JP4896009B2 - オキソ置換されたシクロヘキシル−１，４−ジアミンの酸誘導体 - Google Patents
オキソ置換されたシクロヘキシル−１，４−ジアミンの酸誘導体 Download PDFInfo
- Publication number
- JP4896009B2 JP4896009B2 JP2007512027A JP2007512027A JP4896009B2 JP 4896009 B2 JP4896009 B2 JP 4896009B2 JP 2007512027 A JP2007512027 A JP 2007512027A JP 2007512027 A JP2007512027 A JP 2007512027A JP 4896009 B2 JP4896009 B2 JP 4896009B2
- Authority
- JP
- Japan
- Prior art keywords
- cyclohexyl
- phenyl
- dimethylamino
- oxo
- benzyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 239000002253 acid Substances 0.000 title claims description 18
- 239000003814 drug Substances 0.000 claims description 35
- -1 2- (3-Benzoyl-phenyl) -N- [4-dimethylamino-4- (2-fluoro-benzyl) -cyclohexyl] -propionamide 5-oxo-5-phenyl-valeric acid [4-dimethylamino-4 -(2-fluoro-benzyl) -cyclohexyl] -amide Chemical compound 0.000 claims description 34
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 22
- 208000002193 Pain Diseases 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 229920006395 saturated elastomer Polymers 0.000 claims description 14
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 12
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 12
- 125000001544 thienyl group Chemical group 0.000 claims description 12
- 239000013543 active substance Substances 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 9
- 125000001041 indolyl group Chemical group 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 229940005483 opioid analgesics Drugs 0.000 claims description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 7
- VCUSYDGPHVVMDW-UHFFFAOYSA-N 4-(4-chlorophenyl)-n-[4-(dimethylamino)-4-phenylcyclohexyl]-4-oxobutanamide;hydrochloride Chemical compound Cl.C1CC(N(C)C)(C=2C=CC=CC=2)CCC1NC(=O)CCC(=O)C1=CC=C(Cl)C=C1 VCUSYDGPHVVMDW-UHFFFAOYSA-N 0.000 claims description 6
- 208000000094 Chronic Pain Diseases 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 4
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 208000019901 Anxiety disease Diseases 0.000 claims description 4
- 206010012335 Dependence Diseases 0.000 claims description 4
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 4
- 230000036506 anxiety Effects 0.000 claims description 4
- VKIRRGRTJUUZHS-UHFFFAOYSA-N cyclohexane-1,4-diamine Chemical class NC1CCC(N)CC1 VKIRRGRTJUUZHS-UHFFFAOYSA-N 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- KVBXMQNDDNSVRA-UHFFFAOYSA-N n-[4-(dimethylamino)-4-phenylcyclohexyl]-5-oxo-5-phenylpentanamide Chemical compound C1CC(N(C)C)(C=2C=CC=CC=2)CCC1NC(=O)CCCC(=O)C1=CC=CC=C1 KVBXMQNDDNSVRA-UHFFFAOYSA-N 0.000 claims description 4
- SCHWABGSWZDREQ-UHFFFAOYSA-N n-[4-(dimethylamino)-4-phenylcyclohexyl]-5-oxo-5-phenylpentanamide;hydrochloride Chemical compound Cl.C1CC(N(C)C)(C=2C=CC=CC=2)CCC1NC(=O)CCCC(=O)C1=CC=CC=C1 SCHWABGSWZDREQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000006179 2-methyl benzyl group Chemical group [H]C1=C([H])C(=C(C([H])=C1[H])C([H])([H])*)C([H])([H])[H] 0.000 claims description 3
- 206010012735 Diarrhoea Diseases 0.000 claims description 3
- 206010046543 Urinary incontinence Diseases 0.000 claims description 3
- 208000005298 acute pain Diseases 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 3
- 208000010877 cognitive disease Diseases 0.000 claims description 3
- 230000008878 coupling Effects 0.000 claims description 3
- 238000010168 coupling process Methods 0.000 claims description 3
- 238000005859 coupling reaction Methods 0.000 claims description 3
- 239000002934 diuretic Substances 0.000 claims description 3
- 206010015037 epilepsy Diseases 0.000 claims description 3
- 239000003193 general anesthetic agent Substances 0.000 claims description 3
- 230000001965 increasing effect Effects 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 230000037023 motor activity Effects 0.000 claims description 3
- 208000004296 neuralgia Diseases 0.000 claims description 3
- 230000004770 neurodegeneration Effects 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- 208000021722 neuropathic pain Diseases 0.000 claims description 3
- 239000002858 neurotransmitter agent Substances 0.000 claims description 3
- 230000001777 nootropic effect Effects 0.000 claims description 3
- 125000006239 protecting group Chemical group 0.000 claims description 3
- 208000011117 substance-related disease Diseases 0.000 claims description 3
- QRUCELXGSAWBOY-UHFFFAOYSA-N 2-(3-acetyl-2,2-dimethylcyclobutyl)-N-[4-[(4-chlorophenyl)methyl]-4-(dimethylamino)cyclohexyl]acetamide Chemical compound C(C)(=O)C1C(C(C1)CC(=O)NC1CCC(CC1)(N(C)C)CC1=CC=C(C=C1)Cl)(C)C QRUCELXGSAWBOY-UHFFFAOYSA-N 0.000 claims description 2
- XKFGLKKOGQNCDA-UHFFFAOYSA-N 2-(3-acetyl-2,2-dimethylcyclobutyl)-n-(4-benzyl-4-piperidin-1-ylcyclohexyl)acetamide Chemical compound CC1(C)C(C(=O)C)CC1CC(=O)NC1CCC(CC=2C=CC=CC=2)(N2CCCCC2)CC1 XKFGLKKOGQNCDA-UHFFFAOYSA-N 0.000 claims description 2
- PBLADULXZGPZEM-UHFFFAOYSA-N 2-(3-acetyl-2,2-dimethylcyclobutyl)-n-[4-(dimethylamino)-4-[(2-fluorophenyl)methyl]cyclohexyl]acetamide Chemical compound C1CC(NC(=O)CC2C(C(C(C)=O)C2)(C)C)CCC1(N(C)C)CC1=CC=CC=C1F PBLADULXZGPZEM-UHFFFAOYSA-N 0.000 claims description 2
- KMGIEOGQXHBWRZ-UHFFFAOYSA-N 2-(3-acetyl-2,2-dimethylcyclobutyl)-n-[4-(dimethylamino)-4-[(3-methylphenyl)methyl]cyclohexyl]acetamide Chemical compound C1CC(NC(=O)CC2C(C(C(C)=O)C2)(C)C)CCC1(N(C)C)CC1=CC=CC(C)=C1 KMGIEOGQXHBWRZ-UHFFFAOYSA-N 0.000 claims description 2
- CGMPDBZLLYKFHT-UHFFFAOYSA-N 2-(3-acetyl-2,2-dimethylcyclobutyl)-n-[4-[(3-chlorophenyl)methyl]-4-(dimethylamino)cyclohexyl]acetamide Chemical compound C1CC(NC(=O)CC2C(C(C(C)=O)C2)(C)C)CCC1(N(C)C)CC1=CC=CC(Cl)=C1 CGMPDBZLLYKFHT-UHFFFAOYSA-N 0.000 claims description 2
- BIVISMFVNZSWFM-UHFFFAOYSA-N 2-(3-acetyl-2,2-dimethylcyclobutyl)-n-[4-benzyl-4-(dimethylamino)cyclohexyl]acetamide Chemical compound C1CC(NC(=O)CC2C(C(C(C)=O)C2)(C)C)CCC1(N(C)C)CC1=CC=CC=C1 BIVISMFVNZSWFM-UHFFFAOYSA-N 0.000 claims description 2
- LBUGDZKZSTZSPU-UHFFFAOYSA-N 2-(3-benzoylphenyl)-n-(4-benzyl-4-pyrrolidin-1-ylcyclohexyl)propanamide Chemical compound C=1C=CC(C(=O)C=2C=CC=CC=2)=CC=1C(C)C(=O)NC(CC1)CCC1(N1CCCC1)CC1=CC=CC=C1 LBUGDZKZSTZSPU-UHFFFAOYSA-N 0.000 claims description 2
- AGNBRSNIQDMPLT-UHFFFAOYSA-N 2-(3-benzoylphenyl)-n-(4-phenyl-4-piperidin-1-ylcyclohexyl)propanamide Chemical compound C=1C=CC(C(=O)C=2C=CC=CC=2)=CC=1C(C)C(=O)NC(CC1)CCC1(C=1C=CC=CC=1)N1CCCCC1 AGNBRSNIQDMPLT-UHFFFAOYSA-N 0.000 claims description 2
- OWTRFTYCXTZHNJ-UHFFFAOYSA-N 2-(3-benzoylphenyl)-n-[4-(dimethylamino)-4-(2-phenylethyl)cyclohexyl]propanamide Chemical compound C=1C=CC(C(=O)C=2C=CC=CC=2)=CC=1C(C)C(=O)NC(CC1)CCC1(N(C)C)CCC1=CC=CC=C1 OWTRFTYCXTZHNJ-UHFFFAOYSA-N 0.000 claims description 2
- VYAKFVOLVPXKOM-UHFFFAOYSA-N 2-(3-benzoylphenyl)-n-[4-(dimethylamino)-4-[(2-methylphenyl)methyl]cyclohexyl]propanamide Chemical compound C=1C=CC(C(=O)C=2C=CC=CC=2)=CC=1C(C)C(=O)NC(CC1)CCC1(N(C)C)CC1=CC=CC=C1C VYAKFVOLVPXKOM-UHFFFAOYSA-N 0.000 claims description 2
- NZXXHDHXPVJQQD-UHFFFAOYSA-N 2-(3-benzoylphenyl)-n-[4-(dimethylamino)-4-[(3-methylphenyl)methyl]cyclohexyl]propanamide Chemical compound C=1C=CC(C(=O)C=2C=CC=CC=2)=CC=1C(C)C(=O)NC(CC1)CCC1(N(C)C)CC1=CC=CC(C)=C1 NZXXHDHXPVJQQD-UHFFFAOYSA-N 0.000 claims description 2
- YTOGHMWQACIDSK-UHFFFAOYSA-N 2-(3-benzoylphenyl)-n-[4-(dimethylamino)-4-[(4-methylphenyl)methyl]cyclohexyl]propanamide Chemical compound C=1C=CC(C(=O)C=2C=CC=CC=2)=CC=1C(C)C(=O)NC(CC1)CCC1(N(C)C)CC1=CC=C(C)C=C1 YTOGHMWQACIDSK-UHFFFAOYSA-N 0.000 claims description 2
- VRMJHEJJIQXHJX-UHFFFAOYSA-N 2-(3-benzoylphenyl)-n-[4-[(3-chlorophenyl)methyl]-4-(dimethylamino)cyclohexyl]propanamide Chemical compound C=1C=CC(C(=O)C=2C=CC=CC=2)=CC=1C(C)C(=O)NC(CC1)CCC1(N(C)C)CC1=CC=CC(Cl)=C1 VRMJHEJJIQXHJX-UHFFFAOYSA-N 0.000 claims description 2
- QXDKUFHYJVHZBL-UHFFFAOYSA-N 2-(3-benzoylphenyl)-n-[4-benzyl-4-(dimethylamino)cyclohexyl]propanamide Chemical compound C=1C=CC(C(=O)C=2C=CC=CC=2)=CC=1C(C)C(=O)NC(CC1)CCC1(N(C)C)CC1=CC=CC=C1 QXDKUFHYJVHZBL-UHFFFAOYSA-N 0.000 claims description 2
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 2
- 125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- WCKUHSJENYGSEL-UHFFFAOYSA-N 4-(4-chlorophenyl)-n-(4-morpholin-4-yl-4-phenylcyclohexyl)-4-oxobutanamide Chemical compound C1=CC(Cl)=CC=C1C(=O)CCC(=O)NC1CCC(C=2C=CC=CC=2)(N2CCOCC2)CC1 WCKUHSJENYGSEL-UHFFFAOYSA-N 0.000 claims description 2
- XFMIBQVLHKDRJB-UHFFFAOYSA-N 4-(4-chlorophenyl)-n-[4-(dimethylamino)-4-[(3-fluorophenyl)methyl]cyclohexyl]-4-oxobutanamide Chemical compound C1CC(NC(=O)CCC(=O)C=2C=CC(Cl)=CC=2)CCC1(N(C)C)CC1=CC=CC(F)=C1 XFMIBQVLHKDRJB-UHFFFAOYSA-N 0.000 claims description 2
- MBJMGSOAYZIFRE-UHFFFAOYSA-N 4-(4-chlorophenyl)-n-[4-(dimethylamino)-4-[(4-methylphenyl)methyl]cyclohexyl]-4-oxobutanamide Chemical compound C1CC(NC(=O)CCC(=O)C=2C=CC(Cl)=CC=2)CCC1(N(C)C)CC1=CC=C(C)C=C1 MBJMGSOAYZIFRE-UHFFFAOYSA-N 0.000 claims description 2
- OFXTXOFRRFIADV-UHFFFAOYSA-N 4-(4-chlorophenyl)-n-[4-[(2-chlorophenyl)methyl]-4-(dimethylamino)cyclohexyl]-4-oxobutanamide Chemical compound C1CC(NC(=O)CCC(=O)C=2C=CC(Cl)=CC=2)CCC1(N(C)C)CC1=CC=CC=C1Cl OFXTXOFRRFIADV-UHFFFAOYSA-N 0.000 claims description 2
- IHAGUOIXHBTIPF-UHFFFAOYSA-N 4-(4-fluorophenyl)-4-oxo-n-(4-phenyl-4-piperidin-1-ylcyclohexyl)butanamide Chemical compound C1=CC(F)=CC=C1C(=O)CCC(=O)NC1CCC(C=2C=CC=CC=2)(N2CCCCC2)CC1 IHAGUOIXHBTIPF-UHFFFAOYSA-N 0.000 claims description 2
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 2
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 2
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- ZLNGKMMTTDNAQE-UHFFFAOYSA-N 4-oxo-4-phenyl-n-(4-phenyl-4-piperidin-1-ylcyclohexyl)butanamide Chemical compound C1CC(C=2C=CC=CC=2)(N2CCCCC2)CCC1NC(=O)CCC(=O)C1=CC=CC=C1 ZLNGKMMTTDNAQE-UHFFFAOYSA-N 0.000 claims description 2
- 206010006895 Cachexia Diseases 0.000 claims description 2
- 208000009132 Catalepsy Diseases 0.000 claims description 2
- 206010011878 Deafness Diseases 0.000 claims description 2
- 206010013654 Drug abuse Diseases 0.000 claims description 2
- 208000017228 Gastrointestinal motility disease Diseases 0.000 claims description 2
- 206010020772 Hypertension Diseases 0.000 claims description 2
- 208000019695 Migraine disease Diseases 0.000 claims description 2
- 208000016285 Movement disease Diseases 0.000 claims description 2
- KZDFWALHBNDHDR-UHFFFAOYSA-N N-(4-benzyl-4-piperidin-1-ylcyclohexyl)-4-oxo-4-phenylbutanamide N-[4-(dimethylamino)-4-[(4-methylphenyl)methyl]cyclohexyl]-4-(4-fluorophenyl)-4-oxobutanamide Chemical compound CN(C)C1(Cc2ccc(C)cc2)CCC(CC1)NC(=O)CCC(=O)c1ccc(F)cc1.O=C(CCC(=O)c1ccccc1)NC1CCC(Cc2ccccc2)(CC1)N1CCCCC1 KZDFWALHBNDHDR-UHFFFAOYSA-N 0.000 claims description 2
- 208000003251 Pruritus Diseases 0.000 claims description 2
- 206010039966 Senile dementia Diseases 0.000 claims description 2
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 2
- 208000009205 Tinnitus Diseases 0.000 claims description 2
- 206010047853 Waxy flexibility Diseases 0.000 claims description 2
- 230000003444 anaesthetic effect Effects 0.000 claims description 2
- 239000001961 anticonvulsive agent Substances 0.000 claims description 2
- 239000002249 anxiolytic agent Substances 0.000 claims description 2
- 230000000949 anxiolytic effect Effects 0.000 claims description 2
- 230000004596 appetite loss Effects 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 229940030606 diuretics Drugs 0.000 claims description 2
- 230000029142 excretion Effects 0.000 claims description 2
- 230000010370 hearing loss Effects 0.000 claims description 2
- 231100000888 hearing loss Toxicity 0.000 claims description 2
- 208000016354 hearing loss disease Diseases 0.000 claims description 2
- 208000019017 loss of appetite Diseases 0.000 claims description 2
- 235000021266 loss of appetite Nutrition 0.000 claims description 2
- 206010027599 migraine Diseases 0.000 claims description 2
- 239000003158 myorelaxant agent Substances 0.000 claims description 2
- LUMJDZUCCQIHEG-UHFFFAOYSA-N n-(4-benzyl-4-piperidin-1-ylcyclohexyl)-4-(4-fluorophenyl)-4-oxobutanamide Chemical compound C1=CC(F)=CC=C1C(=O)CCC(=O)NC1CCC(CC=2C=CC=CC=2)(N2CCCCC2)CC1 LUMJDZUCCQIHEG-UHFFFAOYSA-N 0.000 claims description 2
- RGQDZJZYMFOUCS-UHFFFAOYSA-N n-(4-morpholin-4-yl-4-phenylcyclohexyl)-6-oxoheptanamide Chemical compound C1CC(NC(=O)CCCCC(=O)C)CCC1(C=1C=CC=CC=1)N1CCOCC1 RGQDZJZYMFOUCS-UHFFFAOYSA-N 0.000 claims description 2
- JFKNRQNJJSINFK-UHFFFAOYSA-N n-[4-(dimethylamino)-4-(2-phenylethyl)cyclohexyl]-2-(1h-indol-3-yl)-2-oxoacetamide Chemical compound C1CC(NC(=O)C(=O)C=2C3=CC=CC=C3NC=2)CCC1(N(C)C)CCC1=CC=CC=C1 JFKNRQNJJSINFK-UHFFFAOYSA-N 0.000 claims description 2
- ZSBRUECKKQYGSW-UHFFFAOYSA-N n-[4-(dimethylamino)-4-(2-phenylethyl)cyclohexyl]-4-oxo-4-phenylbutanamide Chemical compound C1CC(NC(=O)CCC(=O)C=2C=CC=CC=2)CCC1(N(C)C)CCC1=CC=CC=C1 ZSBRUECKKQYGSW-UHFFFAOYSA-N 0.000 claims description 2
- OGWCCMHJLPUJGR-UHFFFAOYSA-N n-[4-(dimethylamino)-4-(2-phenylethyl)cyclohexyl]-5-oxo-5-phenylpentanamide Chemical compound C1CC(NC(=O)CCCC(=O)C=2C=CC=CC=2)CCC1(N(C)C)CCC1=CC=CC=C1 OGWCCMHJLPUJGR-UHFFFAOYSA-N 0.000 claims description 2
- NMBWYIGIOCHPFY-UHFFFAOYSA-N n-[4-(dimethylamino)-4-(3-fluorophenyl)cyclohexyl]-2-(1h-indol-3-yl)-2-oxoacetamide Chemical compound C1CC(NC(=O)C(=O)C=2C3=CC=CC=C3NC=2)CCC1(N(C)C)C1=CC=CC(F)=C1 NMBWYIGIOCHPFY-UHFFFAOYSA-N 0.000 claims description 2
- XWKNYXKXHQRHLE-UHFFFAOYSA-N n-[4-(dimethylamino)-4-[(2-fluorophenyl)methyl]cyclohexyl]-2-(1h-indol-3-yl)-2-oxoacetamide Chemical compound C1CC(NC(=O)C(=O)C=2C3=CC=CC=C3NC=2)CCC1(N(C)C)CC1=CC=CC=C1F XWKNYXKXHQRHLE-UHFFFAOYSA-N 0.000 claims description 2
- HLBPWJMKNVREMM-UHFFFAOYSA-N n-[4-(dimethylamino)-4-[(2-fluorophenyl)methyl]cyclohexyl]-4-(4-fluorophenyl)-4-oxobutanamide Chemical compound C1CC(NC(=O)CCC(=O)C=2C=CC(F)=CC=2)CCC1(N(C)C)CC1=CC=CC=C1F HLBPWJMKNVREMM-UHFFFAOYSA-N 0.000 claims description 2
- IZSLLPPEYGOFJF-UHFFFAOYSA-N n-[4-(dimethylamino)-4-[(2-methylphenyl)methyl]cyclohexyl]-4-oxo-4-phenylbutanamide Chemical compound C1CC(NC(=O)CCC(=O)C=2C=CC=CC=2)CCC1(N(C)C)CC1=CC=CC=C1C IZSLLPPEYGOFJF-UHFFFAOYSA-N 0.000 claims description 2
- WSTAMKONIVHJQP-UHFFFAOYSA-N n-[4-(dimethylamino)-4-[(3-fluorophenyl)methyl]cyclohexyl]-4-(4-fluorophenyl)-4-oxobutanamide Chemical compound C1CC(NC(=O)CCC(=O)C=2C=CC(F)=CC=2)CCC1(N(C)C)CC1=CC=CC(F)=C1 WSTAMKONIVHJQP-UHFFFAOYSA-N 0.000 claims description 2
- MIMCDTANDFLVIN-UHFFFAOYSA-N n-[4-(dimethylamino)-4-[(3-methylphenyl)methyl]cyclohexyl]-2-(1h-indol-3-yl)-2-oxoacetamide Chemical compound C1CC(NC(=O)C(=O)C=2C3=CC=CC=C3NC=2)CCC1(N(C)C)CC1=CC=CC(C)=C1 MIMCDTANDFLVIN-UHFFFAOYSA-N 0.000 claims description 2
- YAMVUYMTYOBGAK-UHFFFAOYSA-N n-[4-(dimethylamino)-4-[(3-methylphenyl)methyl]cyclohexyl]-4-oxo-4-phenylbutanamide Chemical compound C1CC(NC(=O)CCC(=O)C=2C=CC=CC=2)CCC1(N(C)C)CC1=CC=CC(C)=C1 YAMVUYMTYOBGAK-UHFFFAOYSA-N 0.000 claims description 2
- FZUKZMFYJKZBBM-UHFFFAOYSA-N n-[4-(dimethylamino)-4-[(4-fluorophenyl)methyl]cyclohexyl]-2-(1h-indol-3-yl)-2-oxoacetamide Chemical compound C1CC(NC(=O)C(=O)C=2C3=CC=CC=C3NC=2)CCC1(N(C)C)CC1=CC=C(F)C=C1 FZUKZMFYJKZBBM-UHFFFAOYSA-N 0.000 claims description 2
- ZSAQIGFEBHYDEX-UHFFFAOYSA-N n-[4-(dimethylamino)-4-[(4-fluorophenyl)methyl]cyclohexyl]-4-oxo-4-phenylbutanamide Chemical compound C1CC(NC(=O)CCC(=O)C=2C=CC=CC=2)CCC1(N(C)C)CC1=CC=C(F)C=C1 ZSAQIGFEBHYDEX-UHFFFAOYSA-N 0.000 claims description 2
- JVAUXRJMHXNGIR-UHFFFAOYSA-N n-[4-(dimethylamino)-4-[(4-methylphenyl)methyl]cyclohexyl]-7-oxooctanamide Chemical compound C=1C=C(C)C=CC=1CC1(N(C)C)CCC(NC(=O)CCCCCC(C)=O)CC1 JVAUXRJMHXNGIR-UHFFFAOYSA-N 0.000 claims description 2
- ZPQMDFPMMVCQBY-UHFFFAOYSA-N n-[4-(dimethylamino)-4-thiophen-2-ylcyclohexyl]-4-(4-fluorophenyl)-4-oxobutanamide Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCC1NC(=O)CCC(=O)C1=CC=C(F)C=C1 ZPQMDFPMMVCQBY-UHFFFAOYSA-N 0.000 claims description 2
- RHLZKILNPXAJQZ-UHFFFAOYSA-N n-[4-[(2-chlorophenyl)methyl]-4-(dimethylamino)cyclohexyl]-2-(1h-indol-3-yl)-2-oxoacetamide Chemical compound C1CC(NC(=O)C(=O)C=2C3=CC=CC=C3NC=2)CCC1(N(C)C)CC1=CC=CC=C1Cl RHLZKILNPXAJQZ-UHFFFAOYSA-N 0.000 claims description 2
- CJDZTTYBWFZFJH-UHFFFAOYSA-N n-[4-[(2-chlorophenyl)methyl]-4-(dimethylamino)cyclohexyl]-4-oxo-4-phenylbutanamide Chemical compound C1CC(NC(=O)CCC(=O)C=2C=CC=CC=2)CCC1(N(C)C)CC1=CC=CC=C1Cl CJDZTTYBWFZFJH-UHFFFAOYSA-N 0.000 claims description 2
- CXRCODHKRPEEJG-UHFFFAOYSA-N n-[4-[(3-chlorophenyl)methyl]-4-(dimethylamino)cyclohexyl]-4-(4-fluorophenyl)-4-oxobutanamide Chemical compound C1CC(NC(=O)CCC(=O)C=2C=CC(F)=CC=2)CCC1(N(C)C)CC1=CC=CC(Cl)=C1 CXRCODHKRPEEJG-UHFFFAOYSA-N 0.000 claims description 2
- HAQKLYAYADKHMB-UHFFFAOYSA-N n-[4-[(3-chlorophenyl)methyl]-4-(dimethylamino)cyclohexyl]-5-oxo-5-phenylpentanamide Chemical compound C1CC(NC(=O)CCCC(=O)C=2C=CC=CC=2)CCC1(N(C)C)CC1=CC=CC(Cl)=C1 HAQKLYAYADKHMB-UHFFFAOYSA-N 0.000 claims description 2
- ZAEYRIJYCIRNJD-UHFFFAOYSA-N n-[4-[(3-chlorophenyl)methyl]-4-(dimethylamino)cyclohexyl]-6-oxoheptanamide Chemical compound C=1C=CC(Cl)=CC=1CC1(N(C)C)CCC(NC(=O)CCCCC(C)=O)CC1 ZAEYRIJYCIRNJD-UHFFFAOYSA-N 0.000 claims description 2
- HDRSMTFDRVOREL-UHFFFAOYSA-N n-[4-[(4-chlorophenyl)methyl]-4-(dimethylamino)cyclohexyl]-5-oxo-5-phenylpentanamide Chemical compound C1CC(NC(=O)CCCC(=O)C=2C=CC=CC=2)CCC1(N(C)C)CC1=CC=C(Cl)C=C1 HDRSMTFDRVOREL-UHFFFAOYSA-N 0.000 claims description 2
- NACRCIBOZBLULL-UHFFFAOYSA-N n-[4-[(4-chlorophenyl)methyl]-4-(dimethylamino)cyclohexyl]-6-oxoheptanamide Chemical compound C=1C=C(Cl)C=CC=1CC1(N(C)C)CCC(NC(=O)CCCCC(C)=O)CC1 NACRCIBOZBLULL-UHFFFAOYSA-N 0.000 claims description 2
- MKGVHMKZVWUFKR-UHFFFAOYSA-N n-[4-benzyl-4-(dimethylamino)cyclohexyl]-4-(4-chlorophenyl)-4-oxobutanamide Chemical compound C1CC(NC(=O)CCC(=O)C=2C=CC(Cl)=CC=2)CCC1(N(C)C)CC1=CC=CC=C1 MKGVHMKZVWUFKR-UHFFFAOYSA-N 0.000 claims description 2
- OHOYASBFQBCRDM-UHFFFAOYSA-N n-[4-benzyl-4-(dimethylamino)cyclohexyl]-4-(4-fluorophenyl)-4-oxobutanamide Chemical compound C1CC(NC(=O)CCC(=O)C=2C=CC(F)=CC=2)CCC1(N(C)C)CC1=CC=CC=C1 OHOYASBFQBCRDM-UHFFFAOYSA-N 0.000 claims description 2
- 235000015816 nutrient absorption Nutrition 0.000 claims description 2
- 239000000014 opioid analgesic Substances 0.000 claims description 2
- 229940052318 opioid anesthetics Drugs 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 2
- 231100000872 sexual dysfunction Toxicity 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 231100000886 tinnitus Toxicity 0.000 claims description 2
- 239000012453 solvate Substances 0.000 claims 2
- ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 claims 1
- 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 claims 1
- SHKWSBAVRQZYLE-UHFFFAOYSA-N 5-oxo-5-phenylpentanoic acid Chemical compound OC(=O)CCCC(=O)C1=CC=CC=C1 SHKWSBAVRQZYLE-UHFFFAOYSA-N 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- 208000001953 Hypotension Diseases 0.000 claims 1
- 208000020358 Learning disease Diseases 0.000 claims 1
- 208000026139 Memory disease Diseases 0.000 claims 1
- 229910052776 Thorium Inorganic materials 0.000 claims 1
- 230000004913 activation Effects 0.000 claims 1
- 230000001773 anti-convulsant effect Effects 0.000 claims 1
- 229960003965 antiepileptics Drugs 0.000 claims 1
- 230000000747 cardiac effect Effects 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 230000036543 hypotension Effects 0.000 claims 1
- 201000003723 learning disability Diseases 0.000 claims 1
- RJOZFODSLXLIQJ-UHFFFAOYSA-N n-[4-(dimethylamino)-4-[(4-methylphenyl)methyl]cyclohexyl]-4-oxo-4-phenylbutanamide Chemical compound C1CC(NC(=O)CCC(=O)C=2C=CC=CC=2)CCC1(N(C)C)CC1=CC=C(C)C=C1 RJOZFODSLXLIQJ-UHFFFAOYSA-N 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 150000003254 radicals Chemical class 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- 125000003118 aryl group Chemical group 0.000 description 26
- 150000001875 compounds Chemical class 0.000 description 18
- 125000001072 heteroaryl group Chemical group 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- 125000000753 cycloalkyl group Chemical group 0.000 description 11
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 125000002541 furyl group Chemical group 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 125000001624 naphthyl group Chemical group 0.000 description 8
- 125000003373 pyrazinyl group Chemical group 0.000 description 8
- 125000004076 pyridyl group Chemical group 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 125000002877 alkyl aryl group Chemical group 0.000 description 7
- 150000001450 anions Chemical class 0.000 description 7
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 7
- 230000027455 binding Effects 0.000 description 7
- 150000001768 cations Chemical class 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 108010020615 nociceptin receptor Proteins 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 125000000714 pyrimidinyl group Chemical group 0.000 description 7
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- 102000003840 Opioid Receptors Human genes 0.000 description 6
- 108090000137 Opioid Receptors Proteins 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 6
- 125000000168 pyrrolyl group Chemical group 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 230000000966 norepinephrine reuptake Effects 0.000 description 5
- 230000000697 serotonin reuptake Effects 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical class OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 4
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 125000005213 alkyl heteroaryl group Chemical group 0.000 description 4
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 4
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 125000002883 imidazolyl group Chemical group 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 125000003386 piperidinyl group Chemical group 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000010626 work up procedure Methods 0.000 description 4
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 3
- AHVASTJJVAYFPY-UHFFFAOYSA-N 4-(4-chlorophenyl)-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)C1=CC=C(Cl)C=C1 AHVASTJJVAYFPY-UHFFFAOYSA-N 0.000 description 3
- 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 3
- BBIHAMWDGBUIKY-UHFFFAOYSA-N 5-oxo-5-phenylpentanoic acid Chemical compound OC(=O)CCCC(=O)C1=CC=CC=C1.OC(=O)CCCC(=O)C1=CC=CC=C1 BBIHAMWDGBUIKY-UHFFFAOYSA-N 0.000 description 3
- 101001122476 Homo sapiens Mu-type opioid receptor Proteins 0.000 description 3
- 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 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- 102100028647 Mu-type opioid receptor Human genes 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Chemical class OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 150000001735 carboxylic acids Chemical class 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 238000006073 displacement reaction Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 3
- 125000001786 isothiazolyl group Chemical group 0.000 description 3
- 125000000842 isoxazolyl group Chemical group 0.000 description 3
- 229960005181 morphine Drugs 0.000 description 3
- 102000051367 mu Opioid Receptors Human genes 0.000 description 3
- 229960002748 norepinephrine Drugs 0.000 description 3
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 3
- 125000002971 oxazolyl group Chemical group 0.000 description 3
- 125000003226 pyrazolyl group Chemical group 0.000 description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 125000001425 triazolyl group Chemical group 0.000 description 3
- 238000010792 warming Methods 0.000 description 3
- 108020001612 μ-opioid receptors Proteins 0.000 description 3
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 2
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical class OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 description 2
- TVYLLZQTGLZFBW-ZBFHGGJFSA-N (R,R)-tramadol Chemical compound COC1=CC=CC([C@]2(O)[C@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-ZBFHGGJFSA-N 0.000 description 2
- KVRGHMFZWJMOBY-UHFFFAOYSA-N 1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C=1C=CC=CC=1C1(N(C)C)CCC(N)CC1 KVRGHMFZWJMOBY-UHFFFAOYSA-N 0.000 description 2
- VIKBNMWOLLIQPG-UHFFFAOYSA-N 2-methyldecanedioic acid Chemical compound OC(=O)C(C)CCCCCCCC(O)=O VIKBNMWOLLIQPG-UHFFFAOYSA-N 0.000 description 2
- AJHPGXZOIAYYDW-UHFFFAOYSA-N 3-(2-cyanophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CC1=CC=CC=C1C#N AJHPGXZOIAYYDW-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- 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 2
- OWCNTICGLJWRQQ-UHFFFAOYSA-N 4-(4-chlorophenyl)-n-[4-(dimethylamino)-4-phenylcyclohexyl]-4-oxobutanamide Chemical compound C1CC(N(C)C)(C=2C=CC=CC=2)CCC1NC(=O)CCC(=O)C1=CC=C(Cl)C=C1 OWCNTICGLJWRQQ-UHFFFAOYSA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 101001122499 Homo sapiens Nociceptin receptor Proteins 0.000 description 2
- 206010022998 Irritability Diseases 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- OKJIRPAQVSHGFK-UHFFFAOYSA-N N-acetylglycine Chemical class CC(=O)NCC(O)=O OKJIRPAQVSHGFK-UHFFFAOYSA-N 0.000 description 2
- 102100028646 Nociceptin receptor Human genes 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Chemical class OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229940035676 analgesics Drugs 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 230000037007 arousal Effects 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 2
- 239000012964 benzotriazole Substances 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001767 cationic compounds Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 239000006196 drop Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 235000011087 fumaric acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- FYAQQULBLMNGAH-UHFFFAOYSA-N hexane-1-sulfonic acid Chemical compound CCCCCCS(O)(=O)=O FYAQQULBLMNGAH-UHFFFAOYSA-N 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 229910001411 inorganic cation Inorganic materials 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 235000019136 lipoic acid Nutrition 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 159000000003 magnesium salts Chemical class 0.000 description 2
- 229960002510 mandelic acid Drugs 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 206010027175 memory impairment Diseases 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 229960004127 naloxone Drugs 0.000 description 2
- 230000002981 neuropathic effect Effects 0.000 description 2
- 229960003512 nicotinic acid Drugs 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000011505 plaster Substances 0.000 description 2
- 159000000001 potassium salts Chemical class 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000002287 radioligand Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 210000003568 synaptosome Anatomy 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 229960002663 thioctic acid Drugs 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 229960004380 tramadol Drugs 0.000 description 2
- TVYLLZQTGLZFBW-GOEBONIOSA-N tramadol Natural products COC1=CC=CC([C@@]2(O)[C@@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-GOEBONIOSA-N 0.000 description 2
- 125000004306 triazinyl group Chemical group 0.000 description 2
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- NAOLWIGVYRIGTP-UHFFFAOYSA-N 1,3,5-trihydroxyanthracene-9,10-dione Chemical compound C1=CC(O)=C2C(=O)C3=CC(O)=CC(O)=C3C(=O)C2=C1 NAOLWIGVYRIGTP-UHFFFAOYSA-N 0.000 description 1
- VAEKJOSISDWDMF-UHFFFAOYSA-N 1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(N)CCC1(N)C1=CC=CC=C1 VAEKJOSISDWDMF-UHFFFAOYSA-N 0.000 description 1
- PDQRQJVPEFGVRK-UHFFFAOYSA-N 2,1,3-benzothiadiazole Chemical compound C1=CC=CC2=NSN=C21 PDQRQJVPEFGVRK-UHFFFAOYSA-N 0.000 description 1
- FFFIRKXTFQCCKJ-UHFFFAOYSA-N 2,4,6-trimethylbenzoic acid Chemical compound CC1=CC(C)=C(C(O)=O)C(C)=C1 FFFIRKXTFQCCKJ-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- FZIPCQLKPTZZIM-UHFFFAOYSA-N 2-oxidanylpropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O FZIPCQLKPTZZIM-UHFFFAOYSA-N 0.000 description 1
- TYEYBOSBBBHJIV-UHFFFAOYSA-N 2-oxobutanoic acid Chemical compound CCC(=O)C(O)=O TYEYBOSBBBHJIV-UHFFFAOYSA-N 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- YUALQSSMNCNBMV-UHFFFAOYSA-N 4-(4-chlorophenyl)-n-[4-(dimethylamino)-4-[(2-methylphenyl)methyl]cyclohexyl]-4-oxobutanamide Chemical compound C1CC(NC(=O)CCC(=O)C=2C=CC(Cl)=CC=2)CCC1(N(C)C)CC1=CC=CC=C1C YUALQSSMNCNBMV-UHFFFAOYSA-N 0.000 description 1
- ALYNCZNDIQEVRV-PZFLKRBQSA-N 4-amino-3,5-ditritiobenzoic acid Chemical compound [3H]c1cc(cc([3H])c1N)C(O)=O ALYNCZNDIQEVRV-PZFLKRBQSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- LOVVOOWEUPFPNM-UHFFFAOYSA-N CC1=CC=C(CC(CC2)(CCC2C(CC(C2=CC=CC=C2)=O)C(N)=O)N(C)C)C=C1 Chemical compound CC1=CC=C(CC(CC2)(CCC2C(CC(C2=CC=CC=C2)=O)C(N)=O)N(C)C)C=C1 LOVVOOWEUPFPNM-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 208000001860 Eye Infections Diseases 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020710 Hyperphagia Diseases 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 208000004880 Polyuria 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
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 108010046516 Wheat Germ Agglutinins Proteins 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000001598 anti-natriuretic effect Effects 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 239000002830 appetite depressant Substances 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical class OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 1
- 150000001934 cyclohexanes Chemical class 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000005469 ethylenyl group Chemical group 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 230000008570 general process Effects 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 1
- 229960003132 halothane Drugs 0.000 description 1
- UYXAWHWODHRRMR-UHFFFAOYSA-N hexobarbital Chemical compound O=C1N(C)C(=O)NC(=O)C1(C)C1=CCCCC1 UYXAWHWODHRRMR-UHFFFAOYSA-N 0.000 description 1
- 229960002456 hexobarbital Drugs 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000008991 intestinal motility Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical class OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Chemical class 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 208000008013 morphine dependence Diseases 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 230000008450 motivation Effects 0.000 description 1
- 229940035363 muscle relaxants Drugs 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 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
- 230000009871 nonspecific binding Effects 0.000 description 1
- 239000002664 nootropic agent Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000020830 overeating Nutrition 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 208000021090 palsy Diseases 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 230000020341 sensory perception of pain Effects 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 229940126589 solid medicine Drugs 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229940086542 triethylamine Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 208000009935 visceral pain Diseases 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/72—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms
- C07C235/74—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of a saturated carbon skeleton
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/06—Anti-spasmodics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- 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
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
-
- 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
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/22—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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- 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
- A61P27/16—Otologicals
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- 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
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/72—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms
- C07C235/80—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms having carbon atoms of carboxamide groups and keto groups bound to the same carbon atom, e.g. acetoacetamides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Addiction (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Reproductive Health (AREA)
- Gynecology & Obstetrics (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Child & Adolescent Psychology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Anesthesiology (AREA)
- Psychology (AREA)
- Nutrition Science (AREA)
- Dermatology (AREA)
- Pregnancy & Childbirth (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102004023501A DE102004023501A1 (de) | 2004-05-10 | 2004-05-10 | Oxosubstituierte Cyclohexyl-1,4-diamin-Derivate |
| DE102004023501.5 | 2004-05-10 | ||
| PCT/EP2005/004907 WO2005110970A1 (de) | 2004-05-10 | 2005-05-06 | Oxosubstituierte cyclohexyl-1,4-diamin-derivate |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2007536317A JP2007536317A (ja) | 2007-12-13 |
| JP2007536317A5 JP2007536317A5 (https=) | 2011-11-24 |
| JP4896009B2 true JP4896009B2 (ja) | 2012-03-14 |
Family
ID=34968416
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007512027A Expired - Fee Related JP4896009B2 (ja) | 2004-05-10 | 2005-05-06 | オキソ置換されたシクロヘキシル−１，４−ジアミンの酸誘導体 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US7476763B2 (https=) |
| EP (1) | EP1751088B1 (https=) |
| JP (1) | JP4896009B2 (https=) |
| CA (1) | CA2566210C (https=) |
| DE (1) | DE102004023501A1 (https=) |
| WO (1) | WO2005110970A1 (https=) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008110351A2 (en) * | 2007-03-15 | 2008-09-18 | Dompe' Pha.R.Ma S.P.A. | Use of (r) and (s)-2-aryl-propionic acid derivatives as antiseptic agents |
| AU2009228647B2 (en) | 2008-03-27 | 2013-07-04 | Grunenthal Gmbh | Substituted spirocyclic cyclohexane derivatives |
| JP5529843B2 (ja) | 2008-03-27 | 2014-06-25 | グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング | 置換シクロヘキシルジアミン |
| EP2280941B1 (de) | 2008-03-27 | 2015-05-06 | Grünenthal GmbH | (hetero-)aryl-cyclohexan-derivate |
| ES2375543T3 (es) | 2008-03-27 | 2012-03-01 | Grünenthal GmbH | Derivados de espiro(5.5)undecano. |
| ES2464102T3 (es) | 2008-03-27 | 2014-05-30 | Grünenthal GmbH | Derivados de 4-aminociclohexano sustituidos |
| CN102046591B (zh) | 2008-03-27 | 2014-12-03 | 格吕伦塔尔有限公司 | 羟甲基环己胺 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001097978A (ja) * | 1999-08-27 | 2001-04-10 | Adir | 新しいピリジン化合物、これらの製造方法及びこれらを含む医薬組成物 |
| JP2002544223A (ja) * | 1999-05-12 | 2002-12-24 | ソルベイ・フアーマシユーチカルズ・ベー・ブイ | 精神病性障害の治療方法 |
| JP2004514719A (ja) * | 2000-11-29 | 2004-05-20 | ラボラトリオス、ビタ、ソシエダッド、アノニマ | ベンゾチオフェン誘導体化合物、その製造方法および使用 |
| WO2004043909A1 (de) * | 2002-11-11 | 2004-05-27 | Grünenthal GmbH | Cyclohexyl-harnstoff-derivate |
| JP2005518395A (ja) * | 2001-12-21 | 2005-06-23 | ハー・ルンドベック・アクチエゼルスカベット | セロトニン及びノルエピネフリン取り込み阻害剤としてのアミノインダン誘導体 |
| JP2007536323A (ja) * | 2004-05-10 | 2007-12-13 | グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング | 置換されたシクロヘキシル−１，４−ジアミンの酸誘導体 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5304479A (en) | 1991-12-06 | 1994-04-19 | Diagnostic Reagents, Inc. | Phencyclidine compounds and assays for its determination |
| GB0012240D0 (en) | 2000-05-19 | 2000-07-12 | Merck Sharp & Dohme | Therapeutic agents |
| DE10123163A1 (de) * | 2001-05-09 | 2003-01-16 | Gruenenthal Gmbh | Substituierte Cyclohexan-1,4-diaminderivate |
| US6571525B2 (en) | 2001-08-01 | 2003-06-03 | J. David Coleman | Construction block |
| US6818772B2 (en) * | 2002-02-22 | 2004-11-16 | Abbott Laboratories | Antagonists of melanin concentrating hormone effects on the melanin concentrating hormone receptor |
| DE10252665A1 (de) | 2002-11-11 | 2004-06-03 | Grünenthal GmbH | 4-Aminomethyl-1-aryl-cyclohexylamin-Derivate |
-
2004
- 2004-05-10 DE DE102004023501A patent/DE102004023501A1/de not_active Withdrawn
-
2005
- 2005-05-06 WO PCT/EP2005/004907 patent/WO2005110970A1/de not_active Ceased
- 2005-05-06 EP EP05738450.5A patent/EP1751088B1/de not_active Expired - Lifetime
- 2005-05-06 CA CA2566210A patent/CA2566210C/en not_active Expired - Fee Related
- 2005-05-06 JP JP2007512027A patent/JP4896009B2/ja not_active Expired - Fee Related
-
2006
- 2006-11-09 US US11/594,952 patent/US7476763B2/en not_active Expired - Fee Related
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002544223A (ja) * | 1999-05-12 | 2002-12-24 | ソルベイ・フアーマシユーチカルズ・ベー・ブイ | 精神病性障害の治療方法 |
| JP2001097978A (ja) * | 1999-08-27 | 2001-04-10 | Adir | 新しいピリジン化合物、これらの製造方法及びこれらを含む医薬組成物 |
| JP2004514719A (ja) * | 2000-11-29 | 2004-05-20 | ラボラトリオス、ビタ、ソシエダッド、アノニマ | ベンゾチオフェン誘導体化合物、その製造方法および使用 |
| JP2005518395A (ja) * | 2001-12-21 | 2005-06-23 | ハー・ルンドベック・アクチエゼルスカベット | セロトニン及びノルエピネフリン取り込み阻害剤としてのアミノインダン誘導体 |
| WO2004043909A1 (de) * | 2002-11-11 | 2004-05-27 | Grünenthal GmbH | Cyclohexyl-harnstoff-derivate |
| JP2007536323A (ja) * | 2004-05-10 | 2007-12-13 | グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング | 置換されたシクロヘキシル−１，４−ジアミンの酸誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| US20070088034A1 (en) | 2007-04-19 |
| EP1751088B1 (de) | 2014-10-08 |
| EP1751088A1 (de) | 2007-02-14 |
| JP2007536317A (ja) | 2007-12-13 |
| DE102004023501A1 (de) | 2005-12-01 |
| US7476763B2 (en) | 2009-01-13 |
| CA2566210A1 (en) | 2005-11-24 |
| WO2005110970A1 (de) | 2005-11-24 |
| CA2566210C (en) | 2013-08-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4885733B2 (ja) | Ｏｒｌ１レセプターに対する親和性を有するスピロ環状シクロヘキサン誘導体 | |
| JP4791374B2 (ja) | スピロ環状シクロヘキサン誘導体 | |
| JP4982357B2 (ja) | ヘテロアリール−置換されたシクロヘキシル−１，４−ジアミン誘導体 | |
| JP4852536B2 (ja) | 置換されたシクロヘキシル酢酸誘導体 | |
| JP5084498B2 (ja) | シクロヘキシル−１，４−ジアミンの酸誘導体 | |
| JP4896009B2 (ja) | オキソ置換されたシクロヘキシル−１，４−ジアミンの酸誘導体 | |
| JP5037337B2 (ja) | 置換されたシクロヘキシル−１，４−ジアミンの酸誘導体 | |
| JP5037336B2 (ja) | 鎖長が延ばされ、置換されたシクロヘキシル−１，４−ジアミンの酸誘導体 | |
| JP4874237B2 (ja) | 置換されたシクロヘキシルカルボン酸誘導体 | |
| JP5645673B2 (ja) | 痛みの治療のための置換された４−アミノシクロヘキサン誘導体 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080125 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20100518 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20101130 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110225 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110304 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110329 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110405 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110428 |
|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20110510 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110511 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110719 |
|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20111003 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20111122 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20111220 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150106 Year of fee payment: 3 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |