TW200815009A - Combination of a hypnotic agent and substituted bis aryl and heteroaryl compound and therapeutic application thereof - Google Patents

Info

Publication number

TW200815009A

TW200815009A TW095130323A TW95130323A TW200815009A TW 200815009 A TW200815009 A TW 200815009A TW 095130323 A TW095130323 A TW 095130323A TW 95130323 A TW95130323 A TW 95130323A TW 200815009 A TW200815009 A TW 200815009A

Authority

TW

Taiwan

Prior art keywords

alkyl

group

compound

heteroaryl

aryl

Prior art date

2005-08-19

Links

• Espacenet
• Global Dossier
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• 239000003326 hypnotic agent Substances 0.000 title claims abstract description 92
• -1 heteroaryl compound Chemical class 0.000 title claims description 170
• 125000003118 aryl group Chemical group 0.000 title claims description 49
• 230000001225 therapeutic effect Effects 0.000 title claims description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 124
• 208000019116 sleep disease Diseases 0.000 claims abstract description 41
• 230000007958 sleep Effects 0.000 claims description 111
• 239000000203 mixture Substances 0.000 claims description 106
• 125000000217 alkyl group Chemical group 0.000 claims description 103
• 230000000147 hypnotic effect Effects 0.000 claims description 72
• 239000003826 tablet Substances 0.000 claims description 72
• 239000012729 immediate-release (IR) formulation Substances 0.000 claims description 65
• 239000006187 pill Substances 0.000 claims description 46
• 239000003814 drug Substances 0.000 claims description 40
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 37
• 125000001072 heteroaryl group Chemical group 0.000 claims description 37
• 125000000623 heterocyclic group Chemical group 0.000 claims description 37
• 150000003839 salts Chemical class 0.000 claims description 35
• 229910052757 nitrogen Inorganic materials 0.000 claims description 34
• 238000013268 sustained release Methods 0.000 claims description 33
• 239000012730 sustained-release form Substances 0.000 claims description 33
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 31
• 206010022437 insomnia Diseases 0.000 claims description 31
• 229940079593 drug Drugs 0.000 claims description 28
• 239000002775 capsule Substances 0.000 claims description 27
• 239000008194 pharmaceutical composition Substances 0.000 claims description 26
• 238000002360 preparation method Methods 0.000 claims description 26
• 239000002253 acid Substances 0.000 claims description 25
• 125000001424 substituent group Chemical group 0.000 claims description 25
• 125000003545 alkoxy group Chemical group 0.000 claims description 22
• 229960001475 zolpidem Drugs 0.000 claims description 22
• ZAFYATHCZYHLPB-UHFFFAOYSA-N zolpidem Chemical compound N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 ZAFYATHCZYHLPB-UHFFFAOYSA-N 0.000 claims description 21
• 239000002904 solvent Substances 0.000 claims description 19
• 239000001257 hydrogen Substances 0.000 claims description 18
• 229910052739 hydrogen Inorganic materials 0.000 claims description 18
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
• 238000000576 coating method Methods 0.000 claims description 15
• 208000020016 psychiatric disease Diseases 0.000 claims description 14
• 125000005842 heteroatom Chemical group 0.000 claims description 13
• 239000000126 substance Substances 0.000 claims description 12
• 239000011248 coating agent Substances 0.000 claims description 11
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
• 208000020685 sleep-wake disease Diseases 0.000 claims description 11
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 10
• 239000007789 gas Substances 0.000 claims description 10
• 239000008188 pellet Substances 0.000 claims description 10
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 8
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 8
• 125000005843 halogen group Chemical group 0.000 claims description 8
• 239000000463 material Substances 0.000 claims description 8
• 239000012453 solvate Substances 0.000 claims description 8
• 125000003342 alkenyl group Chemical group 0.000 claims description 7
• NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 7
• 239000007939 sustained release tablet Substances 0.000 claims description 7
• 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
• 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 5
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 5
• 229940049706 benzodiazepine Drugs 0.000 claims description 5
• 125000002619 bicyclic group Chemical group 0.000 claims description 5
• 229910052799 carbon Inorganic materials 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 210000003296 saliva Anatomy 0.000 claims description 5
• 229910052717 sulfur Inorganic materials 0.000 claims description 5
• 102000004300 GABA-A Receptors Human genes 0.000 claims description 4
• 108090000839 GABA-A Receptors Proteins 0.000 claims description 4
• 125000005605 benzo group Chemical group 0.000 claims description 4
• 239000007942 layered tablet Substances 0.000 claims description 4
• 108020003175 receptors Proteins 0.000 claims description 4
• 102000005962 receptors Human genes 0.000 claims description 4
• GBBSUAFBMRNDJC-MRXNPFEDSA-N (5R)-zopiclone Chemical compound C1CN(C)CCN1C(=O)O[C@@H]1C2=NC=CN=C2C(=O)N1C1=CC=C(Cl)C=N1 GBBSUAFBMRNDJC-MRXNPFEDSA-N 0.000 claims description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
• 239000000556 agonist Substances 0.000 claims description 3
• 125000003282 alkyl amino group Chemical group 0.000 claims description 3
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 3
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
• 229910052794 bromium Inorganic materials 0.000 claims description 3
• 125000001246 bromo group Chemical group Br* 0.000 claims description 3
• 230000008859 change Effects 0.000 claims description 3
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 3
• 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 3
• 229960004010 zaleplon Drugs 0.000 claims description 3
• HUNXMJYCHXQEGX-UHFFFAOYSA-N zaleplon Chemical compound CCN(C(C)=O)C1=CC=CC(C=2N3N=CC(=C3N=CC=2)C#N)=C1 HUNXMJYCHXQEGX-UHFFFAOYSA-N 0.000 claims description 3
• 229960000820 zopiclone Drugs 0.000 claims description 3
• LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 claims description 2
• SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims description 2
• 102000001419 Melatonin receptor Human genes 0.000 claims description 2
• 108050009605 Melatonin receptor Proteins 0.000 claims description 2
• 150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
• 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims description 2
• 239000002662 enteric coated tablet Substances 0.000 claims description 2
• 238000009472 formulation Methods 0.000 claims description 2
• 239000003688 hormone derivative Substances 0.000 claims description 2
• 239000001397 quillaja saponaria molina bark Substances 0.000 claims description 2
• 229930182490 saponin Natural products 0.000 claims description 2
• 150000007949 saponins Chemical class 0.000 claims description 2
• 239000002689 soil Substances 0.000 claims description 2
• JOFWLTCLBGQGBO-UHFFFAOYSA-N triazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1Cl JOFWLTCLBGQGBO-UHFFFAOYSA-N 0.000 claims description 2
• 229960003386 triazolam Drugs 0.000 claims description 2
• 125000000753 cycloalkyl group Chemical group 0.000 claims 5
• YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 claims 4
• 229960003987 melatonin Drugs 0.000 claims 4
• DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 claims 4
• 150000002431 hydrogen Chemical group 0.000 claims 3
• MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 claims 2
• 235000017166 Bambusa arundinacea Nutrition 0.000 claims 1
• 235000017491 Bambusa tulda Nutrition 0.000 claims 1
• 241001330002 Bambuseae Species 0.000 claims 1
• 229910019142 PO4 Inorganic materials 0.000 claims 1
• 235000015334 Phyllostachys viridis Nutrition 0.000 claims 1
• 241000239226 Scorpiones Species 0.000 claims 1
• 125000000278 alkyl amino alkyl group Chemical group 0.000 claims 1
• 125000005001 aminoaryl group Chemical group 0.000 claims 1
• 239000011425 bamboo Substances 0.000 claims 1
• 239000000969 carrier Substances 0.000 claims 1
• 229940125898 compound 5 Drugs 0.000 claims 1
• 125000004991 fluoroalkenyl group Chemical group 0.000 claims 1
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims 1
• 239000010452 phosphate Substances 0.000 claims 1
• 239000004575 stone Substances 0.000 claims 1
• 238000000034 method Methods 0.000 description 60
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 53
• 239000010410 layer Substances 0.000 description 42
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• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 26
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• 235000019439 ethyl acetate Nutrition 0.000 description 25
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
• 150000001412 amines Chemical class 0.000 description 24
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 24
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 23
• 229940023488 pill Drugs 0.000 description 21
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• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 15
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