BRPI0619633A2 - 5-(arilsulfonil)-pirazolopiperidinas - Google Patents

Info

Publication number

BRPI0619633A2

BRPI0619633A2 BRPI0619633-0A BRPI0619633A BRPI0619633A2 BR PI0619633 A2 BRPI0619633 A2 BR PI0619633A2 BR PI0619633 A BRPI0619633 A BR PI0619633A BR PI0619633 A2 BRPI0619633 A2 BR PI0619633A2

Authority

BR

Brazil

Prior art keywords

alkyl

formula

compounds

pyrazolo

methyl

Prior art date

2005-12-01

Links

• Espacenet
• Global Dossier
• Discuss

• 125000004391 aryl sulfonyl group Chemical group 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 1032
• 238000000034 method Methods 0.000 claims abstract description 70
• 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 34
• -1 -S (O) 0-2R ' Chemical group 0.000 claims description 386
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 331
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 323
• 125000004076 pyridyl group Chemical group 0.000 claims description 305
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 261
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 178
• 229910052736 halogen Inorganic materials 0.000 claims description 176
• 150000002367 halogens Chemical class 0.000 claims description 175
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 161
• 125000000335 thiazolyl group Chemical group 0.000 claims description 157
• 125000002883 imidazolyl group Chemical group 0.000 claims description 150
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 97
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 94
• 229910052739 hydrogen Inorganic materials 0.000 claims description 91
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 83
• 125000000217 alkyl group Chemical group 0.000 claims description 80
• 239000000203 mixture Substances 0.000 claims description 76
• 125000005843 halogen group Chemical group 0.000 claims description 68
• 125000002971 oxazolyl group Chemical group 0.000 claims description 66
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 63
• 229910052799 carbon Inorganic materials 0.000 claims description 62
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 62
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 61
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 58
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 57
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 56
• 125000001072 heteroaryl group Chemical group 0.000 claims description 52
• 125000003118 aryl group Chemical group 0.000 claims description 51
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 50
• 125000001589 carboacyl group Chemical group 0.000 claims description 49
• 125000003545 alkoxy group Chemical group 0.000 claims description 48
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 43
• OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 43
• 125000001188 haloalkyl group Chemical group 0.000 claims description 42
• 239000001257 hydrogen Substances 0.000 claims description 39
• 239000002904 solvent Substances 0.000 claims description 37
• 229910052717 sulfur Inorganic materials 0.000 claims description 35
• 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 35
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 32
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 30
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 30
• 125000002632 imidazolidinyl group Chemical group 0.000 claims description 29
• 150000003839 salts Chemical class 0.000 claims description 29
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 28
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 25
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 24
• 125000002757 morpholinyl group Chemical group 0.000 claims description 24
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 23
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 22
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 22
• 125000001544 thienyl group Chemical group 0.000 claims description 22
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 21
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 20
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 19
• 125000003342 alkenyl group Chemical group 0.000 claims description 18
• 125000004104 aryloxy group Chemical group 0.000 claims description 18
• 125000004193 piperazinyl group Chemical group 0.000 claims description 17
• 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 14
• 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 14
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 14
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 14
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 14
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 13
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 13
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 13
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 13
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 13
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical group [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 13
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 12
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 12
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 12
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 12
• 125000001425 triazolyl group Chemical group 0.000 claims description 12
• 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 11
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 11
• 125000003072 pyrazolidinyl group Chemical group 0.000 claims description 11
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 11
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
• 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 9
• 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 9
• 239000002671 adjuvant Substances 0.000 claims description 8
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 7
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 7
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
• 239000004305 biphenyl Substances 0.000 claims description 7
• 235000010290 biphenyl Nutrition 0.000 claims description 7
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 7
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 7
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
• 229910052760 oxygen Inorganic materials 0.000 claims description 6
• 125000003386 piperidinyl group Chemical group 0.000 claims description 6
• 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 5
• GRHZLQBPAJAHDM-SPRQWYLLSA-N [(3as,4r,6ar)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl] n-[(2s,4s,5s)-5-[[2-(2,6-dimethylphenoxy)acetyl]amino]-4-hydroxy-1,6-diphenylhexan-2-yl]carbamate Chemical compound CC1=CC=CC(C)=C1OCC(=O)N[C@H]([C@@H](O)C[C@H](CC=1C=CC=CC=1)NC(=O)O[C@@H]1[C@@H]2CCO[C@@H]2OC1)CC1=CC=CC=C1 GRHZLQBPAJAHDM-SPRQWYLLSA-N 0.000 claims description 5
• 239000011230 binding agent Substances 0.000 claims description 5
• 125000005842 heteroatom Chemical group 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
• 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims description 4
• 125000005605 benzo group Chemical group 0.000 claims description 4
• 239000007884 disintegrant Substances 0.000 claims description 4
• 125000001041 indolyl group Chemical group 0.000 claims description 4
• SELYJABLPLKXOY-UHFFFAOYSA-N methyl n,n-dimethylcarbamate Chemical compound COC(=O)N(C)C SELYJABLPLKXOY-UHFFFAOYSA-N 0.000 claims description 4
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
• 125000004429 atom Chemical group 0.000 claims description 3
• BXGYYDRIMBPOMN-UHFFFAOYSA-N 2-(hydroxymethoxy)ethoxymethanol Chemical compound OCOCCOCO BXGYYDRIMBPOMN-UHFFFAOYSA-N 0.000 claims description 2
• AFQAMIJGYNKWLC-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-4,6-diethyl-N-methoxy-4,6-dihydro-1H-pyrazolo[4,3-c]pyridin-7-imine Chemical compound CCC1C(=NOC)C=2NN=CC=2C(CC)N1S(=O)(=O)C1=CC=C(Cl)C=C1 AFQAMIJGYNKWLC-UHFFFAOYSA-N 0.000 claims description 2
• FRDWVNKKBQHREV-UHFFFAOYSA-N diethyl 5-(4-chlorophenyl)sulfonyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine-4,6-dicarboxylate Chemical compound CCOC(=O)C1CC=2NN=CC=2C(C(=O)OCC)N1S(=O)(=O)C1=CC=C(Cl)C=C1 FRDWVNKKBQHREV-UHFFFAOYSA-N 0.000 claims description 2
• YNXVSPCMOHSORF-UHFFFAOYSA-N ethyl 5-(4-chlorophenyl)sulfonyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine-4-carboxylate Chemical compound C1CC=2NN=CC=2C(C(=O)OCC)N1S(=O)(=O)C1=CC=C(Cl)C=C1 YNXVSPCMOHSORF-UHFFFAOYSA-N 0.000 claims description 2
• UFJNSBIBVKVMPK-UHFFFAOYSA-N ethyl 5-(4-chlorophenyl)sulfonyl-6-ethyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine-4-carboxylate Chemical compound CCC1CC=2NN=CC=2C(C(=O)OCC)N1S(=O)(=O)C1=CC=C(Cl)C=C1 UFJNSBIBVKVMPK-UHFFFAOYSA-N 0.000 claims description 2
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 2
• 239000012948 isocyanate Substances 0.000 claims description 2
• 150000002513 isocyanates Chemical class 0.000 claims description 2
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
• VCFVIFBFKJBPAG-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-4,6-bis(trifluoromethoxymethyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound FC(F)(F)OCC1CC=2NN=CC=2C(COC(F)(F)F)N1S(=O)(=O)C1=CC=C(Cl)C=C1 VCFVIFBFKJBPAG-UHFFFAOYSA-N 0.000 claims 1
• 150000002923 oximes Chemical class 0.000 claims 1
• SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims 1
• 208000010877 cognitive disease Diseases 0.000 abstract description 10
• 239000008194 pharmaceutical composition Substances 0.000 abstract description 7
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 121
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 60
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 56
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 54
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 43
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 41
• 239000000460 chlorine Substances 0.000 description 35
• 238000003786 synthesis reaction Methods 0.000 description 34
• 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 description 30
• 230000015572 biosynthetic process Effects 0.000 description 30
• 239000000047 product Substances 0.000 description 29
• 239000000243 solution Substances 0.000 description 28
• 229910052801 chlorine Inorganic materials 0.000 description 27
• 229910052731 fluorine Inorganic materials 0.000 description 27
• 235000019439 ethyl acetate Nutrition 0.000 description 26
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 23
• 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 23
• 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 23
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 23
• 125000003282 alkyl amino group Chemical group 0.000 description 22
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
• 238000006243 chemical reaction Methods 0.000 description 21
• 238000002360 preparation method Methods 0.000 description 21
• 125000004663 dialkyl amino group Chemical group 0.000 description 20
• 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 18
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
• 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 17
• 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 17
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
• 239000012267 brine Substances 0.000 description 17
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
• 239000012044 organic layer Substances 0.000 description 16
• 235000002639 sodium chloride Nutrition 0.000 description 16
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• 239000004480 active ingredient Substances 0.000 description 15
• 229910052757 nitrogen Inorganic materials 0.000 description 15
• 238000009472 formulation Methods 0.000 description 14
• 239000003921 oil Substances 0.000 description 14
• 235000019198 oils Nutrition 0.000 description 14
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 14
• 125000001624 naphthyl group Chemical group 0.000 description 13
• 238000000746 purification Methods 0.000 description 13
• 239000000725 suspension Substances 0.000 description 13
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
• 102000014736 Notch Human genes 0.000 description 12
• 108010070047 Notch Receptors Proteins 0.000 description 12
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 12
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
• 238000004587 chromatography analysis Methods 0.000 description 12
• 150000002148 esters Chemical class 0.000 description 12
• 239000007787 solid Substances 0.000 description 12
• 239000011593 sulfur Substances 0.000 description 12
• 238000005160 1H NMR spectroscopy Methods 0.000 description 11
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 11
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 10
• 210000004027 cell Anatomy 0.000 description 10
• 239000000651 prodrug Substances 0.000 description 10
• 229940002612 prodrug Drugs 0.000 description 10
• 125000006239 protecting group Chemical group 0.000 description 10
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
• 108010050254 Presenilins Proteins 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• 229940024606 amino acid Drugs 0.000 description 9
• 235000001014 amino acid Nutrition 0.000 description 9
• 150000001413 amino acids Chemical class 0.000 description 9
• 239000003153 chemical reaction reagent Substances 0.000 description 9
• 238000002425 crystallisation Methods 0.000 description 9
• 230000008025 crystallization Effects 0.000 description 9
• 201000010099 disease Diseases 0.000 description 9
• 239000003814 drug Substances 0.000 description 9
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 9
• 231100000252 nontoxic Toxicity 0.000 description 9
• 230000003000 nontoxic effect Effects 0.000 description 9
• 239000011541 reaction mixture Substances 0.000 description 9
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 8
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 8
• 102000015499 Presenilins Human genes 0.000 description 8
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 8
• 238000003776 cleavage reaction Methods 0.000 description 8
• 229940079593 drug Drugs 0.000 description 8
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 8
• 238000003818 flash chromatography Methods 0.000 description 8
• 125000000623 heterocyclic group Chemical group 0.000 description 8
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 8
• 230000035772 mutation Effects 0.000 description 8
• 108090000623 proteins and genes Proteins 0.000 description 8
• 230000007017 scission Effects 0.000 description 8
• 239000011734 sodium Substances 0.000 description 8
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 7
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 7
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
• 102100022033 Presenilin-1 Human genes 0.000 description 7
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
• 239000003995 emulsifying agent Substances 0.000 description 7
• 125000004994 halo alkoxy alkyl group Chemical group 0.000 description 7
• 230000002829 reductive effect Effects 0.000 description 7
• 229920006395 saturated elastomer Polymers 0.000 description 7
• 125000001424 substituent group Chemical group 0.000 description 7
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 6
• 208000037259 Amyloid Plaque Diseases 0.000 description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
• 241000699670 Mus sp. Species 0.000 description 6
• 210000004556 brain Anatomy 0.000 description 6
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
• 229910052794 bromium Inorganic materials 0.000 description 6
• 125000004432 carbon atom Chemical group C* 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
• 235000014113 dietary fatty acids Nutrition 0.000 description 6
• 230000000694 effects Effects 0.000 description 6
• 239000000839 emulsion Substances 0.000 description 6
• 235000019441 ethanol Nutrition 0.000 description 6
• 239000000194 fatty acid Substances 0.000 description 6
• 229930195729 fatty acid Natural products 0.000 description 6
• 239000000796 flavoring agent Substances 0.000 description 6
• 239000003540 gamma secretase inhibitor Substances 0.000 description 6
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
• 235000019341 magnesium sulphate Nutrition 0.000 description 6
• 230000001404 mediated effect Effects 0.000 description 6
• 239000002480 mineral oil Substances 0.000 description 6
• 238000012545 processing Methods 0.000 description 6
• 238000010992 reflux Methods 0.000 description 6
• 238000002390 rotary evaporation Methods 0.000 description 6
• 238000003756 stirring Methods 0.000 description 6
• 239000003765 sweetening agent Substances 0.000 description 6
• 102000013455 Amyloid beta-Peptides Human genes 0.000 description 5
• 108010090849 Amyloid beta-Peptides Proteins 0.000 description 5
• 206010012289 Dementia Diseases 0.000 description 5
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
• 239000004793 Polystyrene Substances 0.000 description 5
• 229920002472 Starch Polymers 0.000 description 5
• 150000001768 cations Chemical class 0.000 description 5
• 239000006071 cream Substances 0.000 description 5
• 239000003925 fat Substances 0.000 description 5
• 235000019197 fats Nutrition 0.000 description 5
• 150000004665 fatty acids Chemical class 0.000 description 5
• 235000003599 food sweetener Nutrition 0.000 description 5
• 238000004128 high performance liquid chromatography Methods 0.000 description 5
• 150000002576 ketones Chemical class 0.000 description 5
• 238000004519 manufacturing process Methods 0.000 description 5
• 239000012528 membrane Substances 0.000 description 5
• 235000010446 mineral oil Nutrition 0.000 description 5
• 230000000269 nucleophilic effect Effects 0.000 description 5
• 230000036961 partial effect Effects 0.000 description 5
• 239000000843 powder Substances 0.000 description 5
• 239000002243 precursor Substances 0.000 description 5
• 239000003755 preservative agent Substances 0.000 description 5
• 235000018102 proteins Nutrition 0.000 description 5
• 102000004169 proteins and genes Human genes 0.000 description 5
• 150000003217 pyrazoles Chemical class 0.000 description 5
• 229910052708 sodium Inorganic materials 0.000 description 5
• 239000008107 starch Substances 0.000 description 5
• 235000019698 starch Nutrition 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 5
• 239000003981 vehicle Substances 0.000 description 5
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
• 125000006656 (C2-C4) alkenyl group Chemical group 0.000 description 4
• 206010059245 Angiopathy Diseases 0.000 description 4
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
• 241000282412 Homo Species 0.000 description 4
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
• 101000579647 Penaeus vannamei Penaeidin-2a Proteins 0.000 description 4
• 108010036933 Presenilin-1 Proteins 0.000 description 4
• 108010029485 Protein Isoforms Proteins 0.000 description 4
• 102000001708 Protein Isoforms Human genes 0.000 description 4
• BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
• 239000013543 active substance Substances 0.000 description 4
• 101150089041 aph-1 gene Proteins 0.000 description 4
• 239000007900 aqueous suspension Substances 0.000 description 4
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
• 239000003795 chemical substances by application Substances 0.000 description 4
• 239000003086 colorant Substances 0.000 description 4
• 238000011161 development Methods 0.000 description 4
• 230000018109 developmental process Effects 0.000 description 4
• 239000003085 diluting agent Substances 0.000 description 4
• 239000002270 dispersing agent Substances 0.000 description 4
• 150000002084 enol ethers Chemical class 0.000 description 4
• 235000013355 food flavoring agent Nutrition 0.000 description 4
• 125000000524 functional group Chemical group 0.000 description 4
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
• 239000000543 intermediate Substances 0.000 description 4
• 230000003902 lesion Effects 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 102000046701 nicastrin Human genes 0.000 description 4
• 108700022821 nicastrin Proteins 0.000 description 4
• 239000012038 nucleophile Substances 0.000 description 4
• 239000012071 phase Substances 0.000 description 4
• 238000010791 quenching Methods 0.000 description 4
• 230000000171 quenching effect Effects 0.000 description 4
• 239000000741 silica gel Substances 0.000 description 4
• 229910002027 silica gel Inorganic materials 0.000 description 4
• 238000010898 silica gel chromatography Methods 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 239000000758 substrate Substances 0.000 description 4
• 239000000375 suspending agent Substances 0.000 description 4
• 210000001519 tissue Anatomy 0.000 description 4
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 3
• ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 4-chlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=C1 ZLYBFBAHAQEEQQ-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
• 208000024667 ABeta amyloidosis, Dutch type Diseases 0.000 description 3
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 3
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
• 208000028698 Cognitive impairment Diseases 0.000 description 3
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 3
• 229920000084 Gum arabic Polymers 0.000 description 3
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 3
• 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 3
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
• ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 3
• 235000019483 Peanut oil Nutrition 0.000 description 3
• 102100022036 Presenilin-2 Human genes 0.000 description 3
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
• 229930006000 Sucrose Natural products 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 125000002252 acyl group Chemical group 0.000 description 3
• 125000004423 acyloxy group Chemical group 0.000 description 3
• 125000002947 alkylene group Chemical group 0.000 description 3
• 125000003277 amino group Chemical group 0.000 description 3
• 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 description 3
• 239000011575 calcium Substances 0.000 description 3
• 229910052791 calcium Inorganic materials 0.000 description 3
• 230000008878 coupling Effects 0.000 description 3
• 238000010168 coupling process Methods 0.000 description 3
• 238000005859 coupling reaction Methods 0.000 description 3
• 239000013058 crude material Substances 0.000 description 3
• 125000004093 cyano group Chemical group *C#N 0.000 description 3
• 125000004122 cyclic group Chemical group 0.000 description 3
• 125000000392 cycloalkenyl group Chemical group 0.000 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 description 3
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
• 230000002950 deficient Effects 0.000 description 3
• 230000007850 degeneration Effects 0.000 description 3
• 230000008021 deposition Effects 0.000 description 3
• 235000020188 drinking water Nutrition 0.000 description 3
• 239000003651 drinking water Substances 0.000 description 3
• 239000003937 drug carrier Substances 0.000 description 3
• 208000036536 dutch type ABeta amyloidosis Diseases 0.000 description 3
• 239000012039 electrophile Substances 0.000 description 3
• WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 3
• 239000012634 fragment Substances 0.000 description 3
• 230000006870 function Effects 0.000 description 3
• 239000008187 granular material Substances 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 229940057995 liquid paraffin Drugs 0.000 description 3
• 229910052744 lithium Inorganic materials 0.000 description 3
• 239000011777 magnesium Substances 0.000 description 3
• 229910052749 magnesium Inorganic materials 0.000 description 3
• 208000027061 mild cognitive impairment Diseases 0.000 description 3
• 239000002674 ointment Substances 0.000 description 3
• 125000004043 oxo group Chemical group O=* 0.000 description 3
• 239000000312 peanut oil Substances 0.000 description 3
• 108090000765 processed proteins & peptides Proteins 0.000 description 3
• 230000000750 progressive effect Effects 0.000 description 3
• 230000011664 signaling Effects 0.000 description 3
• 239000003381 stabilizer Substances 0.000 description 3
• 239000005720 sucrose Substances 0.000 description 3
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 3
• 229940124530 sulfonamide Drugs 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• 235000015112 vegetable and seed oil Nutrition 0.000 description 3
• 239000008158 vegetable oil Substances 0.000 description 3
• 239000000080 wetting agent Substances 0.000 description 3
• JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 2
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
• UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
• YHELEFVIRTYOLH-UHFFFAOYSA-N 1,5-bis[(4-chlorophenyl)sulfonyl]-6-phenyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C(C=2C=CC=CC=2)CC(N(N=C2)S(=O)(=O)C=3C=CC(Cl)=CC=3)=C2C1 YHELEFVIRTYOLH-UHFFFAOYSA-N 0.000 description 2
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
• MXCHFWLKPVDOPC-UHFFFAOYSA-N 4,6-dimethyl-5-[4-(trifluoromethyl)phenyl]sulfonyl-4,6-dihydro-1h-pyrazolo[4,3-c]pyridin-7-one Chemical compound CC1C(=O)C2=NNC=C2C(C)N1S(=O)(=O)C1=CC=C(C(F)(F)F)C=C1 MXCHFWLKPVDOPC-UHFFFAOYSA-N 0.000 description 2
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
• XQABVLBGNWBWIV-UHFFFAOYSA-N 4-methoxypyridine Chemical compound COC1=CC=NC=C1 XQABVLBGNWBWIV-UHFFFAOYSA-N 0.000 description 2
• VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 2
• INFDFYKJYGGPKY-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-4-pyrimidin-5-yl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C(C=2C=NC=NC=2)C(C=NN2)=C2CC1 INFDFYKJYGGPKY-UHFFFAOYSA-N 0.000 description 2
• SHPWXEFRRYKBDM-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-6-phenyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C(C=2C=CC=CC=2)CC2=NNC=C2C1 SHPWXEFRRYKBDM-UHFFFAOYSA-N 0.000 description 2
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
• 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 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
• 239000004215 Carbon black (E152) Substances 0.000 description 2
• 102000000844 Cell Surface Receptors Human genes 0.000 description 2
• 108010001857 Cell Surface Receptors Proteins 0.000 description 2
• 206010008111 Cerebral haemorrhage Diseases 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
• CDEMHJCJMMOFMB-UHFFFAOYSA-M ClC1=CC=C([Mg]Br)C=C1 Chemical compound ClC1=CC=C([Mg]Br)C=C1 CDEMHJCJMMOFMB-UHFFFAOYSA-M 0.000 description 2
• 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 2
• 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 2
• YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
• 201000010374 Down Syndrome Diseases 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• 239000007821 HATU Substances 0.000 description 2
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
• 240000007472 Leucaena leucocephala Species 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• 206010027374 Mental impairment Diseases 0.000 description 2
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
• VZUNGTLZRAYYDE-UHFFFAOYSA-N N-methyl-N'-nitro-N-nitrosoguanidine Chemical compound O=NN(C)C(=N)N[N+]([O-])=O VZUNGTLZRAYYDE-UHFFFAOYSA-N 0.000 description 2
• 238000005481 NMR spectroscopy Methods 0.000 description 2
• 102400000552 Notch 1 intracellular domain Human genes 0.000 description 2
• 101800001628 Notch 1 intracellular domain Proteins 0.000 description 2
• 239000004698 Polyethylene Substances 0.000 description 2
• 229920001214 Polysorbate 60 Polymers 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
• 235000021355 Stearic acid Nutrition 0.000 description 2
• 229920001615 Tragacanth Polymers 0.000 description 2
• BOGSOFADOWIECK-UHFFFAOYSA-N [N].C=1C=NNC=1 Chemical compound [N].C=1C=NNC=1 BOGSOFADOWIECK-UHFFFAOYSA-N 0.000 description 2
• 238000010521 absorption reaction Methods 0.000 description 2
• 235000010489 acacia gum Nutrition 0.000 description 2
• 239000000205 acacia gum Substances 0.000 description 2
• SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
• 230000004913 activation Effects 0.000 description 2
• 230000010933 acylation Effects 0.000 description 2
• 238000005917 acylation reaction Methods 0.000 description 2
• 239000000853 adhesive Substances 0.000 description 2
• 230000001070 adhesive effect Effects 0.000 description 2
• 230000029936 alkylation Effects 0.000 description 2
• 238000005804 alkylation reaction Methods 0.000 description 2
• 125000000304 alkynyl group Chemical group 0.000 description 2
• 150000001408 amides Chemical class 0.000 description 2
• 150000001412 amines Chemical class 0.000 description 2
• 206010002022 amyloidosis Diseases 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical group N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 2
• 239000000305 astragalus gummifer gum Substances 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
• 125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 2
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 210000005013 brain tissue Anatomy 0.000 description 2
• 230000031709 bromination Effects 0.000 description 2
• 238000005893 bromination reaction Methods 0.000 description 2
• 235000019437 butane-1,3-diol Nutrition 0.000 description 2
• 229910000019 calcium carbonate Inorganic materials 0.000 description 2
• 235000010216 calcium carbonate Nutrition 0.000 description 2
• 239000001506 calcium phosphate Substances 0.000 description 2
• 229910000389 calcium phosphate Inorganic materials 0.000 description 2
• 235000011010 calcium phosphates Nutrition 0.000 description 2
• BHKTVMNUHSVTFH-UHFFFAOYSA-N carbamic acid;1h-pyrazole Chemical compound NC(O)=O.C=1C=NNC=1 BHKTVMNUHSVTFH-UHFFFAOYSA-N 0.000 description 2
• 239000003054 catalyst Substances 0.000 description 2
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• 239000012043 crude product Substances 0.000 description 2
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 230000034994 death Effects 0.000 description 2
• 230000007812 deficiency Effects 0.000 description 2
• 230000003412 degenerative effect Effects 0.000 description 2
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• 230000006866 deterioration Effects 0.000 description 2
• 235000005911 diet Nutrition 0.000 description 2
• 230000037213 diet Effects 0.000 description 2
• 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 2
• 208000035475 disorder Diseases 0.000 description 2
• 210000001671 embryonic stem cell Anatomy 0.000 description 2
• 150000002085 enols Chemical class 0.000 description 2
• 238000010931 ester hydrolysis Methods 0.000 description 2
• 239000000706 filtrate Substances 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 235000011187 glycerol Nutrition 0.000 description 2
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
• 150000002429 hydrazines Chemical class 0.000 description 2
• 229930195733 hydrocarbon Natural products 0.000 description 2
• 230000002779 inactivation Effects 0.000 description 2
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
• 230000002401 inhibitory effect Effects 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 239000000787 lecithin Substances 0.000 description 2
• 235000010445 lecithin Nutrition 0.000 description 2
• 229940067606 lecithin Drugs 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 238000001819 mass spectrum Methods 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• 229920000609 methyl cellulose Polymers 0.000 description 2
• 239000001923 methylcellulose Substances 0.000 description 2
• 235000010981 methylcellulose Nutrition 0.000 description 2
• 239000003094 microcapsule Substances 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 125000005186 naphthyloxy group Chemical group C1(=CC=CC2=CC=CC=C12)O* 0.000 description 2
• 210000002569 neuron Anatomy 0.000 description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
• 239000000346 nonvolatile oil Substances 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
• 239000004006 olive oil Substances 0.000 description 2
• 235000008390 olive oil Nutrition 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 239000012074 organic phase Substances 0.000 description 2
• 230000001590 oxidative effect Effects 0.000 description 2
• 239000001301 oxygen Substances 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• 239000012188 paraffin wax Substances 0.000 description 2
• 230000035515 penetration Effects 0.000 description 2
• CXVWVEAHZKABIU-UHFFFAOYSA-N piperidine;1h-pyrazole Chemical compound C=1C=NNC=1.C1CCNCC1 CXVWVEAHZKABIU-UHFFFAOYSA-N 0.000 description 2
• 125000003367 polycyclic group Chemical group 0.000 description 2
• 229920000728 polyester Polymers 0.000 description 2
• 229920000573 polyethylene Polymers 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• 102000004196 processed proteins & peptides Human genes 0.000 description 2
• 235000013772 propylene glycol Nutrition 0.000 description 2
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
• 230000017854 proteolysis Effects 0.000 description 2
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 2
• 229910052703 rhodium Inorganic materials 0.000 description 2
• 239000010948 rhodium Substances 0.000 description 2
• MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 2
• 239000008159 sesame oil Substances 0.000 description 2
• 235000011803 sesame oil Nutrition 0.000 description 2
• 235000010413 sodium alginate Nutrition 0.000 description 2
• 239000000661 sodium alginate Substances 0.000 description 2
• 229940005550 sodium alginate Drugs 0.000 description 2
• 239000000600 sorbitol Substances 0.000 description 2
• 235000010356 sorbitol Nutrition 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 239000008117 stearic acid Substances 0.000 description 2
• 125000000547 substituted alkyl group Chemical group 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• 150000003456 sulfonamides Chemical class 0.000 description 2
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
• 239000000829 suppository Substances 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
• 235000012222 talc Nutrition 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
• 238000004809 thin layer chromatography Methods 0.000 description 2
• 125000003396 thiol group Chemical group [H]S* 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 238000000844 transformation Methods 0.000 description 2
• 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 2
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
• 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 230000002792 vascular Effects 0.000 description 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
• GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 description 1
• VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 1
• RZABKAGQMPNUFJ-RYUDHWBXSA-N (2s,6s)-1-benzyl-2,6-dimethylpiperidin-4-one Chemical compound C[C@H]1CC(=O)C[C@H](C)N1CC1=CC=CC=C1 RZABKAGQMPNUFJ-RYUDHWBXSA-N 0.000 description 1
• FNHHVPPSBFQMEL-KQHDFZBMSA-N (3S)-5-N-[(1S,5R)-3-hydroxy-6-bicyclo[3.1.0]hexanyl]-7-N,3-dimethyl-3-phenyl-2H-1-benzofuran-5,7-dicarboxamide Chemical compound CNC(=O)c1cc(cc2c1OC[C@@]2(C)c1ccccc1)C(=O)NC1[C@H]2CC(O)C[C@@H]12 FNHHVPPSBFQMEL-KQHDFZBMSA-N 0.000 description 1
• TYZNGDLYLRYJCS-KGLIPLIRSA-N (4r,6s)-5-(4-chlorophenyl)sulfonyl-4,6-diethyl-4,6-dihydro-1h-pyrazolo[4,3-c]pyridin-7-one Chemical compound N1([C@@H](C=2C=NNC=2C(=O)[C@@H]1CC)CC)S(=O)(=O)C1=CC=C(Cl)C=C1 TYZNGDLYLRYJCS-KGLIPLIRSA-N 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• JSMZYVDGBUGFNA-YCVOCTCCSA-N (NZ)-N-[(4R,6S)-5-(4-chlorophenyl)sulfonyl-4,6-diethyl-4,6-dihydro-1H-pyrazolo[4,3-c]pyridin-7-ylidene]hydroxylamine Chemical compound N1([C@@H](C=2C=NNC=2C(=N\O)/[C@@H]1CC)CC)S(=O)(=O)C1=CC=C(Cl)C=C1 JSMZYVDGBUGFNA-YCVOCTCCSA-N 0.000 description 1
• QMMJWQMCMRUYTG-UHFFFAOYSA-N 1,2,4,5-tetrachloro-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=C(Cl)C(Cl)=CC(Cl)=C1Cl QMMJWQMCMRUYTG-UHFFFAOYSA-N 0.000 description 1
• MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical group C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 1
• GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
• KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• NFKGGDIYTBYWBU-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonyl-2-pyrimidin-5-ylpiperidin-4-one Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C(C=2C=NC=NC=2)CC(=O)CC1 NFKGGDIYTBYWBU-UHFFFAOYSA-N 0.000 description 1
• BAJLQUSEZZKKOM-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonyl-5-(dimethylaminomethylidene)-2-pyrimidin-5-ylpiperidin-4-one Chemical compound C1C(=O)C(=CN(C)C)CN(S(=O)(=O)C=2C=CC(Cl)=CC=2)C1C1=CN=CN=C1 BAJLQUSEZZKKOM-UHFFFAOYSA-N 0.000 description 1
• 125000006083 1-bromoethyl group Chemical group 0.000 description 1
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
• LGEZTMRIZWCDLW-UHFFFAOYSA-N 14-methylpentadecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC(C)C LGEZTMRIZWCDLW-UHFFFAOYSA-N 0.000 description 1
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
• LSJVQKDTVCDSPE-UHFFFAOYSA-N 1h-pyrazole-5-sulfonamide Chemical compound NS(=O)(=O)C=1C=CNN=1 LSJVQKDTVCDSPE-UHFFFAOYSA-N 0.000 description 1
• KEQTWHPMSVAFDA-UHFFFAOYSA-N 2,3-dihydro-1h-pyrazole Chemical compound C1NNC=C1 KEQTWHPMSVAFDA-UHFFFAOYSA-N 0.000 description 1
• WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 description 1
• WRRJHCNAZPQZOV-UHFFFAOYSA-N 2-(1h-indol-2-yloxy)-1h-indole Chemical compound C1=CC=C2NC(OC=3NC4=CC=CC=C4C=3)=CC2=C1 WRRJHCNAZPQZOV-UHFFFAOYSA-N 0.000 description 1
• VCUXVXLUOHDHKK-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-4-(2-chloro-4-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound ClC1=CC(OC)=CC=C1C1=C(C(N)=O)SC(C=2N=C(N)N=CC=2)=N1 VCUXVXLUOHDHKK-UHFFFAOYSA-N 0.000 description 1
• ACNYNTHNQRJDBF-UHFFFAOYSA-N 2-[(4-chlorophenyl)sulfonyl-pent-1-yn-3-ylamino]butanoic acid Chemical compound CCC(C#C)N(C(CC)C(O)=O)S(=O)(=O)C1=CC=C(Cl)C=C1 ACNYNTHNQRJDBF-UHFFFAOYSA-N 0.000 description 1
• ICLCLISNCTWXGA-UHFFFAOYSA-N 2-[5-(4-chlorophenyl)sulfonyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-6-yl]-1,3-thiazole Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C(C=2SC=CN=2)CC(NN=C2)=C2C1 ICLCLISNCTWXGA-UHFFFAOYSA-N 0.000 description 1
• FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 description 1
• VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 description 1
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
• YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• DFRAKBCRUYUFNT-UHFFFAOYSA-N 3,8-dicyclohexyl-2,4,7,9-tetrahydro-[1,3]oxazino[5,6-h][1,3]benzoxazine Chemical compound C1CCCCC1N1CC(C=CC2=C3OCN(C2)C2CCCCC2)=C3OC1 DFRAKBCRUYUFNT-UHFFFAOYSA-N 0.000 description 1
• NXRZKGGVMMFNQG-UHFFFAOYSA-N 3-(2H-1,3-oxazol-3-yloxy)-2H-1,3-oxazole Chemical compound O1CN(C=C1)ON1COC=C1 NXRZKGGVMMFNQG-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
• OXTNCQMOKLOUAM-UHFFFAOYSA-N 3-Oxoglutaric acid Chemical compound OC(=O)CC(=O)CC(O)=O OXTNCQMOKLOUAM-UHFFFAOYSA-N 0.000 description 1
• FGNJDIUCLQMEJV-UHFFFAOYSA-N 3-[(4-chlorophenyl)sulfonyl-pent-1-yn-3-ylamino]-1-diazoniopent-1-en-2-olate Chemical compound [N-]=[N+]=CC(=O)C(CC)N(C(C#C)CC)S(=O)(=O)C1=CC=C(Cl)C=C1 FGNJDIUCLQMEJV-UHFFFAOYSA-N 0.000 description 1
• 125000005917 3-methylpentyl group Chemical group 0.000 description 1
• 125000005925 3-methylpentyloxy group Chemical group 0.000 description 1
• 125000001845 4 membered carbocyclic group Chemical group 0.000 description 1
• RTTBBADOMOOPTQ-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1h-pyrazolo[4,3-b]pyridine Chemical class C1CCNC2=C1NN=C2 RTTBBADOMOOPTQ-UHFFFAOYSA-N 0.000 description 1
• WDWZCPBEJNKJHZ-UHFFFAOYSA-N 4,6-diethyl-5-(4-fluorophenyl)sulfonyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound CCC1CC2=NNC=C2C(CC)N1S(=O)(=O)C1=CC=C(F)C=C1 WDWZCPBEJNKJHZ-UHFFFAOYSA-N 0.000 description 1
• CMEPURNZGZVVGK-UHFFFAOYSA-N 4,6-dimethyl-5-pyridin-2-ylsulfonyl-4,6-dihydro-1h-pyrazolo[4,3-c]pyridin-7-one Chemical compound CC1C(=O)C=2NN=CC=2C(C)N1S(=O)(=O)C1=CC=CC=N1 CMEPURNZGZVVGK-UHFFFAOYSA-N 0.000 description 1
• HAQUEDTVQZIXFB-UHFFFAOYSA-N 4-(1h-benzimidazol-2-yl)-5-(4-chlorophenyl)sulfonyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C(C=2NC3=CC=CC=C3N=2)C2=CNN=C2CC1 HAQUEDTVQZIXFB-UHFFFAOYSA-N 0.000 description 1
• IBPGHBHJUCHEIJ-UHFFFAOYSA-N 4-(4-chlorophenyl)-1,5-bis[(4-chlorophenyl)sulfonyl]-6-ethyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridine Chemical compound C=1C=C(Cl)C=CC=1C1N(S(=O)(=O)C=2C=CC(Cl)=CC=2)C(CC)CC2=C1C=NN2S(=O)(=O)C1=CC=C(Cl)C=C1 IBPGHBHJUCHEIJ-UHFFFAOYSA-N 0.000 description 1
• XAHSJYNMPZPURS-UHFFFAOYSA-N 4-(4-chlorophenyl)-2,5-bis[(4-chlorophenyl)sulfonyl]-6-ethyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridine Chemical compound CCC1CC2=NN(S(=O)(=O)C=3C=CC(Cl)=CC=3)C=C2C(C=2C=CC(Cl)=CC=2)N1S(=O)(=O)C1=CC=C(Cl)C=C1 XAHSJYNMPZPURS-UHFFFAOYSA-N 0.000 description 1
• FNVZIUZHHCMTFP-UHFFFAOYSA-N 4-(4-chlorophenyl)-5-(4-chlorophenyl)sulfonyl-6-ethyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound CCC1CC2=NNC=C2C(C=2C=CC(Cl)=CC=2)N1S(=O)(=O)C1=CC=C(Cl)C=C1 FNVZIUZHHCMTFP-UHFFFAOYSA-N 0.000 description 1
• HHHDJHHNEURCNV-UHFFFAOYSA-N 4-chlorobenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(Cl)C=C1 HHHDJHHNEURCNV-UHFFFAOYSA-N 0.000 description 1
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
• HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
• DFAPLCUDTXZPSZ-UHFFFAOYSA-N 4-pyrimidin-5-yl-5-[4-(trifluoromethyl)phenyl]sulfonyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound C1=CC(C(F)(F)F)=CC=C1S(=O)(=O)N1C(C=2C=NC=NC=2)C(C=NN2)=C2CC1 DFAPLCUDTXZPSZ-UHFFFAOYSA-N 0.000 description 1
• 125000001054 5 membered carbocyclic group Chemical group 0.000 description 1
• FWFPFPVMQRARFK-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-4,6-bis(1,1-difluoroethyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound CC(F)(F)C1CC=2NN=CC=2C(C(C)(F)F)N1S(=O)(=O)C1=CC=C(Cl)C=C1 FWFPFPVMQRARFK-UHFFFAOYSA-N 0.000 description 1
• IJKKVNQKLIUEKZ-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-4,6-bis(2,2,2-trifluoroethyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound FC(F)(F)CC1CC=2NN=CC=2C(CC(F)(F)F)N1S(=O)(=O)C1=CC=C(Cl)C=C1 IJKKVNQKLIUEKZ-UHFFFAOYSA-N 0.000 description 1
• VQICZUMHISWBRF-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-4,6-bis(2,2-difluoroethenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound FC(F)=CC1CC=2NN=CC=2C(C=C(F)F)N1S(=O)(=O)C1=CC=C(Cl)C=C1 VQICZUMHISWBRF-UHFFFAOYSA-N 0.000 description 1
• LPOKCOBIKCGVBE-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-4,6-bis(2,2-difluoroethyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound FC(F)CC1CC=2NN=CC=2C(CC(F)F)N1S(=O)(=O)C1=CC=C(Cl)C=C1 LPOKCOBIKCGVBE-UHFFFAOYSA-N 0.000 description 1
• JGAFDAJFEDNFIR-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-4,6-bis(difluoromethyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound FC(F)C1CC=2NN=CC=2C(C(F)F)N1S(=O)(=O)C1=CC=C(Cl)C=C1 JGAFDAJFEDNFIR-UHFFFAOYSA-N 0.000 description 1
• FTXBIZQXDZLQIN-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-4,6-bis(fluoromethyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound FCC1CC=2NN=CC=2C(CF)N1S(=O)(=O)C1=CC=C(Cl)C=C1 FTXBIZQXDZLQIN-UHFFFAOYSA-N 0.000 description 1
• TVGCMTFAICEQPV-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-4,6-bis(trifluoromethyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound FC(F)(F)C1CC=2NN=CC=2C(C(F)(F)F)N1S(=O)(=O)C1=CC=C(Cl)C=C1 TVGCMTFAICEQPV-UHFFFAOYSA-N 0.000 description 1
• LDJVTIWSHGAJBZ-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-4,6-bis[difluoro(methoxy)methyl]-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound COC(F)(F)C1CC=2NN=CC=2C(C(F)(F)OC)N1S(=O)(=O)C1=CC=C(Cl)C=C1 LDJVTIWSHGAJBZ-UHFFFAOYSA-N 0.000 description 1
• MGBJJPSCKFZVTC-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-4,6-di(propan-2-yl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound CC(C)C1CC=2NN=CC=2C(C(C)C)N1S(=O)(=O)C1=CC=C(Cl)C=C1 MGBJJPSCKFZVTC-UHFFFAOYSA-N 0.000 description 1
• MQMZGGJQWVAGCT-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-4,6-dicyclopropyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C(C2CC2)C(C=NN2)=C2CC1C1CC1 MQMZGGJQWVAGCT-UHFFFAOYSA-N 0.000 description 1
• QTNJCLYRWVYMLP-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-4,6-diethyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-7-amine Chemical compound CCC1C(N)C=2NN=CC=2C(CC)N1S(=O)(=O)C1=CC=C(Cl)C=C1 QTNJCLYRWVYMLP-UHFFFAOYSA-N 0.000 description 1
• LBUIKNKQOBTCII-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-4,6-diethyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound CCC1CC=2NN=CC=2C(CC)N1S(=O)(=O)C1=CC=C(Cl)C=C1 LBUIKNKQOBTCII-UHFFFAOYSA-N 0.000 description 1
• UYXLRRKFIURBQN-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-4,6-diethyl-7,7-difluoro-4,6-dihydro-1h-pyrazolo[4,3-c]pyridine Chemical compound CCC1C(F)(F)C=2NN=CC=2C(CC)N1S(=O)(=O)C1=CC=C(Cl)C=C1 UYXLRRKFIURBQN-UHFFFAOYSA-N 0.000 description 1
• PLRQKVQGIULJSB-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-4,6-diethyl-n,n-dimethyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-7-amine Chemical compound CCC1C(N(C)C)C=2NN=CC=2C(CC)N1S(=O)(=O)C1=CC=C(Cl)C=C1 PLRQKVQGIULJSB-UHFFFAOYSA-N 0.000 description 1
• NEUBWALUOOQMFO-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-4-propan-2-yl-4,6-dihydro-1h-pyrazolo[4,3-c]pyridin-7-one Chemical compound C1C(=O)C=2NN=CC=2C(C(C)C)N1S(=O)(=O)C1=CC=C(Cl)C=C1 NEUBWALUOOQMFO-UHFFFAOYSA-N 0.000 description 1
• PJWCXGDPACNDRU-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-4-pyrimidin-5-yl-4,6-dihydro-1h-pyrazolo[4,3-c]pyridin-7-one Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C(C=2C=NC=NC=2)C(C=NN2)=C2C(=O)C1 PJWCXGDPACNDRU-UHFFFAOYSA-N 0.000 description 1
• ABPUPKAKVGTPJW-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-6-(3,5-difluorophenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound FC1=CC(F)=CC(C2N(CC=3C=NNC=3C2)S(=O)(=O)C=2C=CC(Cl)=CC=2)=C1 ABPUPKAKVGTPJW-UHFFFAOYSA-N 0.000 description 1
• GURVCFNDFPUXLC-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-6-cyclopropyl-6,7-dihydro-1h-pyrazolo[4,3-c]pyridin-4-one Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C(=O)C(C=NN2)=C2CC1C1CC1 GURVCFNDFPUXLC-UHFFFAOYSA-N 0.000 description 1
• XYGOBGUUUWYZHO-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-6-ethyl-6,7-dihydro-1h-pyrazolo[4,3-c]pyridin-4-one Chemical compound CCC1CC=2NN=CC=2C(=O)N1S(=O)(=O)C1=CC=C(Cl)C=C1 XYGOBGUUUWYZHO-UHFFFAOYSA-N 0.000 description 1
• TWLIVHHOFPVVPT-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-6-methyl-4-pyrimidin-5-yl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound CC1CC=2NN=CC=2C(C=2C=NC=NC=2)N1S(=O)(=O)C1=CC=C(Cl)C=C1 TWLIVHHOFPVVPT-UHFFFAOYSA-N 0.000 description 1
• BVXHINMPEZLERH-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-6-propan-2-yl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound CC(C)C1CC=2NN=CC=2CN1S(=O)(=O)C1=CC=C(Cl)C=C1 BVXHINMPEZLERH-UHFFFAOYSA-N 0.000 description 1
• DHZZUOUZBFLGOY-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-6-pyrimidin-5-yl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C(C=2C=NC=NC=2)CC(NN=C2)=C2C1 DHZZUOUZBFLGOY-UHFFFAOYSA-N 0.000 description 1
• BLXAFOWVHKZTSV-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-6-pyrimidin-5-yl-4,6-dihydro-1h-pyrazolo[4,3-c]pyridin-7-one Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C(C=2C=NC=NC=2)C(=O)C(NN=C2)=C2C1 BLXAFOWVHKZTSV-UHFFFAOYSA-N 0.000 description 1
• PSBVASZJNLJDAQ-UHFFFAOYSA-N 5-(4-fluorophenyl)sulfonyl-4,6-dimethyl-4,6-dihydro-1h-pyrazolo[4,3-c]pyridin-7-one Chemical compound CC1C(=O)C=2NN=CC=2C(C)N1S(=O)(=O)C1=CC=C(F)C=C1 PSBVASZJNLJDAQ-UHFFFAOYSA-N 0.000 description 1
• 125000004008 6 membered carbocyclic group Chemical group 0.000 description 1
• ZRCZGEIHIFDAPM-UHFFFAOYSA-N 6-(4-chlorophenyl)-5-(4-chlorophenyl)sulfonyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1N(S(=O)(=O)C=2C=CC(Cl)=CC=2)CC(C=NN2)=C2C1 ZRCZGEIHIFDAPM-UHFFFAOYSA-N 0.000 description 1
• NLFUWFNEKPIFHZ-UHFFFAOYSA-N 6-benzyl-5-(4-chlorophenyl)sulfonyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C(CC=2C=CC=CC=2)CC(NN=C2)=C2C1 NLFUWFNEKPIFHZ-UHFFFAOYSA-N 0.000 description 1
• GDUANFXPOZTYKS-UHFFFAOYSA-N 6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid Chemical compound FC1=CC(OC)=CC(F)=C1C(=O)NC1=CC(Br)=CC2=C1OC(C(O)=O)=CC2=O GDUANFXPOZTYKS-UHFFFAOYSA-N 0.000 description 1
• NYKKLADUPJMJDI-UHFFFAOYSA-N 6-methyl-4-(1,3-thiazol-2-yl)-5-[4-(trifluoromethyl)phenyl]sulfonyl-4,6-dihydro-1h-pyrazolo[4,3-c]pyridin-7-one Chemical compound C1=2C=NNC=2C(=O)C(C)N(S(=O)(=O)C=2C=CC(=CC=2)C(F)(F)F)C1C1=NC=CS1 NYKKLADUPJMJDI-UHFFFAOYSA-N 0.000 description 1
• OSXXSBWDLVDOPD-UHFFFAOYSA-N 6-methyl-4-pyridin-3-yl-5-[4-(trifluoromethyl)phenyl]sulfonyl-4,6-dihydro-1h-pyrazolo[4,3-c]pyridin-7-one Chemical compound C1=2C=NNC=2C(=O)C(C)N(S(=O)(=O)C=2C=CC(=CC=2)C(F)(F)F)C1C1=CC=CN=C1 OSXXSBWDLVDOPD-UHFFFAOYSA-N 0.000 description 1
• MGPOXPHMAOQZOW-UHFFFAOYSA-N 6-methyl-4-pyridin-4-yl-5-[4-(trifluoromethyl)phenyl]sulfonyl-4,6-dihydro-1h-pyrazolo[4,3-c]pyridin-7-one Chemical compound C1=2C=NNC=2C(=O)C(C)N(S(=O)(=O)C=2C=CC(=CC=2)C(F)(F)F)C1C1=CC=NC=C1 MGPOXPHMAOQZOW-UHFFFAOYSA-N 0.000 description 1
• NBQFIIANGXHOLA-UHFFFAOYSA-N 6-methyl-4-pyrimidin-5-yl-5-[4-(trifluoromethyl)phenyl]sulfonyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound CC1CC=2NN=CC=2C(C=2C=NC=NC=2)N1S(=O)(=O)C1=CC=C(C(F)(F)F)C=C1 NBQFIIANGXHOLA-UHFFFAOYSA-N 0.000 description 1
• VXZAMCUMOIFIDF-UHFFFAOYSA-N 6-methyl-4-pyrimidin-5-yl-5-[4-(trifluoromethyl)phenyl]sulfonyl-4,6-dihydro-1h-pyrazolo[4,3-c]pyridin-7-one Chemical compound C1=2C=NNC=2C(=O)C(C)N(S(=O)(=O)C=2C=CC(=CC=2)C(F)(F)F)C1C1=CN=CN=C1 VXZAMCUMOIFIDF-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• XASOHFCUIQARJT-UHFFFAOYSA-N 8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C(N1C(=O)C2=C(OC)C=C(C=3N4C(=NC=3)C=C(C=C4)OCCN3CCOCC3)C=C2CC1)C(F)(F)F XASOHFCUIQARJT-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• 235000006491 Acacia senegal Nutrition 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• 208000000044 Amnesia Diseases 0.000 description 1
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
• 208000014644 Brain disease Diseases 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• 239000004358 Butane-1, 3-diol Substances 0.000 description 1
• JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 description 1
• 102400000577 C83 Human genes 0.000 description 1
• 101800001508 C83 Proteins 0.000 description 1
• BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 description 1
• PKMUHQIDVVOXHQ-HXUWFJFHSA-N C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O Chemical compound C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O PKMUHQIDVVOXHQ-HXUWFJFHSA-N 0.000 description 1
• 244000060011 Cocos nucifera Species 0.000 description 1
• 235000013162 Cocos nucifera Nutrition 0.000 description 1
• 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
• 229920002261 Corn starch Polymers 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
• 230000009946 DNA mutation Effects 0.000 description 1
• 238000005698 Diels-Alder reaction Methods 0.000 description 1
• QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 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
• JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 description 1
• 206010018341 Gliosis Diseases 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
• 239000004471 Glycine Substances 0.000 description 1
• 244000068988 Glycine max Species 0.000 description 1
• 235000010469 Glycine max Nutrition 0.000 description 1
• HHLFWLYXYJOTON-UHFFFAOYSA-N Glyoxylic acid Natural products OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 1
• 229910004373 HOAc Inorganic materials 0.000 description 1
• 108010081348 HRT1 protein Hairy Proteins 0.000 description 1
• 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 description 1
• 208000032843 Hemorrhage Diseases 0.000 description 1
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• 239000002841 Lewis acid Substances 0.000 description 1
• 239000012448 Lithium borohydride Substances 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 206010025421 Macule Diseases 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 102000018697 Membrane Proteins Human genes 0.000 description 1
• 108010052285 Membrane Proteins Proteins 0.000 description 1
• 208000027382 Mental deterioration Diseases 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
• LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 1
• JSMZYVDGBUGFNA-UHFFFAOYSA-N N-[5-(4-chlorophenyl)sulfonyl-4,6-diethyl-4,6-dihydro-1H-pyrazolo[4,3-c]pyridin-7-ylidene]hydroxylamine Chemical compound CCC1C(=NO)C=2NN=CC=2C(CC)N1S(=O)(=O)C1=CC=C(Cl)C=C1 JSMZYVDGBUGFNA-UHFFFAOYSA-N 0.000 description 1
• 208000009668 Neurobehavioral Manifestations Diseases 0.000 description 1
• 102100023181 Neurogenic locus notch homolog protein 1 Human genes 0.000 description 1
• 108700037638 Neurogenic locus notch homolog protein 1 Proteins 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 102000001759 Notch1 Receptor Human genes 0.000 description 1
• 108010029755 Notch1 Receptor Proteins 0.000 description 1
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 102000035195 Peptidases Human genes 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• 102000007079 Peptide Fragments Human genes 0.000 description 1
• 108010033276 Peptide Fragments Proteins 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 239000004372 Polyvinyl alcohol Substances 0.000 description 1
• 108010036908 Presenilin-2 Proteins 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
• STSCVKRWJPWALQ-UHFFFAOYSA-N TRIFLUOROACETIC ACID ETHYL ESTER Chemical compound CCOC(=O)C(F)(F)F STSCVKRWJPWALQ-UHFFFAOYSA-N 0.000 description 1
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
• 229910003074 TiCl4 Inorganic materials 0.000 description 1
• 108091005906 Type I transmembrane proteins Proteins 0.000 description 1
• WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 1
• SIZMAOAIVRSPAF-UHFFFAOYSA-N [4-pyrimidin-5-yl-5-[4-(trifluoromethyl)phenyl]sulfonyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-6-yl]methanol Chemical compound OCC1CC=2NN=CC=2C(C=2C=NC=NC=2)N1S(=O)(=O)C1=CC=C(C(F)(F)F)C=C1 SIZMAOAIVRSPAF-UHFFFAOYSA-N 0.000 description 1
• 230000037374 absorbed through the skin Effects 0.000 description 1
• 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 1
• QLDHWVVRQCGZLE-UHFFFAOYSA-N acetyl cyanide Chemical compound CC(=O)C#N QLDHWVVRQCGZLE-UHFFFAOYSA-N 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000011149 active material Substances 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 150000001335 aliphatic alkanes Chemical class 0.000 description 1
• 125000002877 alkyl aryl group Chemical group 0.000 description 1
• 229920013820 alkyl cellulose Polymers 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• 125000005275 alkylenearyl group Chemical group 0.000 description 1
• 230000003281 allosteric effect Effects 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• 238000010640 amide synthesis reaction Methods 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 230000003110 anti-inflammatory effect Effects 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 230000003078 antioxidant effect Effects 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 101150031224 app gene Proteins 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 239000003125 aqueous solvent Substances 0.000 description 1
• 150000001543 aryl boronic acids Chemical class 0.000 description 1
• 125000005160 aryl oxy alkyl group Chemical group 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229960001230 asparagine Drugs 0.000 description 1
• 235000009582 asparagine Nutrition 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 238000011914 asymmetric synthesis Methods 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 1
• KFTPQNQURGTUJT-UHFFFAOYSA-N benzyl 2-(4-chlorophenyl)-4-oxopiperidine-1-carboxylate Chemical compound C1=CC(Cl)=CC=C1C1N(C(=O)OCC=2C=CC=CC=2)CCC(=O)C1 KFTPQNQURGTUJT-UHFFFAOYSA-N 0.000 description 1
• CIAZQGCLUWDXQZ-UHFFFAOYSA-N benzyl 2-(4-chlorophenyl)-6-ethyl-4-oxopiperidine-1-carboxylate Chemical compound CCC1CC(=O)CC(C=2C=CC(Cl)=CC=2)N1C(=O)OCC1=CC=CC=C1 CIAZQGCLUWDXQZ-UHFFFAOYSA-N 0.000 description 1
• UEEHKOIVROOWTK-UHFFFAOYSA-N benzyl 2-ethyl-4-oxo-2,3-dihydropyridine-1-carboxylate Chemical compound CCC1CC(=O)C=CN1C(=O)OCC1=CC=CC=C1 UEEHKOIVROOWTK-UHFFFAOYSA-N 0.000 description 1
• OAKHYPNVCUHASC-UHFFFAOYSA-N benzyl 4-oxo-2,3-dihydropyridine-1-carboxylate Chemical compound C1CC(=O)C=CN1C(=O)OCC1=CC=CC=C1 OAKHYPNVCUHASC-UHFFFAOYSA-N 0.000 description 1
• VZOVOHRDLOYBJX-UHFFFAOYSA-N benzyl 4-oxopiperidine-1-carboxylate Chemical compound C1CC(=O)CCN1C(=O)OCC1=CC=CC=C1 VZOVOHRDLOYBJX-UHFFFAOYSA-N 0.000 description 1
• MIFYJPMVLSDWBL-UHFFFAOYSA-N benzyl 6-bromo-1,4-dioxa-8-azaspiro[4.5]decane-8-carboxylate Chemical compound BrC1CN(C(=O)OCC=2C=CC=CC=2)CCC11OCCO1 MIFYJPMVLSDWBL-UHFFFAOYSA-N 0.000 description 1
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-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
• 238000001574 biopsy Methods 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 229910052796 boron Inorganic materials 0.000 description 1
• 230000005587 bubbling Effects 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• DCZVGZMUJCEUTC-UHFFFAOYSA-N buta-1,3-dien-2-yl(trimethyl)silane Chemical compound C[Si](C)(C)C(=C)C=C DCZVGZMUJCEUTC-UHFFFAOYSA-N 0.000 description 1
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
• 229910000024 caesium carbonate Inorganic materials 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 150000001721 carbon Chemical class 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 239000012876 carrier material Substances 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 230000002490 cerebral effect Effects 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 238000004296 chiral HPLC Methods 0.000 description 1
• 229910001914 chlorine tetroxide Inorganic materials 0.000 description 1
• FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
• 125000004617 chromonyl group Chemical group O1C(=CC(C2=CC=CC=C12)=O)* 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 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
• 239000012230 colorless oil Substances 0.000 description 1
• 229940127113 compound 57 Drugs 0.000 description 1
• 229940125900 compound 59 Drugs 0.000 description 1
• 229940126179 compound 72 Drugs 0.000 description 1
• 235000008504 concentrate Nutrition 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
• 239000002285 corn oil Substances 0.000 description 1
• 235000005687 corn oil Nutrition 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 230000001054 cortical effect Effects 0.000 description 1
• 239000002537 cosmetic Substances 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 230000001186 cumulative effect Effects 0.000 description 1
• 238000006352 cycloaddition reaction Methods 0.000 description 1
• 125000001316 cycloalkyl alkyl group Chemical group 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
• SHALBPKEGDBVKK-VOTSOKGWSA-N danishefsky's diene Chemical compound CO\C=C\C(=C)O[Si](C)(C)C SHALBPKEGDBVKK-VOTSOKGWSA-N 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• SASYSVUEVMOWPL-NXVVXOECSA-N decyl oleate Chemical compound CCCCCCCCCCOC(=O)CCCCCCC\C=C/CCCCCCCC SASYSVUEVMOWPL-NXVVXOECSA-N 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• 239000010432 diamond Substances 0.000 description 1
• GRTGGSXWHGKRSB-UHFFFAOYSA-N dichloromethyl methyl ether Chemical compound COC(Cl)Cl GRTGGSXWHGKRSB-UHFFFAOYSA-N 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• 125000005992 dihydrobenzisothiazinyl group Chemical group 0.000 description 1
• 125000005993 dihydrobenzisoxazinyl group Chemical group 0.000 description 1
• 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
• 125000005046 dihydronaphthyl group Chemical group 0.000 description 1
• 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
• 125000005052 dihydropyrazolyl group Chemical group N1(NCC=C1)* 0.000 description 1
• 125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 description 1
• IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 1
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 239000000890 drug combination Substances 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 239000003974 emollient agent Substances 0.000 description 1
• 230000002996 emotional effect Effects 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 239000008387 emulsifying waxe Substances 0.000 description 1
• 239000008393 encapsulating agent Substances 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• FGTCQDBLQPQPQE-UHFFFAOYSA-N ethyl 5-(4-chlorophenyl)sulfonyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine-6-carboxylate Chemical compound CCOC(=O)C1CC=2NN=CC=2CN1S(=O)(=O)C1=CC=C(Cl)C=C1 FGTCQDBLQPQPQE-UHFFFAOYSA-N 0.000 description 1
• PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000003889 eye drop Substances 0.000 description 1
• 229940012356 eye drops Drugs 0.000 description 1
• 235000013861 fat-free Nutrition 0.000 description 1
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• VWWMTZUQZBRXJY-UHFFFAOYSA-N formyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC=O VWWMTZUQZBRXJY-UHFFFAOYSA-N 0.000 description 1
• 230000022244 formylation Effects 0.000 description 1
• 238000006170 formylation reaction Methods 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 230000014509 gene expression Effects 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 230000007387 gliosis Effects 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
• 229940075507 glyceryl monostearate Drugs 0.000 description 1
• 125000001475 halogen functional group Chemical group 0.000 description 1
• 239000007902 hard capsule Substances 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 125000000268 heptanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000004404 heteroalkyl group Chemical group 0.000 description 1
• 125000005553 heteroaryloxy group Chemical group 0.000 description 1
• FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 1
• 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 239000008309 hydrophilic cream Substances 0.000 description 1
• WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 238000005286 illumination Methods 0.000 description 1
• 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 1
• 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 description 1
• 125000005945 imidazopyridyl group Chemical group 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 239000003112 inhibitor Substances 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 229940102213 injectable suspension Drugs 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 229940078545 isocetyl stearate Drugs 0.000 description 1
• 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
• 125000005956 isoquinolyl group Chemical group 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 239000010410 layer Substances 0.000 description 1
• 231100000518 lethal Toxicity 0.000 description 1
• 230000001665 lethal effect Effects 0.000 description 1
• 150000007517 lewis acids Chemical class 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 230000002366 lipolytic effect Effects 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
• 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
• 239000003589 local anesthetic agent Substances 0.000 description 1
• 229960005015 local anesthetics Drugs 0.000 description 1
• 230000004807 localization Effects 0.000 description 1
• 231100000863 loss of memory Toxicity 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 239000000395 magnesium oxide Substances 0.000 description 1
• CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
• 235000012245 magnesium oxide Nutrition 0.000 description 1
• FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
• AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 230000035800 maturation Effects 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000006386 memory function Effects 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• UTVMMYAYJZXJFO-UHFFFAOYSA-N methyl 2-[(4-chlorophenyl)sulfonylamino]butanoate Chemical compound COC(=O)C(CC)NS(=O)(=O)C1=CC=C(Cl)C=C1 UTVMMYAYJZXJFO-UHFFFAOYSA-N 0.000 description 1
• UIUAZDMKZNNOOB-UHFFFAOYSA-N methylamino butanoate Chemical compound CCCC(=O)ONC UIUAZDMKZNNOOB-UHFFFAOYSA-N 0.000 description 1
• DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
• 239000002808 molecular sieve Substances 0.000 description 1
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 210000004877 mucosa Anatomy 0.000 description 1
• 229940043348 myristyl alcohol Drugs 0.000 description 1
• DWLVWMUCHSLGSU-UHFFFAOYSA-M n,n-dimethylcarbamate Chemical compound CN(C)C([O-])=O DWLVWMUCHSLGSU-UHFFFAOYSA-M 0.000 description 1
• PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
• IHYNKGRWCDKNEG-UHFFFAOYSA-N n-(4-bromophenyl)-2,6-dihydroxybenzamide Chemical compound OC1=CC=CC(O)=C1C(=O)NC1=CC=C(Br)C=C1 IHYNKGRWCDKNEG-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 208000015122 neurodegenerative disease Diseases 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• 231100000344 non-irritating Toxicity 0.000 description 1
• GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 1
• 125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 description 1
• 239000003883 ointment base Substances 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 125000002734 organomagnesium group Chemical group 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 238000000059 patterning Methods 0.000 description 1
• RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
• 238000010647 peptide synthesis reaction Methods 0.000 description 1
• VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
• 239000008251 pharmaceutical emulsion Substances 0.000 description 1
• AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• 150000008300 phosphoramidites Chemical class 0.000 description 1
• DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 229920001184 polypeptide Polymers 0.000 description 1
• 229920002223 polystyrene Polymers 0.000 description 1
• 229920002451 polyvinyl alcohol Polymers 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 201000002212 progressive supranuclear palsy Diseases 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
• 230000005180 public health Effects 0.000 description 1
• BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 1
• FREJAOSUHFGDBW-UHFFFAOYSA-N pyrimidine-5-carbaldehyde Chemical compound O=CC1=CN=CN=C1 FREJAOSUHFGDBW-UHFFFAOYSA-N 0.000 description 1
• 125000001422 pyrrolinyl group Chemical group 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 230000000306 recurrent effect Effects 0.000 description 1
• 230000000979 retarding effect Effects 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 150000003333 secondary alcohols Chemical class 0.000 description 1
• 230000011218 segmentation Effects 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 229910052709 silver Inorganic materials 0.000 description 1
• 239000004332 silver Substances 0.000 description 1
• 235000015424 sodium Nutrition 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 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
• 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 239000007790 solid phase Substances 0.000 description 1
• 239000006104 solid solution Substances 0.000 description 1
• 210000002023 somite Anatomy 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 239000012128 staining reagent Substances 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 125000004426 substituted alkynyl group Chemical group 0.000 description 1
• 150000005846 sugar alcohols Polymers 0.000 description 1
• 125000000542 sulfonic acid group Chemical group 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• ZZIKGBYOHWQFFK-UHFFFAOYSA-N tert-butyl 5-(hydroxymethylidene)-4-oxo-2-phenylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(=CO)C(=O)CC1C1=CC=CC=C1 ZZIKGBYOHWQFFK-UHFFFAOYSA-N 0.000 description 1
• HRNNWJHAGDNBQH-UHFFFAOYSA-N tert-butyl 6-phenyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine-5-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC=2C=NNC=2CC1C1=CC=CC=C1 HRNNWJHAGDNBQH-UHFFFAOYSA-N 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 150000003509 tertiary alcohols Chemical class 0.000 description 1
• 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 125000005297 thienyloxy group Chemical group S1C(=CC=C1)O* 0.000 description 1
• HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
• 230000030968 tissue homeostasis Effects 0.000 description 1
• 229940100611 topical cream Drugs 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 229940042129 topical gel Drugs 0.000 description 1
• 229940100615 topical ointment Drugs 0.000 description 1
• 239000012049 topical pharmaceutical composition Substances 0.000 description 1
• 230000002110 toxicologic effect Effects 0.000 description 1
• 231100000027 toxicology Toxicity 0.000 description 1
• 230000007704 transition Effects 0.000 description 1
• 230000005945 translocation Effects 0.000 description 1
• 108091005703 transmembrane proteins Proteins 0.000 description 1
• 102000035160 transmembrane proteins Human genes 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 239000005051 trimethylchlorosilane Substances 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 238000012800 visualization Methods 0.000 description 1
• 238000010792 warming Methods 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 239000008096 xylene Substances 0.000 description 1