ES2393331T3 - Derivados de piperidintriol como inhibidores de la glucosiliceramida sintasa - Google Patents
Derivados de piperidintriol como inhibidores de la glucosiliceramida sintasa Download PDFInfo
- Publication number
- ES2393331T3 ES2393331T3 ES03764025T ES03764025T ES2393331T3 ES 2393331 T3 ES2393331 T3 ES 2393331T3 ES 03764025 T ES03764025 T ES 03764025T ES 03764025 T ES03764025 T ES 03764025T ES 2393331 T3 ES2393331 T3 ES 2393331T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- compound
- phenyl
- methanol
- optionally substituted
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 239000003112 inhibitor Substances 0.000 title claims description 18
- KHANGFJTBIHUNK-UHFFFAOYSA-N 1-hydroxypiperidine-2,2-diol Chemical class ON1CCCCC1(O)O KHANGFJTBIHUNK-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 210
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 97
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 76
- 125000001424 substituent group Chemical group 0.000 claims abstract description 73
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 62
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 58
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 48
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 34
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 33
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 32
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 21
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 16
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 16
- 101150047265 COR2 gene Proteins 0.000 claims abstract description 13
- 101100467189 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) QCR2 gene Proteins 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 12
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 9
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 9
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims abstract description 5
- 238000011282 treatment Methods 0.000 claims description 65
- 229930186217 Glycolipid Natural products 0.000 claims description 52
- 238000000034 method Methods 0.000 claims description 44
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 37
- 239000003814 drug Substances 0.000 claims description 35
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 claims description 32
- 230000015572 biosynthetic process Effects 0.000 claims description 31
- 201000010099 disease Diseases 0.000 claims description 29
- 238000003786 synthesis reaction Methods 0.000 claims description 28
- 238000004519 manufacturing process Methods 0.000 claims description 27
- 210000004027 cell Anatomy 0.000 claims description 25
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 206010028980 Neoplasm Diseases 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 208000027866 inflammatory disease Diseases 0.000 claims description 12
- 230000001537 neural effect Effects 0.000 claims description 12
- 238000003860 storage Methods 0.000 claims description 12
- 230000002159 abnormal effect Effects 0.000 claims description 11
- 150000002305 glucosylceramides Chemical class 0.000 claims description 11
- 208000015181 infectious disease Diseases 0.000 claims description 11
- 210000002540 macrophage Anatomy 0.000 claims description 11
- 150000002270 gangliosides Chemical class 0.000 claims description 10
- 230000002458 infectious effect Effects 0.000 claims description 10
- 201000011510 cancer Diseases 0.000 claims description 9
- 208000024827 Alzheimer disease Diseases 0.000 claims description 8
- 208000002678 Mucopolysaccharidoses Diseases 0.000 claims description 8
- 206010028093 mucopolysaccharidosis Diseases 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 208000018737 Parkinson disease Diseases 0.000 claims description 7
- 208000006011 Stroke Diseases 0.000 claims description 7
- 230000004913 activation Effects 0.000 claims description 7
- 230000007115 recruitment Effects 0.000 claims description 7
- 208000015872 Gaucher disease Diseases 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 6
- QPJBWNIQKHGLAU-IQZHVAEDSA-N ganglioside GM1 Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](NC(=O)CCCCCCCCCCCCCCCCC)[C@H](O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@H](O)CO)C(O)=O)[C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O3)O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 QPJBWNIQKHGLAU-IQZHVAEDSA-N 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 208000011231 Crohn disease Diseases 0.000 claims description 5
- 201000008892 GM1 Gangliosidosis Diseases 0.000 claims description 5
- 208000008955 Mucolipidoses Diseases 0.000 claims description 5
- 208000008589 Obesity Diseases 0.000 claims description 5
- 208000021811 Sandhoff disease Diseases 0.000 claims description 5
- 206010040047 Sepsis Diseases 0.000 claims description 5
- 208000022292 Tay-Sachs disease Diseases 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 206010015037 epilepsy Diseases 0.000 claims description 5
- 235000020824 obesity Nutrition 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- 208000020431 spinal cord injury Diseases 0.000 claims description 5
- 102100022548 Beta-hexosaminidase subunit alpha Human genes 0.000 claims description 4
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 4
- 208000024720 Fabry Disease Diseases 0.000 claims description 4
- 208000027933 Mannosidase Deficiency disease Diseases 0.000 claims description 4
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 4
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- 208000025919 mucopolysaccharidosis type 7 Diseases 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000003053 toxin Substances 0.000 claims description 4
- 231100000765 toxin Toxicity 0.000 claims description 4
- 108700012359 toxins Proteins 0.000 claims description 4
- 208000034578 Multiple myelomas Diseases 0.000 claims description 3
- 206010029260 Neuroblastoma Diseases 0.000 claims description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 3
- 238000010511 deprotection reaction Methods 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 244000005700 microbiome Species 0.000 claims description 3
- 208000036710 mucopolysaccharidosis type 3A Diseases 0.000 claims description 3
- 208000036709 mucopolysaccharidosis type 3B Diseases 0.000 claims description 3
- 238000006268 reductive amination reaction Methods 0.000 claims description 3
- 208000016691 refractory malignant neoplasm Diseases 0.000 claims description 3
- 208000007930 Type C Niemann-Pick Disease Diseases 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 208000021267 infertility disease Diseases 0.000 claims description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 238000009877 rendering Methods 0.000 claims 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 477
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 111
- 239000000243 solution Substances 0.000 description 101
- 239000000203 mixture Substances 0.000 description 83
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 75
- 239000011347 resin Substances 0.000 description 72
- 229920005989 resin Polymers 0.000 description 72
- -1 for example Substances 0.000 description 56
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 46
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 46
- 239000000908 ammonium hydroxide Substances 0.000 description 46
- 239000011541 reaction mixture Substances 0.000 description 43
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 36
- 239000002253 acid Substances 0.000 description 35
- 239000006227 byproduct Substances 0.000 description 35
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 28
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- 239000007787 solid Substances 0.000 description 27
- LXBIFEVIBLOUGU-AZGQCCRYSA-N (2s,3r,4s,5s)-2-(hydroxymethyl)piperidine-3,4,5-triol Chemical compound OC[C@@H]1NC[C@H](O)[C@H](O)[C@@H]1O LXBIFEVIBLOUGU-AZGQCCRYSA-N 0.000 description 26
- 238000005160 1H NMR spectroscopy Methods 0.000 description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 21
- 239000004480 active ingredient Substances 0.000 description 19
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 15
- 238000010828 elution Methods 0.000 description 14
- 239000000377 silicon dioxide Substances 0.000 description 14
- 238000005481 NMR spectroscopy Methods 0.000 description 13
- 230000005764 inhibitory process Effects 0.000 description 13
- 239000003981 vehicle Substances 0.000 description 13
- 238000004440 column chromatography Methods 0.000 description 11
- LXBIFEVIBLOUGU-UNTFVMJOSA-N (2s,3r,4r,5s)-2-(hydroxymethyl)piperidine-3,4,5-triol Chemical compound OC[C@@H]1NC[C@H](O)[C@@H](O)[C@@H]1O LXBIFEVIBLOUGU-UNTFVMJOSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 241000700605 Viruses Species 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 208000035475 disorder Diseases 0.000 description 8
- 239000000725 suspension Substances 0.000 description 7
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
- 239000006071 cream Substances 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 5
- 102000044956 Ceramide glucosyltransferases Human genes 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 208000036142 Viral infection Diseases 0.000 description 5
- 108091000114 ceramide glucosyltransferase Proteins 0.000 description 5
- 230000002132 lysosomal effect Effects 0.000 description 5
- UQRORFVVSGFNRO-UTINFBMNSA-N miglustat Chemical compound CCCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO UQRORFVVSGFNRO-UTINFBMNSA-N 0.000 description 5
- 229960001512 miglustat Drugs 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 230000009385 viral infection Effects 0.000 description 5
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 4
- BGNGWHSBYQYVRX-UHFFFAOYSA-N 4-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=C(C=O)C=C1 BGNGWHSBYQYVRX-UHFFFAOYSA-N 0.000 description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 206010038468 Renal hypertrophy Diseases 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
- 201000008627 kidney hypertrophy Diseases 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 208000030761 polycystic kidney disease Diseases 0.000 description 4
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 4
- 229940080818 propionamide Drugs 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- JXCALVWIRLVTDI-VNTMZGSJSA-N (2s,3r,4r,5s)-2-(hydroxymethyl)-1-[(4-phenylmethoxyphenyl)methyl]piperidine-3,4,5-triol Chemical compound OC[C@H]1[C@@H](O)[C@H](O)[C@@H](O)CN1CC(C=C1)=CC=C1OCC1=CC=CC=C1 JXCALVWIRLVTDI-VNTMZGSJSA-N 0.000 description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 3
- CMLFRMDBDNHMRA-UHFFFAOYSA-N 2h-1,2-benzoxazine Chemical compound C1=CC=C2C=CNOC2=C1 CMLFRMDBDNHMRA-UHFFFAOYSA-N 0.000 description 3
- 208000035473 Communicable disease Diseases 0.000 description 3
- 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 3
- 101000981050 Homo sapiens Ceramide glucosyltransferase Proteins 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- HSCJRCZFDFQWRP-JZMIEXBBSA-N UDP-alpha-D-glucose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OP(O)(=O)OP(O)(=O)OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 HSCJRCZFDFQWRP-JZMIEXBBSA-N 0.000 description 3
- HSCJRCZFDFQWRP-UHFFFAOYSA-N Uridindiphosphoglukose Natural products OC1C(O)C(O)C(CO)OC1OP(O)(=O)OP(O)(=O)OCC1C(O)C(O)C(N2C(NC(=O)C=C2)=O)O1 HSCJRCZFDFQWRP-UHFFFAOYSA-N 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 239000002158 endotoxin Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 3
- 150000003053 piperidines Chemical class 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 238000011200 topical administration Methods 0.000 description 3
- 239000008215 water for injection Substances 0.000 description 3
- UQRORFVVSGFNRO-XFWSIPNHSA-N (2r,3s,4r,5s)-1-butyl-2-(hydroxymethyl)piperidine-3,4,5-triol Chemical compound CCCCN1C[C@H](O)[C@@H](O)[C@@H](O)[C@H]1CO UQRORFVVSGFNRO-XFWSIPNHSA-N 0.000 description 2
- MJJAXQMMEWETPB-RAUXBKROSA-N (2s,3r,4r,5s)-1-[(3-chloro-4-phenylmethoxyphenyl)methyl]-2-(hydroxymethyl)piperidine-3,4,5-triol Chemical compound OC[C@H]1[C@@H](O)[C@H](O)[C@@H](O)CN1CC(C=C1Cl)=CC=C1OCC1=CC=CC=C1 MJJAXQMMEWETPB-RAUXBKROSA-N 0.000 description 2
- LAAKAOBAYXRRQD-INDMIFKZSA-N (2s,3r,4r,5s)-2-(hydroxymethyl)-1-[(4-phenoxyphenyl)methyl]piperidine-3,4,5-triol Chemical compound OC[C@H]1[C@@H](O)[C@H](O)[C@@H](O)CN1CC(C=C1)=CC=C1OC1=CC=CC=C1 LAAKAOBAYXRRQD-INDMIFKZSA-N 0.000 description 2
- YFXLXAPIGKFCIZ-FMWKFLBASA-N 2-phenyl-n-[4-[[(2s,3r,4r,5s)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]methyl]phenyl]acetamide Chemical compound OC[C@H]1[C@@H](O)[C@H](O)[C@@H](O)CN1CC(C=C1)=CC=C1NC(=O)CC1=CC=CC=C1 YFXLXAPIGKFCIZ-FMWKFLBASA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 201000007336 Cryptococcosis Diseases 0.000 description 2
- 241000221204 Cryptococcus neoformans Species 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
- 241000233866 Fungi Species 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 102000004547 Glucosylceramidase Human genes 0.000 description 2
- 108010017544 Glucosylceramidase Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 2
- 208000014060 Niemann-Pick disease Diseases 0.000 description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical group C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 208000020339 Spinal injury Diseases 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 125000002877 alkyl aryl group Chemical group 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 210000000709 aorta Anatomy 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000003143 atherosclerotic effect Effects 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229940106189 ceramide Drugs 0.000 description 2
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 2
- 239000003892 ceramide glucosyltransferase inhibitor Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 229940125921 glucosylceramide synthase inhibitor Drugs 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 125000001072 heteroaryl group Chemical group 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
- 239000004615 ingredient Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 208000005340 mucopolysaccharidosis III Diseases 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- LISONWISWHOVSY-JYDHQNPFSA-N n-(1-phenylethyl)-4-[[(2s,3r,4r,5s)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]methyl]benzamide Chemical compound C=1C=CC=CC=1C(C)NC(=O)C(C=C1)=CC=C1CN1C[C@H](O)[C@@H](O)[C@H](O)[C@@H]1CO LISONWISWHOVSY-JYDHQNPFSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000003883 ointment base Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 201000011303 renal artery atheroma Diseases 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 229930192474 thiophene Chemical group 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 150000003852 triazoles Chemical group 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- FTCPXXPSLODLCS-GFCCVEGCSA-N (2r)-n-(4-formylphenyl)-2-phenylpropanamide Chemical compound O=C([C@H](C)C=1C=CC=CC=1)NC1=CC=C(C=O)C=C1 FTCPXXPSLODLCS-GFCCVEGCSA-N 0.000 description 1
- 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 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- FTCPXXPSLODLCS-LBPRGKRZSA-N (2s)-n-(4-formylphenyl)-2-phenylpropanamide Chemical compound O=C([C@@H](C)C=1C=CC=CC=1)NC1=CC=C(C=O)C=C1 FTCPXXPSLODLCS-LBPRGKRZSA-N 0.000 description 1
- IGBVWKXXQGSEJY-UOVKNHIHSA-N (2s,3r,4r,5s)-1-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-2-(hydroxymethyl)piperidine-3,4,5-triol Chemical compound OC[C@H]1[C@@H](O)[C@H](O)[C@@H](O)CN1CC1=CC=C(OCCO2)C2=C1 IGBVWKXXQGSEJY-UOVKNHIHSA-N 0.000 description 1
- OYCCJAUEWCZOOE-DDHJSBNISA-N (2s,3r,4r,5s)-1-(2,3-dihydro-1-benzofuran-5-ylmethyl)-2-(hydroxymethyl)piperidine-3,4,5-triol Chemical compound OC[C@H]1[C@@H](O)[C@H](O)[C@@H](O)CN1CC1=CC=C(OCC2)C2=C1 OYCCJAUEWCZOOE-DDHJSBNISA-N 0.000 description 1
- VQGICNOSPJDSQJ-UWHLTILDSA-N (2s,3r,4r,5s)-1-[(3,5-dimethyl-4-phenylmethoxyphenyl)methyl]-2-(hydroxymethyl)piperidine-3,4,5-triol Chemical compound C=1C(C)=C(OCC=2C=CC=CC=2)C(C)=CC=1CN1C[C@H](O)[C@@H](O)[C@H](O)[C@@H]1CO VQGICNOSPJDSQJ-UWHLTILDSA-N 0.000 description 1
- OLWLEADVJKYUHX-BYNSBNAKSA-N (2s,3r,4r,5s)-1-[[2-chloro-4-(dimethylamino)phenyl]methyl]-2-(hydroxymethyl)piperidine-3,4,5-triol Chemical compound ClC1=CC(N(C)C)=CC=C1CN1[C@@H](CO)[C@@H](O)[C@H](O)[C@@H](O)C1 OLWLEADVJKYUHX-BYNSBNAKSA-N 0.000 description 1
- MTZDZJGDVAVOCY-FMWKFLBASA-N (2s,3r,4r,5s)-2-(hydroxymethyl)-1-[(2-methoxy-4-phenylmethoxyphenyl)methyl]piperidine-3,4,5-triol Chemical compound C=1C=C(CN2[C@H]([C@@H](O)[C@H](O)[C@@H](O)C2)CO)C(OC)=CC=1OCC1=CC=CC=C1 MTZDZJGDVAVOCY-FMWKFLBASA-N 0.000 description 1
- RXUQHEKLWAVEJM-VNTMZGSJSA-N (2s,3r,4r,5s)-2-(hydroxymethyl)-1-[(3-phenylmethoxyphenyl)methyl]piperidine-3,4,5-triol Chemical compound OC[C@H]1[C@@H](O)[C@H](O)[C@@H](O)CN1CC1=CC=CC(OCC=2C=CC=CC=2)=C1 RXUQHEKLWAVEJM-VNTMZGSJSA-N 0.000 description 1
- JHGNSYHRODEMMR-WNRNVDISSA-N (2s,3r,4r,5s)-2-(hydroxymethyl)-1-[(4-pyridin-2-ylphenyl)methyl]piperidine-3,4,5-triol Chemical compound OC[C@H]1[C@@H](O)[C@H](O)[C@@H](O)CN1CC1=CC=C(C=2N=CC=CC=2)C=C1 JHGNSYHRODEMMR-WNRNVDISSA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 description 1
- LXBIFEVIBLOUGU-UHFFFAOYSA-N 1-deoxynojirimycin Chemical compound OCC1NCC(O)C(O)C1O LXBIFEVIBLOUGU-UHFFFAOYSA-N 0.000 description 1
- 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 1
- CWKXDPPQCVWXAG-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-6-carbaldehyde Chemical compound O1CCOC2=CC(C=O)=CC=C21 CWKXDPPQCVWXAG-UHFFFAOYSA-N 0.000 description 1
- QFGBDJDMBCDTFM-UHFFFAOYSA-N 2-(dimethylamino)-5-formylbenzonitrile Chemical compound CN(C)C1=CC=C(C=O)C=C1C#N QFGBDJDMBCDTFM-UHFFFAOYSA-N 0.000 description 1
- XSQFAWMDRFSIMY-UHFFFAOYSA-N 2-chloro-4-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=C(C=O)C(Cl)=C1 XSQFAWMDRFSIMY-UHFFFAOYSA-N 0.000 description 1
- HOMYIYLRRDTKAA-UHFFFAOYSA-N 2-hydroxy-N-[3-hydroxy-1-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoctadeca-4,8-dien-2-yl]hexadecanamide Chemical compound CCCCCCCCCCCCCCC(O)C(=O)NC(C(O)C=CCCC=CCCCCCCCCC)COC1OC(CO)C(O)C(O)C1O HOMYIYLRRDTKAA-UHFFFAOYSA-N 0.000 description 1
- HZLNIOUBXRIFML-UHFFFAOYSA-N 2-methoxy-4-phenylmethoxybenzaldehyde Chemical compound C1=C(C=O)C(OC)=CC(OCC=2C=CC=CC=2)=C1 HZLNIOUBXRIFML-UHFFFAOYSA-N 0.000 description 1
- PBEJTRAJWCNHRS-UHFFFAOYSA-N 2-phenylmethoxybenzaldehyde Chemical compound O=CC1=CC=CC=C1OCC1=CC=CC=C1 PBEJTRAJWCNHRS-UHFFFAOYSA-N 0.000 description 1
- GSYUTKRSEZMBNC-UHFFFAOYSA-N 3,5-dimethyl-4-phenylmethoxybenzaldehyde Chemical compound CC1=CC(C=O)=CC(C)=C1OCC1=CC=CC=C1 GSYUTKRSEZMBNC-UHFFFAOYSA-N 0.000 description 1
- VFKKDKHWDCSVHW-UHFFFAOYSA-N 4-(3,4-dihydro-2h-quinoline-1-carbonyl)benzaldehyde Chemical compound C1=CC(C=O)=CC=C1C(=O)N1C2=CC=CC=C2CCC1 VFKKDKHWDCSVHW-UHFFFAOYSA-N 0.000 description 1
- VNWPLOWYHIDMEB-UHFFFAOYSA-N 4-(dibutylamino)benzaldehyde Chemical compound CCCCN(CCCC)C1=CC=C(C=O)C=C1 VNWPLOWYHIDMEB-UHFFFAOYSA-N 0.000 description 1
- CLXSBHRRZNBTRT-VOTSOKGWSA-N 4-[(e)-2-phenylethenyl]benzaldehyde Chemical compound C1=CC(C=O)=CC=C1\C=C\C1=CC=CC=C1 CLXSBHRRZNBTRT-VOTSOKGWSA-N 0.000 description 1
- QWLHJVDRPZNVBS-UHFFFAOYSA-N 4-phenoxybenzaldehyde Chemical compound C1=CC(C=O)=CC=C1OC1=CC=CC=C1 QWLHJVDRPZNVBS-UHFFFAOYSA-N 0.000 description 1
- NMLYGLCBSFKJFI-UHFFFAOYSA-N 4-pyridin-2-ylbenzaldehyde Chemical compound C1=CC(C=O)=CC=C1C1=CC=CC=N1 NMLYGLCBSFKJFI-UHFFFAOYSA-N 0.000 description 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
- TUCLUYWNLLPXNV-CWLKWCNXSA-N 6-(diethylamino)-2-fluoro-3-[[(2s,3r,4r,5s)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]methyl]benzonitrile Chemical compound FC1=C(C#N)C(N(CC)CC)=CC=C1CN1[C@@H](CO)[C@@H](O)[C@H](O)[C@@H](O)C1 TUCLUYWNLLPXNV-CWLKWCNXSA-N 0.000 description 1
- FOSZCWIVBXTPPV-UHFFFAOYSA-N 6-(diethylamino)-2-fluoro-3-formylbenzonitrile Chemical compound CCN(CC)C1=CC=C(C=O)C(F)=C1C#N FOSZCWIVBXTPPV-UHFFFAOYSA-N 0.000 description 1
- AOQCUDZQCVTYLS-WMHQRMGPSA-N 6-(dimethylamino)-2-fluoro-3-[[(2s,3r,4r,5s)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]methyl]benzonitrile Chemical compound FC1=C(C#N)C(N(C)C)=CC=C1CN1[C@@H](CO)[C@@H](O)[C@H](O)[C@@H](O)C1 AOQCUDZQCVTYLS-WMHQRMGPSA-N 0.000 description 1
- ZGQREXNGDAXSQI-UHFFFAOYSA-N 6-(dimethylamino)-2-fluoro-3-formylbenzonitrile Chemical compound CN(C)C1=CC=C(C=O)C(F)=C1C#N ZGQREXNGDAXSQI-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 231100000699 Bacterial toxin Toxicity 0.000 description 1
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 101100037762 Caenorhabditis elegans rnh-2 gene Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 102000009016 Cholera Toxin Human genes 0.000 description 1
- 108010049048 Cholera Toxin Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- 241000725619 Dengue virus Species 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- 206010014596 Encephalitis Japanese B Diseases 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 241000710831 Flavivirus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 206010017533 Fungal infection 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
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 241000711549 Hepacivirus C Species 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 208000035343 Infantile neurovisceral acid sphingomyelinase deficiency Diseases 0.000 description 1
- 206010021929 Infertility male Diseases 0.000 description 1
- 201000005807 Japanese encephalitis Diseases 0.000 description 1
- 241000710842 Japanese encephalitis virus Species 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 241001466978 Kyasanur forest disease virus Species 0.000 description 1
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 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 1
- 241000710769 Louping ill virus Species 0.000 description 1
- 208000007466 Male Infertility Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 206010072930 Mucolipidosis type IV Diseases 0.000 description 1
- 102100026502 Mucolipin-1 Human genes 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000710908 Murray Valley encephalitis virus Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 201000000794 Niemann-Pick disease type A Diseases 0.000 description 1
- 208000010577 Niemann-Pick disease type C Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 241000725177 Omsk hemorrhagic fever virus Species 0.000 description 1
- 229910002666 PdCl2 Inorganic materials 0.000 description 1
- 241000710778 Pestivirus Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000710884 Powassan virus Species 0.000 description 1
- 241000725643 Respiratory syncytial virus Species 0.000 description 1
- 102000015785 Serine C-Palmitoyltransferase Human genes 0.000 description 1
- 108010024814 Serine C-palmitoyltransferase Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 241000710888 St. Louis encephalitis virus Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 241000710771 Tick-borne encephalitis virus Species 0.000 description 1
- 102000008233 Toll-Like Receptor 4 Human genes 0.000 description 1
- 108010060804 Toll-Like Receptor 4 Proteins 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 208000007824 Type A Niemann-Pick Disease Diseases 0.000 description 1
- 201000006449 West Nile encephalitis Diseases 0.000 description 1
- 206010057293 West Nile viral infection Diseases 0.000 description 1
- 241000710772 Yellow fever virus Species 0.000 description 1
- ZCHPKWUIAASXPV-UHFFFAOYSA-N acetic acid;methanol Chemical compound OC.CC(O)=O ZCHPKWUIAASXPV-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000002830 appetite depressant Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- ZFSFDELZPURLKD-UHFFFAOYSA-N azanium;hydroxide;hydrate Chemical compound N.O.O ZFSFDELZPURLKD-UHFFFAOYSA-N 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000000688 bacterial toxin Substances 0.000 description 1
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 1
- WPIHMWBQRSAMDE-YCZTVTEBSA-N beta-D-galactosyl-(1->4)-beta-D-galactosyl-N-(pentacosanoyl)sphingosine Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@@H](CO[C@@H]1O[C@H](CO)[C@H](O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@H]1O)[C@H](O)\C=C\CCCCCCCCCCCCC WPIHMWBQRSAMDE-YCZTVTEBSA-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
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 108010037444 diisopropylglutathione ester Proteins 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 244000053095 fungal pathogen Species 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000009395 genetic defect Effects 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
- 239000008309 hydrophilic cream Substances 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- 239000002583 male contraceptive agent Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 125000000311 mannosyl group Chemical class C1([C@@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 125000005905 mesyloxy group Chemical group 0.000 description 1
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical group COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- OWMJAQBUFVTERI-UHFFFAOYSA-N n-(2-formylphenyl)acetamide Chemical compound CC(=O)NC1=CC=CC=C1C=O OWMJAQBUFVTERI-UHFFFAOYSA-N 0.000 description 1
- VXBXXBYZYVBRSA-UHFFFAOYSA-N n-(4-formylphenyl)-2-phenylacetamide Chemical compound C1=CC(C=O)=CC=C1NC(=O)CC1=CC=CC=C1 VXBXXBYZYVBRSA-UHFFFAOYSA-N 0.000 description 1
- SXMRPYYGXIIWCY-UHFFFAOYSA-N n-(4-formylphenyl)benzamide Chemical compound C1=CC(C=O)=CC=C1NC(=O)C1=CC=CC=C1 SXMRPYYGXIIWCY-UHFFFAOYSA-N 0.000 description 1
- ZHQUQGCHHYLPSD-UHFFFAOYSA-N n-(4-formylphenyl)benzenesulfonamide Chemical compound C1=CC(C=O)=CC=C1NS(=O)(=O)C1=CC=CC=C1 ZHQUQGCHHYLPSD-UHFFFAOYSA-N 0.000 description 1
- UMMDFLKMDDQMIJ-IQRXFYDRSA-N n-[(1r)-1-(4-fluorophenyl)ethyl]-4-[[(2s,3r,4r,5s)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]methyl]benzamide Chemical compound N([C@H](C)C=1C=CC(F)=CC=1)C(=O)C(C=C1)=CC=C1CN1C[C@H](O)[C@@H](O)[C@H](O)[C@@H]1CO UMMDFLKMDDQMIJ-IQRXFYDRSA-N 0.000 description 1
- WGJBAJWHRJNEPP-LLVKDONJSA-N n-[(1r)-1-(4-fluorophenyl)ethyl]-4-formylbenzamide Chemical compound N([C@H](C)C=1C=CC(F)=CC=1)C(=O)C1=CC=C(C=O)C=C1 WGJBAJWHRJNEPP-LLVKDONJSA-N 0.000 description 1
- LISONWISWHOVSY-NKXUHPISSA-N n-[(1r)-1-phenylethyl]-4-[[(2s,3r,4r,5s)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]methyl]benzamide Chemical compound N([C@H](C)C=1C=CC=CC=1)C(=O)C(C=C1)=CC=C1CN1C[C@H](O)[C@@H](O)[C@H](O)[C@@H]1CO LISONWISWHOVSY-NKXUHPISSA-N 0.000 description 1
- SPHIITYBTKLGBR-NSHDSACASA-N n-[(1s)-1-(4-fluorophenyl)ethyl]-4-formylbenzenesulfonamide Chemical compound N([C@@H](C)C=1C=CC(F)=CC=1)S(=O)(=O)C1=CC=C(C=O)C=C1 SPHIITYBTKLGBR-NSHDSACASA-N 0.000 description 1
- LISONWISWHOVSY-QLGJKCLRSA-N n-[(1s)-1-phenylethyl]-4-[[(2s,3r,4r,5s)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]methyl]benzamide Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(=O)C(C=C1)=CC=C1CN1C[C@H](O)[C@@H](O)[C@H](O)[C@@H]1CO LISONWISWHOVSY-QLGJKCLRSA-N 0.000 description 1
- RMLFKLXFAHMCPE-VNTMZGSJSA-N n-[(4-fluorophenyl)methyl]-4-[[(2s,3r,4r,5s)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]methyl]benzamide Chemical compound OC[C@H]1[C@@H](O)[C@H](O)[C@@H](O)CN1CC1=CC=C(C(=O)NCC=2C=CC(F)=CC=2)C=C1 RMLFKLXFAHMCPE-VNTMZGSJSA-N 0.000 description 1
- AOUCINQZVRQPJT-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-4-formyl-n-methylbenzamide Chemical compound C=1C=C(C=O)C=CC=1C(=O)N(C)CC1=CC=C(F)C=C1 AOUCINQZVRQPJT-UHFFFAOYSA-N 0.000 description 1
- NGCQFFVQZVSHCQ-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-4-formylbenzamide Chemical compound C1=CC(F)=CC=C1CNC(=O)C1=CC=C(C=O)C=C1 NGCQFFVQZVSHCQ-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- KUCUUMQYZNIEMR-INDMIFKZSA-N n-hexyl-4-[[(2s,3r,4r,5s)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]methyl]benzamide Chemical compound C1=CC(C(=O)NCCCCCC)=CC=C1CN1[C@@H](CO)[C@@H](O)[C@H](O)[C@@H](O)C1 KUCUUMQYZNIEMR-INDMIFKZSA-N 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 210000003024 peritoneal macrophage Anatomy 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
- VUAOIXANWIFYCU-UHFFFAOYSA-N quinoline-6-carbaldehyde Chemical compound N1=CC=CC2=CC(C=O)=CC=C21 VUAOIXANWIFYCU-UHFFFAOYSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 229940100611 topical cream Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940100615 topical ointment Drugs 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000037455 tumor specific immune response Effects 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 238000009834 vaporization Methods 0.000 description 1
- 230000008016 vaporization Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/16—Masculine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Oncology (AREA)
- Child & Adolescent Psychology (AREA)
- Communicable Diseases (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Vascular Medicine (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0216656A GB0216656D0 (en) | 2002-07-17 | 2002-07-17 | Novel compounds |
| GB0216656 | 2002-07-17 | ||
| GB0301480A GB0301480D0 (en) | 2003-01-22 | 2003-01-22 | Novel compounds |
| GB0301480 | 2003-01-22 | ||
| GB0313679A GB0313679D0 (en) | 2003-06-13 | 2003-06-13 | Novel compounds |
| GB0313679 | 2003-06-13 | ||
| PCT/GB2003/003099 WO2004007453A1 (en) | 2002-07-17 | 2003-07-17 | Piperidinetriol derivatives as inhibitors of glycosylceramide synthase |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2393331T3 true ES2393331T3 (es) | 2012-12-20 |
Family
ID=30118831
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES03764025T Expired - Lifetime ES2393331T3 (es) | 2002-07-17 | 2003-07-17 | Derivados de piperidintriol como inhibidores de la glucosiliceramida sintasa |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US7985760B2 (enExample) |
| EP (1) | EP1534676B1 (enExample) |
| JP (1) | JP4575156B2 (enExample) |
| AU (1) | AU2003246942B2 (enExample) |
| CA (1) | CA2492404C (enExample) |
| ES (1) | ES2393331T3 (enExample) |
| WO (1) | WO2004007453A1 (enExample) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0100889D0 (en) | 2001-01-12 | 2001-02-21 | Oxford Glycosciences Uk Ltd | Compounds |
| AU2003248960B2 (en) * | 2002-07-17 | 2009-06-25 | Idorsia Pharmaceuticals Ltd | Piperidinetriol derivatives as inhibitors of glycosylceramidsynthase |
| ES2393331T3 (es) | 2002-07-17 | 2012-12-20 | Actelion Pharmaceuticals Ltd. | Derivados de piperidintriol como inhibidores de la glucosiliceramida sintasa |
| GB0313677D0 (en) * | 2003-06-13 | 2003-07-16 | Oxford Glycosciences Uk Ltd | Novel compound |
| GB0313678D0 (en) * | 2003-06-13 | 2003-07-16 | Oxford Glycosciences Uk Ltd | Novel compounds |
| EP1528056A1 (en) | 2003-10-29 | 2005-05-04 | Academisch Ziekenhuis bij de Universiteit van Amsterdam | Deoxynojirimycin analogues and their uses as glucosylceramidase inhibitors |
| WO2005092334A2 (en) * | 2004-03-25 | 2005-10-06 | David Priestman | Use of n-substituted imino sugars for appetite suppression |
| BRPI0517701A8 (pt) * | 2004-11-10 | 2018-01-23 | Genzyme Corp | métodos de tratamento de diabetes mellitus |
| ES2546181T3 (es) | 2006-05-09 | 2015-09-21 | Genzyme Corporation | Métodos de tratar la enfermedad del hígado graso mediante inhibición de la síntesis de glucoesfingolípidos |
| EP2594565B1 (en) | 2007-05-31 | 2018-10-24 | Genzyme Corporation | 2-acylaminopropanol-type glucosylceramide synthase inhibitors |
| KR101640263B1 (ko) | 2007-10-05 | 2016-07-15 | 젠자임 코포레이션 | 세라마이드 유도체로 다낭성 신장질환을 치료하는 방법 |
| JP2011529500A (ja) * | 2008-07-28 | 2011-12-08 | ジェンザイム コーポレーション | 虚脱性糸球体症および他の糸球体疾患の処置のためのグルコシルセラミドシンターゼ阻害 |
| CN102271678B (zh) | 2008-10-03 | 2017-06-30 | 简詹姆公司 | 2‑酰胺基丙醇型葡糖神经酰胺合成酶抑制剂 |
| WO2011085544A1 (zh) * | 2010-01-13 | 2011-07-21 | 安徽辉克药业有限公司 | 有效清除肿瘤细胞的化合物 |
| LT2685986T (lt) * | 2011-03-18 | 2020-03-10 | Genzyme Corporation | Gliukozilceramido sintazės slopiklis |
| MA37975B2 (fr) | 2012-09-11 | 2021-03-31 | Genzyme Corp | Inhibiteurs de synthase de glucosylcéramide |
| CA2966893C (en) | 2014-11-05 | 2023-10-24 | Emergent Virology Llc | Iminosugars |
| EP3377476B1 (en) * | 2015-11-16 | 2022-10-26 | PTC Therapeutics, Inc. | Hydrogen isotope-enriched analogues of 1,2,4-oxadiazole benzoic acid compounds, compositions and uses thereof |
| PT3920912T (pt) | 2019-02-04 | 2025-09-09 | Genzyme Corp | Tratamento de ciliopatias usando inibidores da glucosilceramida sintase (gcs) |
| US12612380B2 (en) | 2019-05-10 | 2026-04-28 | Alectos Therapeutics 1Nc | Non-lysosomal glucosylceramidase inhibitors and uses thereof |
| IL295255A (en) | 2020-02-03 | 2022-10-01 | Genzyme Corp | Methods for treating neurological symptoms associated with lysosomal storage diseases |
| PE20231423A1 (es) * | 2020-05-07 | 2023-09-13 | Alectos Therapeutics Inc | Inhibidores de glucosilceramidasa no lisosomal y los usos de los mismos |
| JP7674389B2 (ja) * | 2020-05-07 | 2025-05-09 | アレクトス セラピューティックス インコーポレイテッド | 非リソソームグルコシルセラミダーゼ阻害剤及びその使用 |
| IL300090A (en) | 2020-07-24 | 2023-03-01 | Genzyme Corp | Pharmaceutical preparations containing VENGLUSTAT |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3495570A (en) * | 1967-07-03 | 1970-02-17 | Amchem Prod | Applicator for liquid chemical conversion coating material |
| NO154918C (no) * | 1977-08-27 | 1987-01-14 | Bayer Ag | Analogifremgangsmaate til fremstilling av terapeutisk aktive derivater av 3,4,5-trihydroksypiperidin. |
| DE3007078A1 (de) * | 1980-02-26 | 1981-09-10 | Bayer Ag, 5090 Leverkusen | Neue derivate von 3,4,5-trihydroxypiperidin, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel sowie in der tierernaehrung |
| DE3024901A1 (de) | 1980-07-01 | 1982-01-28 | Bayer Ag, 5090 Leverkusen | Herbizide mittel auf basis von piperidin-derivaten |
| DE3247615A1 (de) * | 1982-12-23 | 1984-07-05 | Hoechst Ag, 6230 Frankfurt | Substituierte phenylsulfonyloxybenzimidazolcarbaminate, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
| DE3737523A1 (de) * | 1987-11-05 | 1989-05-18 | Bayer Ag | Verwendung von substituierten hydroxypiperidinen als antivirale mittel |
| US5003072A (en) * | 1988-11-03 | 1991-03-26 | G. D. Searle & Co. | 1,5-dideoxy-1,5-imino-D-glucitol derivatives |
| JPH02306962A (ja) * | 1989-05-19 | 1990-12-20 | Meiji Seika Kaisha Ltd | 新規ｎ―置換―１―デオキシノジリマイシン誘導体及びそれを含有する癌細胞転移抑制剤 |
| JPH0324057A (ja) | 1989-06-22 | 1991-02-01 | Tosoh Corp | ポリヒドロキシピペリジン類及びその製造法 |
| WO1991003242A1 (en) | 1989-09-07 | 1991-03-21 | Nippon Shinyaku Co., Ltd. | Antiviral drug |
| EP0536402A4 (en) | 1990-06-29 | 1993-05-12 | Nippon Shinyaku Company, Limited | Piperidine derivative |
| US5276120A (en) * | 1991-05-30 | 1994-01-04 | The Scripps Research Institute | Process for forming omega-deuxy-azasugars |
| JP3506434B2 (ja) | 1993-05-05 | 2004-03-15 | ロシュ ダイアグノスティックス ゲーエムベーハー | ブレビバクテリウム・ステロリカム由来のコレステロールオキシダーゼ |
| US5798366A (en) | 1993-05-13 | 1998-08-25 | Monsanto Company | Method for treatment of CNS-involved lysosomal storage diseases |
| US6291657B1 (en) | 1993-05-13 | 2001-09-18 | Monsanto Company | Deoxygalactonojirimycin derivatives |
| US6177447B1 (en) | 1996-07-15 | 2001-01-23 | Universiteit Van Amsterdam | Deoxynojirimycin derivatives and their uses as glucosylceramidase inhibitors |
| IL132170A0 (en) * | 1997-05-06 | 2001-03-19 | Novo Nordisk As | Novel heterocyclic compounds |
| WO1999001555A1 (en) * | 1997-07-03 | 1999-01-14 | The United States Of America Represented By The Secretary, Department Of Health And Human Services | Genes for niemann-pick type c disease |
| JP2001522833A (ja) | 1997-11-10 | 2001-11-20 | ジー・ディー・サール・アンド・カンパニー | 多剤耐性を治療するためのアルキル化イミノ糖類の使用 |
| US6610703B1 (en) | 1998-12-10 | 2003-08-26 | G.D. Searle & Co. | Method for treatment of glycolipid storage diseases |
| WO2000056334A1 (en) | 1999-03-19 | 2000-09-28 | The Trustees Of Boston College | Use of imino sugars for anti-tumor therapy |
| GB0100889D0 (en) * | 2001-01-12 | 2001-02-21 | Oxford Glycosciences Uk Ltd | Compounds |
| GB9909064D0 (en) | 1999-04-20 | 1999-06-16 | Oxford Glycosciences Uk Ltd | Therapies |
| JP2003505430A (ja) * | 1999-07-26 | 2003-02-12 | ジー・ディー・サール・アンド・カンパニー | デオキシノジリマイシンの長鎖ｎ−アルキル誘導体およびグルコセレブロシダーゼ酵素の糖脂質異常蓄積疾患の治療用の薬剤の製造のための使用 |
| DE60037664T2 (de) | 1999-08-10 | 2008-12-24 | The Chancellor, Masters And Scholars Of The University Of Oxford | Langkettige n-alkyl verbindungen und deren oxa-derivate zur verwendung als anitvirale mittel |
| US7256005B2 (en) * | 1999-08-10 | 2007-08-14 | The Chancellor, Masters And Scholars Of The University Of Oxford | Methods for identifying iminosugar derivatives that inhibit HCV p7 ion channel activity |
| DE60308378T2 (de) * | 2002-03-13 | 2007-09-20 | Unither Pharmaceuticals, Inc. | Nicht-Hormonal Verfahren zur männlichen Verhütung |
| ES2393331T3 (es) | 2002-07-17 | 2012-12-20 | Actelion Pharmaceuticals Ltd. | Derivados de piperidintriol como inhibidores de la glucosiliceramida sintasa |
| AU2003248960B2 (en) * | 2002-07-17 | 2009-06-25 | Idorsia Pharmaceuticals Ltd | Piperidinetriol derivatives as inhibitors of glycosylceramidsynthase |
| GB0313678D0 (en) * | 2003-06-13 | 2003-07-16 | Oxford Glycosciences Uk Ltd | Novel compounds |
| GB0313677D0 (en) | 2003-06-13 | 2003-07-16 | Oxford Glycosciences Uk Ltd | Novel compound |
| GB0400812D0 (en) | 2004-01-14 | 2004-02-18 | Celltech R&D Ltd | Novel compounds |
-
2003
- 2003-07-17 ES ES03764025T patent/ES2393331T3/es not_active Expired - Lifetime
- 2003-07-17 JP JP2004520900A patent/JP4575156B2/ja not_active Expired - Fee Related
- 2003-07-17 WO PCT/GB2003/003099 patent/WO2004007453A1/en not_active Ceased
- 2003-07-17 CA CA2492404A patent/CA2492404C/en not_active Expired - Fee Related
- 2003-07-17 EP EP03764025A patent/EP1534676B1/en not_active Expired - Lifetime
- 2003-07-17 AU AU2003246942A patent/AU2003246942B2/en not_active Ceased
- 2003-07-17 US US10/522,208 patent/US7985760B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP4575156B2 (ja) | 2010-11-04 |
| CA2492404C (en) | 2012-02-07 |
| EP1534676B1 (en) | 2012-09-12 |
| WO2004007453A1 (en) | 2004-01-22 |
| US7985760B2 (en) | 2011-07-26 |
| JP2005536503A (ja) | 2005-12-02 |
| EP1534676A1 (en) | 2005-06-01 |
| AU2003246942A1 (en) | 2004-02-02 |
| CA2492404A1 (en) | 2004-01-22 |
| AU2003246942B2 (en) | 2009-06-25 |
| US20060058349A1 (en) | 2006-03-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2003246942B2 (en) | Piperidinetriol derivatives as inhibitors of glycosylceramide synthase | |
| US20080234324A1 (en) | Piperidine Derivatives as Gcs Inhibitors | |
| KR100879651B1 (ko) | 약제학적으로 활성인 피페리딘 유도체 | |
| ES2393919T3 (es) | Derivados de PIPERIDINETRIOL como inhibidores de GLUCOSILCERAMIDA SINTASA | |
| JP4780785B2 (ja) | Ｇｃｓ阻害剤としてのピペリジン誘導体 | |
| JP4780784B2 (ja) | Ｇｃｓ阻害性ピペリジン誘導体 |