BRPI0708725A2 - formulação de poliálcool de ciclohexano para o tratamento de doenças de agregação de proteìna - Google Patents

Info

Publication number

BRPI0708725A2

BRPI0708725A2 BRPI0708725-0A BRPI0708725A BRPI0708725A2 BR PI0708725 A2 BRPI0708725 A2 BR PI0708725A2 BR PI0708725 A BRPI0708725 A BR PI0708725A BR PI0708725 A2 BRPI0708725 A2 BR PI0708725A2

Authority

BR

Brazil

Prior art keywords

compound

dosage form

alkyl

cyclohexane

alkoxy

Prior art date

2006-03-09

Links

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• 150000005846 sugar alcohols Polymers 0.000 title claims abstract description 243
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 title claims abstract description 208
• 239000000203 mixture Substances 0.000 title claims abstract description 155
• 238000009472 formulation Methods 0.000 title claims abstract description 111
• 238000011282 treatment Methods 0.000 title claims abstract description 45
• 230000004845 protein aggregation Effects 0.000 title claims abstract description 11
• 201000010099 disease Diseases 0.000 title abstract description 78
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 78
• 150000001875 compounds Chemical class 0.000 claims abstract description 511
• 239000002552 dosage form Substances 0.000 claims abstract description 209
• 210000004556 brain Anatomy 0.000 claims abstract description 86
• 230000036470 plasma concentration Effects 0.000 claims abstract description 28
• 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 25
• 238000009825 accumulation Methods 0.000 claims abstract description 21
• 230000003941 amyloidogenesis Effects 0.000 claims abstract description 17
• 238000004220 aggregation Methods 0.000 claims abstract description 14
• 230000012846 protein folding Effects 0.000 claims abstract description 11
• 239000003085 diluting agent Substances 0.000 claims abstract description 9
• 230000007082 Aβ accumulation Effects 0.000 claims abstract description 8
• -1 epi-cyclohexanehexol compound Chemical class 0.000 claims description 413
• 238000000034 method Methods 0.000 claims description 53
• 208000024827 Alzheimer disease Diseases 0.000 claims description 46
• 230000002035 prolonged effect Effects 0.000 claims description 41
• 239000003814 drug Substances 0.000 claims description 38
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• 208000024891 symptom Diseases 0.000 claims description 23
• 238000004090 dissolution Methods 0.000 claims description 19
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• 238000000338 in vitro Methods 0.000 claims description 9
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• 230000001976 improved effect Effects 0.000 claims description 6
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• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 161
• 125000000217 alkyl group Chemical group 0.000 description 149
• 125000005843 halogen group Chemical group 0.000 description 128
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• 125000000753 cycloalkyl group Chemical group 0.000 description 108
• 125000003118 aryl group Chemical group 0.000 description 96
• 125000000623 heterocyclic group Chemical group 0.000 description 76
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• 125000003396 thiol group Chemical class [H]S* 0.000 description 59
• 125000004432 carbon atom Chemical group C* 0.000 description 56
• CDAISMWEOUEBRE-UHFFFAOYSA-N inositol Chemical class OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 56
• 125000002252 acyl group Chemical group 0.000 description 55
• 125000000304 alkynyl group Chemical group 0.000 description 54
• 235000019441 ethanol Nutrition 0.000 description 53
• 229910052739 hydrogen Inorganic materials 0.000 description 52
• 239000000460 chlorine Chemical group 0.000 description 50
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• 239000001257 hydrogen Substances 0.000 description 49
• 125000001072 heteroaryl group Chemical group 0.000 description 48
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• CDAISMWEOUEBRE-CDRYSYESSA-N scyllo-inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O CDAISMWEOUEBRE-CDRYSYESSA-N 0.000 description 39
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 37
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 37
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• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 36
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• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 36
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 36
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• 125000005000 thioaryl group Chemical group 0.000 description 34
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• NPPQSCRMBWNHMW-UHFFFAOYSA-N Meprobamate Chemical compound NC(=O)OCC(C)(CCC)COC(N)=O NPPQSCRMBWNHMW-UHFFFAOYSA-N 0.000 description 26
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• 125000003435 aroyl group Chemical group 0.000 description 26
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• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 25
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• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 21
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• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 20
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 20
• 239000002245 particle Substances 0.000 description 20
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• 125000003710 aryl alkyl group Chemical group 0.000 description 18
• 238000000151 deposition Methods 0.000 description 18
• CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical class O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 18
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• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
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