SG178102A1 - Isoform selective phospholipase d inhibitors - Google Patents

Info

Publication number

SG178102A1

SG178102A1 SG2012005252A SG2012005252A SG178102A1 SG 178102 A1 SG178102 A1 SG 178102A1 SG 2012005252 A SG2012005252 A SG 2012005252A SG 2012005252 A SG2012005252 A SG 2012005252A SG 178102 A1 SG178102 A1 SG 178102A1

Authority

SG

Singapore

Prior art keywords

optionally substituted

cycloalkyl

alkyl

compound

alkoxy

Prior art date

2009-07-24

Links

• Espacenet
• Global Dossier
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• 108090000553 Phospholipase D Proteins 0.000 title claims description 115
• 102000011420 Phospholipase D Human genes 0.000 title description 17
• 239000003112 inhibitor Substances 0.000 title description 10
• 108010029485 Protein Isoforms Proteins 0.000 title description 7
• 102000001708 Protein Isoforms Human genes 0.000 title description 7
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 339
• 150000001875 compounds Chemical class 0.000 claims description 277
• 229910052739 hydrogen Inorganic materials 0.000 claims description 273
• 239000001257 hydrogen Substances 0.000 claims description 273
• 150000002431 hydrogen Chemical class 0.000 claims description 246
• -1 i-pentyl Chemical group 0.000 claims description 200
• 125000003545 alkoxy group Chemical group 0.000 claims description 189
• 150000004820 halides Chemical class 0.000 claims description 181
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 177
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 172
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 172
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 172
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 172
• 125000005518 carboxamido group Chemical group 0.000 claims description 171
• DYMRYCZRMAHYKE-UHFFFAOYSA-N n-diazonitramide Chemical compound [O-][N+](=O)N=[N+]=[N-] DYMRYCZRMAHYKE-UHFFFAOYSA-N 0.000 claims description 171
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 170
• 125000003118 aryl group Chemical group 0.000 claims description 119
• 238000000034 method Methods 0.000 claims description 115
• 125000001072 heteroaryl group Chemical group 0.000 claims description 108
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 84
• 125000000217 alkyl group Chemical group 0.000 claims description 78
• 229910052799 carbon Inorganic materials 0.000 claims description 66
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 65
• 125000001424 substituent group Chemical group 0.000 claims description 65
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 64
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 63
• 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 63
• 230000000694 effects Effects 0.000 claims description 58
• 208000035475 disorder Diseases 0.000 claims description 43
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
• 241000124008 Mammalia Species 0.000 claims description 24
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 24
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 23
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 23
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 23
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
• 201000010099 disease Diseases 0.000 claims description 20
• 229910052757 nitrogen Inorganic materials 0.000 claims description 19
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 17
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 17
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 17
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 17
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 17
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 13
• 125000006239 protecting group Chemical group 0.000 claims description 13
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 12
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 12
• 238000000926 separation method Methods 0.000 claims description 11
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 6
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• 125000001041 indolyl group Chemical group 0.000 claims description 6
• 125000001624 naphthyl group Chemical group 0.000 claims description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
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• 125000003107 substituted aryl group Chemical group 0.000 claims description 4
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• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
• 125000005872 benzooxazolyl group Chemical group 0.000 claims description 3
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000001207 fluorophenyl group Chemical group 0.000 claims description 3
• 125000002541 furyl group Chemical group 0.000 claims description 3
• 125000002883 imidazolyl group Chemical group 0.000 claims description 3
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 3
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 3
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• 125000002098 pyridazinyl group Chemical group 0.000 claims description 3
• 125000004076 pyridyl group Chemical group 0.000 claims description 3
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• 125000001544 thienyl group Chemical group 0.000 claims description 3
• 125000004306 triazinyl group Chemical group 0.000 claims description 3
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• 101001040875 Homo sapiens Glucosidase 2 subunit beta Proteins 0.000 description 20
• 101000730665 Homo sapiens Phospholipase D1 Proteins 0.000 description 20
• 101000964266 Loxosceles laeta Dermonecrotic toxin Proteins 0.000 description 20
• 150000003839 salts Chemical class 0.000 description 20
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 19
• 239000002904 solvent Substances 0.000 description 19
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
• 125000003342 alkenyl group Chemical group 0.000 description 18
• 125000000304 alkynyl group Chemical group 0.000 description 18
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