNAUOWEJWGTE-UHFFFAOYSA-N 2-(3-methoxyphenyl)acetonitrile Chemical compound COC1=CC=CC(CC#N)=C1 LXKNAUOWEJWGTE-UHFFFAOYSA-N 0.000 description 1
LILXDMFJXYAKMK-UHFFFAOYSA-N 2-bromo-1,1-diethoxyethane Chemical compound CCOC(CBr)OCC LILXDMFJXYAKMK-UHFFFAOYSA-N 0.000 description 1
QSKPIOLLBIHNAC-UHFFFAOYSA-N 2-chloro-acetaldehyde Chemical compound ClCC=O QSKPIOLLBIHNAC-UHFFFAOYSA-N 0.000 description 1
GELVZYOEQVJIRR-UHFFFAOYSA-N 2-chloropyrazine Chemical compound ClC1=CN=CC=N1 GELVZYOEQVJIRR-UHFFFAOYSA-N 0.000 description 1
UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 1
CGERYHYIVJQVLJ-UHFFFAOYSA-N 2-methylbutane Chemical compound CC[C](C)C CGERYHYIVJQVLJ-UHFFFAOYSA-N 0.000 description 1
HCGFLVDMFDHYJD-UHFFFAOYSA-N 2-piperazin-1-ylpyrazine Chemical compound C1CNCCN1C1=CN=CC=N1 HCGFLVDMFDHYJD-UHFFFAOYSA-N 0.000 description 1
VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical class C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 description 1
IHBVNSPHKMCPST-UHFFFAOYSA-N 3-bromopropanoyl chloride Chemical compound ClC(=O)CCBr IHBVNSPHKMCPST-UHFFFAOYSA-N 0.000 description 1
ROLMZTIHUMKEAI-UHFFFAOYSA-N 4,5-difluoro-2-hydroxybenzonitrile Chemical compound OC1=CC(F)=C(F)C=C1C#N ROLMZTIHUMKEAI-UHFFFAOYSA-N 0.000 description 1
XJPZKYIHCLDXST-UHFFFAOYSA-N 4,6-dichloropyrimidine Chemical compound ClC1=CC(Cl)=NC=N1 XJPZKYIHCLDXST-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
ACKHHBDZZHPXKZ-UHFFFAOYSA-N 4-(3-methoxyphenyl)piperidin-4-ol Chemical compound COC1=CC=CC(C2(O)CCNCC2)=C1 ACKHHBDZZHPXKZ-UHFFFAOYSA-N 0.000 description 1
LZAYOZUFUAMFLD-UHFFFAOYSA-N 4-(4-chlorophenyl)-4-hydroxypiperidine Chemical compound C=1C=C(Cl)C=CC=1C1(O)CCNCC1 LZAYOZUFUAMFLD-UHFFFAOYSA-N 0.000 description 1
DPBWFNDFMCCGGJ-UHFFFAOYSA-N 4-Piperidine carboxamide Chemical compound NC(=O)C1CCNCC1 DPBWFNDFMCCGGJ-UHFFFAOYSA-N 0.000 description 1
BWTKIGGLLXUFSV-UHFFFAOYSA-N 4-chloro-n'-(2-quinolin-2-ylsulfanylacetyl)benzohydrazide Chemical compound C1=CC(Cl)=CC=C1C(=O)NNC(=O)CSC1=CC=C(C=CC=C2)C2=N1 BWTKIGGLLXUFSV-UHFFFAOYSA-N 0.000 description 1
IVYMIRMKXZAHRV-UHFFFAOYSA-N 4-chlorophenylacetonitrile Chemical compound ClC1=CC=C(CC#N)C=C1 IVYMIRMKXZAHRV-UHFFFAOYSA-N 0.000 description 1
CRDTXSIFSPYXNN-UHFFFAOYSA-N 4-piperazin-1-yl-1h-pyridazin-6-one;hydrochloride Chemical compound Cl.C1=NNC(=O)C=C1N1CCNCC1 CRDTXSIFSPYXNN-UHFFFAOYSA-N 0.000 description 1
HJUFMYKBVXHYEN-UHFFFAOYSA-N 4-piperazin-1-ylpyrimidine;dihydrochloride Chemical compound Cl.Cl.C1CNCCN1C1=CC=NC=N1 HJUFMYKBVXHYEN-UHFFFAOYSA-N 0.000 description 1
CJNWUCQWWYYYNG-UHFFFAOYSA-N 5-(4-benzylpiperazin-1-yl)-3,4-dichloropyridazine Chemical compound ClC1=NN=CC(N2CCN(CC=3C=CC=CC=3)CC2)=C1Cl CJNWUCQWWYYYNG-UHFFFAOYSA-N 0.000 description 1
GYCPLYCTMDTEPU-UHFFFAOYSA-N 5-bromopyrimidine Chemical compound BrC1=CN=CN=C1 GYCPLYCTMDTEPU-UHFFFAOYSA-N 0.000 description 1
YBETUEKOSIAOLN-UHFFFAOYSA-N 5-piperazin-1-ylpyrimidine;hydrochloride Chemical compound Cl.C1CNCCN1C1=CN=CN=C1 YBETUEKOSIAOLN-UHFFFAOYSA-N 0.000 description 1
101500020117 Aedes aegypti Sialokinin Proteins 0.000 description 1
208000000044 Amnesia Diseases 0.000 description 1
208000031091 Amnestic disease Diseases 0.000 description 1
102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
201000006474 Brain Ischemia Diseases 0.000 description 1
102100037597 Brain-derived neurotrophic factor Human genes 0.000 description 1
108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 1
YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
HFQYJCVJLPOROO-UHFFFAOYSA-N CCC(C)[O] Chemical compound CCC(C)[O] HFQYJCVJLPOROO-UHFFFAOYSA-N 0.000 description 1
101100443249 Caenorhabditis elegans dig-1 gene Proteins 0.000 description 1
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
208000031229 Cardiomyopathies Diseases 0.000 description 1
206010008120 Cerebral ischaemia Diseases 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
102000008186 Collagen Human genes 0.000 description 1
108010035532 Collagen Proteins 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
229920000742 Cotton Polymers 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
241001397104 Dima Species 0.000 description 1
201000010374 Down Syndrome Diseases 0.000 description 1
229910052691 Erbium Inorganic materials 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
230000005526 G1 to G0 transition Effects 0.000 description 1
241000287828 Gallus gallus Species 0.000 description 1
102000003886 Glycoproteins Human genes 0.000 description 1
108090000288 Glycoproteins Proteins 0.000 description 1
206010019280 Heart failures Diseases 0.000 description 1
208000013875 Heart injury Diseases 0.000 description 1
102000006947 Histones Human genes 0.000 description 1
108010033040 Histones Proteins 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
241000343235 Maso Species 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
239000007832 Na2SO4 Substances 0.000 description 1
206010028851 Necrosis Diseases 0.000 description 1
102000015336 Nerve Growth Factor Human genes 0.000 description 1
108090000742 Neurotrophin 3 Proteins 0.000 description 1
102100029268 Neurotrophin-3 Human genes 0.000 description 1
108010077641 Nogo Proteins Proteins 0.000 description 1
102000010410 Nogo Proteins Human genes 0.000 description 1
108010005298 Oligodendrocyte-Myelin Glycoprotein Proteins 0.000 description 1
102100026746 Oligodendrocyte-myelin glycoprotein Human genes 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
208000001132 Osteoporosis Diseases 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
101100018694 Rattus norvegicus Il24 gene Proteins 0.000 description 1
206010039966 Senile dementia Diseases 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 description 1
DDSZWBCJXDRQDU-UHFFFAOYSA-N [N].C1CCNCC1 Chemical group [N].C1CCNCC1 DDSZWBCJXDRQDU-UHFFFAOYSA-N 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
230000004913 activation Effects 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
231100000360 alopecia Toxicity 0.000 description 1
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
230000006986 amnesia Effects 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
230000019552 anatomical structure morphogenesis Effects 0.000 description 1
230000002725 anti-mycoplasma Effects 0.000 description 1
230000001640 apoptogenic effect Effects 0.000 description 1
238000003782 apoptosis assay Methods 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
230000028600 axonogenesis Effects 0.000 description 1
RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000008827 biological function Effects 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
229940077737 brain-derived neurotrophic factor Drugs 0.000 description 1
210000000481 breast Anatomy 0.000 description 1
239000000872 buffer Substances 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
244000309466 calf Species 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
210000004413 cardiac myocyte Anatomy 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
230000005779 cell damage Effects 0.000 description 1
208000037887 cell injury Diseases 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
229940106189 ceramide Drugs 0.000 description 1
ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
208000026106 cerebrovascular disease Diseases 0.000 description 1
150000001793 charged compounds Chemical class 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
229920001436 collagen Polymers 0.000 description 1
230000006835 compression Effects 0.000 description 1
238000007906 compression Methods 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
239000006071 cream Substances 0.000 description 1
230000001086 cytosolic effect Effects 0.000 description 1
230000034994 death Effects 0.000 description 1
238000010908 decantation Methods 0.000 description 1
238000006356 dehydrogenation reaction Methods 0.000 description 1
238000001514 detection method Methods 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
230000004069 differentiation Effects 0.000 description 1
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
238000006471 dimerization reaction Methods 0.000 description 1
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
238000001035 drying Methods 0.000 description 1
238000007787 electrohydrodynamic spraying Methods 0.000 description 1
230000013020 embryo development Effects 0.000 description 1
206010015037 epilepsy Diseases 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
LBAQSKZHMLAFHH-UHFFFAOYSA-N ethoxyethane;hydron;chloride Chemical compound Cl.CCOCC LBAQSKZHMLAFHH-UHFFFAOYSA-N 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
210000000720 eyelash Anatomy 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000008098 formaldehyde solution Substances 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
239000012634 fragment Substances 0.000 description 1
239000012737 fresh medium Substances 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
235000012907 honey Nutrition 0.000 description 1
208000010544 human prion disease Diseases 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
230000000642 iatrogenic effect Effects 0.000 description 1
239000007943 implant Substances 0.000 description 1
230000006698 induction Effects 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
230000002458 infectious effect Effects 0.000 description 1
102000003898 interleukin-24 Human genes 0.000 description 1
XMBWDFGMSWQBCA-YPZZEJLDSA-N iodane Chemical compound [125IH] XMBWDFGMSWQBCA-YPZZEJLDSA-N 0.000 description 1
229940044173 iodine-125 Drugs 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
230000002427 irreversible effect Effects 0.000 description 1
230000000302 ischemic effect Effects 0.000 description 1
125000006316 iso-butyl amino group Chemical group [H]N(*)C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000002955 isolation Methods 0.000 description 1
235000015110 jellies Nutrition 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
210000005229 liver cell Anatomy 0.000 description 1
239000006210 lotion Substances 0.000 description 1
208000020816 lung neoplasm Diseases 0.000 description 1
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
230000008774 maternal effect Effects 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
102000006240 membrane receptors Human genes 0.000 description 1
108020004084 membrane receptors Proteins 0.000 description 1
WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 1
108010030017 midkine receptors Proteins 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
208000031225 myocardial ischemia Diseases 0.000 description 1
230000017074 necrotic cell death Effects 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229940053128 nerve growth factor Drugs 0.000 description 1
230000007514 neuronal growth Effects 0.000 description 1
229940032018 neurotrophin 3 Drugs 0.000 description 1
229940097998 neurotrophin 4 Drugs 0.000 description 1
VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
239000002674 ointment Substances 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
230000037361 pathway Effects 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
239000002953 phosphate buffered saline Substances 0.000 description 1
230000008288 physiological mechanism Effects 0.000 description 1
150000003053 piperidines Chemical class 0.000 description 1
125000003367 polycyclic group Chemical group 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000011533 pre-incubation Methods 0.000 description 1
230000001023 pro-angiogenic effect Effects 0.000 description 1
230000005522 programmed cell death Effects 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
210000002307 prostate Anatomy 0.000 description 1
238000000746 purification Methods 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
DRGCXLJWMQGVJA-UHFFFAOYSA-N pyrimidine;dihydrochloride Chemical compound Cl.Cl.C1=CN=CN=C1 DRGCXLJWMQGVJA-UHFFFAOYSA-N 0.000 description 1
150000003230 pyrimidines Chemical class 0.000 description 1
238000011002 quantification Methods 0.000 description 1
150000003242 quaternary ammonium salts Chemical class 0.000 description 1
235000011835 quiches Nutrition 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
230000010410 reperfusion Effects 0.000 description 1
229910052702 rhenium Inorganic materials 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
201000000980 schizophrenia Diseases 0.000 description 1
210000004116 schwann cell Anatomy 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000013049 sediment Substances 0.000 description 1
238000000926 separation method Methods 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
230000011664 signaling Effects 0.000 description 1
210000000813 small intestine Anatomy 0.000 description 1
210000000329 smooth muscle myocyte Anatomy 0.000 description 1
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
235000017550 sodium carbonate Nutrition 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
ZQSUUNQAAQFFOC-UHFFFAOYSA-N tert-butyl 4-(3-chlorophenyl)-4-cyanopiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1(C#N)C1=CC=CC(Cl)=C1 ZQSUUNQAAQFFOC-UHFFFAOYSA-N 0.000 description 1
GAAZJKMOIVSYQD-UHFFFAOYSA-N tert-butyl 4-(4-chlorophenyl)-4-cyanopiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1(C#N)C1=CC=C(Cl)C=C1 GAAZJKMOIVSYQD-UHFFFAOYSA-N 0.000 description 1
SPSXSTDJXLNVJF-UHFFFAOYSA-N tert-butyl 4-(4-chloropyrimidin-2-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC=CC(Cl)=N1 SPSXSTDJXLNVJF-UHFFFAOYSA-N 0.000 description 1
CAWFUTWCSVOOPD-UHFFFAOYSA-N tert-butyl 4-cyano-4-(3-methoxyphenyl)piperidine-1-carboxylate Chemical compound COC1=CC=CC(C2(CCN(CC2)C(=O)OC(C)(C)C)C#N)=C1 CAWFUTWCSVOOPD-UHFFFAOYSA-N 0.000 description 1
KNCRBGIXAOVMQM-UHFFFAOYSA-N tert-butyl 4-pyridazin-3-ylpiperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=CN=N1 KNCRBGIXAOVMQM-UHFFFAOYSA-N 0.000 description 1
NDRUXAAEJIXVPK-UHFFFAOYSA-N tert-butyl 4-pyrimidin-4-ylpiperazine-1-carboxylate;hydrochloride Chemical compound Cl.C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=NC=N1 NDRUXAAEJIXVPK-UHFFFAOYSA-N 0.000 description 1
JWFIRRWHYFDUCF-UHFFFAOYSA-N tert-butyl 4-pyrimidin-5-ylpiperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CN=CN=C1 JWFIRRWHYFDUCF-UHFFFAOYSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
230000007704 transition Effects 0.000 description 1
108091007466 transmembrane glycoproteins Proteins 0.000 description 1
230000000472 traumatic effect Effects 0.000 description 1
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
NCKDZTAODISTPK-UHFFFAOYSA-N trimethylsilyl cyanate Chemical compound C[Si](C)(C)OC#N NCKDZTAODISTPK-UHFFFAOYSA-N 0.000 description 1
230000006439 vascular pathology Effects 0.000 description 1
230000004862 vasculogenesis Effects 0.000 description 1
230000000304 vasodilatating effect Effects 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- 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
- C07D417/14—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 three or more hetero rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- 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
- A61P25/28—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
- A61P27/00—Drugs for disorders of the senses
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Physical Education & Sports Medicine (AREA)
Rheumatology (AREA)
Pain & Pain Management (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Diabetes (AREA)
Orthopedic Medicine & Surgery (AREA)
Psychology (AREA)
Dermatology (AREA)
Psychiatry (AREA)
Oncology (AREA)
Hematology (AREA)
Immunology (AREA)
Hospice & Palliative Care (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Obesity (AREA)
Ophthalmology & Optometry (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)

UA20041210010A 2002-06-07 2003-05-06 Substituted derivatives of 1-piperazineacylpiperidine, a method for the preparation thereof and their use in therapy UA77526C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
FR0207001		2002-06-07
PCT/FR2003/001685 WO2003104225A1 (fr)	2002-06-07	2003-06-05	Derives de piperazinylacylpiperidine, leur preparation et leur application en therapeutique

Publications (1)

Publication Number	Publication Date
UA77526C2 true UA77526C2 (en)	2006-12-15

Family

ID=29724874

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA20041210010A UA77526C2 (en)	2002-06-07	2003-05-06	Substituted derivatives of 1-piperazineacylpiperidine, a method for the preparation thereof and their use in therapy

Country Status (29)

Country	Link
US (2)	US7294628B2 (xx)
EP (2)	EP1513836B1 (xx)
JP (2)	JP4437075B2 (xx)
KR (1)	KR100970812B1 (xx)
CN (1)	CN100448875C (xx)
AR (2)	AR040247A1 (xx)
AT (2)	ATE336491T1 (xx)
AU (2)	AU2003255644B2 (xx)
BR (1)	BR0311828A (xx)
CA (1)	CA2487840C (xx)
CY (2)	CY1107330T1 (xx)
DE (2)	DE60307632T2 (xx)
DK (2)	DK1513836T3 (xx)
EA (1)	EA007501B1 (xx)
ES (2)	ES2264001T3 (xx)
HR (1)	HRP20041157B1 (xx)
IS (1)	IS2302B (xx)
MA (1)	MA27233A1 (xx)
ME (1)	MEP11508A (xx)
MX (1)	MXPA04012341A (xx)
NO (1)	NO329669B1 (xx)
NZ (1)	NZ537044A (xx)
PL (1)	PL208711B1 (xx)
PT (2)	PT1513836E (xx)
RS (2)	RS20050014A (xx)
TW (2)	TWI319400B (xx)
UA (1)	UA77526C2 (xx)
WO (2)	WO2003104226A1 (xx)
ZA (1)	ZA200409823B (xx)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
RU2497819C2 (ru) *	2007-05-21	2013-11-10	Ривайва Фармасьютикалс, Инк.	Композиции, синтез и способы применения атипичных нейролептиков на основе хинолина

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2862968B1 (fr) *	2003-12-01	2006-08-04	Sanofi Synthelabo	Derives de 4-[(arylmethyl)aminomethyl]piperidine, leur preparation et leur application en therapeutique
FR2862967B1 (fr) *	2003-12-01	2006-08-04	Sanofi Synthelabo	Derives de (4-phenylpiperazin-1-yl)acylpiperidine, leur preparation et leur application en therapeutique
US7723362B2 (en) *	2004-01-08	2010-05-25	Syngenta Crop Protection, Inc.	Pesticidal heterocyclic dihaloallyl compounds
CN1984910A (zh) *	2004-07-16	2007-06-20	詹森药业有限公司	适用于神经变性疾病治疗的哌啶、哌嗪或者吗啉或它们的7元类似物的二聚化合物
US7919496B2 (en) *	2004-09-20	2011-04-05	Xenon Pharmaceuticals Inc.	Heterocyclic derivatives for the treatment of diseases mediated by stearoyl-CoA desaturase enzymes
EP2586445A1 (en)	2005-04-15	2013-05-01	University Of North Carolina At Chapel Hill	Methods of facilitating cell survival using neurotrophin mimetics
US8232274B2 (en) *	2007-03-15	2012-07-31	Albany Molecular Research, Inc.	Pyridazinone derivatives useful as glucan synthase inhibitors
DE102007026341A1 (de)	2007-06-06	2008-12-11	Merck Patent Gmbh	Benzoxazolonderivate
DE102007032507A1 (de)	2007-07-12	2009-04-02	Merck Patent Gmbh	Pyridazinonderivate
FR2932482B1 (fr) *	2008-06-13	2010-10-08	Sanofi Aventis	Nouveaux derives de (phenyl-3,6-dihydro-2h-pyridinyl)- (piperazinyl ponte)-1-alcanone et leur utilisation comme inhibiteurs de p75
FR2932481B1 (fr) *	2008-06-13	2010-10-08	Sanofi Aventis	Derives de 4-{2-°4-phenyl-3,6-dihydro-2h-pyridin-1-yl!-2- oxo-alkyl}-1-piperazin-2-one, leur preparation et leur application en therapeutique.
US10273219B2 (en)	2009-11-12	2019-04-30	Pharmatrophix, Inc.	Crystalline forms of neurotrophin mimetic compounds and their salts
EP3470402B1 (en)	2009-11-12	2021-01-06	Pharmatrophix Inc.	Crystalline forms of neurotrophin mimetic compounds and their salts
BR112012014164A2 (pt)	2009-12-14	2016-05-17	Merck Patent Gmbh	inibidores da esfingosina quinase
FR2953836B1 (fr) *	2009-12-14	2012-03-16	Sanofi Aventis	Nouveaux derives (heterocycle-tetrahydro-pyridine)-(piperazinyl)-1-alcanone et (heterocycle-dihydro-pyrrolidine)-(piperazinyl)-1-alcanone et leur utilisation comme inhibiteurs de p75
FR2953839A1 (fr) *	2009-12-14	2011-06-17	Sanofi Aventis	Nouveaux derives d'(heterocycle-piperidine condensee)-(piperazinyl)-1alcanone ou d'(heterocycle-pyrrolidine condensee)-(piperazinyl)-1alcanone et leur utilisation comme inhibiteurs de p75
EP2606894A1 (en)	2011-12-20	2013-06-26	Sanofi	Novel therapeutic use of p75 receptor antagonists
US12435078B2 (en)	2017-09-18	2025-10-07	Gfb (Abc), Llc	Pyridazinones and methods of use thereof
KR20250171415A (ko)	2018-09-18	2025-12-08	쥐에프비(에이비씨), 엘엘씨	피리다지논 및 이의 사용 방법
EP3858439A1 (en) *	2020-02-03	2021-08-04	Esteve Pharmaceuticals, S.A.	Amide derivatives having multimodal activity against pain

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
HU208690B (en) *	1987-10-26	1993-12-28	Pfizer	Process for producing 1-hjeterocyclic sulfonyl-3-(pyrimidinyl piperazinyl)-propane derivatives and pharmaceutical compositions comprising same
FR2747041B1 (fr) *	1996-04-05	1998-05-22	Cird Galderma	Utilisation de derives benzonaphtaleniques pour la fabrication de medicaments destines au traitement des neuropathies
US6468990B1 (en) *	1999-05-17	2002-10-22	Queen's University At Kingston	Method of inhibiting binding of nerve growth factor to p75 NTR receptor
FR2803593B1 (fr)	2000-01-06	2002-02-15	Sanofi Synthelabo	Nouvelles tetrahydropyridines, procede pour leur preparation et compositions pharmaceutiques les contenant

2003
- 2003-05-06 UA UA20041210010A patent/UA77526C2/uk unknown
- 2003-06-05 AU AU2003255644A patent/AU2003255644B2/en not_active Ceased
- 2003-06-05 PL PL374729A patent/PL208711B1/pl not_active IP Right Cessation
- 2003-06-05 CA CA2487840A patent/CA2487840C/en not_active Expired - Fee Related
- 2003-06-05 DE DE60307632T patent/DE60307632T2/de not_active Expired - Lifetime
- 2003-06-05 HR HR20041157 patent/HRP20041157B1/xx not_active IP Right Cessation
- 2003-06-05 ME MEP-115/08A patent/MEP11508A/xx unknown
- 2003-06-05 DE DE60305037T patent/DE60305037T2/de not_active Expired - Lifetime
- 2003-06-05 WO PCT/FR2003/001686 patent/WO2003104226A1/fr not_active Ceased
- 2003-06-05 ES ES03757109T patent/ES2264001T3/es not_active Expired - Lifetime
- 2003-06-05 DK DK03757109T patent/DK1513836T3/da active
- 2003-06-05 EP EP03757109A patent/EP1513836B1/fr not_active Expired - Lifetime
- 2003-06-05 PT PT03757109T patent/PT1513836E/pt unknown
- 2003-06-05 EP EP03757108A patent/EP1513835B1/fr not_active Expired - Lifetime
- 2003-06-05 MX MXPA04012341A patent/MXPA04012341A/es active IP Right Grant
- 2003-06-05 KR KR1020047019860A patent/KR100970812B1/ko not_active Expired - Fee Related
- 2003-06-05 EA EA200401470A patent/EA007501B1/ru not_active IP Right Cessation
- 2003-06-05 RS YUP-2005/0014A patent/RS20050014A/sr unknown
- 2003-06-05 WO PCT/FR2003/001685 patent/WO2003104225A1/fr not_active Ceased
- 2003-06-05 US US10/516,808 patent/US7294628B2/en not_active Expired - Lifetime
- 2003-06-05 AU AU2003255645A patent/AU2003255645A1/en not_active Abandoned
- 2003-06-05 PT PT03757108T patent/PT1513835E/pt unknown
- 2003-06-05 CN CNB038188082A patent/CN100448875C/zh not_active Expired - Fee Related
- 2003-06-05 JP JP2004511295A patent/JP4437075B2/ja not_active Expired - Fee Related
- 2003-06-05 DK DK03757108T patent/DK1513835T3/da active
- 2003-06-05 AT AT03757108T patent/ATE336491T1/de active
- 2003-06-05 BR BR0311828-2A patent/BR0311828A/pt not_active IP Right Cessation
- 2003-06-05 US US10/516,704 patent/US7468368B2/en not_active Expired - Lifetime
- 2003-06-05 NZ NZ537044A patent/NZ537044A/en not_active IP Right Cessation
- 2003-06-05 RS RS20050014A patent/RS52588B/sr unknown
- 2003-06-05 ES ES03757108T patent/ES2271637T3/es not_active Expired - Lifetime
- 2003-06-05 JP JP2004511296A patent/JP4441401B2/ja not_active Expired - Fee Related
- 2003-06-05 AT AT03757109T patent/ATE325122T1/de active
- 2003-06-06 TW TW092115443A patent/TWI319400B/zh not_active IP Right Cessation
- 2003-06-06 AR ARP030102018A patent/AR040247A1/es active IP Right Grant
- 2003-06-06 TW TW092115416A patent/TWI283671B/zh not_active IP Right Cessation
- 2003-06-06 AR ARP030102017A patent/AR040246A1/es active IP Right Grant
2004
- 2004-12-02 IS IS7579A patent/IS2302B/is unknown
- 2004-12-03 ZA ZA200409823A patent/ZA200409823B/en unknown
- 2004-12-03 MA MA27980A patent/MA27233A1/fr unknown
- 2004-12-06 NO NO20045331A patent/NO329669B1/no not_active IP Right Cessation
2006
- 2006-08-03 CY CY20061101094T patent/CY1107330T1/el unknown
- 2006-11-15 CY CY20061101660T patent/CY1105784T1/el unknown

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
RU2497819C2 (ru) *	2007-05-21	2013-11-10	Ривайва Фармасьютикалс, Инк.	Композиции, синтез и способы применения атипичных нейролептиков на основе хинолина

Also Published As

Publication number	Publication date
MA27233A1 (fr)	2005-02-01
EP1513835A1 (fr)	2005-03-16
BR0311828A (pt)	2005-03-29
MXPA04012341A (es)	2005-09-30
TW200400185A (en)	2004-01-01
HRP20041157B1 (en)	2012-11-30
CA2487840C (en)	2011-05-17
TWI319400B (en)	2010-01-11
CN100448875C (zh)	2009-01-07
JP4437075B2 (ja)	2010-03-24
AU2003255644A1 (en)	2003-12-22
CN1675203A (zh)	2005-09-28
EP1513836B1 (fr)	2006-05-03
PT1513835E (pt)	2006-12-29
US20060167007A1 (en)	2006-07-27
ATE336491T1 (de)	2006-09-15
WO2003104226A1 (fr)	2003-12-18
PL374729A1 (en)	2005-10-31
AR040246A1 (es)	2005-03-23
JP2005534661A (ja)	2005-11-17
RS20050014A (sr)	2007-06-04
KR20050008802A (ko)	2005-01-21
HRP20041157A2 (en)	2005-06-30
ZA200409823B (en)	2006-07-26
KR100970812B1 (ko)	2010-07-16
DE60307632T2 (de)	2007-08-09
AR040247A1 (es)	2005-03-23
TW200407321A (en)	2004-05-16
CY1105784T1 (el)	2011-02-02
NO329669B1 (no)	2010-11-29
DK1513835T3 (da)	2006-12-27
MEP11508A (en)	2010-06-10
RS52588B (sr)	2013-04-30
PT1513836E (pt)	2006-09-29
DE60305037D1 (de)	2006-06-08
ES2271637T3 (es)	2007-04-16
PL208711B1 (pl)	2011-05-31
IS2302B (is)	2007-10-15
DK1513836T3 (da)	2006-09-11
US7468368B2 (en)	2008-12-23
AU2003255644B2 (en)	2009-02-05
EP1513836A1 (fr)	2005-03-16
EA200401470A1 (ru)	2005-06-30
ATE325122T1 (de)	2006-06-15
US20050176722A1 (en)	2005-08-11
WO2003104225A1 (fr)	2003-12-18
EP1513835B1 (fr)	2006-08-16
CA2487840A1 (en)	2003-12-18
JP2005533051A (ja)	2005-11-04
EA007501B1 (ru)	2006-10-27
US7294628B2 (en)	2007-11-13
AU2003255645A1 (en)	2003-12-22
ES2264001T3 (es)	2006-12-16
NO20045331L (no)	2005-03-07
DE60307632D1 (de)	2006-09-28
TWI283671B (en)	2007-07-11
CY1107330T1 (el)	2012-11-21
NZ537044A (en)	2006-08-31
JP4441401B2 (ja)	2010-03-31
HK1076110A1 (zh)	2006-01-06
DE60305037T2 (de)	2006-12-14
IS7579A (is)	2004-12-02

Publication	Publication Date	Title
UA77526C2 (en)	2006-12-15	Substituted derivatives of 1-piperazineacylpiperidine, a method for the preparation thereof and their use in therapy
EP4129986A1 (en)	2023-02-08	Substituted pyridazine compound
CA2753434C (en)	2014-07-15	Soluble guanylate cyclase activators
EP2804861B1 (en)	2018-02-28	Substituted pyrimidine compounds and their use as syk inhibitors
EP1592426A1 (en)	2005-11-09	2-cyanopyrrolopyrimidines and pharmaceutical uses thereof
CN102325754B (zh)	2014-03-12	含杂原子的环状化合物
JP2003522773A (ja)	2003-07-29	血管形成および／またはｖｅｇｆ受容体チロシンキナーゼを阻害するピリジン誘導体
AU2014230215A1 (en)	2015-09-03	Acylaminocycloalkyl compounds suitable for treating disorders that respond to modulation of dopamine D3 receptor
JP2023535096A (ja)	2023-08-15	キナーゼ阻害活性を有する化合物
CN105916506A (zh)	2016-08-31	作为tam家族激酶抑制剂的喹唑啉衍生物
ES2378380T3 (es)	2012-04-11	Derivados de 2-oxo-alquil-1-piperazin-2-ona,su preparación y su aplicación en terapéutica
CA3195193A1 (en)	2022-05-05	N-linked isoquinoline amides as lrrk2 inhibitors, pharmaceutical compositions, and uses thereof
AU2013211414B2 (en)	2017-08-10	Piperazinyl pyrimidine derivatives, preparation method and use thereof
CA2562602A1 (en)	2005-10-27	2-aminopyridine derivative
AU2015316472C1 (en)	2020-10-29	N-(hetero)aryl-substituted heteroyclic derivatives useful for the treatment of diseases or conditions related to the central nervous system
CN116135851B (zh)	2025-09-23	一种芳香胺化合物及其应用
CA3160508C (en)	2025-11-04	Substituted ((((6-benzylamino-5-fluoropyrimidin-4-yl)amino)methyl)-piperidin-1-yl)acetamide compounds active towards nuclear receptors
IL165420A (en)	2010-06-30	Piperazinylacylpiperidine and homopiperazinylacylpiperidine derivatives, their preparation and their use in the preparation of medicaments
HK1076110B (en)	2009-04-09	Piperazinylacylpiperidine derivatives, their preparation and therapeutic use thereof

UA77526C2 - Substituted derivatives of 1-piperazineacylpiperidine, a method for the preparation thereof and their use in therapy - Google Patents

Info

Links

Classifications

Landscapes

Applications Claiming Priority (2)

Publications (1)

Family

ID=29724874

Family Applications (1)

Country Status (29)

Cited By (1)

Families Citing this family (20)

Family Cites Families (4)

Cited By (1)

Also Published As

Similar Documents