JP2020514341A5 - - Google Patents

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Publication number

JP2020514341A5

JP2020514341A5 JP2019549365A JP2019549365A JP2020514341A5 JP 2020514341 A5 JP2020514341 A5 JP 2020514341A5 JP 2019549365 A JP2019549365 A JP 2019549365A JP 2019549365 A JP2019549365 A JP 2019549365A JP 2020514341 A5 JP2020514341 A5 JP 2020514341A5

Authority

JP

Japan

Prior art keywords

formula

alkyl

propan

methyl

pyrazolo

Prior art date

2018-03-12

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.)

Granted

Links

• Espacenet
• Global Dossier
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• 125000000217 alkyl group Chemical group 0.000 claims 18
• 150000001875 compounds Chemical class 0.000 claims 18
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 10
• 125000003545 alkoxy group Chemical group 0.000 claims 9
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 9
• 150000003839 salts Chemical class 0.000 claims 9
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 8
• 125000005843 halogen group Chemical group 0.000 claims 7
• PYUBSDNTYTUBEV-VWLOTQADSA-N (3R)-1-[2-[3-fluoro-4-(trifluoromethyl)phenyl]-5-methyl-6-propan-2-ylpyrazolo[1,5-a]pyrimidin-7-yl]-3-propan-2-ylpiperidine-3-carboxylic acid Chemical compound FC=1C=C(C=CC=1C(F)(F)F)C1=NN2C(N=C(C(=C2N2C[C@](CCC2)(C(=O)O)C(C)C)C(C)C)C)=C1 PYUBSDNTYTUBEV-VWLOTQADSA-N 0.000 claims 5
• 239000002207 metabolite Substances 0.000 claims 5
• 229940002612 prodrug Drugs 0.000 claims 5
• 239000000651 prodrug Substances 0.000 claims 5
• 239000012453 solvate Substances 0.000 claims 5
• XJLSEXAGTJCILF-RXMQYKEDSA-N (R)-nipecotic acid zwitterion Chemical compound OC(=O)[C@@H]1CCCNC1 XJLSEXAGTJCILF-RXMQYKEDSA-N 0.000 claims 4
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 4
• -1 Propane-2-yl Chemical group 0.000 claims 4
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
• 208000035475 disorder Diseases 0.000 claims 4
• 230000003287 optical effect Effects 0.000 claims 4
• 239000008194 pharmaceutical composition Substances 0.000 claims 4
• 125000001424 substituent group Chemical group 0.000 claims 4
• PXDRLHFOQFIHJS-XMMPIXPASA-N (3R)-1-[2-(4-chlorophenyl)-5-methyl-6-propan-2-ylpyrazolo[1,5-a]pyrimidin-7-yl]-3-ethylpiperidine-3-carboxylic acid Chemical compound CC[C@]1(CCCN(C1)C1=C(C(C)C)C(C)=NC2=CC(=NN12)C1=CC=C(Cl)C=C1)C(O)=O PXDRLHFOQFIHJS-XMMPIXPASA-N 0.000 claims 3
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 3
• 229940126027 positive allosteric modulator Drugs 0.000 claims 3
• 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims 2
• 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 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 2
• 208000002193 Pain Diseases 0.000 claims 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 2
• 239000004480 active ingredient Substances 0.000 claims 2
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 2
• 229910052799 carbon Inorganic materials 0.000 claims 2
• 150000001735 carboxylic acids Chemical class 0.000 claims 2
• 238000006243 chemical reaction Methods 0.000 claims 2
• ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims 2
• 125000000753 cycloalkyl group Chemical group 0.000 claims 2
• 125000004663 dialkyl amino group Chemical group 0.000 claims 2
• 230000000694 effects Effects 0.000 claims 2
• 229960003692 gamma aminobutyric acid Drugs 0.000 claims 2
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims 2
• 150000004677 hydrates Chemical class 0.000 claims 2
• 229910052739 hydrogen Inorganic materials 0.000 claims 2
• 239000001257 hydrogen Substances 0.000 claims 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
• 238000000034 method Methods 0.000 claims 2
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
• 229910052757 nitrogen Inorganic materials 0.000 claims 2
• 229910052760 oxygen Inorganic materials 0.000 claims 2
• 239000001301 oxygen Substances 0.000 claims 2
• 229920006395 saturated elastomer Polymers 0.000 claims 2
• 229910052717 sulfur Inorganic materials 0.000 claims 2
• 239000011593 sulfur Substances 0.000 claims 2
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims 2
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 2
• 230000001225 therapeutic effect Effects 0.000 claims 2
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims 1
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims 1
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
• NEURYOYRKPFLKH-UHFFFAOYSA-N 2-chloro-1-isocyanato-4-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC=C(N=C=O)C(Cl)=C1 NEURYOYRKPFLKH-UHFFFAOYSA-N 0.000 claims 1
• USVZHTBPMMSRHY-UHFFFAOYSA-N 8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-[2-(2-chlorophenyl)ethyl]purin-6-amine Chemical compound C=1C=2OCOC=2C=C(Br)C=1SC1=NC=2C(N)=NC=NC=2N1CCC1=CC=CC=C1Cl USVZHTBPMMSRHY-UHFFFAOYSA-N 0.000 claims 1
• 208000019901 Anxiety disease Diseases 0.000 claims 1
• 206010011224 Cough Diseases 0.000 claims 1
• 206010013654 Drug abuse Diseases 0.000 claims 1
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
• 208000001914 Fragile X syndrome Diseases 0.000 claims 1
• 206010020710 Hyperphagia Diseases 0.000 claims 1
• 208000008238 Muscle Spasticity Diseases 0.000 claims 1
• 206010052904 Musculoskeletal stiffness Diseases 0.000 claims 1
• 208000029726 Neurodevelopmental disease Diseases 0.000 claims 1
• 208000008589 Obesity Diseases 0.000 claims 1
• ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims 1
• 206010046543 Urinary incontinence Diseases 0.000 claims 1
• 150000007960 acetonitrile Chemical class 0.000 claims 1
• 239000002253 acid Substances 0.000 claims 1
• 229910052783 alkali metal Inorganic materials 0.000 claims 1
• 125000004414 alkyl thio group Chemical group 0.000 claims 1
• 125000003277 amino group Chemical group 0.000 claims 1
• 230000036506 anxiety Effects 0.000 claims 1
• 208000006673 asthma Diseases 0.000 claims 1
• 208000029560 autism spectrum disease Diseases 0.000 claims 1
• 239000002585 base Substances 0.000 claims 1
• 206010008129 cerebral palsy Diseases 0.000 claims 1
• 239000003795 chemical substances by application Substances 0.000 claims 1
• 229940126523 co-drug Drugs 0.000 claims 1
• 229960003920 cocaine Drugs 0.000 claims 1
• 208000010877 cognitive disease Diseases 0.000 claims 1
• 125000004093 cyano group Chemical group *C#N 0.000 claims 1
• 239000003814 drug Substances 0.000 claims 1
• 239000003937 drug carrier Substances 0.000 claims 1
• 206010015037 epilepsy Diseases 0.000 claims 1
• 201000006517 essential tremor Diseases 0.000 claims 1
• 150000002148 esters Chemical class 0.000 claims 1
• XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical class CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 claims 1
• 208000021302 gastroesophageal reflux disease Diseases 0.000 claims 1
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
• 208000002551 irritable bowel syndrome Diseases 0.000 claims 1
• 201000010901 lateral sclerosis Diseases 0.000 claims 1
• 210000000111 lower esophageal sphincter Anatomy 0.000 claims 1
• 238000004519 manufacturing process Methods 0.000 claims 1
• 239000000203 mixture Substances 0.000 claims 1
• 238000012986 modification Methods 0.000 claims 1
• 230000004048 modification Effects 0.000 claims 1
• 208000005264 motor neuron disease Diseases 0.000 claims 1
• 201000006417 multiple sclerosis Diseases 0.000 claims 1
• 210000003205 muscle Anatomy 0.000 claims 1
• 230000001123 neurodevelopmental effect Effects 0.000 claims 1
• 229960002715 nicotine Drugs 0.000 claims 1
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims 1
• 235000020824 obesity Nutrition 0.000 claims 1
• 201000008482 osteoarthritis Diseases 0.000 claims 1
• 235000020830 overeating Nutrition 0.000 claims 1
• 208000019906 panic disease Diseases 0.000 claims 1
• 230000002265 prevention Effects 0.000 claims 1
• 208000020016 psychiatric disease Diseases 0.000 claims 1
• LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical class N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 claims 1
• 125000004076 pyridyl group Chemical group 0.000 claims 1
• 238000007127 saponification reaction Methods 0.000 claims 1
• 201000000980 schizophrenia Diseases 0.000 claims 1
• 210000002027 skeletal muscle Anatomy 0.000 claims 1
• 208000018198 spasticity Diseases 0.000 claims 1
• 208000020431 spinal cord injury Diseases 0.000 claims 1
• 208000011117 substance-related disease Diseases 0.000 claims 1
• 230000001052 transient effect Effects 0.000 claims 1
• 208000009935 visceral pain Diseases 0.000 claims 1