CZ122899A3 - Způsob a sloučeniny pro inhibici uvolňování a/nebo syntézy beta-amyloidového peptidu - Google Patents

Info

Publication number

CZ122899A3

CZ122899A3 CZ991228A CZ122899A CZ122899A3 CZ 122899 A3 CZ122899 A3 CZ 122899A3 CZ 991228 A CZ991228 A CZ 991228A CZ 122899 A CZ122899 A CZ 122899A CZ 122899 A3 CZ122899 A3 CZ 122899A3

Authority

CZ

Czechia

Prior art keywords

difluorophenylacetyl

alaninyl

hydrogen

methyl

butyl

Prior art date

1996-11-22

Links

• Espacenet
• Global Dossier
• Discuss

• 238000000034 method Methods 0.000 title claims abstract description 240
• 150000001875 compounds Chemical class 0.000 title claims abstract description 181
• 230000015572 biosynthetic process Effects 0.000 title claims abstract description 98
• 238000003786 synthesis reaction Methods 0.000 title claims abstract description 92
• DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 title claims abstract description 28
• 230000008569 process Effects 0.000 title claims description 9
• 230000005764 inhibitory process Effects 0.000 title 1
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 46
• 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 45
• -1 3-nitrophenyl Chemical group 0.000 claims description 1675
• 229910052739 hydrogen Inorganic materials 0.000 claims description 293
• 239000001257 hydrogen Substances 0.000 claims description 293
• 150000002431 hydrogen Chemical class 0.000 claims description 268
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 148
• 125000000217 alkyl group Chemical group 0.000 claims description 122
• 125000003118 aryl group Chemical group 0.000 claims description 111
• 125000001072 heteroaryl group Chemical group 0.000 claims description 106
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 92
• 125000000623 heterocyclic group Chemical group 0.000 claims description 87
• KIYRSYYOVDHSPG-ZETCQYMHSA-N (2s)-2-amino-2-phenylacetamide Chemical compound NC(=O)[C@@H](N)C1=CC=CC=C1 KIYRSYYOVDHSPG-ZETCQYMHSA-N 0.000 claims description 83
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 83
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 81
• 150000004702 methyl esters Chemical class 0.000 claims description 75
• 239000000203 mixture Substances 0.000 claims description 60
• 125000003342 alkenyl group Chemical group 0.000 claims description 57
• 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 55
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 45
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 43
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 43
• 125000003545 alkoxy group Chemical group 0.000 claims description 41
• BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 claims description 40
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 39
• 125000005017 substituted alkenyl group Chemical group 0.000 claims description 39
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 38
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 37
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 37
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 36
• 229910052757 nitrogen Chemical group 0.000 claims description 36
• 125000005309 thioalkoxy group Chemical group 0.000 claims description 34
• 125000000304 alkynyl group Chemical group 0.000 claims description 32
• 229960005190 phenylalanine Drugs 0.000 claims description 30
• 125000004432 carbon atom Chemical group C* 0.000 claims description 28
• 125000004426 substituted alkynyl group Chemical group 0.000 claims description 27
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 24
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 24
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
• ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 claims description 24
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 24
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 24
• 150000002148 esters Chemical class 0.000 claims description 24
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
• 125000005415 substituted alkoxy group Chemical group 0.000 claims description 24
• 229960003767 alanine Drugs 0.000 claims description 23
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
• 101100298295 Drosophila melanogaster flfl gene Proteins 0.000 claims description 22
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 22
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 21
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 21
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 20
• ZGUNAGUHMKGQNY-SSDOTTSWSA-N D-alpha-phenylglycine Chemical compound OC(=O)[C@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-SSDOTTSWSA-N 0.000 claims description 20
• 239000004471 Glycine Substances 0.000 claims description 20
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 19
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 17
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 17
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 17
• HQMLIDZJXVVKCW-REOHCLBHSA-N L-alaninamide Chemical compound C[C@H](N)C(N)=O HQMLIDZJXVVKCW-REOHCLBHSA-N 0.000 claims description 15
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 15
• 125000004122 cyclic group Chemical group 0.000 claims description 15
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 14
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 13
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 13
• 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 13
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 12
• 229910052717 sulfur Inorganic materials 0.000 claims description 12
• GXBRYTMUEZNYJT-UHFFFAOYSA-N 2-anilinoacetamide Chemical compound NC(=O)CNC1=CC=CC=C1 GXBRYTMUEZNYJT-UHFFFAOYSA-N 0.000 claims description 11
• 125000003412 L-alanyl group Chemical group [H]N([H])[C@@](C([H])([H])[H])(C(=O)[*])[H] 0.000 claims description 11
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 11
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 11
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 11
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
• 150000003839 salts Chemical class 0.000 claims description 11
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 10
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 10
• QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 claims description 10
• QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 claims description 10
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 10
• 230000002401 inhibitory effect Effects 0.000 claims description 10
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 10
• 150000003573 thiols Chemical class 0.000 claims description 10
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 9
• 125000004494 ethyl ester group Chemical group 0.000 claims description 9
• 229910052731 fluorine Inorganic materials 0.000 claims description 9
• 125000001153 fluoro group Chemical group F* 0.000 claims description 9
• KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 claims description 9
• 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 9
• 125000003107 substituted aryl group Chemical group 0.000 claims description 9
• 125000004434 sulfur atom Chemical group 0.000 claims description 9
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 8
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 8
• 125000005842 heteroatom Chemical group 0.000 claims description 8
• 125000004429 atom Chemical group 0.000 claims description 7
• 229960003136 leucine Drugs 0.000 claims description 7
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 7
• BHFLUDRTVIDDOR-QMMMGPOBSA-N methyl (2s)-2-amino-2-phenylacetate Chemical compound COC(=O)[C@@H](N)C1=CC=CC=C1 BHFLUDRTVIDDOR-QMMMGPOBSA-N 0.000 claims description 7
• 229960002429 proline Drugs 0.000 claims description 7
• 125000004076 pyridyl group Chemical group 0.000 claims description 7
• 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 6
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 6
• AYFVYJQAPQTCCC-STHAYSLISA-N D-threonine Chemical compound C[C@H](O)[C@@H](N)C(O)=O AYFVYJQAPQTCCC-STHAYSLISA-N 0.000 claims description 6
• 229930182822 D-threonine Natural products 0.000 claims description 6
• 239000004395 L-leucine Substances 0.000 claims description 6
• VSDUZFOSJDMAFZ-VIFPVBQESA-N methyl L-phenylalaninate Chemical compound COC(=O)[C@@H](N)CC1=CC=CC=C1 VSDUZFOSJDMAFZ-VIFPVBQESA-N 0.000 claims description 6
• 125000004043 oxo group Chemical group O=* 0.000 claims description 6
• 229910052760 oxygen Inorganic materials 0.000 claims description 6
• 239000001301 oxygen Substances 0.000 claims description 6
• 238000006467 substitution reaction Methods 0.000 claims description 6
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 5
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 5
• OBSIQMZKFXFYLV-QMMMGPOBSA-N L-phenylalanine amide Chemical compound NC(=O)[C@@H](N)CC1=CC=CC=C1 OBSIQMZKFXFYLV-QMMMGPOBSA-N 0.000 claims description 5
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 5
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 5
• HNNJFUDLLWOVKZ-VKHMYHEASA-N (2s)-2-aminobutanamide Chemical compound CC[C@H](N)C(N)=O HNNJFUDLLWOVKZ-VKHMYHEASA-N 0.000 claims description 4
• DQUHYEDEGRNAFO-QMMMGPOBSA-N (2s)-6-amino-2-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CCCCN DQUHYEDEGRNAFO-QMMMGPOBSA-N 0.000 claims description 4
• 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 4
• GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 4
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 4
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 4
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 4
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 4
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 4
• 125000005917 3-methylpentyl group Chemical group 0.000 claims description 4
• 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 claims description 4
• 101150065749 Churc1 gene Proteins 0.000 claims description 4
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 4
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 4
• LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 claims description 4
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 4
• 102100038239 Protein Churchill Human genes 0.000 claims description 4
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 4
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 4
• 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 4
• 125000006378 chloropyridyl group Chemical group 0.000 claims description 4
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
• 125000006379 fluoropyridyl group Chemical group 0.000 claims description 4
• 229960000310 isoleucine Drugs 0.000 claims description 4
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 4
• BLWYXBNNBYXPPL-YFKPBYRVSA-N methyl (2s)-pyrrolidine-2-carboxylate Chemical compound COC(=O)[C@@H]1CCCN1 BLWYXBNNBYXPPL-YFKPBYRVSA-N 0.000 claims description 4
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 4
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 4
• 125000004574 piperidin-2-yl group Chemical group N1C(CCCC1)* 0.000 claims description 4
• 229940080818 propionamide Drugs 0.000 claims description 4
• 229960001153 serine Drugs 0.000 claims description 4
• HJLYKRGXTOVWFL-UHFFFAOYSA-N tert-butyl 2-amino-2-phenylacetate Chemical compound CC(C)(C)OC(=O)C(N)C1=CC=CC=C1 HJLYKRGXTOVWFL-UHFFFAOYSA-N 0.000 claims description 4
• 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 4
• 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 claims description 4
• VRPHWBFEDIRKMX-UHFFFAOYSA-N amino pentanoate Chemical compound CCCCC(=O)ON VRPHWBFEDIRKMX-UHFFFAOYSA-N 0.000 claims description 3
• 230000006866 deterioration Effects 0.000 claims description 3
• NTNZTEQNFHNYBC-UHFFFAOYSA-N ethyl 2-aminoacetate Chemical compound CCOC(=O)CN NTNZTEQNFHNYBC-UHFFFAOYSA-N 0.000 claims description 3
• KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 3
• UWYZHKAOTLEWKK-UHFFFAOYSA-N tetrahydro-isoquinoline Natural products C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims description 3
• KLDOZDNQLZNRLQ-ZETCQYMHSA-N (2S)-2-amino-2-phenylacetohydrazide Chemical compound N[C@@H](C1=CC=CC=C1)C(=O)NN KLDOZDNQLZNRLQ-ZETCQYMHSA-N 0.000 claims description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 2
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
• 125000004265 thionaphthen-2-yl group Chemical group [H]C1=C(*)SC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 2
• 229960004441 tyrosine Drugs 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 26
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 24
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 9
• HCLZWWBOYHLGME-UHFFFAOYSA-N 2-amino-n,2-diphenylacetamide Chemical compound C=1C=CC=CC=1C(N)C(=O)NC1=CC=CC=C1 HCLZWWBOYHLGME-UHFFFAOYSA-N 0.000 claims 6
• MWYKYPSXTVKJAC-ZETCQYMHSA-N (2S)-2-amino-2-phenylethanethioamide Chemical compound N[C@@H](C1=CC=CC=C1)C(N)=S MWYKYPSXTVKJAC-ZETCQYMHSA-N 0.000 claims 5
• KIYRSYYOVDHSPG-UHFFFAOYSA-N 2-amino-2-phenylacetamide Chemical compound NC(=O)C(N)C1=CC=CC=C1 KIYRSYYOVDHSPG-UHFFFAOYSA-N 0.000 claims 5
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 5
• 239000011737 fluorine Substances 0.000 claims 5
• 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 4
• 239000004473 Threonine Substances 0.000 claims 4
• 239000011593 sulfur Chemical group 0.000 claims 4
• 229960002898 threonine Drugs 0.000 claims 4
• NCPLOFZQPMSMOH-YFKPBYRVSA-N (2s)-2-amino-n-methylpentanamide Chemical compound CCC[C@H](N)C(=O)NC NCPLOFZQPMSMOH-YFKPBYRVSA-N 0.000 claims 3
• CKQYFZPCICOPMQ-VKHMYHEASA-N (2s)-2-amino-n-methylpropanamide Chemical compound CNC(=O)[C@H](C)N CKQYFZPCICOPMQ-VKHMYHEASA-N 0.000 claims 3
• VRAHHDPULBZDGB-UHFFFAOYSA-N 2-amino-2-(4-bromophenyl)acetamide Chemical compound NC(=O)C(N)C1=CC=C(Br)C=C1 VRAHHDPULBZDGB-UHFFFAOYSA-N 0.000 claims 3
• DQSACLYOIBPCJU-UHFFFAOYSA-N 2-azaniumyl-2-(2-methoxyphenyl)acetate Chemical compound COC1=CC=CC=C1C(N)C(O)=O DQSACLYOIBPCJU-UHFFFAOYSA-N 0.000 claims 3
• 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims 3
• 125000006288 3,5-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(C([H])=C1F)C([H])([H])* 0.000 claims 3
• 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims 3
• MHYHEUFNXXJUHF-UHFFFAOYSA-N 3-phenylpropyl 2-aminoacetate Chemical compound NCC(=O)OCCCC1=CC=CC=C1 MHYHEUFNXXJUHF-UHFFFAOYSA-N 0.000 claims 3
• 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims 3
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 3
• 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims 3
• 125000001318 4-trifluoromethylbenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C(F)(F)F 0.000 claims 3
• DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims 3
• 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims 3
• JKFYKCYQEWQPTM-ZETCQYMHSA-N (2s)-2-amino-2-(4-fluorophenyl)acetic acid Chemical compound OC(=O)[C@@H](N)C1=CC=C(F)C=C1 JKFYKCYQEWQPTM-ZETCQYMHSA-N 0.000 claims 2
• PZUOEYPTQJILHP-GBXIJSLDSA-N (2s,3r)-2-amino-3-hydroxybutanamide Chemical compound C[C@@H](O)[C@H](N)C(N)=O PZUOEYPTQJILHP-GBXIJSLDSA-N 0.000 claims 2
• JKFYKCYQEWQPTM-UHFFFAOYSA-N 2-azaniumyl-2-(4-fluorophenyl)acetate Chemical compound OC(=O)C(N)C1=CC=C(F)C=C1 JKFYKCYQEWQPTM-UHFFFAOYSA-N 0.000 claims 2
• 125000006291 3-hydroxybenzyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(=C1[H])C([H])([H])* 0.000 claims 2
• JXYACYYPACQCDM-UHFFFAOYSA-N Benzyl glycinate Chemical compound NCC(=O)OCC1=CC=CC=C1 JXYACYYPACQCDM-UHFFFAOYSA-N 0.000 claims 2
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims 2
• CXJKLNCCCSASBM-UHFFFAOYSA-N amino 2-(4-methoxyphenyl)acetate Chemical compound COC1=CC=C(CC(=O)ON)C=C1 CXJKLNCCCSASBM-UHFFFAOYSA-N 0.000 claims 2
• YPGCWEMNNLXISK-UHFFFAOYSA-N hydratropic acid Chemical compound OC(=O)C(C)C1=CC=CC=C1 YPGCWEMNNLXISK-UHFFFAOYSA-N 0.000 claims 2
• 229940017219 methyl propionate Drugs 0.000 claims 2
• 125000005484 neopentoxy group Chemical group 0.000 claims 2
• 125000005544 phthalimido group Chemical group 0.000 claims 2
• HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 claims 2
• 125000001544 thienyl group Chemical group 0.000 claims 2
• HYBIFLOQMMPNFT-JTQLQIEISA-N (2S)-2-amino-N-tert-butyl-2-phenylacetamide Chemical compound CC(C)(C)NC(=O)[C@@H](N)C1=CC=CC=C1 HYBIFLOQMMPNFT-JTQLQIEISA-N 0.000 claims 1
• JBULSURVMXPBNA-RXMQYKEDSA-N (2s)-2-amino-3,3-dimethylbutan-1-ol Chemical compound CC(C)(C)[C@H](N)CO JBULSURVMXPBNA-RXMQYKEDSA-N 0.000 claims 1
• UHRXMHNADRAFIS-UHFFFAOYSA-N 1,3-thiazol-4-yl propanoate Chemical compound CCC(=O)OC1=CSC=N1 UHRXMHNADRAFIS-UHFFFAOYSA-N 0.000 claims 1
• IKOYGCFHRDLQGP-JTQLQIEISA-N 2-[[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]oxyacetic acid Chemical compound COC([C@@H](NOCC(=O)O)CC1=CC=CC=C1)=O IKOYGCFHRDLQGP-JTQLQIEISA-N 0.000 claims 1
• ZKUPSAFYAKFTLX-UHFFFAOYSA-N 2-amino-n-ethyl-2-phenylacetamide Chemical compound CCNC(=O)C(N)C1=CC=CC=C1 ZKUPSAFYAKFTLX-UHFFFAOYSA-N 0.000 claims 1
• LIWNVVQJSOCDPV-UHFFFAOYSA-N 2-amino-n-methylhexanamide Chemical compound CCCCC(N)C(=O)NC LIWNVVQJSOCDPV-UHFFFAOYSA-N 0.000 claims 1
• OPOBBDXDRHKTJF-UHFFFAOYSA-N 2-aminohex-4-enoic acid Chemical compound CC=CCC(N)C(O)=O OPOBBDXDRHKTJF-UHFFFAOYSA-N 0.000 claims 1
• ODQJQEROUCVZNG-UHFFFAOYSA-N 5-fluoropyridine Chemical compound FC1=C=NC=C[CH]1 ODQJQEROUCVZNG-UHFFFAOYSA-N 0.000 claims 1
• FMAZQSYXRGRESX-UHFFFAOYSA-N Glycidamide Chemical compound NC(=O)C1CO1 FMAZQSYXRGRESX-UHFFFAOYSA-N 0.000 claims 1
• YHBTXTFFTYXOFV-UHFFFAOYSA-N Liquid thiophthene Chemical compound C1=CSC2=C1C=CS2 YHBTXTFFTYXOFV-UHFFFAOYSA-N 0.000 claims 1
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims 1
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 1
• 125000001207 fluorophenyl group Chemical group 0.000 claims 1
• DXSRQHCLOHVMKH-AWEZNQCLSA-N methyl (2S)-2-amino-2-(4-phenylphenyl)acetate Chemical compound C1=CC([C@H](N)C(=O)OC)=CC=C1C1=CC=CC=C1 DXSRQHCLOHVMKH-AWEZNQCLSA-N 0.000 claims 1
• WBLGPKGZZDMIPA-YJBOKZPZSA-N methyl (2s)-3-phenyl-2-[[(2s)-2-[(2-phenylacetyl)amino]propanoyl]amino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H](C)NC(=O)CC=1C=CC=CC=1)C1=CC=CC=C1 WBLGPKGZZDMIPA-YJBOKZPZSA-N 0.000 claims 1
• VXGRMCZTYDXKQW-UHFFFAOYSA-N methyl 2-aminopentanoate Chemical class CCCC(N)C(=O)OC VXGRMCZTYDXKQW-UHFFFAOYSA-N 0.000 claims 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
• 238000006243 chemical reaction Methods 0.000 description 91
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 73
• 238000000746 purification Methods 0.000 description 67
• 238000005481 NMR spectroscopy Methods 0.000 description 66
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 65
• 229910002027 silica gel Inorganic materials 0.000 description 63
• 238000004809 thin layer chromatography Methods 0.000 description 63
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 62
• 239000000741 silica gel Substances 0.000 description 62
• 238000004949 mass spectrometry Methods 0.000 description 49
• 229940024606 amino acid Drugs 0.000 description 45
• 235000001014 amino acid Nutrition 0.000 description 45
• 238000001914 filtration Methods 0.000 description 40
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
• 238000005859 coupling reaction Methods 0.000 description 31
• 235000019439 ethyl acetate Nutrition 0.000 description 31
• 239000000243 solution Substances 0.000 description 31
• 150000001413 amino acids Chemical class 0.000 description 29
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 29
• 230000008878 coupling Effects 0.000 description 28
• 238000010168 coupling process Methods 0.000 description 28
• 239000011541 reaction mixture Substances 0.000 description 27
• 230000002829 reductive effect Effects 0.000 description 27
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
• 239000003153 chemical reaction reagent Substances 0.000 description 25
• 238000002360 preparation method Methods 0.000 description 25
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
• 239000004480 active ingredient Substances 0.000 description 23
• 125000001424 substituent group Chemical group 0.000 description 23
• 239000000047 product Substances 0.000 description 22
• 239000002904 solvent Substances 0.000 description 21
• SZHJHAOHDNDHMA-LURJTMIESA-N 2-methylpropyl (2s)-2-aminopropanoate Chemical compound CC(C)COC(=O)[C@H](C)N SZHJHAOHDNDHMA-LURJTMIESA-N 0.000 description 20
• QZRMWMCNVOAIAU-UHFFFAOYSA-N 2-methylpropyl 2-aminobutanoate Chemical compound CCC(N)C(=O)OCC(C)C QZRMWMCNVOAIAU-UHFFFAOYSA-N 0.000 description 20
• 239000002253 acid Substances 0.000 description 20
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
• 239000007787 solid Substances 0.000 description 18
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
• 239000000460 chlorine Substances 0.000 description 15
• 239000011734 sodium Substances 0.000 description 15
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 14
• 150000001412 amines Chemical class 0.000 description 14
• 229920005989 resin Polymers 0.000 description 14
• 239000011347 resin Substances 0.000 description 14
• 238000005406 washing Methods 0.000 description 14
• 239000004615 ingredient Substances 0.000 description 13
• 230000035772 mutation Effects 0.000 description 13
• 239000012267 brine Substances 0.000 description 12
• 238000000605 extraction Methods 0.000 description 12
• 239000010410 layer Substances 0.000 description 12
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 11
• 239000000126 substance Substances 0.000 description 11
• 239000003826 tablet Substances 0.000 description 11
• 229910001868 water Inorganic materials 0.000 description 11
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
• JQXKMZBUNUSFPQ-RGMNGODLSA-N 2-methylpropyl (2s)-2-aminopropanoate;hydrochloride Chemical compound Cl.CC(C)COC(=O)[C@H](C)N JQXKMZBUNUSFPQ-RGMNGODLSA-N 0.000 description 10
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
• 229920002472 Starch Polymers 0.000 description 10
• 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 10
• ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 10
• 229920000642 polymer Polymers 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• 235000019698 starch Nutrition 0.000 description 10
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
• 239000003921 oil Substances 0.000 description 9
• 235000019198 oils Nutrition 0.000 description 9
• 229920006395 saturated elastomer Polymers 0.000 description 9
• 239000008107 starch Substances 0.000 description 9
• 239000007858 starting material Substances 0.000 description 9
• 238000003756 stirring Methods 0.000 description 9
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
• 108091000041 Phosphoenolpyruvate Carboxylase Proteins 0.000 description 8
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 8
• 201000010099 disease Diseases 0.000 description 8
• 239000003814 drug Substances 0.000 description 8
• 239000003480 eluent Substances 0.000 description 8
• 235000019359 magnesium stearate Nutrition 0.000 description 8
• 230000008018 melting Effects 0.000 description 8
• 238000002844 melting Methods 0.000 description 8
• 239000000546 pharmaceutical excipient Substances 0.000 description 8
• NONJJLVGHLVQQM-JHXYUMNGSA-N phenethicillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C(C)OC1=CC=CC=C1 NONJJLVGHLVQQM-JHXYUMNGSA-N 0.000 description 8
• 238000011282 treatment Methods 0.000 description 8
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 7
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
• 125000002252 acyl group Chemical group 0.000 description 7
• 125000000266 alpha-aminoacyl group Chemical group 0.000 description 7
• 150000001718 carbodiimides Chemical class 0.000 description 7
• 238000004587 chromatography analysis Methods 0.000 description 7
• 125000004093 cyano group Chemical group *C#N 0.000 description 7
• 229940079593 drug Drugs 0.000 description 7
• 125000004185 ester group Chemical group 0.000 description 7
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 7
• 239000012044 organic layer Substances 0.000 description 7
• 125000005254 oxyacyl group Chemical group 0.000 description 7
• KSXWPWDMLRUMEA-ZETCQYMHSA-N (2s)-2-[[2-(3-chlorophenyl)acetyl]amino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)CC1=CC=CC(Cl)=C1 KSXWPWDMLRUMEA-ZETCQYMHSA-N 0.000 description 6
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 229910052736 halogen Inorganic materials 0.000 description 6
• 150000002367 halogens Chemical class 0.000 description 6
• 238000004811 liquid chromatography Methods 0.000 description 6
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 6
• 239000000843 powder Substances 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 238000005809 transesterification reaction Methods 0.000 description 6
• 208000037259 Amyloid Plaque Diseases 0.000 description 5
• 125000003047 N-acetyl group Chemical group 0.000 description 5
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 5
• 229960000583 acetic acid Drugs 0.000 description 5
• 235000004279 alanine Nutrition 0.000 description 5
• 150000001298 alcohols Chemical class 0.000 description 5
• 125000002947 alkylene group Chemical group 0.000 description 5
• 150000001408 amides Chemical class 0.000 description 5
• 125000003277 amino group Chemical group 0.000 description 5
• 230000000903 blocking effect Effects 0.000 description 5
• 210000004556 brain Anatomy 0.000 description 5
• 230000003197 catalytic effect Effects 0.000 description 5
• 238000007796 conventional method Methods 0.000 description 5
• HRKQOINLCJTGBK-UHFFFAOYSA-N dihydroxidosulfur Chemical compound OSO HRKQOINLCJTGBK-UHFFFAOYSA-N 0.000 description 5
• 238000005886 esterification reaction Methods 0.000 description 5
• 239000007903 gelatin capsule Substances 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• 230000003287 optical effect Effects 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• 108090000765 processed proteins & peptides Proteins 0.000 description 5
• 108090000623 proteins and genes Proteins 0.000 description 5
• 238000001953 recrystallisation Methods 0.000 description 5
• 125000004953 trihalomethyl group Chemical group 0.000 description 5
• VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 4
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
• 102000013455 Amyloid beta-Peptides Human genes 0.000 description 4
• 108010090849 Amyloid beta-Peptides Proteins 0.000 description 4
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 4
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
• 125000004442 acylamino group Chemical group 0.000 description 4
• 238000004458 analytical method Methods 0.000 description 4
• 239000007864 aqueous solution Substances 0.000 description 4
• 125000004104 aryloxy group Chemical group 0.000 description 4
• 239000002585 base Substances 0.000 description 4
• 230000008499 blood brain barrier function Effects 0.000 description 4
• 210000004027 cell Anatomy 0.000 description 4
• 229910052801 chlorine Inorganic materials 0.000 description 4
• 238000004140 cleaning Methods 0.000 description 4
• 239000012043 crude product Substances 0.000 description 4
• 230000032050 esterification Effects 0.000 description 4
• 239000000706 filtrate Substances 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• 230000007062 hydrolysis Effects 0.000 description 4
• 238000006460 hydrolysis reaction Methods 0.000 description 4
• 229940035429 isobutyl alcohol Drugs 0.000 description 4
• 230000003902 lesion Effects 0.000 description 4
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 4
• 239000008108 microcrystalline cellulose Substances 0.000 description 4
• 229940016286 microcrystalline cellulose Drugs 0.000 description 4
• BEENTKNKPLFNKS-UHFFFAOYSA-N n-ethyl-n'-(3-pyrrolidin-1-ylpropyl)methanediimine Chemical compound CCN=C=NCCCN1CCCC1 BEENTKNKPLFNKS-UHFFFAOYSA-N 0.000 description 4
• 239000006187 pill Substances 0.000 description 4
• 235000018102 proteins Nutrition 0.000 description 4
• 102000004169 proteins and genes Human genes 0.000 description 4
• 238000010898 silica gel chromatography Methods 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• 208000024891 symptom Diseases 0.000 description 4
• ZWXDAANEJMSCEX-UHFFFAOYSA-N 1-(3-anilinophenyl)ethanone Chemical compound CC(=O)C1=CC=CC(NC=2C=CC=CC=2)=C1 ZWXDAANEJMSCEX-UHFFFAOYSA-N 0.000 description 3
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
• VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 3
• WFPMUFXQDKMVCO-UHFFFAOYSA-N 2-(3-chlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Cl)=C1 WFPMUFXQDKMVCO-UHFFFAOYSA-N 0.000 description 3
• JQXKMZBUNUSFPQ-UHFFFAOYSA-N 2-methylpropyl 2-aminopropanoate;hydrochloride Chemical compound Cl.CC(C)COC(=O)C(C)N JQXKMZBUNUSFPQ-UHFFFAOYSA-N 0.000 description 3
• 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 description 3
• 206010059245 Angiopathy Diseases 0.000 description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• 150000008575 L-amino acids Chemical class 0.000 description 3
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
• NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 3
• 108010029485 Protein Isoforms Proteins 0.000 description 3
• 102000001708 Protein Isoforms Human genes 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 229930006000 Sucrose Natural products 0.000 description 3
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
• 239000000654 additive Substances 0.000 description 3
• 101150031224 app gene Proteins 0.000 description 3
• XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
• 210000005013 brain tissue Anatomy 0.000 description 3
• YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 3
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 238000001816 cooling Methods 0.000 description 3
• 230000008021 deposition Effects 0.000 description 3
• 125000004663 dialkyl amino group Chemical group 0.000 description 3
• 208000025688 early-onset autosomal dominant Alzheimer disease Diseases 0.000 description 3
• 239000012458 free base Substances 0.000 description 3
• 125000005843 halogen group Chemical group 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 229910052740 iodine Inorganic materials 0.000 description 3
• 238000002955 isolation Methods 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
• 235000019341 magnesium sulphate Nutrition 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 239000012299 nitrogen atmosphere Substances 0.000 description 3
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 3
• 239000002245 particle Substances 0.000 description 3
• 238000005897 peptide coupling reaction Methods 0.000 description 3
• 229960003424 phenylacetic acid Drugs 0.000 description 3
• 239000003279 phenylacetic acid Substances 0.000 description 3
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
• 150000003141 primary amines Chemical class 0.000 description 3
• 238000011321 prophylaxis Methods 0.000 description 3
• 238000010992 reflux Methods 0.000 description 3
• 229910000104 sodium hydride Inorganic materials 0.000 description 3
• 229910052938 sodium sulfate Inorganic materials 0.000 description 3
• 235000011152 sodium sulphate Nutrition 0.000 description 3
• 239000005720 sucrose Substances 0.000 description 3
• 239000000829 suppository Substances 0.000 description 3
• CCVYRRGZDBSHFU-UHFFFAOYSA-N (2-hydroxyphenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1O CCVYRRGZDBSHFU-UHFFFAOYSA-N 0.000 description 2
• FDWFFCURSPACFQ-QMMMGPOBSA-N (2s)-2-[(2-phenylacetyl)amino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)CC1=CC=CC=C1 FDWFFCURSPACFQ-QMMMGPOBSA-N 0.000 description 2
• MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 2
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
• GHGUBEHGXLMGTM-UHFFFAOYSA-N 2-(2-phenyl-1,3-oxazol-4-yl)acetic acid Chemical compound OC(=O)CC1=COC(C=2C=CC=CC=2)=N1 GHGUBEHGXLMGTM-UHFFFAOYSA-N 0.000 description 2
• ZOUPGSMSNQLUNW-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(Cl)C(Cl)=C1 ZOUPGSMSNQLUNW-UHFFFAOYSA-N 0.000 description 2
• RERINLRFXYGZEE-UHFFFAOYSA-N 2-(3,5-dichlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC(Cl)=CC(Cl)=C1 RERINLRFXYGZEE-UHFFFAOYSA-N 0.000 description 2
• IGGNSAVLXJKCNH-UHFFFAOYSA-N 2-(3,5-difluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC(F)=CC(F)=C1 IGGNSAVLXJKCNH-UHFFFAOYSA-N 0.000 description 2
• POEFJFLAFQWOTL-UHFFFAOYSA-N 2-(3-methyl-1,2-oxazol-5-yl)acetic acid Chemical compound CC=1C=C(CC(O)=O)ON=1 POEFJFLAFQWOTL-UHFFFAOYSA-N 0.000 description 2
• GXXXUZIRGXYDFP-UHFFFAOYSA-N 2-(4-methylphenyl)acetic acid Chemical compound CC1=CC=C(CC(O)=O)C=C1 GXXXUZIRGXYDFP-UHFFFAOYSA-N 0.000 description 2
• VYSRZETUSAOIMP-UHFFFAOYSA-N 2-furanacetic acid Chemical compound OC(=O)CC1=CC=CO1 VYSRZETUSAOIMP-UHFFFAOYSA-N 0.000 description 2
• HBAHZZVIEFRTEY-UHFFFAOYSA-N 2-heptylcyclohex-2-en-1-one Chemical compound CCCCCCCC1=CCCCC1=O HBAHZZVIEFRTEY-UHFFFAOYSA-N 0.000 description 2
• QPRQEDXDYOZYLA-UHFFFAOYSA-N 2-methylbutan-1-ol Chemical compound CCC(C)CO QPRQEDXDYOZYLA-UHFFFAOYSA-N 0.000 description 2
• VIBOGIYPPWLDTI-UHFFFAOYSA-N 2-naphthylacetic acid Chemical compound C1=CC=CC2=CC(CC(=O)O)=CC=C21 VIBOGIYPPWLDTI-UHFFFAOYSA-N 0.000 description 2
• RCNOGGGBSSVMAS-UHFFFAOYSA-N 2-thiophen-3-ylacetic acid Chemical compound OC(=O)CC=1C=CSC=1 RCNOGGGBSSVMAS-UHFFFAOYSA-N 0.000 description 2
• ZJSQZQMVXKZAGW-UHFFFAOYSA-N 2H-benzotriazol-4-ol hydrate Chemical compound O.OC1=CC=CC2=C1N=NN2 ZJSQZQMVXKZAGW-UHFFFAOYSA-N 0.000 description 2
• VPBWZBGZWHDNKL-UHFFFAOYSA-N 3-pyrrolidin-1-ylpropan-1-amine Chemical compound NCCCN1CCCC1 VPBWZBGZWHDNKL-UHFFFAOYSA-N 0.000 description 2
• CDPKJZJVTHSESZ-UHFFFAOYSA-N 4-chlorophenylacetic acid Chemical compound OC(=O)CC1=CC=C(Cl)C=C1 CDPKJZJVTHSESZ-UHFFFAOYSA-N 0.000 description 2
• OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
• UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 2
• 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 2
• 102000009091 Amyloidogenic Proteins Human genes 0.000 description 2
• 108010048112 Amyloidogenic Proteins Proteins 0.000 description 2
• 229920000742 Cotton Polymers 0.000 description 2
• 108010016626 Dipeptides Proteins 0.000 description 2
• GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 2
• 235000019454 L-leucine Nutrition 0.000 description 2
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
• 239000004472 Lysine Substances 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• 229920001367 Merrifield resin Polymers 0.000 description 2
• 230000006181 N-acylation Effects 0.000 description 2
• 101000986989 Naja kaouthia Acidic phospholipase A2 CM-II Proteins 0.000 description 2
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
• 150000001242 acetic acid derivatives Chemical class 0.000 description 2
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
• 210000004204 blood vessel Anatomy 0.000 description 2
• 210000001218 blood-brain barrier Anatomy 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 230000005587 bubbling Effects 0.000 description 2
• 239000004202 carbamide Substances 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 230000001413 cellular effect Effects 0.000 description 2
• 235000010980 cellulose Nutrition 0.000 description 2
• 229920002678 cellulose Polymers 0.000 description 2
• 239000001913 cellulose Substances 0.000 description 2
• 230000002490 cerebral effect Effects 0.000 description 2
• 239000003795 chemical substances by application Substances 0.000 description 2
• 125000001309 chloro group Chemical group Cl* 0.000 description 2
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 2
• 239000004927 clay Substances 0.000 description 2
• 238000004040 coloring Methods 0.000 description 2
• 239000012230 colorless oil Substances 0.000 description 2
• 230000027326 copulation Effects 0.000 description 2
• 230000034994 death Effects 0.000 description 2
• 230000003111 delayed effect Effects 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 238000003745 diagnosis Methods 0.000 description 2
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 239000008387 emulsifying waxe Substances 0.000 description 2
• 239000012055 enteric layer Substances 0.000 description 2
• WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 2
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 208000015756 familial Alzheimer disease Diseases 0.000 description 2
• 239000012634 fragment Substances 0.000 description 2
• 125000002541 furyl group Chemical group 0.000 description 2
• 125000005456 glyceride group Chemical group 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 125000005553 heteroaryloxy group Chemical group 0.000 description 2
• 125000005844 heterocyclyloxy group Chemical group 0.000 description 2
• 150000003840 hydrochlorides Chemical class 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 238000001802 infusion Methods 0.000 description 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
• 150000002576 ketones Chemical class 0.000 description 2
• 150000002632 lipids Chemical class 0.000 description 2
• 239000002502 liposome Substances 0.000 description 2
• 229940057995 liquid paraffin Drugs 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• 229960004452 methionine Drugs 0.000 description 2
• FMXYCZVOMYLMKM-LURJTMIESA-N methyl (2s)-2-hydroxy-2-methylbutanoate Chemical compound CC[C@](C)(O)C(=O)OC FMXYCZVOMYLMKM-LURJTMIESA-N 0.000 description 2
• SZJUWKPNWWCOPG-UHFFFAOYSA-N methyl 2-anilinoacetate Chemical compound COC(=O)CNC1=CC=CC=C1 SZJUWKPNWWCOPG-UHFFFAOYSA-N 0.000 description 2
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• TYRGLVWXHJRKMT-QMMMGPOBSA-N n-benzyloxycarbonyl-l-serine-betalactone Chemical compound OC(=O)[C@H](C)NC(=O)OCC1=CC=CC=C1 TYRGLVWXHJRKMT-QMMMGPOBSA-N 0.000 description 2
• 125000001624 naphthyl group Chemical group 0.000 description 2
• 210000002682 neurofibrillary tangle Anatomy 0.000 description 2
• 239000012074 organic phase Substances 0.000 description 2
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
• 239000012188 paraffin wax Substances 0.000 description 2
• 230000008506 pathogenesis Effects 0.000 description 2
• 239000008177 pharmaceutical agent Substances 0.000 description 2
• 229940124531 pharmaceutical excipient Drugs 0.000 description 2
• RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 description 2
• 239000002798 polar solvent Substances 0.000 description 2
• 238000001556 precipitation Methods 0.000 description 2
• ASUAYTHWZCLXAN-UHFFFAOYSA-N prenol Chemical compound CC(C)=CCO ASUAYTHWZCLXAN-UHFFFAOYSA-N 0.000 description 2
• 230000002265 prevention Effects 0.000 description 2
• 102000004196 processed proteins & peptides Human genes 0.000 description 2
• 230000000750 progressive effect Effects 0.000 description 2
• 230000000069 prophylactic effect Effects 0.000 description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
• 239000000523 sample Substances 0.000 description 2
• 235000003441 saturated fatty acids Nutrition 0.000 description 2
• 150000004671 saturated fatty acids Chemical class 0.000 description 2
• 210000002966 serum Anatomy 0.000 description 2
• WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
• 239000004299 sodium benzoate Substances 0.000 description 2
• 235000010234 sodium benzoate Nutrition 0.000 description 2
• 235000017557 sodium bicarbonate Nutrition 0.000 description 2
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 239000008247 solid mixture Substances 0.000 description 2
• 239000008223 sterile water Substances 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 238000002560 therapeutic procedure Methods 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• 229930192474 thiophene Natural products 0.000 description 2
• VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 2
• 229960004295 valine Drugs 0.000 description 2
• 235000012431 wafers Nutrition 0.000 description 2
• 238000005303 weighing Methods 0.000 description 2
• 239000000230 xanthan gum Substances 0.000 description 2
• 235000010493 xanthan gum Nutrition 0.000 description 2
• 229920001285 xanthan gum Polymers 0.000 description 2
• 229940082509 xanthan gum Drugs 0.000 description 2
• PIZQWRXTMGASCZ-UHFFFAOYSA-N (1-methylcyclopropyl)methanol Chemical compound OCC1(C)CC1 PIZQWRXTMGASCZ-UHFFFAOYSA-N 0.000 description 1
• BGNBFPSUOYHHGT-NSHDSACASA-N (1-methylcyclopropyl)methyl (2s)-2-[[2-(3-chlorophenyl)acetyl]amino]propanoate Chemical compound N([C@@H](C)C(=O)OCC1(C)CC1)C(=O)CC1=CC=CC(Cl)=C1 BGNBFPSUOYHHGT-NSHDSACASA-N 0.000 description 1
• YNUZCFGSDYYNNN-AVERBVTBSA-N (2-methylcyclopentyl) (2s)-2-[[2-(3-chlorophenyl)acetyl]amino]propanoate Chemical compound N([C@@H](C)C(=O)OC1C(CCC1)C)C(=O)CC1=CC=CC(Cl)=C1 YNUZCFGSDYYNNN-AVERBVTBSA-N 0.000 description 1
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
• YPSZFFSPFRTNFJ-LURJTMIESA-N (2s)-2-[(2-thiophen-3-ylacetyl)amino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)CC=1C=CSC=1 YPSZFFSPFRTNFJ-LURJTMIESA-N 0.000 description 1
• KRDGDFDPKITWSD-QMMMGPOBSA-N (2s)-2-[[2-(1-benzothiophen-3-yl)acetyl]amino]propanoic acid Chemical compound C1=CC=C2C(CC(=O)N[C@@H](C)C(O)=O)=CSC2=C1 KRDGDFDPKITWSD-QMMMGPOBSA-N 0.000 description 1
• CYMCGPJNAGVWQE-NSHDSACASA-N (2s)-2-[[2-(2-phenyl-1,3-benzoxazol-5-yl)acetyl]amino]propanoic acid Chemical compound N=1C2=CC(CC(=O)N[C@@H](C)C(O)=O)=CC=C2OC=1C1=CC=CC=C1 CYMCGPJNAGVWQE-NSHDSACASA-N 0.000 description 1
• KAJQJVBKNOIJEZ-JTQLQIEISA-N (2s)-2-[[2-(2-phenylsulfanylthiophen-3-yl)acetyl]amino]propanoic acid Chemical compound C1=CSC(SC=2C=CC=CC=2)=C1CC(=O)N[C@@H](C)C(O)=O KAJQJVBKNOIJEZ-JTQLQIEISA-N 0.000 description 1
• WMFFVAZKIWXNQV-LURJTMIESA-N (2s)-2-[[2-(3,5-difluorophenyl)acetyl]amino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)CC1=CC(F)=CC(F)=C1 WMFFVAZKIWXNQV-LURJTMIESA-N 0.000 description 1
• ZDLVTLONHJDXEV-LURJTMIESA-N (2s)-2-[[2-(3-methyl-1,2-oxazol-5-yl)acetyl]amino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)CC1=CC(C)=NO1 ZDLVTLONHJDXEV-LURJTMIESA-N 0.000 description 1
• CNHMYYYNNKWRNF-VIFPVBQESA-N (2s)-2-[[2-(3-methylphenyl)acetyl]amino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)CC1=CC=CC(C)=C1 CNHMYYYNNKWRNF-VIFPVBQESA-N 0.000 description 1
• ASXIRJZZEJHXTM-QMMMGPOBSA-N (2s)-2-[[2-(3-methylsulfanylphenyl)acetyl]amino]propanoic acid Chemical compound CSC1=CC=CC(CC(=O)N[C@@H](C)C(O)=O)=C1 ASXIRJZZEJHXTM-QMMMGPOBSA-N 0.000 description 1
• JVIDELROSQWNKB-YFKPBYRVSA-N (2s)-2-[[2-(5-chlorothiophen-2-yl)acetyl]amino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)CC1=CC=C(Cl)S1 JVIDELROSQWNKB-YFKPBYRVSA-N 0.000 description 1
• MBIQENSCDNJOIY-YFKPBYRVSA-N (2s)-2-hydroxy-2-methylbutanoic acid Chemical compound CC[C@](C)(O)C(O)=O MBIQENSCDNJOIY-YFKPBYRVSA-N 0.000 description 1
• FJGOZOLLBLTSIJ-LBPRGKRZSA-N (2s)-3-methyl-2-[(2-phenylacetyl)amino]butanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)CC1=CC=CC=C1 FJGOZOLLBLTSIJ-LBPRGKRZSA-N 0.000 description 1
• IZQISDWUSBXSGT-LBPRGKRZSA-N (2s)-4-methyl-2-[(2-phenylacetyl)amino]pentanoic acid Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CC1=CC=CC=C1 IZQISDWUSBXSGT-LBPRGKRZSA-N 0.000 description 1
• OZQCZEAFOVHVSC-NSHDSACASA-N (2s)-4-methylsulfanyl-2-[(2-phenylacetyl)amino]butanoic acid Chemical compound CSCC[C@@H](C(O)=O)NC(=O)CC1=CC=CC=C1 OZQCZEAFOVHVSC-NSHDSACASA-N 0.000 description 1
• VSNNLLQKDRCKCB-UHFFFAOYSA-N (3,5-dichlorophenyl)methanol Chemical compound OCC1=CC(Cl)=CC(Cl)=C1 VSNNLLQKDRCKCB-UHFFFAOYSA-N 0.000 description 1
• DRJNZSRYIPTBQU-UHFFFAOYSA-N (3,5-dichlorophenyl)methyl methanesulfonate Chemical compound CS(=O)(=O)OCC1=CC(Cl)=CC(Cl)=C1 DRJNZSRYIPTBQU-UHFFFAOYSA-N 0.000 description 1
• IGIDLTISMCAULB-YFKPBYRVSA-N (3s)-3-methylpentanoic acid Chemical compound CC[C@H](C)CC(O)=O IGIDLTISMCAULB-YFKPBYRVSA-N 0.000 description 1
• YBADLXQNJCMBKR-UHFFFAOYSA-N (4-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C([N+]([O-])=O)C=C1 YBADLXQNJCMBKR-UHFFFAOYSA-N 0.000 description 1
• 230000006269 (delayed) early viral mRNA transcription Effects 0.000 description 1
• CHRJZRDFSQHIFI-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;styrene Chemical class C=CC1=CC=CC=C1.C=CC1=CC=CC=C1C=C CHRJZRDFSQHIFI-UHFFFAOYSA-N 0.000 description 1
• OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
• ILYVXUGGBVATGA-UHFFFAOYSA-N 1-carboxyethylazanium;chloride Chemical compound Cl.CC(N)C(O)=O ILYVXUGGBVATGA-UHFFFAOYSA-N 0.000 description 1
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
• SSPYAVLRIVLKGK-UHFFFAOYSA-N 1-ethyl-3-(3-pyrrolidin-1-ylpropyl)urea Chemical compound CCNC(=O)NCCCN1CCCC1 SSPYAVLRIVLKGK-UHFFFAOYSA-N 0.000 description 1
• 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 description 1
• PRPINYUDVPFIRX-UHFFFAOYSA-N 1-naphthaleneacetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CC=CC2=C1 PRPINYUDVPFIRX-UHFFFAOYSA-N 0.000 description 1
• 239000005971 1-naphthylacetic acid Substances 0.000 description 1
• WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
• TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
• VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
• ODVLMCWNGKLROU-UHFFFAOYSA-N 2-(1,3-benzodioxol-5-yl)acetic acid Chemical compound OC(=O)CC1=CC=C2OCOC2=C1 ODVLMCWNGKLROU-UHFFFAOYSA-N 0.000 description 1
• ZYIXXVCNAOYWQA-UHFFFAOYSA-N 2-(1-benzofuran-2-yl)acetic acid Chemical compound C1=CC=C2OC(CC(=O)O)=CC2=C1 ZYIXXVCNAOYWQA-UHFFFAOYSA-N 0.000 description 1
• GXMWLJKTGBZMBH-UHFFFAOYSA-N 2-(2,4-dichlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(Cl)C=C1Cl GXMWLJKTGBZMBH-UHFFFAOYSA-N 0.000 description 1
• RPTRFSADOICSSK-UHFFFAOYSA-N 2-(2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1F RPTRFSADOICSSK-UHFFFAOYSA-N 0.000 description 1
• RZWGTXHSYZGXKF-UHFFFAOYSA-N 2-(2-methylphenyl)acetic acid Chemical compound CC1=CC=CC=C1CC(O)=O RZWGTXHSYZGXKF-UHFFFAOYSA-N 0.000 description 1
• YNCGENOZYCNMNL-UHFFFAOYSA-N 2-(2-phenylsulfanylthiophen-3-yl)acetic acid Chemical compound C1=CSC(SC=2C=CC=CC=2)=C1CC(=O)O YNCGENOZYCNMNL-UHFFFAOYSA-N 0.000 description 1
• DLAKEJZPXICNSC-UHFFFAOYSA-N 2-(3,5-dichlorophenyl)acetonitrile Chemical compound ClC1=CC(Cl)=CC(CC#N)=C1 DLAKEJZPXICNSC-UHFFFAOYSA-N 0.000 description 1
• KYNNBXCGXUOREX-UHFFFAOYSA-N 2-(3-bromophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1 KYNNBXCGXUOREX-UHFFFAOYSA-N 0.000 description 1
• YEAUYVGUXSZCFI-UHFFFAOYSA-N 2-(3-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(F)=C1 YEAUYVGUXSZCFI-UHFFFAOYSA-N 0.000 description 1
• AKYCOAMUNLESIH-UHFFFAOYSA-N 2-(3-methylsulfanylphenyl)acetic acid Chemical compound CSC1=CC=CC(CC(O)=O)=C1 AKYCOAMUNLESIH-UHFFFAOYSA-N 0.000 description 1
• OCKTUFNDRKUHQG-UHFFFAOYSA-N 2-(3-phenyl-1,2,4-thiadiazol-5-yl)acetic acid Chemical compound S1C(CC(=O)O)=NC(C=2C=CC=CC=2)=N1 OCKTUFNDRKUHQG-UHFFFAOYSA-N 0.000 description 1
• MGKPFALCNDRSQD-UHFFFAOYSA-N 2-(4-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(F)C=C1 MGKPFALCNDRSQD-UHFFFAOYSA-N 0.000 description 1
• SLLKFGIERSPJDF-NSHDSACASA-N 2-(dimethylamino)ethyl (2s)-2-[[2-(3-chlorophenyl)acetyl]amino]propanoate Chemical compound CN(C)CCOC(=O)[C@H](C)NC(=O)CC1=CC=CC(Cl)=C1 SLLKFGIERSPJDF-NSHDSACASA-N 0.000 description 1
• DYABLFHJCQDJHY-UHFFFAOYSA-N 2-[(2-phenylacetyl)amino]butanoic acid Chemical compound CCC(C(O)=O)NC(=O)CC1=CC=CC=C1 DYABLFHJCQDJHY-UHFFFAOYSA-N 0.000 description 1
• MMDZDDQUUGTMBH-UHFFFAOYSA-N 2-[(2-pyridin-4-ylacetyl)amino]propanoic acid Chemical compound OC(=O)C(C)NC(=O)CC1=CC=NC=C1 MMDZDDQUUGTMBH-UHFFFAOYSA-N 0.000 description 1
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
• BLXXCCIBGGBDHI-UHFFFAOYSA-N 2-[3-(trifluoromethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(C(F)(F)F)=C1 BLXXCCIBGGBDHI-UHFFFAOYSA-N 0.000 description 1
• STFCPPGBSRDFOV-UHFFFAOYSA-N 2-[[2-(1,3-benzodioxol-5-yl)acetyl]amino]butanoic acid Chemical compound CCC(C(O)=O)NC(=O)CC1=CC=C2OCOC2=C1 STFCPPGBSRDFOV-UHFFFAOYSA-N 0.000 description 1
• MWYKYPSXTVKJAC-UHFFFAOYSA-N 2-amino-2-phenylethanethioamide Chemical compound NC(=S)C(N)C1=CC=CC=C1 MWYKYPSXTVKJAC-UHFFFAOYSA-N 0.000 description 1
• NAFOOGOADMAIJN-UHFFFAOYSA-N 2-anilino-2-phenylacetamide Chemical compound C=1C=CC=CC=1C(C(=O)N)NC1=CC=CC=C1 NAFOOGOADMAIJN-UHFFFAOYSA-N 0.000 description 1
• LVYBCZIDQKJNFP-UHFFFAOYSA-N 2-azaniumyl-2-(3-fluorophenyl)acetate Chemical compound OC(=O)C(N)C1=CC=CC(F)=C1 LVYBCZIDQKJNFP-UHFFFAOYSA-N 0.000 description 1
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
• DDKIJQTWQVUWBB-JRZJBTRGSA-N 2-methylbutyl (2s)-3-methyl-2-[(2-phenylacetyl)amino]butanoate Chemical compound CCC(C)COC(=O)[C@H](C(C)C)NC(=O)CC1=CC=CC=C1 DDKIJQTWQVUWBB-JRZJBTRGSA-N 0.000 description 1
• BVIJQMCYYASIFP-UHFFFAOYSA-N 2-methylcyclopentan-1-ol Chemical compound CC1CCCC1O BVIJQMCYYASIFP-UHFFFAOYSA-N 0.000 description 1
• BYDRTKVGBRTTIT-UHFFFAOYSA-N 2-methylprop-2-en-1-ol Chemical compound CC(=C)CO BYDRTKVGBRTTIT-UHFFFAOYSA-N 0.000 description 1
• IDIOKKYWBKOMTP-NSHDSACASA-N 2-methylprop-2-enyl (2s)-2-[[2-(3-chlorophenyl)acetyl]amino]propanoate Chemical compound CC(=C)COC(=O)[C@H](C)NC(=O)CC1=CC=CC(Cl)=C1 IDIOKKYWBKOMTP-NSHDSACASA-N 0.000 description 1
• UAEKKSFGISKLAI-NSHDSACASA-N 2-methylpropyl (2s)-2-[[2-(3-chlorophenyl)acetyl]amino]propanoate Chemical compound CC(C)COC(=O)[C@H](C)NC(=O)CC1=CC=CC(Cl)=C1 UAEKKSFGISKLAI-NSHDSACASA-N 0.000 description 1
• FIEXGJWSRIGUIT-LBPRGKRZSA-N 2-methylpropyl (2s)-2-[[2-(6-methoxy-1-benzothiophen-2-yl)acetyl]amino]propanoate Chemical compound COC1=CC=C2C=C(CC(=O)N[C@@H](C)C(=O)OCC(C)C)SC2=C1 FIEXGJWSRIGUIT-LBPRGKRZSA-N 0.000 description 1
• VKWJVDWDHYLKLT-HNNXBMFYSA-N 2-methylpropyl (2s)-4-methylsulfanyl-2-[(2-phenylacetyl)amino]butanoate Chemical compound CC(C)COC(=O)[C@H](CCSC)NC(=O)CC1=CC=CC=C1 VKWJVDWDHYLKLT-HNNXBMFYSA-N 0.000 description 1
• QASLNYVQMCHYCP-UHFFFAOYSA-N 2-methylpropyl 2-(3-phenylpropanoylamino)propanoate Chemical compound CC(C)COC(=O)C(C)NC(=O)CCC1=CC=CC=C1 QASLNYVQMCHYCP-UHFFFAOYSA-N 0.000 description 1
• ACPQDDKNGOZQMS-UHFFFAOYSA-N 2-methylpropyl 2-[(2-naphthalen-2-ylacetyl)amino]butanoate Chemical compound C1=CC=CC2=CC(CC(=O)NC(CC)C(=O)OCC(C)C)=CC=C21 ACPQDDKNGOZQMS-UHFFFAOYSA-N 0.000 description 1
• CUDANYUEYKDDQF-UHFFFAOYSA-N 2-methylpropyl 2-[(2-phenylacetyl)amino]propanoate Chemical compound CC(C)COC(=O)C(C)NC(=O)CC1=CC=CC=C1 CUDANYUEYKDDQF-UHFFFAOYSA-N 0.000 description 1
• KLILUCHUHLBFEY-UHFFFAOYSA-N 2-methylpropyl 2-[(2-pyridin-3-ylacetyl)amino]propanoate Chemical compound CC(C)COC(=O)C(C)NC(=O)CC1=CC=CN=C1 KLILUCHUHLBFEY-UHFFFAOYSA-N 0.000 description 1
• WPYAHBSWYADUCX-UHFFFAOYSA-N 2-methylpropyl 2-[(2-thiophen-2-ylacetyl)amino]butanoate Chemical compound CC(C)COC(=O)C(CC)NC(=O)CC1=CC=CS1 WPYAHBSWYADUCX-UHFFFAOYSA-N 0.000 description 1
• RGQFGCHFLWHYSQ-UHFFFAOYSA-N 2-methylpropyl 2-[(2-thiophen-3-ylacetyl)amino]butanoate Chemical compound CC(C)COC(=O)C(CC)NC(=O)CC=1C=CSC=1 RGQFGCHFLWHYSQ-UHFFFAOYSA-N 0.000 description 1
• HZECIJPGVRYECE-UHFFFAOYSA-N 2-methylpropyl 2-[[2-(1,3-benzothiazol-4-yl)acetyl]amino]butanoate Chemical compound CC(C)COC(=O)C(CC)NC(=O)CC1=CC=CC2=C1N=CS2 HZECIJPGVRYECE-UHFFFAOYSA-N 0.000 description 1
• NRCBTRJGWXTRLX-UHFFFAOYSA-N 2-methylpropyl 2-[[2-(2,4-dichlorophenyl)acetyl]amino]butanoate Chemical compound CC(C)COC(=O)C(CC)NC(=O)CC1=CC=C(Cl)C=C1Cl NRCBTRJGWXTRLX-UHFFFAOYSA-N 0.000 description 1
• AHNHBQYMZKEFBD-UHFFFAOYSA-N 2-methylpropyl 2-[[2-(2-fluorophenyl)acetyl]amino]butanoate Chemical compound CC(C)COC(=O)C(CC)NC(=O)CC1=CC=CC=C1F AHNHBQYMZKEFBD-UHFFFAOYSA-N 0.000 description 1
• CFAQQODWPRECPA-UHFFFAOYSA-N 2-methylpropyl 2-[[2-(2-hydroxyphenyl)acetyl]amino]butanoate Chemical compound CC(C)COC(=O)C(CC)NC(=O)CC1=CC=CC=C1O CFAQQODWPRECPA-UHFFFAOYSA-N 0.000 description 1
• ZYYSYAIOLAGLEE-UHFFFAOYSA-N 2-methylpropyl 2-[[2-(2-methylphenyl)acetyl]amino]butanoate Chemical compound CC(C)COC(=O)C(CC)NC(=O)CC1=CC=CC=C1C ZYYSYAIOLAGLEE-UHFFFAOYSA-N 0.000 description 1
• VFWAEBVDFGJTLO-UHFFFAOYSA-N 2-methylpropyl 2-[[2-(3,4-dichlorophenyl)acetyl]amino]butanoate Chemical compound CC(C)COC(=O)C(CC)NC(=O)CC1=CC=C(Cl)C(Cl)=C1 VFWAEBVDFGJTLO-UHFFFAOYSA-N 0.000 description 1
• CEPVRVBBPBTNOJ-UHFFFAOYSA-N 2-methylpropyl 2-[[2-(3-bromophenyl)acetyl]amino]butanoate Chemical compound CC(C)COC(=O)C(CC)NC(=O)CC1=CC=CC(Br)=C1 CEPVRVBBPBTNOJ-UHFFFAOYSA-N 0.000 description 1
• UIMVUXCMLJRFRH-UHFFFAOYSA-N 2-methylpropyl 2-[[2-(3-chlorophenyl)acetyl]amino]butanoate Chemical compound CC(C)COC(=O)C(CC)NC(=O)CC1=CC=CC(Cl)=C1 UIMVUXCMLJRFRH-UHFFFAOYSA-N 0.000 description 1
• KYFHMTYCWSIXTP-UHFFFAOYSA-N 2-methylpropyl 2-[[2-(3-fluorophenyl)acetyl]amino]butanoate Chemical compound CC(C)COC(=O)C(CC)NC(=O)CC1=CC=CC(F)=C1 KYFHMTYCWSIXTP-UHFFFAOYSA-N 0.000 description 1
• FYAPUXCJEHMUGJ-UHFFFAOYSA-N 2-methylpropyl 2-[[2-(3-methoxyphenyl)acetyl]amino]butanoate Chemical compound CC(C)COC(=O)C(CC)NC(=O)CC1=CC=CC(OC)=C1 FYAPUXCJEHMUGJ-UHFFFAOYSA-N 0.000 description 1
• JOEQDENOYSEMGC-UHFFFAOYSA-N 2-methylpropyl 2-[[2-(3-nitrophenyl)acetyl]amino]butanoate Chemical compound CC(C)COC(=O)C(CC)NC(=O)CC1=CC=CC([N+]([O-])=O)=C1 JOEQDENOYSEMGC-UHFFFAOYSA-N 0.000 description 1
• NIBCSKRKSFKFNQ-UHFFFAOYSA-N 2-methylpropyl 2-[[2-(4-bromophenyl)acetyl]amino]butanoate Chemical compound CC(C)COC(=O)C(CC)NC(=O)CC1=CC=C(Br)C=C1 NIBCSKRKSFKFNQ-UHFFFAOYSA-N 0.000 description 1
• LRJMZBXDYTVYKQ-UHFFFAOYSA-N 2-methylpropyl 2-[[2-(4-chlorophenyl)acetyl]amino]butanoate Chemical compound CC(C)COC(=O)C(CC)NC(=O)CC1=CC=C(Cl)C=C1 LRJMZBXDYTVYKQ-UHFFFAOYSA-N 0.000 description 1
• ODIOLRMVIVODIU-UHFFFAOYSA-N 2-methylpropyl 2-[[2-(4-fluorophenyl)acetyl]amino]butanoate Chemical compound CC(C)COC(=O)C(CC)NC(=O)CC1=CC=C(F)C=C1 ODIOLRMVIVODIU-UHFFFAOYSA-N 0.000 description 1
• FEUATKDJHZIKSU-UHFFFAOYSA-N 2-methylpropyl 2-[[2-(4-nitrophenyl)acetyl]amino]butanoate Chemical compound CC(C)COC(=O)C(CC)NC(=O)CC1=CC=C([N+]([O-])=O)C=C1 FEUATKDJHZIKSU-UHFFFAOYSA-N 0.000 description 1
• NQDYTZPNLPMWFL-UHFFFAOYSA-N 2-methylpropyl 2-[[2-[3-(trifluoromethyl)phenyl]acetyl]amino]butanoate Chemical compound CC(C)COC(=O)C(CC)NC(=O)CC1=CC=CC(C(F)(F)F)=C1 NQDYTZPNLPMWFL-UHFFFAOYSA-N 0.000 description 1
• VLRSADZEDXVUPG-UHFFFAOYSA-N 2-naphthalen-1-ylpyridine Chemical compound N1=CC=CC=C1C1=CC=CC2=CC=CC=C12 VLRSADZEDXVUPG-UHFFFAOYSA-N 0.000 description 1
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
• WKJRYVOTVRPAFN-UHFFFAOYSA-N 2-pyridin-1-ium-4-ylacetic acid;chloride Chemical compound Cl.OC(=O)CC1=CC=NC=C1 WKJRYVOTVRPAFN-UHFFFAOYSA-N 0.000 description 1
• SMJRBWINMFUUDS-UHFFFAOYSA-N 2-thienylacetic acid Chemical compound OC(=O)CC1=CC=CS1 SMJRBWINMFUUDS-UHFFFAOYSA-N 0.000 description 1
• VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
• LEGPZHPSIPPYIO-UHFFFAOYSA-N 3-Methoxyphenylacetic acid Chemical compound COC1=CC=CC(CC(O)=O)=C1 LEGPZHPSIPPYIO-UHFFFAOYSA-N 0.000 description 1
• BOWIFWCBNWWZOG-UHFFFAOYSA-N 3-Thiophenemethanol Chemical compound OCC=1C=CSC=1 BOWIFWCBNWWZOG-UHFFFAOYSA-N 0.000 description 1
• STNORAFOUMMCQW-LBPRGKRZSA-N 3-methylbut-2-enyl (2s)-2-[[2-(3-chlorophenyl)acetyl]amino]propanoate Chemical compound CC(C)=CCOC(=O)[C@H](C)NC(=O)CC1=CC=CC(Cl)=C1 STNORAFOUMMCQW-LBPRGKRZSA-N 0.000 description 1
• MFEILWXBDBCWKF-UHFFFAOYSA-N 3-phenylpropanoyl chloride Chemical compound ClC(=O)CCC1=CC=CC=C1 MFEILWXBDBCWKF-UHFFFAOYSA-N 0.000 description 1
• CBKDCOKSXCTDAA-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1-benzothiophene Chemical compound C1CCCC2=C1C=CS2 CBKDCOKSXCTDAA-UHFFFAOYSA-N 0.000 description 1
• OEBIVOHKFYSBPE-UHFFFAOYSA-N 4-Benzyloxybenzyl alcohol Chemical compound C1=CC(CO)=CC=C1OCC1=CC=CC=C1 OEBIVOHKFYSBPE-UHFFFAOYSA-N 0.000 description 1
• QOWSWEBLNVACCL-UHFFFAOYSA-N 4-Bromophenyl acetate Chemical compound OC(=O)CC1=CC=C(Br)C=C1 QOWSWEBLNVACCL-UHFFFAOYSA-N 0.000 description 1
• 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 1
• GDRVFDDBLLKWRI-UHFFFAOYSA-N 4H-quinolizine Chemical compound C1=CC=CN2CC=CC=C21 GDRVFDDBLLKWRI-UHFFFAOYSA-N 0.000 description 1
• BYHDDXPKOZIZRV-UHFFFAOYSA-N 5-phenylpentanoic acid Chemical compound OC(=O)CCCCC1=CC=CC=C1 BYHDDXPKOZIZRV-UHFFFAOYSA-N 0.000 description 1
• 208000018282 ACys amyloidosis Diseases 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• 208000000044 Amnesia Diseases 0.000 description 1
• 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 1
• BMNVSPMWMICFRV-DCAQKATOSA-N Arg-His-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(O)=O)C(O)=O)CC1=CN=CN1 BMNVSPMWMICFRV-DCAQKATOSA-N 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 208000014644 Brain disease Diseases 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
• 208000005145 Cerebral amyloid angiopathy Diseases 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 108020004705 Codon Proteins 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• 206010012289 Dementia Diseases 0.000 description 1
• BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
• YTIHIRCOUAPRCS-UHFFFAOYSA-N Dl-norleucinamide Chemical compound CCCCC(N)C(N)=O YTIHIRCOUAPRCS-UHFFFAOYSA-N 0.000 description 1
• 201000010374 Down Syndrome Diseases 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
• 239000005977 Ethylene Substances 0.000 description 1
• 208000007487 Familial Cerebral Amyloid Angiopathy Diseases 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 208000032849 Hereditary cerebral hemorrhage with amyloidosis Diseases 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
• NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 1
• 235000019766 L-Lysine Nutrition 0.000 description 1
• FFEARJCKVFRZRR-UHFFFAOYSA-N L-Methionine Natural products CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 1
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
• 229930195722 L-methionine Natural products 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
• 239000012448 Lithium borohydride Substances 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
• 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
• 206010027374 Mental impairment Diseases 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 235000009421 Myristica fragrans Nutrition 0.000 description 1
• UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
• 208000009668 Neurobehavioral Manifestations Diseases 0.000 description 1
• 238000010934 O-alkylation reaction Methods 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
• 241001417495 Serranidae Species 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 101000655609 Streptomyces azureus Thiostrepton Proteins 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 239000005864 Sulphur Chemical group 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
• VJMAITQRABEEKP-UHFFFAOYSA-N [6-(phenylmethoxymethyl)-1,4-dioxan-2-yl]methyl acetate Chemical compound O1C(COC(=O)C)COCC1COCC1=CC=CC=C1 VJMAITQRABEEKP-UHFFFAOYSA-N 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 150000008065 acid anhydrides Chemical class 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 125000005055 alkyl alkoxy group Chemical group 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• 150000001414 amino alcohols Chemical class 0.000 description 1
• 210000003484 anatomy Anatomy 0.000 description 1
• IGIDLTISMCAULB-UHFFFAOYSA-N anteisohexanoic acid Natural products CCC(C)CC(O)=O IGIDLTISMCAULB-UHFFFAOYSA-N 0.000 description 1
• 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
• 239000000010 aprotic solvent Substances 0.000 description 1
• 239000008365 aqueous carrier Substances 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 239000003125 aqueous solvent Substances 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 238000012925 biological evaluation Methods 0.000 description 1
• 239000003181 biological factor Substances 0.000 description 1
• 238000001574 biopsy Methods 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• LVTLACMYEGMHBZ-UHFFFAOYSA-N butyl 2-aminobutanoate Chemical compound CCCCOC(=O)C(N)CC LVTLACMYEGMHBZ-UHFFFAOYSA-N 0.000 description 1
• 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 235000001465 calcium Nutrition 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 239000000378 calcium silicate Substances 0.000 description 1
• 229910052918 calcium silicate Inorganic materials 0.000 description 1
• 229960003340 calcium silicate Drugs 0.000 description 1
• 235000012241 calcium silicate Nutrition 0.000 description 1
• OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 229920002301 cellulose acetate Polymers 0.000 description 1
• 210000004289 cerebral ventricle Anatomy 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
• 238000001311 chemical methods and process Methods 0.000 description 1
• 238000007385 chemical modification Methods 0.000 description 1
• WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 239000003240 coconut oil Substances 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• 230000019771 cognition Effects 0.000 description 1
• 230000003920 cognitive function Effects 0.000 description 1
• 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
• 239000000084 colloidal system Substances 0.000 description 1
• 229940125904 compound 1 Drugs 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 229920001577 copolymer Polymers 0.000 description 1
• 239000002285 corn oil Substances 0.000 description 1
• 235000005687 corn oil Nutrition 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 238000004132 cross linking Methods 0.000 description 1
• 125000006165 cyclic alkyl group Chemical group 0.000 description 1
• PQANGXXSEABURG-UHFFFAOYSA-N cyclohex-2-en-1-ol Chemical compound OC1CCCC=C1 PQANGXXSEABURG-UHFFFAOYSA-N 0.000 description 1
• BITYTUPGXQJSHE-SFVWDYPZSA-N cyclohex-2-en-1-yl (2s)-2-[[2-(3-chlorophenyl)acetyl]amino]propanoate Chemical compound N([C@@H](C)C(=O)OC1C=CCCC1)C(=O)CC1=CC=CC(Cl)=C1 BITYTUPGXQJSHE-SFVWDYPZSA-N 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• GUDMZGLFZNLYEY-UHFFFAOYSA-N cyclopropylmethanol Chemical compound OCC1CC1 GUDMZGLFZNLYEY-UHFFFAOYSA-N 0.000 description 1
• QGVPMDRYCDMTJY-JTQLQIEISA-N cyclopropylmethyl (2s)-2-[[2-(3-chlorophenyl)acetyl]amino]propanoate Chemical compound N([C@@H](C)C(=O)OCC1CC1)C(=O)CC1=CC=CC(Cl)=C1 QGVPMDRYCDMTJY-JTQLQIEISA-N 0.000 description 1
• 230000003412 degenerative effect Effects 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 125000004212 difluorophenyl group Chemical group 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 210000001198 duodenum Anatomy 0.000 description 1
• 239000008157 edible vegetable oil Substances 0.000 description 1
• 230000002996 emotional effect Effects 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• SHTNMBBMYCMXHH-QMMMGPOBSA-N ethyl (2s)-2-[[2-(3,5-difluorophenyl)acetyl]amino]propanoate Chemical compound CCOC(=O)[C@H](C)NC(=O)CC1=CC(F)=CC(F)=C1 SHTNMBBMYCMXHH-QMMMGPOBSA-N 0.000 description 1
• KPWCQEUBJAIORR-RGMNGODLSA-N ethyl (2s)-2-amino-4-methylsulfanylbutanoate;hydrochloride Chemical compound Cl.CCOC(=O)[C@@H](N)CCSC KPWCQEUBJAIORR-RGMNGODLSA-N 0.000 description 1
• ROBXZHNBBCHEIQ-BYPYZUCNSA-N ethyl (2s)-2-aminopropanoate Chemical compound CCOC(=O)[C@H](C)N ROBXZHNBBCHEIQ-BYPYZUCNSA-N 0.000 description 1
• IDRFUWBHMYLZSX-ZDUSSCGKSA-N ethyl (2s)-4-methylsulfanyl-2-[[2-(3-nitrophenyl)acetyl]amino]butanoate Chemical compound CCOC(=O)[C@H](CCSC)NC(=O)CC1=CC=CC([N+]([O-])=O)=C1 IDRFUWBHMYLZSX-ZDUSSCGKSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 239000004744 fabric Substances 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 238000003818 flash chromatography Methods 0.000 description 1
• 239000012054 flavored emulsion Substances 0.000 description 1
• 235000020375 flavoured syrup Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 229940014259 gelatin Drugs 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 238000010448 genetic screening Methods 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 108010028295 histidylhistidine Proteins 0.000 description 1
• 239000008240 homogeneous mixture Substances 0.000 description 1
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 239000000819 hypertonic solution Substances 0.000 description 1
• 229940021223 hypertonic solution Drugs 0.000 description 1
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
• 125000006302 indol-3-yl methyl group Chemical group [H]N1C([H])=C(C2=C([H])C([H])=C([H])C([H])=C12)C([H])([H])* 0.000 description 1
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
• HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 239000011261 inert gas Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 229910001410 inorganic ion Inorganic materials 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
• 125000006229 isopropoxyethyl group Chemical group [H]C([H])([H])C([H])(OC([H])([H])C([H])([H])*)C([H])([H])[H] 0.000 description 1
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
• 239000011344 liquid material Substances 0.000 description 1
• 231100000863 loss of memory Toxicity 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 239000001115 mace Substances 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 230000006386 memory function Effects 0.000 description 1
• 230000003340 mental effect Effects 0.000 description 1
• MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• DLCNTEDUKYKOIF-VIFPVBQESA-N methyl (2s)-2-[(2-phenylacetyl)amino]propanoate Chemical compound COC(=O)[C@H](C)NC(=O)CC1=CC=CC=C1 DLCNTEDUKYKOIF-VIFPVBQESA-N 0.000 description 1
• ZZWPOYPWQTUZDY-UHFFFAOYSA-N methyl 2-aminobutanoate Chemical compound CCC(N)C(=O)OC ZZWPOYPWQTUZDY-UHFFFAOYSA-N 0.000 description 1
• 229940095102 methyl benzoate Drugs 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
• 238000003801 milling Methods 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 210000002569 neuron Anatomy 0.000 description 1
• 150000002825 nitriles Chemical class 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 238000004806 packaging method and process Methods 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 235000010603 pastilles Nutrition 0.000 description 1
• 230000001717 pathogenic effect Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 238000010647 peptide synthesis reaction Methods 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 229950000688 phenothiazine Drugs 0.000 description 1
• 229950009215 phenylbutanoic acid Drugs 0.000 description 1
• LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
• XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
• 229920001184 polypeptide Polymers 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 150000003140 primary amides Chemical class 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
• 229960003415 propylparaben Drugs 0.000 description 1
• ZQZJKHIIQFPZCS-UHFFFAOYSA-N propylurea Chemical compound CCCNC(N)=O ZQZJKHIIQFPZCS-UHFFFAOYSA-N 0.000 description 1
• CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
• 230000005180 public health Effects 0.000 description 1
• 239000008213 purified water Substances 0.000 description 1
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 230000000241 respiratory effect Effects 0.000 description 1
• 230000029058 respiratory gaseous exchange Effects 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
• 238000005204 segregation Methods 0.000 description 1
• 239000012056 semi-solid material Substances 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 239000004208 shellac Substances 0.000 description 1
• ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
• 229940113147 shellac Drugs 0.000 description 1
• 235000013874 shellac Nutrition 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 239000011343 solid material Substances 0.000 description 1
• 239000011877 solvent mixture Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 235000010356 sorbitol Nutrition 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 239000012058 sterile packaged powder Substances 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 239000012258 stirred mixture Substances 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• IYDBQCZYZKQGCD-YWZLYKJASA-N tert-butyl (2s)-2-[[(2s)-2-[[2-(3,5-difluorophenyl)acetyl]amino]propanoyl]amino]-3-phenylpropanoate Chemical compound N([C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)OC(C)(C)C)C(=O)CC1=CC(F)=CC(F)=C1 IYDBQCZYZKQGCD-YWZLYKJASA-N 0.000 description 1
• SJMDMGHPMLKLHQ-UHFFFAOYSA-N tert-butyl 2-aminoacetate Chemical compound CC(C)(C)OC(=O)CN SJMDMGHPMLKLHQ-UHFFFAOYSA-N 0.000 description 1
• CLOXAWYNXXEWBT-UHFFFAOYSA-N tert-butyl n-(3-oxocyclopentyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(=O)C1 CLOXAWYNXXEWBT-UHFFFAOYSA-N 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 125000004001 thioalkyl group Chemical group 0.000 description 1
• 125000005296 thioaryloxy group Chemical group 0.000 description 1
• 125000005404 thioheteroaryloxy group Chemical group 0.000 description 1
• ZPHGMBGIFODUMF-UHFFFAOYSA-N thiophen-2-ylmethanol Chemical compound OCC1=CC=CS1 ZPHGMBGIFODUMF-UHFFFAOYSA-N 0.000 description 1
• ZKQMGZYLARVFFJ-NSHDSACASA-N thiophen-2-ylmethyl (2s)-2-[[2-(3-chlorophenyl)acetyl]amino]propanoate Chemical compound N([C@@H](C)C(=O)OCC=1SC=CC=1)C(=O)CC1=CC=CC(Cl)=C1 ZKQMGZYLARVFFJ-NSHDSACASA-N 0.000 description 1
• JEPPWCFIANJOGN-NSHDSACASA-N thiophen-3-ylmethyl (2s)-2-[[2-(3-chlorophenyl)acetyl]amino]propanoate Chemical compound N([C@@H](C)C(=O)OCC1=CSC=C1)C(=O)CC1=CC=CC(Cl)=C1 JEPPWCFIANJOGN-NSHDSACASA-N 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• 229940025703 topical product Drugs 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
• 230000037317 transdermal delivery Effects 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• 229960004799 tryptophan Drugs 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 239000003039 volatile agent Substances 0.000 description 1
• WAEXFXRVDQXREF-UHFFFAOYSA-N vorinostat Chemical compound ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1 WAEXFXRVDQXREF-UHFFFAOYSA-N 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1