NZ554485A - Method of preventing and treating airway remodeling and pulmonary inflammation using A2B adenosine receptor antagonists - Google Patents

Info

Publication number

NZ554485A

NZ554485A NZ554485A NZ55448505A NZ554485A NZ 554485 A NZ554485 A NZ 554485A NZ 554485 A NZ554485 A NZ 554485A NZ 55448505 A NZ55448505 A NZ 55448505A NZ 554485 A NZ554485 A NZ 554485A

Authority

NZ

New Zealand

Prior art keywords

formula

methyl

amino

dione

compound

Prior art date

2004-10-15

Links

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• 101150078577 Adora2b gene Proteins 0.000 title claims abstract description 32
• 238000000034 method Methods 0.000 title description 65
• 208000036065 Airway Remodeling Diseases 0.000 title description 26
• 206010035664 Pneumonia Diseases 0.000 title description 24
• 229940121359 adenosine receptor antagonist Drugs 0.000 title description 18
• 239000000296 purinergic P1 receptor antagonist Substances 0.000 title description 18
• 238000011282 treatment Methods 0.000 claims abstract description 36
• 208000005069 pulmonary fibrosis Diseases 0.000 claims abstract description 12
• 229940044551 receptor antagonist Drugs 0.000 claims abstract description 8
• 239000002464 receptor antagonist Substances 0.000 claims abstract description 8
• 238000002360 preparation method Methods 0.000 claims description 88
• -1 trifluoromethylphenyl Chemical group 0.000 claims description 82
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 49
• 239000008194 pharmaceutical composition Substances 0.000 claims description 12
• 241000124008 Mammalia Species 0.000 claims description 11
• 238000007912 intraperitoneal administration Methods 0.000 claims description 2
• 238000007918 intramuscular administration Methods 0.000 claims 1
• 238000001990 intravenous administration Methods 0.000 claims 1
• 238000007910 systemic administration Methods 0.000 claims 1
• KOYXXLLNCXWUNF-UHFFFAOYSA-N 3-ethyl-1-propyl-8-[1-[[3-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CC)C=2N=C1C(=C1)C=NN1CC1=CC=CC(C(F)(F)F)=C1 KOYXXLLNCXWUNF-UHFFFAOYSA-N 0.000 abstract description 7
• 208000019693 Lung disease Diseases 0.000 abstract description 5
• 230000001684 chronic effect Effects 0.000 abstract description 5
• 230000000414 obstructive effect Effects 0.000 abstract description 2
• 150000001875 compounds Chemical class 0.000 description 235
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
• 241000699670 Mus sp. Species 0.000 description 90
• 238000006243 chemical reaction Methods 0.000 description 83
• 102000055025 Adenosine deaminases Human genes 0.000 description 80
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• 239000000203 mixture Substances 0.000 description 58
• 125000000217 alkyl group Chemical group 0.000 description 57
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• 125000001424 substituent group Chemical group 0.000 description 45
• 125000003118 aryl group Chemical group 0.000 description 42
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• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 32
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 32
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 32
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 32
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 31
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• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 18
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• 150000002431 hydrogen Chemical class 0.000 description 13
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• 238000000692 Student's t-test Methods 0.000 description 12
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• 239000003814 drug Substances 0.000 description 11
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• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 11
• 239000011734 sodium Substances 0.000 description 11
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• 241001465754 Metazoa Species 0.000 description 10
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• 125000002252 acyl group Chemical group 0.000 description 9
• 125000004442 acylamino group Chemical group 0.000 description 9
• 125000004423 acyloxy group Chemical group 0.000 description 9
• 238000004458 analytical method Methods 0.000 description 9
• 125000005110 aryl thio group Chemical group 0.000 description 9
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• 125000001246 bromo group Chemical group Br* 0.000 description 9
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• 150000003573 thiols Chemical class 0.000 description 9
• NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 8
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