BG108548A - Хетероциклични съединения и използването им като d-аланил-d-аланин лигазни инхибитори - Google Patents

Info

Publication number

BG108548A

BG108548A BG108548A BG10854804A BG108548A BG 108548 A BG108548 A BG 108548A BG 108548 A BG108548 A BG 108548A BG 10854804 A BG10854804 A BG 10854804A BG 108548 A BG108548 A BG 108548A

Authority

BG

Bulgaria

Prior art keywords

alkyl

hydrogen

compound

aryl

nitrogen

Prior art date

2001-06-28

Links

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• 108020003338 D-alanine-D-alanine ligase Proteins 0.000 title claims abstract description 20
• 150000002391 heterocyclic compounds Chemical class 0.000 title abstract description 11
• 239000000436 ligase inhibitor Substances 0.000 title description 5
• 150000001875 compounds Chemical class 0.000 claims abstract description 202
• 230000001580 bacterial effect Effects 0.000 claims abstract description 43
• 238000000034 method Methods 0.000 claims description 80
• 239000000203 mixture Substances 0.000 claims description 64
• 239000001257 hydrogen Substances 0.000 claims description 61
• 229910052739 hydrogen Inorganic materials 0.000 claims description 61
• -1 amino, hydroxy Chemical group 0.000 claims description 54
• 108090000364 Ligases Proteins 0.000 claims description 51
• 102000003960 Ligases Human genes 0.000 claims description 51
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 49
• 125000000524 functional group Chemical group 0.000 claims description 45
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 42
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 39
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 37
• 229910052760 oxygen Inorganic materials 0.000 claims description 37
• 239000001301 oxygen Substances 0.000 claims description 37
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 35
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 30
• 125000000217 alkyl group Chemical group 0.000 claims description 28
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 27
• 229910052757 nitrogen Inorganic materials 0.000 claims description 24
• 230000002401 inhibitory effect Effects 0.000 claims description 21
• 125000003118 aryl group Chemical group 0.000 claims description 20
• 241000588724 Escherichia coli Species 0.000 claims description 17
• 229910052799 carbon Inorganic materials 0.000 claims description 17
• 208000015181 infectious disease Diseases 0.000 claims description 17
• 238000002360 preparation method Methods 0.000 claims description 16
• 229910052736 halogen Inorganic materials 0.000 claims description 14
• 150000002367 halogens Chemical class 0.000 claims description 14
• 239000000543 intermediate Substances 0.000 claims description 14
• 238000009472 formulation Methods 0.000 claims description 13
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• 239000003153 chemical reaction reagent Substances 0.000 claims description 12
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
• 229910052717 sulfur Inorganic materials 0.000 claims description 10
• 230000012010 growth Effects 0.000 claims description 9
• 241000606768 Haemophilus influenzae Species 0.000 claims description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
• 239000011593 sulfur Substances 0.000 claims description 8
• 230000000813 microbial effect Effects 0.000 claims description 7
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• 125000004122 cyclic group Chemical group 0.000 claims description 6
• 125000001624 naphthyl group Chemical group 0.000 claims description 6
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• 125000002252 acyl group Chemical group 0.000 claims description 5
• 125000003277 amino group Chemical group 0.000 claims description 5
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
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• 125000003342 alkenyl group Chemical group 0.000 claims description 4
• 125000000304 alkynyl group Chemical group 0.000 claims description 4
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
• 241000606153 Chlamydia trachomatis Species 0.000 claims description 3
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• DEFJQIDDEAULHB-UHFFFAOYSA-N N-D-alanyl-D-alanine Natural products CC(N)C(=O)NC(C)C(O)=O DEFJQIDDEAULHB-UHFFFAOYSA-N 0.000 claims description 3
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• 125000002877 alkyl aryl group Chemical group 0.000 claims description 3
• 150000007942 carboxylates Chemical group 0.000 claims description 3
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
• 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
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• HFUWQLKNDPPTKF-IMJSIDKUSA-N [(2S)-2-aminopropanoyl] (2S)-2-aminopropaneperoxoate Chemical compound N[C@@H](C)C(=O)OOC([C@@H](N)C)=O HFUWQLKNDPPTKF-IMJSIDKUSA-N 0.000 claims description 2
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• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• 229940038705 chlamydia trachomatis Drugs 0.000 claims description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
• 125000001188 haloalkyl group Chemical group 0.000 claims description 2
• 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 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims 4
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• 229940046939 rickettsia prowazekii Drugs 0.000 claims 1
• 239000003053 toxin Substances 0.000 claims 1
• 231100000765 toxin Toxicity 0.000 claims 1
• 230000000694 effects Effects 0.000 abstract description 36
• 102000004190 Enzymes Human genes 0.000 abstract description 30
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• 229940124350 antibacterial drug Drugs 0.000 abstract 1
• 230000037361 pathway Effects 0.000 abstract 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
• 239000000243 solution Substances 0.000 description 76
• 239000000047 product Substances 0.000 description 46
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
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• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
• XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 23
• 238000006243 chemical reaction Methods 0.000 description 23
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 22
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• ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 20
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