CA2560966A1 - Heterocyclic phenylaminopropanol derivatives as modulators of the monoamine reuptake for the treatment of vasomotor symptoms (vms) - Google Patents

Info

Publication number

CA2560966A1

CA2560966A1 CA002560966A CA2560966A CA2560966A1 CA 2560966 A1 CA2560966 A1 CA 2560966A1 CA 002560966 A CA002560966 A CA 002560966A CA 2560966 A CA2560966 A CA 2560966A CA 2560966 A1 CA2560966 A1 CA 2560966A1

Authority

CA

Canada

Prior art keywords

methylamino

dihydro

pain

benzoxazin

subject

Prior art date

2004-03-30

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
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• 208000024891 symptom Diseases 0.000 title claims abstract description 42
• 230000001457 vasomotor Effects 0.000 title claims abstract description 33
• 230000000407 monoamine reuptake Effects 0.000 title claims abstract description 13
• -1 Heterocyclic phenylaminopropanol derivatives Chemical class 0.000 title claims description 56
• 238000011282 treatment Methods 0.000 title abstract description 24
• 208000002193 Pain Diseases 0.000 claims abstract description 92
• 238000000034 method Methods 0.000 claims abstract description 81
• 230000036407 pain Effects 0.000 claims abstract description 78
• 239000000203 mixture Substances 0.000 claims abstract description 62
• 150000003839 salts Chemical class 0.000 claims abstract description 56
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 31
• 208000035475 disorder Diseases 0.000 claims abstract description 30
• 201000001880 Sexual dysfunction Diseases 0.000 claims abstract description 17
• 231100000872 sexual dysfunction Toxicity 0.000 claims abstract description 17
• 206010066218 Stress Urinary Incontinence Diseases 0.000 claims abstract description 13
• 206010008874 Chronic Fatigue Syndrome Diseases 0.000 claims abstract description 12
• 208000001640 Fibromyalgia Diseases 0.000 claims abstract description 12
• 208000000921 Urge Urinary Incontinence Diseases 0.000 claims abstract description 12
• 230000001668 ameliorated effect Effects 0.000 claims abstract description 12
• 230000002496 gastric effect Effects 0.000 claims abstract description 12
• 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 claims abstract description 12
• 208000011580 syndromic disease Diseases 0.000 claims abstract description 12
• 208000032131 Diabetic Neuropathies Diseases 0.000 claims abstract description 10
• 208000012902 Nervous system disease Diseases 0.000 claims abstract description 10
• 208000024714 major depressive disease Diseases 0.000 claims abstract description 10
• 150000001875 compounds Chemical class 0.000 claims description 213
• 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 48
• 229910052757 nitrogen Inorganic materials 0.000 claims description 30
• 206010060800 Hot flush Diseases 0.000 claims description 23
• 125000004432 carbon atom Chemical group C* 0.000 claims description 22
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 21
• 125000003118 aryl group Chemical group 0.000 claims description 19
• 229910052760 oxygen Inorganic materials 0.000 claims description 17
• 208000004296 neuralgia Diseases 0.000 claims description 16
• 125000000623 heterocyclic group Chemical group 0.000 claims description 15
• 208000021722 neuropathic pain Diseases 0.000 claims description 15
• 229910052720 vanadium Inorganic materials 0.000 claims description 14
• 125000001072 heteroaryl group Chemical group 0.000 claims description 13
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
• 230000002093 peripheral effect Effects 0.000 claims description 12
• 229910052717 sulfur Inorganic materials 0.000 claims description 12
• 125000003342 alkenyl group Chemical group 0.000 claims description 10
• 125000000304 alkynyl group Chemical group 0.000 claims description 10
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
• 125000005843 halogen group Chemical group 0.000 claims description 10
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
• 206010028980 Neoplasm Diseases 0.000 claims description 9
• 125000004423 acyloxy group Chemical group 0.000 claims description 9
• 125000003545 alkoxy group Chemical group 0.000 claims description 9
• 125000005360 alkyl sulfoxide group Chemical group 0.000 claims description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
• 208000009935 visceral pain Diseases 0.000 claims description 9
• 125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 8
• 229910052799 carbon Inorganic materials 0.000 claims description 8
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
• 206010064012 Central pain syndrome Diseases 0.000 claims description 7
• IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 claims description 7
• 208000014674 injury Diseases 0.000 claims description 7
• DAQQEUNYRWDGFD-UHFFFAOYSA-N 1-(3-fluorophenyl)-3-(methylamino)-1-(2-phenyl-2,3-dihydro-1,4-benzoxazin-4-yl)propan-2-ol Chemical compound C=1C=CC(F)=CC=1C(C(O)CNC)N(C1=CC=CC=C1O1)CC1C1=CC=CC=C1 DAQQEUNYRWDGFD-UHFFFAOYSA-N 0.000 claims description 6
• POXIKNMZDSNTEK-UHFFFAOYSA-N 1-(6-chloro-2,3-dihydro-1,4-benzoxazin-4-yl)-3-(methylamino)-1-phenylpropan-2-ol Chemical compound C1COC2=CC=C(Cl)C=C2N1C(C(O)CNC)C1=CC=CC=C1 POXIKNMZDSNTEK-UHFFFAOYSA-N 0.000 claims description 6
• 206010058019 Cancer Pain Diseases 0.000 claims description 6
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• 206010037779 Radiculopathy Diseases 0.000 claims description 6
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• 230000001154 acute effect Effects 0.000 claims description 6
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 6
• 208000015181 infectious disease Diseases 0.000 claims description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical group NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 5
• 206010065390 Inflammatory pain Diseases 0.000 claims description 5
• 206010028391 Musculoskeletal Pain Diseases 0.000 claims description 5
• 125000004104 aryloxy group Chemical group 0.000 claims description 5
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
• 210000000056 organ Anatomy 0.000 claims description 5
• 125000006413 ring segment Chemical group 0.000 claims description 5
• 208000022170 stress incontinence Diseases 0.000 claims description 5
• 238000001356 surgical procedure Methods 0.000 claims description 5
• NYFIIMYTYZYJNH-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzoxazin-4-yl)-3-(methylamino)-1-phenylpropan-2-ol Chemical compound C1COC2=CC=CC=C2N1C(C(O)CNC)C1=CC=CC=C1 NYFIIMYTYZYJNH-UHFFFAOYSA-N 0.000 claims description 4
• 206010005052 Bladder irritation Diseases 0.000 claims description 4
• JJHHIJFTHRNPIK-UHFFFAOYSA-N Diphenyl sulfoxide Chemical group C=1C=CC=CC=1S(=O)C1=CC=CC=C1 JJHHIJFTHRNPIK-UHFFFAOYSA-N 0.000 claims description 4
• 208000028389 Nerve injury Diseases 0.000 claims description 4
• 206010033645 Pancreatitis Diseases 0.000 claims description 4
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
• 230000001684 chronic effect Effects 0.000 claims description 4
• 238000007906 compression Methods 0.000 claims description 4
• 230000006835 compression Effects 0.000 claims description 4
• 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 4
• 125000006622 cycloheptylmethyl group Chemical group 0.000 claims description 4
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
• 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 4
• KZTYYGOKRVBIMI-UHFFFAOYSA-N diphenyl sulfone Chemical group C=1C=CC=CC=1S(=O)(=O)C1=CC=CC=C1 KZTYYGOKRVBIMI-UHFFFAOYSA-N 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 4
• 208000002551 irritable bowel syndrome Diseases 0.000 claims description 4
• 230000008764 nerve damage Effects 0.000 claims description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
• RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 4
• DAQQEUNYRWDGFD-JRFVFWCSSA-N (1s,2r)-1-(3-fluorophenyl)-3-(methylamino)-1-[(2s)-2-phenyl-2,3-dihydro-1,4-benzoxazin-4-yl]propan-2-ol Chemical compound C1([C@H]2CN(C3=CC=CC=C3O2)[C@H]([C@H](O)CNC)C=2C=C(F)C=CC=2)=CC=CC=C1 DAQQEUNYRWDGFD-JRFVFWCSSA-N 0.000 claims description 3
• POXIKNMZDSNTEK-AEFFLSMTSA-N (1s,2r)-1-(6-chloro-2,3-dihydro-1,4-benzoxazin-4-yl)-3-(methylamino)-1-phenylpropan-2-ol Chemical compound C1([C@H](N2C3=CC(Cl)=CC=C3OCC2)[C@H](O)CNC)=CC=CC=C1 POXIKNMZDSNTEK-AEFFLSMTSA-N 0.000 claims description 3
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
• 208000002485 Adiposis dolorosa Diseases 0.000 claims description 3
• 208000006820 Arthralgia Diseases 0.000 claims description 3
• 208000035143 Bacterial infection Diseases 0.000 claims description 3
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• 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
• 208000011231 Crohn disease Diseases 0.000 claims description 3
• 208000007882 Gastritis Diseases 0.000 claims description 3
• 208000021965 Glossopharyngeal Nerve disease Diseases 0.000 claims description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 3
• 208000008930 Low Back Pain Diseases 0.000 claims description 3
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• 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 3
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• 235000018343 nutrient deficiency Nutrition 0.000 claims description 3
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• 239000003053 toxin Substances 0.000 claims description 3
• 231100000765 toxin Toxicity 0.000 claims description 3
• 108700012359 toxins Proteins 0.000 claims description 3
• 206010044652 trigeminal neuralgia Diseases 0.000 claims description 3
• ZXWNVYVRSLCDLQ-MJGOQNOKSA-N (1s,2r)-1-(2,2-dimethyl-3h-1,4-benzoxazin-4-yl)-1-(3-fluorophenyl)-3-(methylamino)propan-2-ol Chemical compound C1([C@H](N2C3=CC=CC=C3OC(C)(C)C2)[C@H](O)CNC)=CC=CC(F)=C1 ZXWNVYVRSLCDLQ-MJGOQNOKSA-N 0.000 claims description 2
• CUYWGZURXSNKCO-MJGOQNOKSA-N (1s,2r)-1-(2,2-dimethyl-3h-1,4-benzoxazin-4-yl)-3-(methylamino)-1-phenylpropan-2-ol Chemical compound C1([C@H](N2C3=CC=CC=C3OC(C)(C)C2)[C@H](O)CNC)=CC=CC=C1 CUYWGZURXSNKCO-MJGOQNOKSA-N 0.000 claims description 2
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