CA2366858A1 - Sorbitol dehydrogenase inhibitors - Google Patents
Sorbitol dehydrogenase inhibitors Download PDFInfo
- Publication number
- CA2366858A1 CA2366858A1 CA002366858A CA2366858A CA2366858A1 CA 2366858 A1 CA2366858 A1 CA 2366858A1 CA 002366858 A CA002366858 A CA 002366858A CA 2366858 A CA2366858 A CA 2366858A CA 2366858 A1 CA2366858 A1 CA 2366858A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- optionally substituted
- hydroxy
- alkoxy
- fluoro
- 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.)
- Abandoned
Links
- 239000003112 inhibitor Substances 0.000 title claims abstract description 29
- 108010009384 L-Iditol 2-Dehydrogenase Proteins 0.000 title claims abstract description 14
- 102100026974 Sorbitol dehydrogenase Human genes 0.000 title claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 525
- 238000000034 method Methods 0.000 claims abstract description 92
- 241000124008 Mammalia Species 0.000 claims abstract description 78
- 208000002249 Diabetes Complications Diseases 0.000 claims abstract description 35
- 206010012655 Diabetic complications Diseases 0.000 claims abstract description 35
- 239000003288 aldose reductase inhibitor Substances 0.000 claims abstract description 25
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 25
- 229940118148 Aldose reductase inhibitor Drugs 0.000 claims abstract description 22
- 102100030980 Sodium/hydrogen exchanger 1 Human genes 0.000 claims abstract description 22
- 108010093115 growth factor-activatable Na-H exchanger NHE-1 Proteins 0.000 claims abstract description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 22
- MNQZXJOMYWMBOU-UHFFFAOYSA-N glyceraldehyde Chemical compound OCC(O)C=O MNQZXJOMYWMBOU-UHFFFAOYSA-N 0.000 claims abstract description 9
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 653
- 125000000217 alkyl group Chemical group 0.000 claims description 598
- -1 vinylenylcarbonyl Chemical group 0.000 claims description 577
- 125000001153 fluoro group Chemical group F* 0.000 claims description 534
- 229940002612 prodrug Drugs 0.000 claims description 414
- 239000000651 prodrug Substances 0.000 claims description 413
- 229910052739 hydrogen Inorganic materials 0.000 claims description 303
- 239000001257 hydrogen Substances 0.000 claims description 303
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 229
- 150000003839 salts Chemical class 0.000 claims description 204
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 191
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 188
- 125000005843 halogen group Chemical group 0.000 claims description 166
- 125000003545 alkoxy group Chemical group 0.000 claims description 155
- 125000001424 substituent group Chemical group 0.000 claims description 110
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 101
- 125000004076 pyridyl group Chemical group 0.000 claims description 96
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 73
- 125000002757 morpholinyl group Chemical group 0.000 claims description 71
- 125000004193 piperazinyl group Chemical group 0.000 claims description 67
- 125000005466 alkylenyl group Chemical group 0.000 claims description 66
- 125000003386 piperidinyl group Chemical group 0.000 claims description 63
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 58
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 57
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 56
- 229910052757 nitrogen Chemical group 0.000 claims description 54
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 53
- 125000002971 oxazolyl group Chemical group 0.000 claims description 52
- 125000000335 thiazolyl group Chemical group 0.000 claims description 52
- 125000002947 alkylene group Chemical group 0.000 claims description 50
- 125000002541 furyl group Chemical group 0.000 claims description 48
- 229920006395 saturated elastomer Polymers 0.000 claims description 48
- 125000001544 thienyl group Chemical group 0.000 claims description 48
- 125000002785 azepinyl group Chemical group 0.000 claims description 45
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 39
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 38
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 38
- 125000002393 azetidinyl group Chemical group 0.000 claims description 36
- ROJNYKZWTOHRNU-UHFFFAOYSA-N 2-chloro-4,5-difluoro-n-[[2-methoxy-5-(methylcarbamoylamino)phenyl]carbamoyl]benzamide Chemical compound CNC(=O)NC1=CC=C(OC)C(NC(=O)NC(=O)C=2C(=CC(F)=C(F)C=2)Cl)=C1 ROJNYKZWTOHRNU-UHFFFAOYSA-N 0.000 claims description 35
- 150000002431 hydrogen Chemical group 0.000 claims description 35
- 229910052717 sulfur Inorganic materials 0.000 claims description 33
- 125000002883 imidazolyl group Chemical group 0.000 claims description 32
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 31
- 229910052760 oxygen Inorganic materials 0.000 claims description 30
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 28
- 125000001624 naphthyl group Chemical group 0.000 claims description 26
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 25
- 239000011593 sulfur Chemical group 0.000 claims description 25
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 24
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 23
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 22
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 22
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 22
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 22
- 239000001301 oxygen Substances 0.000 claims description 22
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 22
- 125000005493 quinolyl group Chemical group 0.000 claims description 22
- 125000001425 triazolyl group Chemical group 0.000 claims description 22
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 20
- 125000002619 bicyclic group Chemical group 0.000 claims description 18
- 125000005842 heteroatom Chemical group 0.000 claims description 18
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
- 150000003254 radicals Chemical group 0.000 claims description 18
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 16
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 16
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 16
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 16
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 16
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 14
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 14
- 125000004306 triazinyl group Chemical group 0.000 claims description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 13
- 239000004305 biphenyl Substances 0.000 claims description 13
- 208000028867 ischemia Diseases 0.000 claims description 13
- 125000005090 alkenylcarbonyl group Chemical group 0.000 claims description 12
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 12
- 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 12
- 125000002950 monocyclic group Chemical group 0.000 claims description 12
- 125000004043 oxo group Chemical group O=* 0.000 claims description 12
- 125000005554 pyridyloxy group Chemical group 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 10
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 10
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 10
- 235000010290 biphenyl Nutrition 0.000 claims description 8
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 8
- 238000005342 ion exchange Methods 0.000 claims description 8
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- NLUNLVTVUDIHFE-UHFFFAOYSA-N cyclooctylcyclooctane Chemical group C1CCCCCCC1C1CCCCCCC1 NLUNLVTVUDIHFE-UHFFFAOYSA-N 0.000 claims description 6
- 125000001041 indolyl group Chemical group 0.000 claims description 6
- 239000012442 inert solvent Substances 0.000 claims description 6
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 claims description 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- AEOZCEMLLBCHQZ-HSHFZTNMSA-N (2r)-2-hydroxypropanimidamide;hydrochloride Chemical compound Cl.C[C@@H](O)C(N)=N AEOZCEMLLBCHQZ-HSHFZTNMSA-N 0.000 claims description 4
- CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 claims description 4
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 4
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 claims description 4
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 4
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 4
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 4
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 4
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- SXQFCVDSOLSHOQ-UWTATZPHSA-N (R)-(+)-Lactamide Chemical compound C[C@@H](O)C(N)=O SXQFCVDSOLSHOQ-UWTATZPHSA-N 0.000 claims description 2
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- 238000012216 screening Methods 0.000 description 1
- LXANPKRCLVQAOG-NSHDSACASA-N sorbinil Chemical compound C12=CC(F)=CC=C2OCC[C@@]21NC(=O)NC2=O LXANPKRCLVQAOG-NSHDSACASA-N 0.000 description 1
- 229950004311 sorbinil Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
- LUBHDINQXIHVLS-UHFFFAOYSA-N tolrestat Chemical compound OC(=O)CN(C)C(=S)C1=CC=CC2=C(C(F)(F)F)C(OC)=CC=C21 LUBHDINQXIHVLS-UHFFFAOYSA-N 0.000 description 1
- 229960003069 tolrestat Drugs 0.000 description 1
- 229950005346 zopolrestat Drugs 0.000 description 1
Classifications
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- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
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- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
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- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
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- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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- 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
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- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
- C07D405/12—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 chain containing hetero atoms as chain links
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- 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
- C07D405/14—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 three or more hetero rings
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
- C07D413/12—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 chain containing hetero atoms as chain links
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
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- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
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- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CA002484282A CA2484282A1 (en) | 1999-04-01 | 2000-03-16 | Pyrimidine derivatives intermediates for producing aminopyrimidines as sorbitol dehydrogenase inhibitors |
Applications Claiming Priority (3)
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| US12743799P | 1999-04-01 | 1999-04-01 | |
| US60/127,437 | 1999-04-01 | ||
| PCT/IB2000/000296 WO2000059510A1 (en) | 1999-04-01 | 2000-03-16 | Aminopyrimidines as sorbitol dehydrogenase inhibitors |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002484282A Division CA2484282A1 (en) | 1999-04-01 | 2000-03-16 | Pyrimidine derivatives intermediates for producing aminopyrimidines as sorbitol dehydrogenase inhibitors |
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| CA2366858A1 true CA2366858A1 (en) | 2000-10-12 |
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| CA002366858A Abandoned CA2366858A1 (en) | 1999-04-01 | 2000-03-16 | Sorbitol dehydrogenase inhibitors |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20220249624A1 (en) * | 2019-05-07 | 2022-08-11 | University Of Miami | Treatment and detection of inherited neuropathies and associated disorders |
| US11590131B2 (en) | 2017-07-28 | 2023-02-28 | Applied Therapeutics, Inc. | Compositions and methods for treating galactosemia |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EA004656B1 (ru) * | 1999-04-01 | 2004-06-24 | Пфайзер Продактс Инк. | Аминопиримидины в качестве ингибиторов сорбитолдегидрогеназы |
| JP2004517053A (ja) * | 2000-10-18 | 2004-06-10 | ファイザー・プロダクツ・インク | スタチン類とソルビトールデヒドロゲナーゼ阻害薬の併用 |
| SE0003795D0 (sv) * | 2000-10-20 | 2000-10-20 | Astrazeneca Ab | Pharmaceutically useful compounds |
| WO2002043762A2 (en) | 2000-11-30 | 2002-06-06 | Pfizer Products Inc. | Combination of gaba agonists and sorbitol dehydrogenase inhibitors |
| CA2433090A1 (en) * | 2000-12-27 | 2002-07-04 | Kyowa Hakko Kogyo Co., Ltd. | Dipeptidyl peptidase iv inhibitor |
| IL147696A0 (en) * | 2001-01-25 | 2002-08-14 | Pfizer Prod Inc | Combination therapy |
| EP1247809A3 (en) | 2001-03-30 | 2003-12-17 | Pfizer Products Inc. | Triazine compounds useful as sorbitol dehydrogenase inhibitors |
| EP1389189A2 (en) | 2001-05-22 | 2004-02-18 | Neurogen Corporation | Melanin concentrating hormone receptor ligands: substituted 1-benzyl-4-aryl piperazine analogues |
| GB0127929D0 (en) * | 2001-11-21 | 2002-01-16 | Celltech R&D Ltd | Chemical compounds |
| US7279470B2 (en) * | 2001-12-14 | 2007-10-09 | Novo Nordisk A/S | Compounds and uses thereof for decreasing activity of hormone-sensitive lipase |
| US7015227B2 (en) | 2002-06-21 | 2006-03-21 | Cgi Pharmaceuticals, Inc. | Certain amino-substituted monocycles as kinase modulators |
| US7582635B2 (en) | 2002-12-24 | 2009-09-01 | Purdue Pharma, L.P. | Therapeutic agents useful for treating pain |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US11590131B2 (en) | 2017-07-28 | 2023-02-28 | Applied Therapeutics, Inc. | Compositions and methods for treating galactosemia |
| US20220249624A1 (en) * | 2019-05-07 | 2022-08-11 | University Of Miami | Treatment and detection of inherited neuropathies and associated disorders |
| US12083168B2 (en) * | 2019-05-07 | 2024-09-10 | University Of Miami | Treatment and detection of inherited neuropathies and associated disorders |
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