TW201121966A - Fused heterocyclic compounds as orexin receptor modulators - Google Patents

Info

Publication number

TW201121966A

TW201121966A TW099136020A TW99136020A TW201121966A TW 201121966 A TW201121966 A TW 201121966A TW 099136020 A TW099136020 A TW 099136020A TW 99136020 A TW99136020 A TW 99136020A TW 201121966 A TW201121966 A TW 201121966A

Authority

TW

Taiwan

Prior art keywords

diazabicyclo

phenyl

octane

fluoro

group

Prior art date

2009-10-23

Links

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• Global Dossier
• Discuss

• 108050000742 Orexin Receptor Proteins 0.000 title abstract 2
• 102000008834 Orexin receptor Human genes 0.000 title abstract 2
• 150000002391 heterocyclic compounds Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 449
• CPGFQLIXICGYSN-UHFFFAOYSA-N 4,7-diazabicyclo[4.2.0]octane Chemical class C1NCCC2CNC21 CPGFQLIXICGYSN-UHFFFAOYSA-N 0.000 claims abstract description 39
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 37
• 238000011282 treatment Methods 0.000 claims abstract description 29
• 230000000694 effects Effects 0.000 claims abstract description 21
• 208000035475 disorder Diseases 0.000 claims abstract description 20
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
• XKEYAOJRNJYJMM-UHFFFAOYSA-N 3,6-diazabicyclo[3.2.0]heptane Chemical class C1NCC2CNC21 XKEYAOJRNJYJMM-UHFFFAOYSA-N 0.000 claims abstract description 6
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims abstract description 5
• 206010022437 insomnia Diseases 0.000 claims abstract description 5
• -1 1H-pyrazol-3-yl group Chemical group 0.000 claims description 408
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 248
• TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 106
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 97
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 48
• 125000000217 alkyl group Chemical group 0.000 claims description 44
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 43
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 42
• 239000007789 gas Substances 0.000 claims description 40
• 150000003839 salts Chemical class 0.000 claims description 40
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 38
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 36
• 102000005962 receptors Human genes 0.000 claims description 34
• 108020003175 receptors Proteins 0.000 claims description 34
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 33
• NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 31
• 229910052757 nitrogen Inorganic materials 0.000 claims description 30
• 239000000126 substance Substances 0.000 claims description 28
• 150000005829 chemical entities Chemical class 0.000 claims description 27
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 26
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 26
• XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 25
• 125000003545 alkoxy group Chemical group 0.000 claims description 24
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 22
• 125000001072 heteroaryl group Chemical group 0.000 claims description 18
• QNXSIUBBGPHDDE-UHFFFAOYSA-N indan-1-one Chemical compound C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 claims description 18
• 201000010099 disease Diseases 0.000 claims description 17
• 125000005843 halogen group Chemical group 0.000 claims description 17
• ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 claims description 16
• SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 15
• 239000003814 drug Substances 0.000 claims description 15
• YLQWCDOCJODRMT-UHFFFAOYSA-N fluoren-9-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3C2=C1 YLQWCDOCJODRMT-UHFFFAOYSA-N 0.000 claims description 15
• MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 claims description 14
• 125000003118 aryl group Chemical group 0.000 claims description 13
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 13
• 229910052739 hydrogen Inorganic materials 0.000 claims description 13
• 150000002576 ketones Chemical class 0.000 claims description 13
• 239000002689 soil Substances 0.000 claims description 13
• 239000001257 hydrogen Substances 0.000 claims description 12
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
• 150000002923 oximes Chemical class 0.000 claims description 11
• 229910052760 oxygen Inorganic materials 0.000 claims description 11
• 239000001301 oxygen Substances 0.000 claims description 11
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 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 9
• 229910052731 fluorine Inorganic materials 0.000 claims description 9
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
• 238000006467 substitution reaction Methods 0.000 claims description 9
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• 239000004305 biphenyl Substances 0.000 claims description 8
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
• 239000011737 fluorine Substances 0.000 claims description 8
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 8
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 8
• 125000004076 pyridyl group Chemical group 0.000 claims description 8
• 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 7
• 239000010949 copper Substances 0.000 claims description 7
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 6
• 206010033307 Overweight Diseases 0.000 claims description 6
• RJGDLRCDCYRQOQ-UHFFFAOYSA-N anthrone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3CC2=C1 RJGDLRCDCYRQOQ-UHFFFAOYSA-N 0.000 claims description 6
• 235000010290 biphenyl Nutrition 0.000 claims description 6
• 229910052802 copper Inorganic materials 0.000 claims description 6
• 125000001153 fluoro group Chemical group F* 0.000 claims description 6
• 208000019116 sleep disease Diseases 0.000 claims description 6
• 229910052717 sulfur Inorganic materials 0.000 claims description 6
• 239000011593 sulfur Substances 0.000 claims description 6
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 6
• 125000001607 1,2,3-triazol-1-yl group Chemical group [*]N1N=NC([H])=C1[H] 0.000 claims description 5
• QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical group C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 5
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
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• 206010013975 Dyspnoeas Diseases 0.000 claims description 5
• 208000008589 Obesity Diseases 0.000 claims description 5
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 5
• 238000001354 calcination Methods 0.000 claims description 5
• 238000001514 detection method Methods 0.000 claims description 5
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 5
• 235000020824 obesity Nutrition 0.000 claims description 5
• 230000007958 sleep Effects 0.000 claims description 5
• FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 claims description 4
• KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 claims description 4
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• 206010038743 Restlessness Diseases 0.000 claims description 4
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• 239000007983 Tris buffer Substances 0.000 claims description 4
• 150000001335 aliphatic alkanes Chemical class 0.000 claims description 4
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
• 208000000509 infertility Diseases 0.000 claims description 4
• 230000036512 infertility Effects 0.000 claims description 4
• 231100000535 infertility Toxicity 0.000 claims description 4
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
• 230000006794 tachycardia Effects 0.000 claims description 4
• 150000003852 triazoles Chemical group 0.000 claims description 4
• FZZMTSNZRBFGGU-UHFFFAOYSA-N 2-chloro-7-fluoroquinazolin-4-amine Chemical compound FC1=CC=C2C(N)=NC(Cl)=NC2=C1 FZZMTSNZRBFGGU-UHFFFAOYSA-N 0.000 claims description 3
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• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 3
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• 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
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• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
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• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
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• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
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• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 2
• YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical compound NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 claims description 2
• CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 claims 14
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• CTTAQNIKFVJOHR-UHFFFAOYSA-N (2-bromophenyl)-[6-(4,6-dimethylpyrimidin-2-yl)-3,6-diazabicyclo[3.2.0]heptan-3-yl]methanone Chemical compound CC1=CC(C)=NC(N2C3CN(CC3C2)C(=O)C=2C(=CC=CC=2)Br)=N1 CTTAQNIKFVJOHR-UHFFFAOYSA-N 0.000 claims 1
• WBFFBCACAZRULE-UHFFFAOYSA-N (2-phenylphenyl)-(6-quinoxalin-2-yl-3,6-diazabicyclo[3.2.0]heptan-3-yl)methanone Chemical compound C1C2CN(C=3N=C4C=CC=CC4=NC=3)C2CN1C(=O)C1=CC=CC=C1C1=CC=CC=C1 WBFFBCACAZRULE-UHFFFAOYSA-N 0.000 claims 1
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 1
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