MXPA03010733A - Compuestos de etilamina aza-hidroxilados. - Google Patents
Compuestos de etilamina aza-hidroxilados.Info
- Publication number
- MXPA03010733A MXPA03010733A MXPA03010733A MXPA03010733A MXPA03010733A MX PA03010733 A MXPA03010733 A MX PA03010733A MX PA03010733 A MXPA03010733 A MX PA03010733A MX PA03010733 A MXPA03010733 A MX PA03010733A MX PA03010733 A MXPA03010733 A MX PA03010733A
- Authority
- MX
- Mexico
- Prior art keywords
- optionally substituted
- oxide
- group
- alkyl
- ari
- Prior art date
Links
- -1 Aza hydroxylated ethyl amine compounds Chemical class 0.000 title claims description 384
- 150000001875 compounds Chemical class 0.000 claims abstract description 279
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 82
- 238000000034 method Methods 0.000 claims abstract description 80
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 69
- 201000010099 disease Diseases 0.000 claims abstract description 63
- 150000003839 salts Chemical class 0.000 claims abstract description 39
- 238000011282 treatment Methods 0.000 claims abstract description 38
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 295
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 285
- 125000001424 substituent group Chemical group 0.000 claims description 245
- 125000000217 alkyl group Chemical group 0.000 claims description 241
- 125000003545 alkoxy group Chemical group 0.000 claims description 156
- 229910052739 hydrogen Inorganic materials 0.000 claims description 120
- 150000002367 halogens Chemical class 0.000 claims description 108
- 229910052736 halogen Inorganic materials 0.000 claims description 99
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 89
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 74
- 229910052717 sulfur Inorganic materials 0.000 claims description 71
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 69
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 68
- 239000001257 hydrogen Substances 0.000 claims description 64
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 60
- 239000000460 chlorine Substances 0.000 claims description 49
- 229910052731 fluorine Inorganic materials 0.000 claims description 46
- 229910052801 chlorine Inorganic materials 0.000 claims description 44
- 229910052799 carbon Inorganic materials 0.000 claims description 39
- 206010012289 Dementia Diseases 0.000 claims description 38
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 37
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 35
- 125000002883 imidazolyl group Chemical group 0.000 claims description 33
- 125000000335 thiazolyl group Chemical group 0.000 claims description 33
- 125000004429 atom Chemical group 0.000 claims description 32
- 125000002971 oxazolyl group Chemical group 0.000 claims description 32
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 31
- 125000003282 alkyl amino group Chemical group 0.000 claims description 31
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 31
- 125000001544 thienyl group Chemical group 0.000 claims description 31
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 28
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 28
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 27
- 125000001041 indolyl group Chemical group 0.000 claims description 27
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 27
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 27
- 125000004076 pyridyl group Chemical group 0.000 claims description 27
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 26
- 125000003386 piperidinyl group Chemical group 0.000 claims description 26
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 25
- 125000003342 alkenyl group Chemical group 0.000 claims description 25
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 25
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 claims description 25
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 25
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 25
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 25
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 25
- 125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 claims description 24
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 24
- 125000002757 morpholinyl group Chemical group 0.000 claims description 24
- 125000004193 piperazinyl group Chemical group 0.000 claims description 23
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 22
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 claims description 22
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 21
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 claims description 21
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 21
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 21
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 21
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 21
- 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 claims description 21
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 21
- 125000005990 isobenzothienyl group Chemical group 0.000 claims description 21
- 125000003151 isocoumarinyl group Chemical group C1(=O)OC(=CC2=CC=CC=C12)* 0.000 claims description 21
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 21
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 21
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 21
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 21
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 21
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 21
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 21
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 21
- 125000004306 triazinyl group Chemical group 0.000 claims description 21
- 125000001425 triazolyl group Chemical group 0.000 claims description 21
- 125000000304 alkynyl group Chemical group 0.000 claims description 20
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 20
- 125000004617 chromonyl group Chemical group O1C(=CC(C2=CC=CC=C12)=O)* 0.000 claims description 20
- 125000002541 furyl group Chemical group 0.000 claims description 20
- 125000005995 isobenzotetrahydrothienyl group Chemical group 0.000 claims description 20
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 20
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 20
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims description 20
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 20
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 20
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 20
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 20
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 19
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 19
- 150000001721 carbon Chemical group 0.000 claims description 19
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 18
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 claims description 18
- 125000005044 dihydroquinolinyl group Chemical group N1(CC=CC2=CC=CC=C12)* 0.000 claims description 18
- 125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 18
- 230000003412 degenerative effect Effects 0.000 claims description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- 125000005994 isobenzotetrahydrofuranyl group Chemical group 0.000 claims description 17
- 125000004620 quinolinyl-N-oxide group Chemical group 0.000 claims description 17
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 16
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 16
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 16
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 16
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 claims description 15
- 125000005052 dihydropyrazolyl group Chemical group N1(NCC=C1)* 0.000 claims description 15
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 claims description 15
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 15
- 125000005958 tetrahydrothienyl group Chemical group 0.000 claims description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
- 125000005046 dihydronaphthyl group Chemical group 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 14
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 14
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 13
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims description 13
- 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 claims description 13
- 125000005053 dihydropyrimidinyl group Chemical group N1(CN=CC=C1)* 0.000 claims description 13
- 125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 claims description 13
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- 125000006710 (C2-C12) alkenyl group Chemical group 0.000 claims description 11
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 11
- 125000005051 dihydropyrazinyl group Chemical group N1(CC=NC=C1)* 0.000 claims description 11
- 125000001624 naphthyl group Chemical group 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000005992 dihydrobenzisothiazinyl group Chemical group 0.000 claims description 10
- 208000028698 Cognitive impairment Diseases 0.000 claims description 9
- 201000010374 Down Syndrome Diseases 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- 208000010877 cognitive disease Diseases 0.000 claims description 9
- 229910052740 iodine Inorganic materials 0.000 claims description 9
- 125000006288 3,5-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(C([H])=C1F)C([H])([H])* 0.000 claims description 8
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 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 8
- 230000002792 vascular Effects 0.000 claims description 8
- 208000032843 Hemorrhage Diseases 0.000 claims description 7
- 208000018737 Parkinson disease Diseases 0.000 claims description 7
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 7
- 230000001054 cortical effect Effects 0.000 claims description 7
- 230000007850 degeneration Effects 0.000 claims description 7
- 125000005993 dihydrobenzisoxazinyl group Chemical group 0.000 claims description 7
- 230000000750 progressive effect Effects 0.000 claims description 7
- 230000000306 recurrent effect Effects 0.000 claims description 7
- 208000018282 ACys amyloidosis Diseases 0.000 claims description 6
- 208000007487 Familial Cerebral Amyloid Angiopathy Diseases 0.000 claims description 6
- 208000032849 Hereditary cerebral hemorrhage with amyloidosis Diseases 0.000 claims description 6
- 206010033799 Paralysis Diseases 0.000 claims description 6
- 210000004558 lewy body Anatomy 0.000 claims description 6
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 5
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 5
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 5
- 125000006413 ring segment Chemical group 0.000 claims description 5
- 229910014585 C2-Ce Inorganic materials 0.000 claims description 4
- 150000001204 N-oxides Chemical class 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 150000003947 ethylamines Chemical class 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- 125000006763 (C3-C9) cycloalkyl group Chemical group 0.000 claims description 2
- 230000001934 delay Effects 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 2
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 1
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 claims 1
- VMUXSMXIQBNMGZ-UHFFFAOYSA-N 3,4-dihydrocoumarin Chemical compound C1=CC=C2OC(=O)CCC2=C1 VMUXSMXIQBNMGZ-UHFFFAOYSA-N 0.000 claims 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 101000603877 Homo sapiens Nuclear receptor subfamily 1 group I member 2 Proteins 0.000 claims 1
- DYDCUQKUCUHJBH-REOHCLBHSA-N L-Cycloserine Chemical compound N[C@H]1CONC1=O DYDCUQKUCUHJBH-REOHCLBHSA-N 0.000 claims 1
- 102100038494 Nuclear receptor subfamily 1 group I member 2 Human genes 0.000 claims 1
- 125000006287 difluorobenzyl group Chemical group 0.000 claims 1
- DMSHWWDRAYHEBS-UHFFFAOYSA-N dihydrocoumarin Natural products C1CC(=O)OC2=C1C=C(OC)C(OC)=C2 DMSHWWDRAYHEBS-UHFFFAOYSA-N 0.000 claims 1
- 239000011737 fluorine Chemical group 0.000 claims 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 abstract description 101
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 abstract description 101
- 239000003112 inhibitor Substances 0.000 abstract description 50
- 108090000765 processed proteins & peptides Proteins 0.000 abstract description 27
- 150000002148 esters Chemical class 0.000 abstract description 22
- 230000015572 biosynthetic process Effects 0.000 abstract description 13
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 4
- 230000008021 deposition Effects 0.000 abstract description 3
- 241000124008 Mammalia Species 0.000 abstract description 2
- 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 96
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 90
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 90
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- 238000003776 cleavage reaction Methods 0.000 description 70
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- 230000002401 inhibitory effect Effects 0.000 description 38
- 102000004190 Enzymes Human genes 0.000 description 34
- 108090000790 Enzymes Proteins 0.000 description 34
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 34
- 229940088598 enzyme Drugs 0.000 description 34
- 238000003556 assay Methods 0.000 description 33
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- 210000004556 brain Anatomy 0.000 description 23
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- 208000037259 Amyloid Plaque Diseases 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 238000011534 incubation Methods 0.000 description 14
- 230000035772 mutation Effects 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 13
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- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- 150000001413 amino acids Chemical class 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 12
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- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical group N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 10
- 241000282412 Homo Species 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 238000001514 detection method Methods 0.000 description 10
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 8
- 125000006711 (C2-C12) alkynyl group Chemical group 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 7
- 210000005013 brain tissue Anatomy 0.000 description 7
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- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000011895 specific detection Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 229960003565 tacrine hydrochloride Drugs 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- CELHDQUVTZTDIQ-GJZGRUSLSA-N tert-butyl n-[[(2s,3s)-3-amino-2-hydroxy-4-phenylbutyl]-ethylamino]carbamate Chemical compound CC(C)(C)OC(=O)NN(CC)C[C@H](O)[C@@H](N)CC1=CC=CC=C1 CELHDQUVTZTDIQ-GJZGRUSLSA-N 0.000 description 1
- YYDXUWFHKOOZMG-GJZGRUSLSA-N tert-butyl n-[[(2s,3s)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-ethylamino]carbamate Chemical compound CC(C)(C)OC(=O)NN(CC)C[C@H](O)[C@@H](N)CC1=CC(F)=CC(F)=C1 YYDXUWFHKOOZMG-GJZGRUSLSA-N 0.000 description 1
- RHGBKMGDLLCUFI-VXKWHMMOSA-N tert-butyl n-[ethyl-[(2s,3s)-2-hydroxy-4-phenyl-3-(phenylmethoxycarbonylamino)butyl]amino]carbamate Chemical compound C([C@@H]([C@@H](O)CN(CC)NC(=O)OC(C)(C)C)NC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 RHGBKMGDLLCUFI-VXKWHMMOSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 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
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 229950010938 valspodar Drugs 0.000 description 1
- 108010082372 valspodar Proteins 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- IHOVFYSQUDPMCN-QKUIIBHLSA-N zosuquidar Chemical compound C([C@H](COC=1C2=CC=CN=C2C=CC=1)O)N(CC1)CCN1C1C2=CC=CC=C2C2C(F)(F)C2C2=CC=CC=C12 IHOVFYSQUDPMCN-QKUIIBHLSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C243/00—Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
- C07C243/24—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids
- C07C243/26—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C243/30—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of an unsaturated carbon skeleton
- C07C243/32—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of an unsaturated carbon skeleton the carbon skeleton containing rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C243/00—Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
- C07C243/24—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids
- C07C243/26—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C243/28—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of a saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/48—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups having nitrogen atoms of sulfonamide groups further bound to another hetero atom
- C07C311/49—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups having nitrogen atoms of sulfonamide groups further bound to another hetero atom to nitrogen atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US29285601P | 2001-05-22 | 2001-05-22 | |
| US30135501P | 2001-06-27 | 2001-06-27 | |
| US36060102P | 2002-03-01 | 2002-03-01 | |
| PCT/US2002/016199 WO2002094768A2 (en) | 2001-05-22 | 2002-05-22 | Aza hydroxylated ethyl amine compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA03010733A true MXPA03010733A (es) | 2004-07-01 |
Family
ID=27404155
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA03010733A MXPA03010733A (es) | 2001-05-22 | 2002-05-22 | Compuestos de etilamina aza-hidroxilados. |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US6960664B2 (enExample) |
| EP (1) | EP1392645A2 (enExample) |
| JP (1) | JP2004534771A (enExample) |
| BR (1) | BR0209985A (enExample) |
| CA (1) | CA2448084A1 (enExample) |
| MX (1) | MXPA03010733A (enExample) |
| WO (1) | WO2002094768A2 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2410680A1 (en) * | 2000-06-30 | 2002-01-10 | Elan Pharmaceuticals, Inc. | Compounds to treat alzheimer's disease |
| RU2357962C2 (ru) * | 2002-09-06 | 2009-06-10 | Элан Фармасьютикалз, Инк. | Пролекарственные производные 1,3-диамино-2-гидроксипропана |
| AU2003279492A1 (en) * | 2002-12-11 | 2004-06-30 | Pharmacia & Upjohn Company Llc | Treatment of diseases with combinations of alpha 7 nicotinic acetylcholine receptor agonists and other compounds |
| US7521481B2 (en) * | 2003-02-27 | 2009-04-21 | Mclaurin Joanne | Methods of preventing, treating and diagnosing disorders of protein aggregation |
| JP5005351B2 (ja) * | 2003-12-11 | 2012-08-22 | アボット・ラボラトリーズ | Ｈｉｖプロテアーゼ阻害性化合物 |
| MX2007012341A (es) | 2005-04-08 | 2008-02-12 | Comentis Inc | Compuestos que inhiben actividad beta-secretasa y metodos de uso de los mismos. |
| UY37592A (es) | 2017-02-06 | 2018-08-31 | Gilead Sciences Inc | Compuestos inhibidores del vih |
| TWI829205B (zh) | 2018-07-30 | 2024-01-11 | 美商基利科學股份有限公司 | 抗hiv化合物 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69333270T2 (de) * | 1992-03-11 | 2004-08-05 | Narhex Ltd. | Aminderivate von oxo- und hydroxy- substituierten kohlenwasserstoffen |
| JPH11514996A (ja) * | 1995-11-21 | 1999-12-21 | ノバルティス アクチエンゲゼルシャフト | レトロウイルスアスパラギン酸プロテアーゼの置換同配体としてのアザヘキサン誘導体 |
| US6087383A (en) * | 1998-01-20 | 2000-07-11 | Bristol-Myers Squibb Company | Bisulfate salt of HIV protease inhibitor |
| CA2410680A1 (en) | 2000-06-30 | 2002-01-10 | Elan Pharmaceuticals, Inc. | Compounds to treat alzheimer's disease |
-
2002
- 2002-05-22 JP JP2002591441A patent/JP2004534771A/ja active Pending
- 2002-05-22 MX MXPA03010733A patent/MXPA03010733A/es not_active Application Discontinuation
- 2002-05-22 BR BR0209985-3A patent/BR0209985A/pt not_active IP Right Cessation
- 2002-05-22 CA CA002448084A patent/CA2448084A1/en not_active Abandoned
- 2002-05-22 WO PCT/US2002/016199 patent/WO2002094768A2/en not_active Ceased
- 2002-05-22 EP EP02739333A patent/EP1392645A2/en not_active Withdrawn
- 2002-05-22 US US10/152,601 patent/US6960664B2/en not_active Expired - Fee Related
-
2005
- 2005-11-01 US US11/264,738 patent/US20060069264A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| BR0209985A (pt) | 2004-06-29 |
| CA2448084A1 (en) | 2002-11-28 |
| EP1392645A2 (en) | 2004-03-03 |
| WO2002094768A2 (en) | 2002-11-28 |
| WO2002094768A3 (en) | 2003-03-20 |
| US20060069264A1 (en) | 2006-03-30 |
| JP2004534771A (ja) | 2004-11-18 |
| US20030229138A1 (en) | 2003-12-11 |
| US6960664B2 (en) | 2005-11-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FA | Abandonment or withdrawal |