UA122121C2 - Біциклічні азотовмісні сполуки як агоністи мускаринового м1 рецептора i/або м4 рецептора - Google Patents

Info

Publication number

UA122121C2

UA122121C2 UAA201609185A UAA201609185A UA122121C2 UA 122121 C2 UA122121 C2 UA 122121C2 UA A201609185 A UAA201609185 A UA A201609185A UA A201609185 A UAA201609185 A UA A201609185A UA 122121 C2 UA122121 C2 UA 122121C2

Authority

UA

Ukraine

Prior art keywords

carboxylate

ethyl

azaspiro

piperidin

octane

Prior art date

2014-02-06

Links

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• 102000007207 Muscarinic M1 Receptor Human genes 0.000 title abstract description 6
• 108010008406 Muscarinic M1 Receptor Proteins 0.000 title abstract description 6
• 108010008414 Muscarinic M4 Receptor Proteins 0.000 title abstract description 4
• 102000007216 Muscarinic M4 Receptor Human genes 0.000 title description 3
• 239000000018 receptor agonist Substances 0.000 title 1
• 229940044601 receptor agonist Drugs 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 482
• 150000003839 salts Chemical class 0.000 claims abstract description 39
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• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 25
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
• 102000017924 CHRM4 Human genes 0.000 claims abstract description 8
• 101100107916 Xenopus laevis chrm4 gene Proteins 0.000 claims abstract description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 236
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 145
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 115
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 92
• 229910052739 hydrogen Inorganic materials 0.000 claims description 70
• 239000001257 hydrogen Substances 0.000 claims description 67
• -1 cyano, hydroxy, amino Chemical group 0.000 claims description 60
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 47
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 47
• 125000005842 heteroatom Chemical group 0.000 claims description 46
• 125000001153 fluoro group Chemical group F* 0.000 claims description 42
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 40
• 229910052731 fluorine Inorganic materials 0.000 claims description 40
• 239000011737 fluorine Substances 0.000 claims description 39
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 37
• 210000005056 cell body Anatomy 0.000 claims description 37
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 37
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• 125000004432 carbon atom Chemical group C* 0.000 claims description 33
• 125000003118 aryl group Chemical group 0.000 claims description 31
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
• 208000010877 cognitive disease Diseases 0.000 claims description 27
• 239000000460 chlorine Substances 0.000 claims description 26
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 25
• 229910052801 chlorine Inorganic materials 0.000 claims description 25
• 125000000623 heterocyclic group Chemical group 0.000 claims description 25
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 24
• 125000000217 alkyl group Chemical group 0.000 claims description 23
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• 108020003175 receptors Proteins 0.000 claims description 22
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 20
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 20
• 229910052794 bromium Inorganic materials 0.000 claims description 20
• 229910052799 carbon Inorganic materials 0.000 claims description 20
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 18
• 125000001424 substituent group Chemical group 0.000 claims description 18
• 230000000694 effects Effects 0.000 claims description 17
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 17
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 15
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• 239000012634 fragment Substances 0.000 claims description 6
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
• KZKRRZFCAYOXQE-UHFFFAOYSA-N 1$l^{2}-azinane Chemical group C1CC[N]CC1 KZKRRZFCAYOXQE-UHFFFAOYSA-N 0.000 claims description 5
• 230000009471 action Effects 0.000 claims description 5
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
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• 235000010469 Glycine max Nutrition 0.000 claims description 4
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• 206010012335 Dependence Diseases 0.000 claims description 3
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• STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 claims description 3
• 229910052770 Uranium Inorganic materials 0.000 claims description 3
• 125000005120 alkyl cycloalkyl alkyl group Chemical group 0.000 claims description 3
• 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 3
• STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 claims description 3
• 229960002646 scopolamine Drugs 0.000 claims description 3
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
• 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 2
• 206010067889 Dementia with Lewy bodies Diseases 0.000 claims description 2
• 244000068988 Glycine max Species 0.000 claims description 2
• 201000002832 Lewy body dementia Diseases 0.000 claims description 2
• 229920001577 copolymer Chemical compound 0.000 claims description 2
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
• 239000000472 muscarinic agonist Substances 0.000 claims description 2
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 9
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims 2
• 101100010712 Caenorhabditis elegans dyn-1 gene Proteins 0.000 claims 1
• 241001522296 Erithacus rubecula Species 0.000 claims 1
• 208000010201 Exanthema Diseases 0.000 claims 1
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• 241000549435 Pria Species 0.000 claims 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 1
• 241000269435 Rana <genus> Species 0.000 claims 1
• 125000001246 bromo group Chemical group Br* 0.000 claims 1
• 201000005884 exanthem Diseases 0.000 claims 1
• 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 claims 1
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• 238000007363 ring formation reaction Methods 0.000 claims 1
• 230000035939 shock Effects 0.000 claims 1
• 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 claims 1
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