NO328885B1 - Heterocykliske sulfonamidinhibitorer av <beta>-amyloidproduksjonen, farmasoytisk preparat omfattende en slik forbindelse samt anvendelse av forbindelsene - Google Patents

Heterocykliske sulfonamidinhibitorer av <beta>-amyloidproduksjonen, farmasoytisk preparat omfattende en slik forbindelse samt anvendelse av forbindelsene Download PDF

Info

Publication number: NO328885B1
Authority: NO; Norway
Prior art keywords: substituted; thiophene; sulfonamide; chloro; hydroxymethyl
Prior art date: 2000-12-13

Application number

NO20032645A

Other languages

English (en)

Norwegian (no)

Other versions

NO20032645D0 (no

NO20032645L (no

Inventor

Derek Cecil Cole

Anthony Frank Kreft

Kevin Roger Woller

Joseph Raymond Stock

George Diamanitis

Dennis Michael Kurbrak

Kristina Martha Kutterer

William Jay Moore

David Scott Casebier

Original Assignee

Wyeth Corp

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2000-12-13

Filing date

2003-06-11

Publication date

2010-06-07

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=22966854&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=NO328885(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2003-06-11 Application filed by Wyeth Corp filed Critical Wyeth Corp

2003-06-11 Publication of NO20032645D0 publication Critical patent/NO20032645D0/no

2003-08-05 Publication of NO20032645L publication Critical patent/NO20032645L/no

2010-06-07 Publication of NO328885B1 publication Critical patent/NO328885B1/no

Links

150000001875 compounds Chemical class 0.000 title claims description 145
-1 Heterocyclic sulfonamide Chemical class 0.000 title claims description 50
229940124530 sulfonamide Drugs 0.000 title claims description 28
238000004519 manufacturing process Methods 0.000 title claims description 16
239000003112 inhibitor Substances 0.000 title description 4
239000008194 pharmaceutical composition Substances 0.000 title description 3
239000000203 mixture Substances 0.000 claims description 68
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 67
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 65
229910052739 hydrogen Inorganic materials 0.000 claims description 57
239000001257 hydrogen Substances 0.000 claims description 57
125000000753 cycloalkyl group Chemical group 0.000 claims description 54
125000000217 alkyl group Chemical group 0.000 claims description 51
229910052736 halogen Inorganic materials 0.000 claims description 50
150000002367 halogens Chemical class 0.000 claims description 50
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 47
239000000460 chlorine Substances 0.000 claims description 39
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 38
125000003342 alkenyl group Chemical group 0.000 claims description 37
125000003545 alkoxy group Chemical group 0.000 claims description 37
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 34
150000002431 hydrogen Chemical class 0.000 claims description 32
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 31
125000005157 alkyl carboxy group Chemical group 0.000 claims description 31
125000004104 aryloxy group Chemical group 0.000 claims description 31
125000001424 substituent group Chemical group 0.000 claims description 31
125000003282 alkyl amino group Chemical group 0.000 claims description 30
125000005110 aryl thio group Chemical group 0.000 claims description 30
125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 27
125000000304 alkynyl group Chemical group 0.000 claims description 26
125000000623 heterocyclic group Chemical group 0.000 claims description 25
150000003839 salts Chemical class 0.000 claims description 25
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
125000003386 piperidinyl group Chemical group 0.000 claims description 22
229910052717 sulfur Inorganic materials 0.000 claims description 22
KTFDYVNEGTXQCV-UHFFFAOYSA-N 2-Thiophenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CS1 KTFDYVNEGTXQCV-UHFFFAOYSA-N 0.000 claims description 21
238000002360 preparation method Methods 0.000 claims description 21
YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 claims description 20
125000006546 (C4-C10) cycloalkyl group Chemical group 0.000 claims description 18
125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 18
125000006383 alkylpyridyl group Chemical group 0.000 claims description 18
102000013455 Amyloid beta-Peptides Human genes 0.000 claims description 16
108010090849 Amyloid beta-Peptides Proteins 0.000 claims description 16
150000003456 sulfonamides Chemical class 0.000 claims description 16
125000003118 aryl group Chemical group 0.000 claims description 14
229910052721 tungsten Inorganic materials 0.000 claims description 13
229910052727 yttrium Inorganic materials 0.000 claims description 12
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
229910052760 oxygen Inorganic materials 0.000 claims description 10
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 9
229910052799 carbon Inorganic materials 0.000 claims description 9
239000003814 drug Substances 0.000 claims description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
150000001408 amides Chemical class 0.000 claims description 8
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
PYZFRRVBPNGCBX-SECBINFHSA-N 5-chloro-n-[(2s)-3-ethyl-1-hydroxypentan-2-yl]thiophene-2-sulfonamide Chemical compound CCC(CC)[C@@H](CO)NS(=O)(=O)C1=CC=C(Cl)S1 PYZFRRVBPNGCBX-SECBINFHSA-N 0.000 claims description 7
201000010099 disease Diseases 0.000 claims description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
239000000825 pharmaceutical preparation Substances 0.000 claims description 7
208000024891 symptom Diseases 0.000 claims description 7
208000024827 Alzheimer disease Diseases 0.000 claims description 6
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 5
201000010374 Down Syndrome Diseases 0.000 claims description 5
241000124008 Mammalia Species 0.000 claims description 5
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 5
125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 5
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 5
UHTXHDAWEXOCFB-LBPRGKRZSA-N 5-chloro-n-[(3s)-4-ethyl-2-hydroxy-2-methylhexan-3-yl]thiophene-2-sulfonamide Chemical compound CCC(CC)[C@@H](C(C)(C)O)NS(=O)(=O)C1=CC=C(Cl)S1 UHTXHDAWEXOCFB-LBPRGKRZSA-N 0.000 claims description 4
206010059245 Angiopathy Diseases 0.000 claims description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
PQNFLJBBNBOBRQ-UHFFFAOYSA-N benzocyclopentane Natural products C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 claims description 4
POCXVQGGJZDTRT-JGVFFNPUSA-N n-[(2s,3s)-1-hydroxy-3-methylpentan-2-yl]-5-iodothiophene-2-sulfonamide Chemical compound CC[C@H](C)[C@@H](CO)NS(=O)(=O)C1=CC=C(I)S1 POCXVQGGJZDTRT-JGVFFNPUSA-N 0.000 claims description 4
RCBHAWYWAUYARP-DTWKUNHWSA-N n-[(2s,3s)-1-hydroxy-3-methylpentan-2-yl]thiophene-2-sulfonamide Chemical compound CC[C@H](C)[C@@H](CO)NS(=O)(=O)C1=CC=CS1 RCBHAWYWAUYARP-DTWKUNHWSA-N 0.000 claims description 4
ZHFHGAVSONLNBW-UHFFFAOYSA-N tert-butyl 4-[1-[(5-chlorothiophen-2-yl)sulfonylamino]-2-hydroxyethyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C(CO)NS(=O)(=O)C1=CC=C(Cl)S1 ZHFHGAVSONLNBW-UHFFFAOYSA-N 0.000 claims description 4
XUXLBEJQKUXLFM-UDNWOFFPSA-N 5-chloro-n-[(1s)-2-hydroxy-1-(4-hydroxycyclohexyl)ethyl]thiophene-2-sulfonamide Chemical compound N([C@H](CO)C1CCC(O)CC1)S(=O)(=O)C1=CC=C(Cl)S1 XUXLBEJQKUXLFM-UDNWOFFPSA-N 0.000 claims description 3
KZEXLAZBQDGQCH-JGVFFNPUSA-N 5-chloro-n-[(2s,3s)-1-hydroxy-3-methylpentan-2-yl]furan-2-sulfonamide Chemical compound CC[C@H](C)[C@@H](CO)NS(=O)(=O)C1=CC=C(Cl)O1 KZEXLAZBQDGQCH-JGVFFNPUSA-N 0.000 claims description 3
TYLJBILOXCVADC-LESKNEHBSA-N 5-chloro-n-[(3s)-4-ethyl-2-hydroxyhexan-3-yl]thiophene-2-sulfonamide Chemical compound CCC(CC)[C@@H](C(C)O)NS(=O)(=O)C1=CC=C(Cl)S1 TYLJBILOXCVADC-LESKNEHBSA-N 0.000 claims description 3
PSSFHAGVVXECJY-JGVFFNPUSA-N 5-fluoro-n-[(2s,3s)-1-hydroxy-3-methylpentan-2-yl]thiophene-2-sulfonamide Chemical compound CC[C@H](C)[C@@H](CO)NS(=O)(=O)C1=CC=C(F)S1 PSSFHAGVVXECJY-JGVFFNPUSA-N 0.000 claims description 3
206010035226 Plasma cell myeloma Diseases 0.000 claims description 3
206010044688 Trisomy 21 Diseases 0.000 claims description 3
235000010290 biphenyl Nutrition 0.000 claims description 3
229910052794 bromium Inorganic materials 0.000 claims description 3
229910052801 chlorine Inorganic materials 0.000 claims description 3
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 3
201000008319 inclusion body myositis Diseases 0.000 claims description 3
OWULTMKADNYVOH-CYBMUJFWSA-N n-[(2s)-3-butyl-1-hydroxyheptan-2-yl]-5-chlorothiophene-2-sulfonamide Chemical compound CCCCC(CCCC)[C@@H](CO)NS(=O)(=O)C1=CC=C(Cl)S1 OWULTMKADNYVOH-CYBMUJFWSA-N 0.000 claims description 3
UGQHSECHHKTCCT-SNVBAGLBSA-N n-[(2s)-3-ethyl-1-hydroxypentan-2-yl]thiophene-2-sulfonamide Chemical compound CCC(CC)[C@@H](CO)NS(=O)(=O)C1=CC=CS1 UGQHSECHHKTCCT-SNVBAGLBSA-N 0.000 claims description 3
YNOPTKUUKHAXAY-UHFFFAOYSA-N n-[1-acetyl-4-(hydroxymethyl)piperidin-4-yl]-5-chlorothiophene-2-sulfonamide Chemical compound C1CN(C(=O)C)CCC1(CO)NS(=O)(=O)C1=CC=C(Cl)S1 YNOPTKUUKHAXAY-UHFFFAOYSA-N 0.000 claims description 3
208000022256 primary systemic amyloidosis Diseases 0.000 claims description 3
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 claims description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
ZQXYOZCYBUFPMO-POYBYMJQSA-N 3-bromo-5-chloro-n-[(2s,3s)-1-hydroxy-3-methylpentan-2-yl]thiophene-2-sulfonamide Chemical compound CC[C@H](C)[C@@H](CO)NS(=O)(=O)C=1SC(Cl)=CC=1Br ZQXYOZCYBUFPMO-POYBYMJQSA-N 0.000 claims description 2
VUKDYEXVXMYVAS-SSDOTTSWSA-N 4,5-dibromo-n-[(2s)-1-hydroxy-3-methylbutan-2-yl]thiophene-2-sulfonamide Chemical compound CC(C)[C@@H](CO)NS(=O)(=O)C1=CC(Br)=C(Br)S1 VUKDYEXVXMYVAS-SSDOTTSWSA-N 0.000 claims description 2
QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 claims description 2
IHUODRLPJKZVMS-SNVBAGLBSA-N 5-bromo-n-[(2s)-1-hydroxy-2,3-dimethylbutan-2-yl]thiophene-2-sulfonamide Chemical compound CC(C)[C@@](C)(CO)NS(=O)(=O)C1=CC=C(Br)S1 IHUODRLPJKZVMS-SNVBAGLBSA-N 0.000 claims description 2
INXUZNRQQQNEAZ-JGVFFNPUSA-N 5-bromo-n-[(2s,3s)-1-hydroxy-3-methylpentan-2-yl]-1,1-dioxothiophene-2-sulfonamide Chemical compound CC[C@H](C)[C@@H](CO)NS(=O)(=O)C1=CC=C(Br)S1(=O)=O INXUZNRQQQNEAZ-JGVFFNPUSA-N 0.000 claims description 2
YRHLGWXITIJBKB-UHFFFAOYSA-N 5-chloro-n-(1-hydroxy-3,4-dimethylhexan-2-yl)thiophene-2-sulfonamide Chemical compound CCC(C)C(C)C(CO)NS(=O)(=O)C1=CC=C(Cl)S1 YRHLGWXITIJBKB-UHFFFAOYSA-N 0.000 claims description 2
POZTWQJOQPVQLW-VQXHTEKXSA-N 5-chloro-n-[(1s)-2-hydroxy-1-(4-methoxycyclohexyl)ethyl]thiophene-2-sulfonamide Chemical compound C1CC(OC)CCC1[C@@H](CO)NS(=O)(=O)C1=CC=C(Cl)S1 POZTWQJOQPVQLW-VQXHTEKXSA-N 0.000 claims description 2
NYBURASDOQSMRI-SNVBAGLBSA-N 5-chloro-n-[(1s)-2-hydroxy-1-phenylethyl]thiophene-2-sulfonamide Chemical compound N([C@H](CO)C=1C=CC=CC=1)S(=O)(=O)C1=CC=C(Cl)S1 NYBURASDOQSMRI-SNVBAGLBSA-N 0.000 claims description 2
MQTKLULUXAJSGA-SECBINFHSA-N 5-chloro-n-[(1s)-2-hydroxy-1-piperidin-4-ylethyl]thiophene-2-sulfonamide Chemical compound N([C@H](CO)C1CCNCC1)S(=O)(=O)C1=CC=C(Cl)S1 MQTKLULUXAJSGA-SECBINFHSA-N 0.000 claims description 2
WULCJHVHOLQJFH-XRZQKMBXSA-N 5-chloro-n-[(1s,2s,3s)-1-cyclohex-2-en-1-yl-1-hydroxy-3-methylpentan-2-yl]thiophene-2-sulfonamide Chemical compound N([C@@H]([C@@H](C)CC)[C@@H](O)C1C=CCCC1)S(=O)(=O)C1=CC=C(Cl)S1 WULCJHVHOLQJFH-XRZQKMBXSA-N 0.000 claims description 2
DDNSMXHHMRQPHY-BRFYHDHCSA-N 5-chloro-n-[(2s)-1-hydroxy-3-(methylamino)pentan-2-yl]thiophene-2-sulfonamide Chemical compound CCC(NC)[C@@H](CO)NS(=O)(=O)C1=CC=C(Cl)S1 DDNSMXHHMRQPHY-BRFYHDHCSA-N 0.000 claims description 2
GRJRMBINESMMLU-SSDOTTSWSA-N 5-chloro-n-[(2s)-1-hydroxy-3-methylbutan-2-yl]thiophene-2-sulfonamide Chemical compound CC(C)[C@@H](CO)NS(=O)(=O)C1=CC=C(Cl)S1 GRJRMBINESMMLU-SSDOTTSWSA-N 0.000 claims description 2
IDPXDQNYPHCBAF-NXEZZACHSA-N 5-chloro-n-[(2s,3r)-1-hydroxy-3,5-dimethylhexan-2-yl]thiophene-2-sulfonamide Chemical compound CC(C)C[C@@H](C)[C@@H](CO)NS(=O)(=O)C1=CC=C(Cl)S1 IDPXDQNYPHCBAF-NXEZZACHSA-N 0.000 claims description 2
FWIOQZCHIPNFCA-DYFXTIRLSA-N 5-chloro-n-[(3s,4s)-1,1,1-trifluoro-2-hydroxy-4-methylhexan-3-yl]thiophene-2-sulfonamide Chemical compound CC[C@H](C)[C@@H](C(O)C(F)(F)F)NS(=O)(=O)C1=CC=C(Cl)S1 FWIOQZCHIPNFCA-DYFXTIRLSA-N 0.000 claims description 2
LPGZIMFELOQYNO-KWQFWETISA-N 5-chloro-n-[(3s,4s)-2-hydroxy-2,4-dimethylhexan-3-yl]thiophene-2-sulfonamide Chemical compound CC[C@H](C)[C@@H](C(C)(C)O)NS(=O)(=O)C1=CC=C(Cl)S1 LPGZIMFELOQYNO-KWQFWETISA-N 0.000 claims description 2
FWLUJMNHKIQJEN-OIWJFHFHSA-N 5-chloro-n-[(3s,4s)-2-hydroxy-4-methylhexan-3-yl]thiophene-2-sulfonamide Chemical compound CC[C@H](C)[C@@H](C(C)O)NS(=O)(=O)C1=CC=C(Cl)S1 FWLUJMNHKIQJEN-OIWJFHFHSA-N 0.000 claims description 2
OEWVXEXPGHZSIH-UHFFFAOYSA-N 5-chloro-n-[1-(hydroxymethyl)cyclohexyl]thiophene-2-sulfonamide Chemical compound C=1C=C(Cl)SC=1S(=O)(=O)NC1(CO)CCCCC1 OEWVXEXPGHZSIH-UHFFFAOYSA-N 0.000 claims description 2
208000018282 ACys amyloidosis Diseases 0.000 claims description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
208000007487 Familial Cerebral Amyloid Angiopathy Diseases 0.000 claims description 2
208000032849 Hereditary cerebral hemorrhage with amyloidosis Diseases 0.000 claims description 2
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 2
239000004305 biphenyl Substances 0.000 claims description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 claims description 2
239000007924 injection Substances 0.000 claims description 2
238000002347 injection Methods 0.000 claims description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
HPZPADGGKJDQOJ-DTWKUNHWSA-N n-[(2s,3s)-1-hydroxy-3-methylpentan-2-yl]furan-2-sulfonamide Chemical compound CC[C@H](C)[C@@H](CO)NS(=O)(=O)C1=CC=CO1 HPZPADGGKJDQOJ-DTWKUNHWSA-N 0.000 claims description 2
RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 3
125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims 3
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 2
HXXDBMRNPGELPH-UONOGXRCSA-N 5-bromo-n-[(2s,3s)-1-hydroxy-5-methyl-3-pyridin-3-ylhexan-2-yl]thiophene-2-sulfonamide Chemical compound N([C@H](CO)[C@@H](CC(C)C)C=1C=NC=CC=1)S(=O)(=O)C1=CC=C(Br)S1 HXXDBMRNPGELPH-UONOGXRCSA-N 0.000 claims 2
AZJYSPORAIDBHM-LPHOPBHVSA-N 5-chloro-n-[(3s,4s)-5-hydroxy-3-methyl-5-pentyldecan-4-yl]thiophene-2-sulfonamide Chemical compound CCCCCC(O)(CCCCC)[C@H]([C@@H](C)CC)NS(=O)(=O)C1=CC=C(Cl)S1 AZJYSPORAIDBHM-LPHOPBHVSA-N 0.000 claims 2
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
FNKDACXETVAYFC-POYBYMJQSA-N 4,5-dichloro-n-[(2s,3s)-1-hydroxy-3-methylpentan-2-yl]thiophene-2-sulfonamide Chemical compound CC[C@H](C)[C@@H](CO)NS(=O)(=O)C1=CC(Cl)=C(Cl)S1 FNKDACXETVAYFC-POYBYMJQSA-N 0.000 claims 1
MUSLXNSOLPLLGI-POYBYMJQSA-N 4-bromo-5-chloro-n-[(2s,3s)-1-hydroxy-3-methylpentan-2-yl]thiophene-2-sulfonamide Chemical compound CC[C@H](C)[C@@H](CO)NS(=O)(=O)C1=CC(Br)=C(Cl)S1 MUSLXNSOLPLLGI-POYBYMJQSA-N 0.000 claims 1
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
LYLHEXBPEUNXGL-UHFFFAOYSA-N 5-bromo-n-(1-hydroxy-2-methylpropan-2-yl)thiophene-2-sulfonamide Chemical compound OCC(C)(C)NS(=O)(=O)C1=CC=C(Br)S1 LYLHEXBPEUNXGL-UHFFFAOYSA-N 0.000 claims 1
WPVMSVPITKWURL-UHFFFAOYSA-N 5-bromo-n-(1-hydroxy-3-phenylbutan-2-yl)thiophene-2-sulfonamide Chemical compound C=1C=CC=CC=1C(C)C(CO)NS(=O)(=O)C1=CC=C(Br)S1 WPVMSVPITKWURL-UHFFFAOYSA-N 0.000 claims 1
HNWXRICGXWBXPV-UHFFFAOYSA-N 5-bromo-n-(1-hydroxyhexan-2-yl)thiophene-2-sulfonamide Chemical compound CCCCC(CO)NS(=O)(=O)C1=CC=C(Br)S1 HNWXRICGXWBXPV-UHFFFAOYSA-N 0.000 claims 1
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FRQFFCZQECDATF-SNVBAGLBSA-N 5-bromo-n-[(1s)-1-cyclohexyl-2-hydroxyethyl]thiophene-2-sulfonamide Chemical compound N([C@H](CO)C1CCCCC1)S(=O)(=O)C1=CC=C(Br)S1 FRQFFCZQECDATF-SNVBAGLBSA-N 0.000 claims 1
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OEHVQBYYVSMBDW-RBUKOAKNSA-N 5-chloro-n-[(2s,3s)-1-hydroxy-3-(4-phenylphenyl)pentan-2-yl]thiophene-2-sulfonamide Chemical compound N([C@H](CO)[C@@H](CC)C=1C=CC(=CC=1)C=1C=CC=CC=1)S(=O)(=O)C1=CC=C(Cl)S1 OEHVQBYYVSMBDW-RBUKOAKNSA-N 0.000 claims 1
XOIGTUGAGLNCAT-WRONEBCDSA-N 5-chloro-n-[(2s,3s)-1-hydroxy-3-methyl-1,1-dinaphthalen-1-ylpentan-2-yl]thiophene-2-sulfonamide Chemical compound N([C@@H]([C@@H](C)CC)C(O)(C=1C2=CC=CC=C2C=CC=1)C=1C2=CC=CC=C2C=CC=1)S(=O)(=O)C1=CC=C(Cl)S1 XOIGTUGAGLNCAT-WRONEBCDSA-N 0.000 claims 1
ROWLINUWHWTBMK-KKSFZXQISA-N 5-chloro-n-[(2s,3s)-1-hydroxy-3-methyl-1,1-diphenylpentan-2-yl]thiophene-2-sulfonamide Chemical compound N([C@@H]([C@@H](C)CC)C(O)(C=1C=CC=CC=1)C=1C=CC=CC=1)S(=O)(=O)C1=CC=C(Cl)S1 ROWLINUWHWTBMK-KKSFZXQISA-N 0.000 claims 1
WPQZOEBYKOPPII-BBYUFZDTSA-N 5-chloro-n-[(2s,3s)-1-hydroxy-3-methyl-1-(4-methylsulfanylphenyl)pentan-2-yl]thiophene-2-sulfonamide Chemical compound N([C@@H]([C@@H](C)CC)C(O)C=1C=CC(SC)=CC=1)S(=O)(=O)C1=CC=C(Cl)S1 WPQZOEBYKOPPII-BBYUFZDTSA-N 0.000 claims 1
JMUDIKBUGNBIFY-QWHCGFSZSA-N 5-chloro-n-[(2s,3s)-3-ethyl-1-hydroxynonan-2-yl]thiophene-2-sulfonamide Chemical compound CCCCCC[C@H](CC)[C@@H](CO)NS(=O)(=O)C1=CC=C(Cl)S1 JMUDIKBUGNBIFY-QWHCGFSZSA-N 0.000 claims 1
JTPRWNLBJYRUJZ-NWDGAFQWSA-N 5-chloro-n-[(2s,3s)-3-ethyl-1-hydroxyoctan-2-yl]thiophene-2-sulfonamide Chemical compound CCCCC[C@H](CC)[C@@H](CO)NS(=O)(=O)C1=CC=C(Cl)S1 JTPRWNLBJYRUJZ-NWDGAFQWSA-N 0.000 claims 1
UGAXENCQXRLHTM-PEMBBPQUSA-N 5-chloro-n-[(3s,4s)-5-hydroxy-3,7-dimethyloct-6-en-4-yl]thiophene-2-sulfonamide Chemical compound CC(C)=CC(O)[C@H]([C@@H](C)CC)NS(=O)(=O)C1=CC=C(Cl)S1 UGAXENCQXRLHTM-PEMBBPQUSA-N 0.000 claims 1
MIYYKMNCTWGAMS-PEMBBPQUSA-N 5-chloro-n-[(3s,4s)-5-hydroxy-3,7-dimethyloctan-4-yl]thiophene-2-sulfonamide Chemical compound CC(C)CC(O)[C@H]([C@@H](C)CC)NS(=O)(=O)C1=CC=C(Cl)S1 MIYYKMNCTWGAMS-PEMBBPQUSA-N 0.000 claims 1
VWQYRBIGECTHGI-PEMBBPQUSA-N 5-chloro-n-[(3s,4s)-5-hydroxy-3-methylnon-8-en-4-yl]thiophene-2-sulfonamide Chemical compound C=CCCC(O)[C@H]([C@@H](C)CC)NS(=O)(=O)C1=CC=C(Cl)S1 VWQYRBIGECTHGI-PEMBBPQUSA-N 0.000 claims 1
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ARHQAERGQLFMNN-BSBHGOPBSA-N 5-chloro-n-[(3s,4s)-5-hydroxy-3-methylundecan-4-yl]thiophene-2-sulfonamide Chemical compound CCCCCCC(O)[C@H]([C@@H](C)CC)NS(=O)(=O)C1=CC=C(Cl)S1 ARHQAERGQLFMNN-BSBHGOPBSA-N 0.000 claims 1
YQDKZDISGNDQGI-WDMOLILDSA-N 5-chloro-n-[(3s,4s,5r)-5-hydroxy-3,7-dimethyloct-7-en-4-yl]thiophene-2-sulfonamide Chemical compound CC(=C)C[C@@H](O)[C@H]([C@@H](C)CC)NS(=O)(=O)C1=CC=C(Cl)S1 YQDKZDISGNDQGI-WDMOLILDSA-N 0.000 claims 1
RSCSJXKJQNRXIH-KWBADKCTSA-N 5-chloro-n-[(3s,4s,5s)-5-hydroxy-3-methyloct-7-en-4-yl]thiophene-2-sulfonamide Chemical compound C=CC[C@H](O)[C@H]([C@@H](C)CC)NS(=O)(=O)C1=CC=C(Cl)S1 RSCSJXKJQNRXIH-KWBADKCTSA-N 0.000 claims 1
UZDHAPLITIFSIJ-ASIDQLCPSA-N 5-chloro-n-[(4s,5s)-1-(1,3-dioxan-2-yl)-3-hydroxy-5-methylheptan-4-yl]thiophene-2-sulfonamide Chemical compound N([C@@H]([C@@H](C)CC)C(O)CCC1OCCCO1)S(=O)(=O)C1=CC=C(Cl)S1 UZDHAPLITIFSIJ-ASIDQLCPSA-N 0.000 claims 1
PSQLVORHEGJCMX-GWCFXTLKSA-N 5-chloro-n-[(4s,5s)-3-ethyl-3-hydroxy-5-methylheptan-4-yl]thiophene-2-sulfonamide Chemical compound CC[C@H](C)[C@@H](C(O)(CC)CC)NS(=O)(=O)C1=CC=C(Cl)S1 PSQLVORHEGJCMX-GWCFXTLKSA-N 0.000 claims 1
DCKQVBQLXOBLJE-PEJSQMDMSA-N 5-chloro-n-[(4s,5s)-3-hydroxy-2,2,5-trimethylheptan-4-yl]thiophene-2-sulfonamide Chemical compound CC[C@H](C)[C@@H](C(O)C(C)(C)C)NS(=O)(=O)C1=CC=C(Cl)S1 DCKQVBQLXOBLJE-PEJSQMDMSA-N 0.000 claims 1
IJHUOMASWRARBK-WFASDCNBSA-N 5-chloro-n-[(4s,5s)-3-hydroxy-2,5-dimethyl-3-prop-1-en-2-ylhept-1-en-4-yl]thiophene-2-sulfonamide Chemical compound CC[C@H](C)[C@@H](C(O)(C(C)=C)C(C)=C)NS(=O)(=O)C1=CC=C(Cl)S1 IJHUOMASWRARBK-WFASDCNBSA-N 0.000 claims 1
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VIKQZRJKTUCJGG-PEJSQMDMSA-N 5-chloro-n-[(4s,5s)-3-hydroxy-2,5-dimethylheptan-4-yl]thiophene-2-sulfonamide Chemical compound CC[C@H](C)[C@@H](C(O)C(C)C)NS(=O)(=O)C1=CC=C(Cl)S1 VIKQZRJKTUCJGG-PEJSQMDMSA-N 0.000 claims 1
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LRJWCFVEHKVMLR-WYLANPJESA-N 5-chloro-n-[(e,3s,4s,5r)-5-hydroxy-3-methyldec-7-en-4-yl]thiophene-2-sulfonamide Chemical compound CC\C=C\C[C@@H](O)[C@H]([C@@H](C)CC)NS(=O)(=O)C1=CC=C(Cl)S1 LRJWCFVEHKVMLR-WYLANPJESA-N 0.000 claims 1
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OKQXQJQRBVFCBN-UHFFFAOYSA-N 5-chloro-n-[1-(1-hydroxybut-3-enyl)cyclohexyl]thiophene-2-sulfonamide Chemical compound C=1C=C(Cl)SC=1S(=O)(=O)NC1(C(CC=C)O)CCCCC1 OKQXQJQRBVFCBN-UHFFFAOYSA-N 0.000 claims 1
NBQALJCGJIPOPL-UHFFFAOYSA-N 5-chloro-n-[1-(hydroxymethyl)cyclopentyl]thiophene-2-sulfonamide Chemical compound C=1C=C(Cl)SC=1S(=O)(=O)NC1(CO)CCCC1 NBQALJCGJIPOPL-UHFFFAOYSA-N 0.000 claims 1
MUNJAYQOFFTZTC-UHFFFAOYSA-N 5-chloro-n-[1-hydroxy-2-(hydroxymethyl)butan-2-yl]thiophene-2-sulfonamide Chemical compound CCC(CO)(CO)NS(=O)(=O)C1=CC=C(Cl)S1 MUNJAYQOFFTZTC-UHFFFAOYSA-N 0.000 claims 1
XXPWXVZHNMEPPN-UHFFFAOYSA-N 5-chloro-n-[2-hydroxy-1-(2,4,6-trimethylcyclohex-3-en-1-yl)ethyl]thiophene-2-sulfonamide Chemical compound CC1CC(C)=CC(C)C1C(CO)NS(=O)(=O)C1=CC=C(Cl)S1 XXPWXVZHNMEPPN-UHFFFAOYSA-N 0.000 claims 1
OZYSULACJSSYRJ-UHFFFAOYSA-N 5-chloro-n-[3-(hydroxymethyl)-3-bicyclo[2.2.1]heptanyl]thiophene-2-sulfonamide Chemical compound C1C(C2)CCC2C1(CO)NS(=O)(=O)C1=CC=C(Cl)S1 OZYSULACJSSYRJ-UHFFFAOYSA-N 0.000 claims 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 claims 1
IGQVCMWBRSQANJ-WXRRBKDZSA-N ethyl 2-[[4-[(1s)-1-[(5-chlorothiophen-2-yl)sulfonylamino]-2-hydroxyethyl]cyclohexyl]amino]acetate Chemical compound C1CC(NCC(=O)OCC)CCC1[C@@H](CO)NS(=O)(=O)C1=CC=C(Cl)S1 IGQVCMWBRSQANJ-WXRRBKDZSA-N 0.000 claims 1
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MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims 1
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VCVMFSYJIJKING-PSIKVXPXSA-N n-[(3s,4s)-5-hydroxy-3-methylnonan-4-yl]thiophene-2-sulfonamide Chemical compound CCCCC(O)[C@H]([C@@H](C)CC)NS(=O)(=O)C1=CC=CS1 VCVMFSYJIJKING-PSIKVXPXSA-N 0.000 claims 1
NKPYCDQGMGNPBC-BJEKPXQXSA-N n-[(3s,4s)-5-hydroxy-3-methyloct-6-yn-4-yl]thiophene-2-sulfonamide Chemical compound CC#CC(O)[C@H]([C@@H](C)CC)NS(=O)(=O)C1=CC=CS1 NKPYCDQGMGNPBC-BJEKPXQXSA-N 0.000 claims 1
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QUXHCILOWRXCEO-UHFFFAOYSA-M magnesium;butane;chloride Chemical compound [Mg+2].[Cl-].CCC[CH2-] QUXHCILOWRXCEO-UHFFFAOYSA-M 0.000 description 1
XWCQLLDGXBLGMD-UHFFFAOYSA-M magnesium;pentane;bromide Chemical compound [Mg+2].[Br-].CCCC[CH2-] XWCQLLDGXBLGMD-UHFFFAOYSA-M 0.000 description 1
UZNGRHDUJIVHQT-UHFFFAOYSA-M magnesium;prop-1-ene;bromide Chemical compound [Mg+2].[Br-].C[C-]=C UZNGRHDUJIVHQT-UHFFFAOYSA-M 0.000 description 1
QBNOPZJAURRQCE-UHFFFAOYSA-M magnesium;prop-1-yne;bromide Chemical compound [Mg+2].[Br-].CC#[C-] QBNOPZJAURRQCE-UHFFFAOYSA-M 0.000 description 1
210000004962 mammalian cell Anatomy 0.000 description 1
239000012528 membrane Substances 0.000 description 1
230000006984 memory degeneration Effects 0.000 description 1
208000023060 memory loss Diseases 0.000 description 1
LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
CBXQPDZONLCKHI-XVKPBYJWSA-N methyl (2S,3S)-2-[(5-bromothiophen-2-yl)sulfonylamino]-3-methylpentanoate Chemical compound CC[C@H](C)[C@@H](C(=O)OC)NS(=O)(=O)C1=CC=C(Br)S1 CBXQPDZONLCKHI-XVKPBYJWSA-N 0.000 description 1
ZKUUVVYMPUDTGJ-UHFFFAOYSA-N methyl 5-hydroxy-4-methoxy-2-nitrobenzoate Chemical compound COC(=O)C1=CC(O)=C(OC)C=C1[N+]([O-])=O ZKUUVVYMPUDTGJ-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
230000035772 mutation Effects 0.000 description 1
XZIQSXNIXKYUOQ-USOZLSCGSA-N n-[(2s)-3-ethyl-1-hydroxypentan-2-yl]-5-trimethylstannylthiophene-2-sulfonamide Chemical compound CCC(CC)[C@@H](CO)NS(=O)(=O)C1=CC=C([Sn](C)(C)C)S1 XZIQSXNIXKYUOQ-USOZLSCGSA-N 0.000 description 1
NULALPLXRDBVIS-XJGUQWRXSA-N n-[(2s,3s)-1-hydroxy-3-methylpentan-2-yl]-5-tributylstannylthiophene-2-sulfonamide Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=C(S(=O)(=O)N[C@H](CO)[C@@H](C)CC)S1 NULALPLXRDBVIS-XJGUQWRXSA-N 0.000 description 1
HKUWOFNOXSLJED-XJGUQWRXSA-N n-[(2s,3s)-1-hydroxy-3-methylpentan-2-yl]-5-trimethylstannylthiophene-2-sulfonamide Chemical compound CC[C@H](C)[C@@H](CO)NS(=O)(=O)C1=CC=C([Sn](C)(C)C)S1 HKUWOFNOXSLJED-XJGUQWRXSA-N 0.000 description 1
CPHCIYGRSFZNRD-UHFFFAOYSA-N n-methyl-1-(4,5,6,7-tetrahydro-1h-indazol-3-yl)methanamine Chemical compound C1CCCC2=C1NN=C2CNC CPHCIYGRSFZNRD-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
229910052754 neon Inorganic materials 0.000 description 1
GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 1
210000002682 neurofibrillary tangle Anatomy 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
238000012261 overproduction Methods 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
150000002923 oximes Chemical class 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
239000012057 packaged powder Substances 0.000 description 1
238000004806 packaging method and process Methods 0.000 description 1
239000002245 particle Substances 0.000 description 1
238000010827 pathological analysis Methods 0.000 description 1
230000008807 pathological lesion Effects 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000008188 pellet Substances 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
125000005561 phenanthryl group Chemical group 0.000 description 1
229960003531 phenolsulfonphthalein Drugs 0.000 description 1
229920000728 polyester Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
125000000075 primary alcohol group Chemical group 0.000 description 1
230000008569 process Effects 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
230000017854 proteolysis Effects 0.000 description 1
HDOUGSFASVGDCS-UHFFFAOYSA-N pyridin-3-ylmethanamine Chemical compound NCC1=CC=CN=C1 HDOUGSFASVGDCS-UHFFFAOYSA-N 0.000 description 1
TXQWFIVRZNOPCK-UHFFFAOYSA-N pyridin-4-ylmethanamine Chemical compound NCC1=CC=NC=C1 TXQWFIVRZNOPCK-UHFFFAOYSA-N 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
238000012216 screening Methods 0.000 description 1
238000007423 screening assay Methods 0.000 description 1
238000011894 semi-preparative HPLC Methods 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
CALYZCCZFAHEPH-UHFFFAOYSA-M sodium 2-[(5-chlorothiophen-2-yl)sulfonylamino]-2-(thian-4-yl)acetic acid hydroxide Chemical compound [OH-].[Na+].ClC1=CC=C(S1)S(=O)(=O)NC(C(=O)O)C1CCSCC1 CALYZCCZFAHEPH-UHFFFAOYSA-M 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
NZYOAGBNMCVQIV-UHFFFAOYSA-N sodium;chloro-(4-methylphenyl)sulfonylazanide;trihydrate Chemical compound O.O.O.[Na+].CC1=CC=C(S(=O)(=O)[N-]Cl)C=C1 NZYOAGBNMCVQIV-UHFFFAOYSA-N 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
239000000758 substrate Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
RGGGSPLXZRWPDA-UHFFFAOYSA-N tert-butyl 4-[(5-chlorothiophen-2-yl)sulfonylamino]-4-(hydroxymethyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1(CO)NS(=O)(=O)C1=CC=C(Cl)S1 RGGGSPLXZRWPDA-UHFFFAOYSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000012360 testing method Methods 0.000 description 1
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
AYEKOFBPNLCAJY-UHFFFAOYSA-O thiamine pyrophosphate Chemical compound CC1=C(CCOP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N AYEKOFBPNLCAJY-UHFFFAOYSA-O 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
229960001479 tosylchloramide sodium Drugs 0.000 description 1
238000012546 transfer Methods 0.000 description 1
238000003146 transient transfection Methods 0.000 description 1
MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 1
RMNIZOOYFMNEJJ-UHFFFAOYSA-K tripotassium;phosphate;hydrate Chemical class O.[K+].[K+].[K+].[O-]P([O-])([O-])=O RMNIZOOYFMNEJJ-UHFFFAOYSA-K 0.000 description 1
238000000825 ultraviolet detection Methods 0.000 description 1
235000019165 vitamin E Nutrition 0.000 description 1
229940046009 vitamin E Drugs 0.000 description 1
239000011709 vitamin E Substances 0.000 description 1
239000003643 water by type Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, ***e
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/64—Sulfur atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Psychiatry (AREA)
Hospice & Palliative Care (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

NO20032645A 2000-12-13 2003-06-11 Heterocykliske sulfonamidinhibitorer av <beta>-amyloidproduksjonen, farmasoytisk preparat omfattende en slik forbindelse samt anvendelse av forbindelsene NO328885B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US25510500P	2000-12-13	2000-12-13
PCT/US2001/048375 WO2002057252A2 (en)	2000-12-13	2001-12-11	Heterocyclic sulfonamide inhibitors of beta amyloid production

Publications (3)

Publication Number	Publication Date
NO20032645D0 NO20032645D0 (no)	2003-06-11
NO20032645L NO20032645L (no)	2003-08-05
NO328885B1 true NO328885B1 (no)	2010-06-07

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NO20032645A NO328885B1 (no)	2000-12-13	2003-06-11	Heterocykliske sulfonamidinhibitorer av <beta>-amyloidproduksjonen, farmasoytisk preparat omfattende en slik forbindelse samt anvendelse av forbindelsene

Country Status (28)

Country	Link
US (5)	US6610734B2 (zh)
EP (1)	EP1341779B1 (zh)
JP (2)	JP2004517892A (zh)
KR (1)	KR100869061B1 (zh)
CN (2)	CN1800176A (zh)
AR (1)	AR035516A1 (zh)
AT (1)	ATE330950T1 (zh)
AU (1)	AU2002245123B2 (zh)
BR (1)	BR0116063A (zh)
CA (1)	CA2436526C (zh)
CY (1)	CY1105441T1 (zh)
DE (1)	DE60121032T2 (zh)
DK (1)	DK1341779T3 (zh)
EA (1)	EA009035B1 (zh)
ES (1)	ES2267853T3 (zh)
HK (1)	HK1059619A1 (zh)
HU (1)	HUP0303857A3 (zh)
IL (3)	IL156268A0 (zh)
MX (1)	MXPA03005255A (zh)
NO (1)	NO328885B1 (zh)
NZ (2)	NZ538100A (zh)
PL (1)	PL365950A1 (zh)
PT (1)	PT1341779E (zh)
SG (1)	SG128491A1 (zh)
SI (1)	SI1341779T1 (zh)
TW (1)	TWI235155B (zh)
WO (1)	WO2002057252A2 (zh)
ZA (1)	ZA200304135B (zh)

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WO2008064320A2 (en) *	2006-11-21	2008-05-29	University Of Virginia Patent Foundation	Hydrindane analogs having sphingosine 1-phosphate receptor agonist activity
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Publication number	Publication date
US20020183361A1 (en)	2002-12-05
US7842718B2 (en)	2010-11-30
US20030229127A1 (en)	2003-12-11
AR035516A1 (es)	2004-06-02
CN1800176A (zh)	2006-07-12
EP1341779A2 (en)	2003-09-10
US20050196813A1 (en)	2005-09-08
PL365950A1 (en)	2005-01-24
KR20040018318A (ko)	2004-03-03
EA009035B1 (ru)	2007-10-26
IL156268A0 (en)	2004-01-04
US6610734B2 (en)	2003-08-26
ZA200304135B (en)	2004-09-03
AU2002245123B2 (en)	2007-05-24
NZ526213A (en)	2005-05-27
EP1341779B1 (en)	2006-06-21
CA2436526C (en)	2010-10-19
HK1059619A1 (en)	2004-07-09
US7691884B2 (en)	2010-04-06
EA200300674A1 (ru)	2004-06-24
IL156268A (en)	2008-04-13
CN1503790A (zh)	2004-06-09
MXPA03005255A (es)	2004-10-14
NO20032645D0 (no)	2003-06-11
WO2002057252A2 (en)	2002-07-25
DE60121032T2 (de)	2007-01-11
US20110034513A1 (en)	2011-02-10
TWI235155B (en)	2005-07-01
CN1263750C (zh)	2006-07-12
PT1341779E (pt)	2006-10-31
ATE330950T1 (de)	2006-07-15
US20100022594A1 (en)	2010-01-28
JP2004517892A (ja)	2004-06-17
NO20032645L (no)	2003-08-05
WO2002057252A3 (en)	2002-12-12
DK1341779T3 (da)	2006-10-30
CA2436526A1 (en)	2002-07-25
HUP0303857A3 (en)	2007-07-30
SG128491A1 (en)	2007-01-30
IL188853A0 (en)	2011-08-01
DE60121032D1 (de)	2006-08-03
CY1105441T1 (el)	2010-07-28
NZ538100A (en)	2006-07-28
HUP0303857A2 (hu)	2004-03-29
BR0116063A (pt)	2004-08-03
JP2010265280A (ja)	2010-11-25
KR100869061B1 (ko)	2008-11-17
ES2267853T3 (es)	2007-03-16
US6878742B2 (en)	2005-04-12
SI1341779T1 (sl)	2006-12-31

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Publication	Publication Date	Title
NO328885B1 (no)	2010-06-07	Heterocykliske sulfonamidinhibitorer av <beta>-amyloidproduksjonen, farmasoytisk preparat omfattende en slik forbindelse samt anvendelse av forbindelsene
AU2002245123A1 (en)	2003-02-13	Heterocyclic sulfonamide inhibitors of beta amyloid production
US7547725B2 (en)	2009-06-16	Fluoro- and trifluoroalkyl-containing heterocyclic sulfonamide inhibitors of beta amyloid production and derivatives thereof
JP4530849B2 (ja)	2010-08-25	βアミロイド産生の置換フェニルスルホンアミド阻害剤