BRPI0413922B1 - xantinas de 8-heteroarila substituída - Google Patents
xantinas de 8-heteroarila substituída Download PDFInfo
- Publication number
- BRPI0413922B1 BRPI0413922B1 BRPI0413922A BRPI0413922A BRPI0413922B1 BR PI0413922 B1 BRPI0413922 B1 BR PI0413922B1 BR PI0413922 A BRPI0413922 A BR PI0413922A BR PI0413922 A BRPI0413922 A BR PI0413922A BR PI0413922 B1 BRPI0413922 B1 BR PI0413922B1
- Authority
- BR
- Brazil
- Prior art keywords
- xanthine
- pyridyl
- alkyl
- dipropyl
- aryl
- Prior art date
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- 229940065721 systemic for obstructive airway disease xanthines Drugs 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 219
- 239000000203 mixture Substances 0.000 claims abstract description 25
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims description 289
- -1 cyan Chemical group 0.000 claims description 218
- 229940075420 xanthine Drugs 0.000 claims description 156
- 125000000217 alkyl group Chemical group 0.000 claims description 134
- 239000001257 hydrogen Substances 0.000 claims description 92
- 229910052739 hydrogen Inorganic materials 0.000 claims description 92
- 125000003118 aryl group Chemical group 0.000 claims description 79
- 125000005843 halogen group Chemical group 0.000 claims description 75
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 60
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 57
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 52
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 51
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 49
- 125000000623 heterocyclic group Chemical group 0.000 claims description 49
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 45
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 45
- 125000001072 heteroaryl group Chemical group 0.000 claims description 44
- 125000001424 substituent group Chemical group 0.000 claims description 43
- 150000002431 hydrogen Chemical class 0.000 claims description 40
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 40
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 35
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 30
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 29
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 27
- 125000003342 alkenyl group Chemical group 0.000 claims description 27
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 26
- 125000000304 alkynyl group Chemical group 0.000 claims description 25
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 25
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 20
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 20
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 20
- 150000001412 amines Chemical class 0.000 claims description 19
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 19
- 241000124008 Mammalia Species 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 16
- 125000004076 pyridyl group Chemical group 0.000 claims description 16
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 15
- 230000000694 effects Effects 0.000 claims description 15
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 15
- 125000006413 ring segment Chemical group 0.000 claims description 15
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 14
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 14
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 13
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 13
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 13
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 12
- 101150078577 Adora2b gene Proteins 0.000 claims description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 125000002785 azepinyl group Chemical group 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- 239000000460 chlorine Substances 0.000 claims description 10
- 125000002757 morpholinyl group Chemical group 0.000 claims description 10
- 125000005936 piperidyl group Chemical group 0.000 claims description 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 208000006673 asthma Diseases 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 9
- 150000002978 peroxides Chemical class 0.000 claims description 9
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 8
- 125000002619 bicyclic group Chemical group 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 125000004193 piperazinyl group Chemical group 0.000 claims description 8
- 208000024891 symptom Diseases 0.000 claims description 8
- 206010022489 Insulin Resistance Diseases 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 7
- 125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 claims description 7
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 7
- 125000006178 methyl benzyl group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- GZRKXKUVVPSREJ-UHFFFAOYSA-N pyridinylpiperazine Chemical compound C1CNCCN1C1=CC=CC=N1 GZRKXKUVVPSREJ-UHFFFAOYSA-N 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 7
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 6
- 206010012735 Diarrhoea Diseases 0.000 claims description 6
- 208000017442 Retinal disease Diseases 0.000 claims description 6
- 206010038923 Retinopathy Diseases 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 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 6
- 206010012601 diabetes mellitus Diseases 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 230000001575 pathological effect Effects 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 125000005592 polycycloalkyl group Polymers 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 125000005493 quinolyl group Chemical group 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 6
- 230000009471 action Effects 0.000 claims description 5
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 5
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 5
- 125000004306 triazinyl group Chemical group 0.000 claims description 5
- 125000001425 triazolyl group Chemical group 0.000 claims description 5
- MRBFGEHILMYPTF-UHFFFAOYSA-N 1-(2-Pyrimidyl)piperazine Chemical compound C1CNCCN1C1=NC=CC=N1 MRBFGEHILMYPTF-UHFFFAOYSA-N 0.000 claims description 4
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
- 208000023275 Autoimmune disease Diseases 0.000 claims description 4
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 4
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 4
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- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- NSMWYRLQHIXVAP-OLQVQODUSA-N (2r,5s)-2,5-dimethylpiperazine Chemical compound C[C@H]1CN[C@H](C)CN1 NSMWYRLQHIXVAP-OLQVQODUSA-N 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 3
- HXKWXZFMPSMNLP-UHFFFAOYSA-N 1-cyclopropyl-8-[6-(2-methoxyethylamino)pyridin-3-yl]-3-propyl-7h-purine-2,6-dione Chemical compound O=C1N(CCC)C=2N=C(C=3C=NC(NCCOC)=CC=3)NC=2C(=O)N1C1CC1 HXKWXZFMPSMNLP-UHFFFAOYSA-N 0.000 claims description 3
- SPEBTNIPAFIDPC-UHFFFAOYSA-N 3-methyl-8-[6-(methylamino)pyridin-3-yl]-1-prop-2-ynyl-7h-purine-2,6-dione Chemical compound C1=NC(NC)=CC=C1C(N1)=NC2=C1C(=O)N(CC#C)C(=O)N2C SPEBTNIPAFIDPC-UHFFFAOYSA-N 0.000 claims description 3
- RWCGREFAXNNUOP-UHFFFAOYSA-N 8-(6-bromopyridin-3-yl)-3-methyl-7h-purine-2,6-dione Chemical compound N1C=2C(=O)NC(=O)N(C)C=2N=C1C1=CC=C(Br)N=C1 RWCGREFAXNNUOP-UHFFFAOYSA-N 0.000 claims description 3
- SWVHDVTVWJZLCE-UHFFFAOYSA-N 8-(6-chloropyridin-3-yl)-1-propyl-3-prop-2-ynyl-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CC#C)C=2N=C1C1=CC=C(Cl)N=C1 SWVHDVTVWJZLCE-UHFFFAOYSA-N 0.000 claims description 3
- AHRGRLCHURXYSA-UHFFFAOYSA-N 8-(6-chloropyridin-3-yl)-3-(4-methoxyphenyl)-1-pentan-2-yl-7H-purine-2,6-dione Chemical compound C(CC)C(C)N1C(=O)N(C=2N=C(NC=2C1=O)C=1C=NC(=CC=1)Cl)C1=CC=C(C=C1)OC AHRGRLCHURXYSA-UHFFFAOYSA-N 0.000 claims description 3
- DFLYGAUEDKTJBE-UHFFFAOYSA-N 8-[6-(2-methoxyethyl)pyridin-3-yl]-3-methyl-7h-purine-2,6-dione Chemical compound C1=NC(CCOC)=CC=C1C(N1)=NC2=C1C(=O)NC(=O)N2C DFLYGAUEDKTJBE-UHFFFAOYSA-N 0.000 claims description 3
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 3
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- KQUAXDUORCKXRU-UHFFFAOYSA-N 1-cyclopropyl-3-ethyl-8-[6-(methylamino)pyridin-3-yl]-7h-purine-2,6-dione Chemical compound O=C1N(CC)C=2N=C(C=3C=NC(NC)=CC=3)NC=2C(=O)N1C1CC1 KQUAXDUORCKXRU-UHFFFAOYSA-N 0.000 claims description 2
- CPAFOHDUXCUDBQ-UHFFFAOYSA-N 1-cyclopropyl-8-[6-(methylamino)pyridin-3-yl]-3-propyl-7h-purine-2,6-dione Chemical compound O=C1N(CCC)C=2N=C(C=3C=NC(NC)=CC=3)NC=2C(=O)N1C1CC1 CPAFOHDUXCUDBQ-UHFFFAOYSA-N 0.000 claims description 2
- QRAJFZIVAGEPQU-UHFFFAOYSA-N 3-(4-methoxyphenyl)-8-[6-(methylamino)pyridin-3-yl]-1-pentan-2-yl-7H-purine-2,6-dione Chemical compound C(CC)C(C)N1C(=O)N(C=2N=C(NC=2C1=O)C=1C=NC(=CC=1)NC)C1=CC=C(C=C1)OC QRAJFZIVAGEPQU-UHFFFAOYSA-N 0.000 claims description 2
- HXCINFYZZQPUQQ-UHFFFAOYSA-N 3-(4-methoxyphenyl)-8-[6-[(2-oxo-2-pyridin-3-ylethyl)amino]pyridin-3-yl]-1-pentan-2-yl-7H-purine-2,6-dione Chemical compound C(CC)C(C)N1C(=O)N(C=2N=C(NC=2C1=O)C=1C=NC(=CC=1)NCC(C1=CN=CC=C1)=O)C1=CC=C(C=C1)OC HXCINFYZZQPUQQ-UHFFFAOYSA-N 0.000 claims description 2
- IWIRXFKTHJBLGG-UHFFFAOYSA-N 3-cyclopropyl-1-ethyl-8-[6-(2-methoxyethylamino)pyridin-3-yl]-7h-purine-2,6-dione Chemical compound C1=2N=C(C=3C=NC(NCCOC)=CC=3)NC=2C(=O)N(CC)C(=O)N1C1CC1 IWIRXFKTHJBLGG-UHFFFAOYSA-N 0.000 claims description 2
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- FXYPFFWMBSZGOL-UHFFFAOYSA-N 3-cyclopropyl-8-[6-(methylamino)pyridin-3-yl]-1-propyl-7h-purine-2,6-dione Chemical compound C1=2N=C(C=3C=NC(NC)=CC=3)NC=2C(=O)N(CCC)C(=O)N1C1CC1 FXYPFFWMBSZGOL-UHFFFAOYSA-N 0.000 claims description 2
- YEYAJHKHEQLJSU-UHFFFAOYSA-N 8-[6-(2,2-dimethoxyethylamino)pyridin-3-yl]-1,3-dipropyl-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C1=CC=C(NCC(OC)OC)N=C1 YEYAJHKHEQLJSU-UHFFFAOYSA-N 0.000 claims description 2
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- ISBHPXONHAEHMW-UHFFFAOYSA-N 8-[6-[[2-(6-chloropyridin-3-yl)-2-oxoethyl]amino]pyridin-3-yl]-1-cyclopropyl-3-propyl-7h-purine-2,6-dione Chemical compound O=C1N(CCC)C=2N=C(C=3C=NC(NCC(=O)C=4C=NC(Cl)=CC=4)=CC=3)NC=2C(=O)N1C1CC1 ISBHPXONHAEHMW-UHFFFAOYSA-N 0.000 claims description 2
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- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
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- 229910052700 potassium Inorganic materials 0.000 description 1
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- 238000011533 pre-incubation Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- ZYHMJXZULPZUED-UHFFFAOYSA-N propargite Chemical compound C1=CC(C(C)(C)C)=CC=C1OC1C(OS(=O)OCC#C)CCCC1 ZYHMJXZULPZUED-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 238000003653 radioligand binding assay Methods 0.000 description 1
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- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 1
- 229950005741 rolipram Drugs 0.000 description 1
- 102220240796 rs553605556 Human genes 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- KSAVQLQVUXSOCR-UHFFFAOYSA-N sodium;2-[dodecanoyl(methyl)amino]acetic acid Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC(O)=O KSAVQLQVUXSOCR-UHFFFAOYSA-N 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000007892 solid unit dosage form Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
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- 230000008685 targeting Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 229940098465 tincture Drugs 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
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960001479 tosylchloramide sodium Drugs 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
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- 230000032258 transport Effects 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
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- 239000001993 wax Substances 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A61P3/00—Drugs for disorders of the metabolism
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- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A61P37/08—Antiallergic agents
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- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
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- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
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- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- C07D473/08—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1 and 3, e.g. theophylline
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Abstract
Description
Claims (58)
- REIVINDICAÇÕES1. Composto, caracterizado pelo fato de que apresenta a fórmulaI :I na qual:R é hidrogênio, (C1-C5)alquila, halo(C1-C8)alquila, (C3-C5)alquenila, ou (C3-C5)alquinila;R1 e R2 são independentemente hidrogênio, (C1-C8)alquila, (C3C8)alquenila, (C3-C8)alquinila, (C1-C8)alcóxi, (C3-C8)cicloalquila, (C3C8)cicloalquil(C1-C8)alquil-, (C4-Cw)heterociclo, (C4-Cw)heterociclo(C1-C8)alquil-, (C6-C10)arila, (C6-C10)aril(C1-Ce)alquil-, (C5-Cw)heteroarila, ou (C5C10)heteroaril(C1-C8)alquil-;X é um anel de heteroarila de 5 a 10 membros tendo um átomo de nitrogênio e opcionalmente interrompido por 1, 2, ou 3 grupos de nãoperóxido óxi (-O-), tio (-S-), sulfinila (-SO-), sulfonila (-S(O)2-) ou amina N(R9)- ;Z é -OR3, -SR3, halo, -S(O)m-NR4R5, -NR4R5, ou (C4Cw)heterociclo onde o heterociclo é opcionalmente substituído com 1, 2, 3, ou 4 substituintes independentemente selecionados de halo, ciano, nitro, ORa, -SRa, (C1-C8)alquila, (C6-C10)arila, -O(C6-C10)arila, hidróxi(C1-C8)alquila, RbRcN(C1-C8)alquila, halo(C1-C8)alquila, -NRbRc, -C(O)Ra, -COORa, e C(O)NRbRc;cada Z1 é independentemente (C1-C8)alquila, (C2-C8)alquenila, (C2-C8)alquinila, -OR6, -SR6, halo, R6O(C1-C8)alquila, R7R8N(C1-C8)alquila, halo(C1-C8)alquila, -NR7R8, R7R8N(C1-C8)alquila, -C(O)R6, -COOR6, e C(O)NR7R8;R3 é (C1-C8)alquila, (C3-C8)alquenila, (C3-C8)alquinila, (C6C10)arila, (C6-C10)aril(C1-C8)alquil-, (C5-C10)heteroarila, (C5-C10)heteroaril(C1C8)alquil-, -C(O)R6, ou -C(O)NR7R8;19/07/2018, pág. 9/27R4 e R5 são independentemente hidrogênio, (Ci-Ce)alquila, (C3C8)alquenila, (C3-Ce)alquinila, (C1-C8)alcóxi, (C3-C8)cicloalquila, (C3Ce)cicloalquil(C1-C8)alquil-, (C6-C18)policicloalquila, (C6-C18)policicloalquil(C1C8)alquil-, (C3-Cw)heterociclo, (C3-Cw)heterociclo(C1-C8)alquil-, -NR7R8, (C6C10)arila, (C6-C10)aril(C1-C8)alquil-, (C5-C10)heteroarila, (C5-C10)heteroaril(C1C8)alquil-, -(C2-C4-Y)q-(CH2)2-4-X1, -C(O)R6, -CO2R6, -C(O)NR7R8, ou -S(O)2NR7R8; ou R4 e R5 juntos com os átomos aos quais eles estão ligados formam um anel mono-, bicíclico ou aromático, saturado ou parcialmente insaturado tendo 3, 4, 5, 6, 7, ou 8 átomos de anel e opcionalmente compreendendo 1, 2, 3, ou 4 heteroátomos selecionados de não-peróxido óxi (-O-), tio (-S-), sulfinila (-SO-), sulfonila (-S(O)2-) e amina -N(R9)- no anel, onde o anel é opcionalmente substituído com 1, 2, 3, ou 4 substituintes independentemente selecionados de halo, ciano, nitro, -ORa, -SRa, (C6-C10)arila, -O(C6C10)arila, hidróxi(C1-C8)alquila, RbRcN(C1-C8)alquila, halo(C1-C8)alquila, NRbRc, -C(O)Ra, -COORa, e -C(O)NRbRc;X1 é -OR6, -C(O)R6, -CO2R6, ou -NR7R8; e Y é óxi (-O-), tio (-S-), sulfinila (-SO-), sulfonila (-S(O)2-) e amina -N(R9)-;onde os grupos de alquila, alquenila, cicloalquila, alquinila, arila, heterociclo, ou heteroarila de grupos de R1, R2, R3, R4 e R5 são opcionalmente substituídos com um ou mais substituintes independentemente selecionados de halo, ciano, nitro, -ORa, -SRa, (C6-Cw)arila, -O(C6-Cw)arila, hidróxi(C1-C8)alquila, RbRcN(C1-C8)alquila, halo(C1-C8)alquila, -NRbRc, C(O)Ra, -COORa, e -C(O)NRbRc ;onde R6 é hidrogênio, (C1-C8)alquila, RaO(C1-C8)alquila, RbRcN(C1-C8)alquila, halo(C1-C8)alquila, (C3-C10)heterociclo, (C3Cw)heterociclo(C1-C8)alquil-, (C6-C10)arila, (C6-C10)aril(C1-Ce)alquil-, (C4C10)heteroarila, (C4-C10)heteroaril(C1-C8)alquil-; onde o heterociclo, heteroarila ou arila são opcionalmente substituídos com 1, 2, 3, ou 4 substituintes independentemente selecionados de halo, ciano, nitro, -ORa, -SRa, (C6C10)arila, -O(C6-C10)arila, hidróxi(C1-C8)alquila, RbRcN(C1-C8)alquila, halo(C1C8)alquila, -NRbRc, -C(O)Ra, -COORa, e -C(O)NRbRc;onde R7, R8 e R9 são independentemente hidrogênio, (C119/07/2018, pág. 10/27Ce)alquila, RaO(Ci-C8)alquila, RbRcN(Ci-C8)alquila, halo(Ci-C8)alquila, (C3Cio)heterociclo, (C6-Cw)arila, (C6-Cw)aril(C1-C8)alquil-, (C4-Cw)heteroarila; COORa, -C(O)Ra, ou -C(O)NRbRc onde o heterociclo, heteroarila ou arila são opcionalmente substituídos com 1, 2, 3, ou 4 substituintes independentemente selecionados de halo, ciano, nitro, -ORa, -SRa, (C6-C10)arila, -O(C6C10)arila, hidróxi(C1-C8)alquila, RbRcN(C1-C8)alquila, halo(C1-C8)alquila, NRbRc, -C(O)Ra, -COORa, e -C(O)NRbRc; ou R7 e R8 juntos com os átomos aos quais eles estão ligados formam um anel mono-, bicíclico ou aromático, saturado ou parcialmente insaturado tendo 3, 4, 5, 6, 7, ou 8 átomos de anel opcionalmente anel tendo de 4 a oito átomos de anel e opcionalmente compreendendo 1, 2, 3, ou 4 heteroátomos selecionados de não-peróxido óxi (O-), tio (-S-), sulfinila (-SO-), sulfonila (-S(O)2-) ou amina -N(Rb)- no anel;Ra é hidrogênio, ou (C1-C6)alquila; Rb e Rc são cada qual independentemente hidrogênio, (C1-C6)alquila, (C1-C6)alcóxi, (C3-C8)ciclo-alquila, (C1-C6)alquiltio, (C6-C10)arila, (C6-C10)aril(C1-C6)alquil-, heteroarila, ou heteroaril(C1-C6)alquil-; ou Rb e Rc juntos com o nitrogênio ao qual eles estão ligados, formam um anel de pirrolidila , piperidila, piperazinila, azepinila, diazepinila, morfolinila, ou tiomorfolinila;onde n é 0, 1, 2, 3, 4, 5, 6, 7, ou 8; m é 1, ou 2; e q é 1, 2, 3, ou 4; ou um sal farmaceuticamente aceitável dos mesmos.
- 2. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R é hidrogênio, metila, etila, alila, propargil, i-propila, n-propila, n-butila, i-butila ou halo(C1-C4)alquila.
- 3. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R é hidrogênio, metila, etila, -CH2-CH2-Cl, -CH2-CH2-Br, ou CH2-CH2-CH2-F.
- 4. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R é hidrogênio.
- 5. Composto de acordo com a reivindicação 1 ou 2, caracterizado pelo fato de que R1 é hidrogênio, (C1-C4)alquila, (C3-C4)alquenila, (C3C4)alquinila, fenila, ou fenil(C1-C4)alquila.
- 6. Composto de acordo com a reivindicação 1, caracterizado pe19/07/2018, pág. 11/27 lo fato de que R1 é (C3-C6)cicloalquila e (C3-C6)cicloalquil(Ci-C4)alquil-.
- 7. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R1 é ciclopropila ou ciclopropilmetila.
- 8. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R1 é hidrogênio, metila, etila, alila, propargil, i-propila, npropila, n-butila, i-butila, fenila, fenetila, benzila, ou (metoxifenil)etila.
- 9. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R1 é etila, n-propila ou alila.
- 10. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R2 é hidrogênio, (C1-C4)alquila, (C3-C4)alquenila, (C3C4)alquinila, fenila, fenil(C1-C4)alquila, ou (metoxifenil)etila .
- 11. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R2 é (C3-C6)cicloalquila ou (C3-C6)cicloalquil(C1-C4)alquil-.
- 12. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R2 é ciclopropila ou ciclopropilmetila.
- 13. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R2 é hidrogênio, metila, etila, alila, propargil, i-propila, npropila, n-butila, i-butila, fenila, fenetila, ou benzila.
- 14. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R2 é etila, n-propila ou alila.
- 15. Composto de acordo com a reivindicação 1, 9 ou 14, caracterizado pelo fato de que Z é -OH, -O(C1-C4)alquila, -O(C6-C10)arila, -O(C6C10)aril(C1-C4)alquila, -NR4R5, F, Cl, Br, ou I.
- 16. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R4 é hidrogênio, (C1-C6)alquila, (C3-C6)cicloalquila, (C3C6)cicloalquil(C1-C4)alquil-, (C3-C6)heterociclo, (C6-Cw)arila, (C6-C10)aril(C1C4)alquil-, (C5-C6)heteroarila, ou (C5-C6)heteroaril(C1-C4)alquil-, -S(O2)NH2, C(O)R6, -CO2R6, ou -C(O)NR6R7.
- 17. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R4 é hidrogênio, (C1-C4)alquila, hidróxi(C2-C4)alquila, (C3C6)cicloalquila, (C6-C10)arila, (C7-C10)aralquila, (C5-C6)heteroarila, -(CH2-CH2O)q-(CH2-CH2)-ORa, -(CH2-CH2-O)q-(CH2-CH2)-COORa, -(CH2-CH2-OMCH219/07/2018, pág. 12/27CH2)-NRaRb, -NR7R8, -C(O)R6, -CO2R6, ou -C(O)NR7R8.
- 18. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R4 é hidrogênio, metila, etila, propila, pentila, hidroxietila, hidroxipropila, etoxietila, dietoxietila, metilbenzila, aminometilbenzila, metoxibenzila, metoxifenetila, furilmetila, ciclopropila, ciclopropilmetila, ciclopentila, ciclohexila, tiofenila, -C(O)R6, -CO2R6, ou -C(O)NHR7.
- 19. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R4 é metila, etila, ciclopropila, ciclopropilmetila, -C(O)R6, CO2R6, ou -C(O)NHR7.
- 20. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R5 é hidrogênio, (C1-C6)alquila, (C3-C6)cicloalquila, (C3C6)cicloalquil(C1-C4)alquil-, (C3-C6)heterociclo, (C6-C10)arila, (C6-C10)aril(C1C4)alquil-, (C5-C6)heteroarila, (C5-C6)heteroaril(C1-C4)alquil-, -S(O2)NH2, C(O)R6, -CO2R6, ou -C(O)NR6R7.
- 21. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R5 é hidrogênio, (C1-C4)alquila, hidróxi(C2-C4)alquila, (C3C6)cicloalquila, (C6-C10)arila, (C7-C10)aralquila, (C5-C6)heteroarila, -(CH2-CH2O)q-(CH2-CH2)-ORa, -(CH2-CH2-O)q-(CH2-CH2)-COORa, -(CH2-CH2-O)q-(CH2CH2)-NRaRb, -NR7R8, -C(O)R6, -CO2R6, ou -C(O)NR7R8.
- 22. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R5 é hidrogênio, metila, etila, propila, pentila, hidroxietila, hidroxipropila, etoxietila, dietoxietila, metilbenzila, aminometilbenzila, metoxibenzila, metoxifenetila, furilmetila, ciclopentila, ciclohexila, tiofenila, -C(O)R6, -CO2R6, ou -C(O)NHR7.
- 23. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R5 é metila, etila, ciclopropila, ciclopropilmetila, -C(O)R6, CO2R6, ou -C(O)NHR7.
- 24. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R4 e R5 considerados juntos com o nitrogênio ao qual eles estão ligados, é um anel de pirrolidila, piperidila, piperazinila, azepinila, diazepinila, morfolinila, ou tiomorfolinila, cada qual opcionalmente substituído com 1, 2, 3, ou 4 substituintes independentemente selecionados de halo,19/07/2018, pág. 13/27 ciano, nitro, -ORa, -SRa, (C6-Cio)arila, -O(C6-Cio)arila, hidróxi(Ci-Cs)alquila,RbRcN(Ci-C8)alquila, halo(C1-Cs)alquila, -NRbRc, -C(O)Ra, -COORa, e C(O)NRbRc
- 25. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R6 é (C1-C6)alquila, (C3-C6)cicloalquila, (C3-C6)cicloalquil(C1C4)alquil-, (C3-C6)heterociclo, (C6-Cw)arila, (C6-Cw)aril(C1-C4)alquil-, (C5C6)heteroarila, ou (C5-C6)heteroaril(C1-C4)-alquil-, cada qual opcionalmente substituído com 1, 2, ou 3 substituintes independentemente selecionados do grupo consistindo em halo, ciano, nitro, (C1-C8)alquila, -ORa, -SRa, (C6Cw)arila, -O(C6-Cw)arila, hidróxi(C1-C8)alquila, RbRcN(C1-C8)alquila, halo(C1C8)alquila, -NRbRc, -C(O)Ra, -COORa, e -C(O)NRbRc.
- 26. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R6 é (C6-C10)arila, (C5-C6)heteroarila, cada qual opcionalmente substituído com 1, 2, ou 3 substituintes independentemente selecionados de halo, ciano, nitro, (C1-C8)alquila, halo(C1-C8)alquila, -COORa, e C(O)NRbRc.
- 27. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R6 é piridila, opcionalmente substituída com F, Cl, Br, I, CF3, ciano, nitro, -COORa, ou -CONHRa.
- 28. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que:R é hidrogênio, metila, ou etila;R1 e R2 são independentemente metila, etila, alila, propargil, i-propila, n-propila, ciclopropila, ciclopropilmetila, ou n-butila; eX é 3-piridila substituída na posição 6 com Z, onde Z é (C4C10)heterociclo ou -NR4R5, onde R4 é metila, etila, ciclopropila, ciclopropilmetila e R5 é -C(O)R6, onde R6 é heteroarila opcionalmente substituída com 1, 2 ou 3 substituintes independentemente selecionados de halo, ciano, nitro, halo(C1-C8)alquila, -C(O)Ra, -COORa, e -C(O)NRbRc, e onde Ra, Rb e Rc são independentemente hidrogênio, metila, etila, propila, isopropila, ou ciclopropila.
- 29. Composto de acordo com a reivindicação 1, caracterizado19/07/2018, pág. 14/27 pelo fato de que R1 e R2 são independentemente hidrogênio, (Ci-C4)alquila, (C3-C4)alquenila, (C3-C4)alquinila, fenila, ou fenil(C1-C4)alquila.
- 30. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R é hidrogênio, metila, etila, alila, propargil, i-propila, npropila, n-butila, i-butila ou halo(C1-C4)alquila; e R1 e R2 são independentemente hidrogênio, metila, etila, alila, propargil, i-propila, n-propila, ciclopropila, ciclopropilmetila, n-butila, i-butila, fenila, fenetila, ou benzila.
- 31. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R é hidrogênio, metila, etila, -CH2-CH2-Cl, -CH2-CH2-Br, ou CH2-CH2-CH2-F; e R1 e R2 são independentemente hidrogênio, metila, etila, alila, propargil, i-propila, n-propila, ciclopropila, ciclopropilmetila, ou (metoxifenil)etila.
- 32. Composto de acordo com a reivindicação 1 ou 29, caracterizado pelo fato de que X é imidazolila, triazolila, triazinila, oxazoíla, isoxazoíla, tiazolila, isotiazoíla, tiodiazolila, pirrolila, pirazinila, tetrazolila, piridinila, pirimidinila, indolila, isoquinolila, ou quinolila, cada qual opcionalmente substituído com 1, 2, ou 3 substituintes independentemente selecionados de halo, ciano, nitro, (C1-Ce)alquila, -ORa, -SRa, (Ce-C10)arila, -O(C6-Cw)arila, hidróxi(C1-C8)alquila, RbRcN(C1-C8)alquila, halo(C1-C8)alquila, -NRbRc, -C(O)Ra, COORa, e -C(O)NRbRc.
- 33. Composto de acordo com a reivindicação 1 ou 29, caracterizado pelo fato de que X é 2-piridinila, 3-piridinila, ou 4-piridinila, cada qual opcionalmente substituído com 1, 2, ou 3 substituintes independentemente selecionados do grupo consistindo em halo, ciano, nitro, (C1-C8)alquila, ORa, -SRa, (C6-C10)arila, -O(C6-C10)arila, hidróxi(C1-C8)alquila, RbRcN(C1C8)alquila, halo(C1-C8)alquila, -NRbRc, -C(O)Ra, -COORa, e -C(O)NRbRc
- 34. Composto de acordo com a reivindicação 33, caracterizado pelo fato de que -X(Z1)n-Z tem a fórmula:>N\\ZZ1 v N >=NZ1NZ19/07/2018, pág. 15/27
- 35. Composto de acordo com a reivindicação 34, caracterizado pelo fato de que -X(Z1)n-Z tem a fórmulaZ
- 36. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que Z é -OH, -O(C1-C4)alquila, -OC(O)NR7R8, (C1-C4)alquila, NR4R5, F, Cl, Br, ou I, onde R4 e R5 são independentemente hidrogênio, (C1C6)alquila, (C3-C6)cicloalquila, (C3-C6)heterociclo, (C6-C10)arila, (C7C12)aralquila, (C5-C6)heteroarila, ou (C5-C6)heteroaril(C1-C4)alquila, S(O2)NH2, -C(O)R6, -CO2R6, ou -C(O)NR6R7.
- 37. Composto de acordo com a reivindicação 1 ou 29, caracterizado pelo fato de que Z é -NR4R5.
- 38. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R4 e R5 juntos com o nitrogênio ao qual eles estão ligados, formam um anel de pirrolidila, piperidila, piperazinila, azepinila, diazepinila, morfolinila, ou tiomorfolinila, onde o anel é opcionalmente substituído com 1, 2, 3, ou 4 substituintes independentemente selecionados de halo, ciano, nitro, -ORa, -SRa, (C6-C10)arila, -O(C6-C10)arila, hidróxi(C1-C8)alquila, RbRcN(C1-C8)alquila, halo(C1-C8)alquila, -NRbRc, -C(O)Ra, -COORa, e C(O)NRbRc.
- 39. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R4 e R5 são independentemente hidrogênio, (C1-C4)alquila, hidróxi(C2-C4)alquila, (C3-C6)cicloalquila, (C6-C10)arila, (C7-C10)aralquila, (C5C6)heteroarila, -(CH2-CH2-O)q-(CH2-CH2)-ORa, -(CH2-CH2-O)q-(CH2-CH2)COORa, -(CH2-CH2-O)q-(CH2-CH2)-NRaRb, -NR7R8, -C(O)R6, -CO2R6, ou C(O)NR7R8.
- 40. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R4 e R5 são independentemente hidrogênio, metila, etila, propila, pentila, hidroxietila, hidroxipropila, etoxietila, dietoxietila, metilbenzila, aminometilbenzila, metoxibenzila, metoxifenetila, furilmetila, ciclopentila, ci19/07/2018, pág. 16/27 clohexila, tiofenila, -C(O)R6, -CO2R6, ou -C(O)NHR7.
- 41. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R6 é metila, metóxi, ou piridila, e R7 é fenila, fluorofenila, ou metoxifenila.
- 42. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que:R é hidrogênio, metila, ou etila;R1 e R2 são independentemente metila, etila, alila, propargil, i-propila, n-propila, ciclopropila, ciclopropilmetila, n-butila, i-butila; eZ é (C4-C10)heterociclo ONDE O heterociclo é opcionalmente substituído com 1, 2, 3, ou 4 substituintes independentemente selecionados de halo, ciano, nitro, -ORa, -SRa, (C6-Cw)arila, -O(C6-Cw)arila, hidróxi(C1-C8)alquila, RbRcN(C1-C8)alquila, halo(Ct-C8)alquila, -NRbRc, -C(O)Ra, -COORa, e C(O)NRbRc.
- 43. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que Z é selecionado do grupo consistindo em:'NH 'NH \\ /—HN n\OHHNNH —N'O (CH»)q ' COOHJN r4N NHR' —N-N 1 4 XR8 r4 R ’ —O(CH2)q-COOHAN r4 (CH2CH2O)q-CH2CH2OH (CH2CH2O)q-CH2CH2NH2 , ouN R4 (CH2CH2O)q-CH2CH2-COOH
- 44. Composto de acordo com a reivindicação 1 ou 29, caracterizado pelo fato de que -X(Z1)n-Z é selecionado do grupo consistindo em:z=N /=N / O OHR\ Nh /oh ,R\ NhMeN=/ HPetição 870180062187, de 19/07/2018, pág. 17/27
- 45. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que R1 e R2 são n-propila; R é hidrogênio e n é zero.
- 46. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que -X(Z1)n-Z é selecionado do grupo consistindo em:Petição 870180062187, de 19/07/2018, pág. 18/27
- 47. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que é:1.3- Dipropil-8-(6-cloro-3-piridil)xantina;1.3- Dipropil-8-(6-etilamino-3-piridil)xantina;5 1,3-Dipropil-8-(6-(2-hidroxietil)amino-3-piridil)xantina;1.3- Dipropil-8-[6-(4-acetilpiperazinil)-3-piridil]xantina;1.3- Dipropil-8-(6-pirrolidinilpirid-3-il)xantina;1.3- Dipropil-8-(6-metilamino-3-piridil)xantina;1.3- Dipropil-8-[6-(2-hidroxipropil)amino-3-piridil]xantina;10 1,3-Dipropil-8-[6-(2,2-dimetoxietil)amino-3-piridil]xantina;1.3- Dipropil-8-[[6-(2-hidroxietóxi)etilamino]-3-piridil]xantina; e1.3- Dipropil-8-[6-[N-nicotinoilmetilamino]-3-piridil]xantina; ou um sal farmaceuticamente aceitável do mesmo.
- 48. Composto de acordo com a reivindicação 1, caracterizado 15 pelo fato de que é:1.3- Dietil-8-[6-[N-nicotinoiletilamino]-3-piridil]xantina;1.3- Dietil-8-[6-[N-nicotinoilmetilamino]-3-piridil]xantina; 8-[6-(2,5-diaza-biciclo[2.2.2]oct-2-il)-piridin-3-il}-1,3-dipropil-3,7-dihidropurina-2,6-diona;20 1,3-Dipropil-8-(6-(2-acetilaminoetil)amino-3-piridil)xantina;Petição 870180062187, de 19/07/2018, pág. 19/271 -(5-(1,3-Dietil-2,3,6,7-tetrahidro-2,6-d ioxo-1 H-purin-8-il)piridin-2-il)-1 -(2metoxietil)-3-(piridina-4-il)uréia;1.3- Dimetil-8-(6-metilamino-3-piridil)xantina;1-Propargil, 3-metil-8-[6-[N-nicotinoilmetilamino]-3-piridil]xantina;1.3- Dietil-8-[6-[N-(isoxazol-5-carbonil)metilamino]-3-piridil]xantina;1.3- Dipropil-8-[6-[N-(2-pirazinacarbonil)metilamino]-3-piridil]xantina;1.3- Dipropil-8-[6-[N-(isoxazol-5-carbonil)metilamino]-3-piridil]xantina; 1-Ciclopropil-3-propil-8-[6-[N-nicotinoilmetilamino]-3-piridil]xantina; e1.3- Dietil-8-[6-[N-nicotinoilciclopropilmetilamino]-3-piridil]xantina;ou um sal farmaceuticamente aceitável do mesmo.
- 49. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que é selecionado do grupo consistindo em:1.3- Dipropil-8-{6-[4-metil(perhidro-1,4-diazaepin-1 -il)]-3-piridil}xantina;1.3- Dipropil-8-[6-(1-hidróxi-2-propil)amino-3-piridil]xantina;1.3- Dipropil-8-(6-morfolino-3-piridil)xantina;1.3- Dipropil-8-(6-dimetilamino-3-piridil)xantina;1.3- Dipropil-8-(6-piperazino-3-piridil)xantina;1.3- Dipropil-8-[6-(4-aminometilbenzilamino)-3-piridil]xantina;1.3- Dipropil-8-(6-ciclopropilamino-3-piridil]xantina;1.3- Dipropil-8-[6-[N-isonicotinoilmetilamino]-3-piridil]xantina; e1.3- Dipropil-8-[6-(hexahidro-1,4-diazaepin-1 -il)-3-piridil]xantina;ou um sal farmaceuticamente aceitável do mesmo.
- 50. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que é selecionado do grupo consistindo em:1.3- Diciclopropilmetil-8-[6-[N-nicotinoilmetilamino]-3-piridil]xantina;1.3- Diciclopropilmetil-8-[6-[N-nicotinoiletilamino]-3-piridil]xantina;1.3- Dietil-8-[6-(2-piridilmetilamino)-3-piridil]xantina;1.3- Dietil-8-[6-(3-piridilmetilamino)-3-piridil]xantina;1.3- Dietil-8-[6-(3-metoxibenzilamino)-3-piridil]xantina;1.3- Dipropil-8-[6-[2-(2-piridil)-etilamino]-3-piridil]xantina;1.3- Dietil-8-[6-[2-(1-pirrolidinil)-etilamino]-3-piridil]xantina;1.3- Dipropil-8-[6-[N-(5-metilisoxazol-3-il-3-carbonil)metilamino]-319/07/2018, pág. 20/27 piridil]xantina; e1.3- Dietil-8-[6-(N-(6-cloronicotinoil)metilamino)-3-piridil]xantina;ou um sal farmaceuticamente aceitável do mesmo.
- 51. Composto de acordo com a reivindicação 1, caracterizado pelo fato de que é selecionado do grupo consistindo em:1.3- Dipropil-8-(6-cloro-3-piridil)xantina;1-Propil-3-propargil-8-(6-cloro-3-piridil)xantina;1.3- Dipropil-8-(6-etilamino-3-piridil)xantina;1.3- Dipropil-8-(6-(2-hidroxietil)amino-3-piridil)xantina;1.3- Dipropil-8-[6-(4-acetilpiperazinil)-3-piridil]xantina;1.3- Dipropil-8-[6-(benzilamino)-3-piridil]xantina;1.3- Dipropil-8-[6-(1-piperidinil)-3-piridil]xantina;1.3- Dipropil-8-(6-pirrolidinilpirid-3-il)xantina;1.3- Dipropil-8-{6-[4-metil(perhidro-1,4-diazaepin-1 -il)]-3-piridil}xantina;1.3- Dipropil-8-(6-metilamino-3-piridil)xantina;1.3- Dipropil-8-[6-(4-metoxibenzilamino)-3-piridil]xantina;1.3- Dipropil-8-[6-(3-metilpiperidino)-3-piridil]xantina;1.3- Dipropil-8-[6-(2-hidroxipropil)amino-3-piridil]xantina;1.3- Dipropil-8-[6-(2,2-dimetoxietil)amino-3-piridil]xantina;1.3- Dipropil-8-[6-(1-hidróxi-2-propil)amino-3-piridil]xantina;1.3- Dipropil-8-(6-morfolino-3-piridil)xantina;1.3- Dipropil-8-(6-dimetilamino-3-piridil)xantina;1.3- Dipropil-8-[[6-(2-hidroxietóxi)etilamino]-3-piridil]xantina;1.3- Dipropil-8-(6-piperazino-3-piridil)xantina;1.3- Dipropil-8-[6-(2-hidróxi-2-feniletil)amino-3-piridil]xantina;1.3- Dipropil-8-[6-(4-aminometilbenzilamino)-3-piridil]xantina;1.3- Dipropil-8-(6-fenilamino-3-piridil]xantina;1.3- Dipropil-8-(6-ciclopropilamino-3-piridil]xantina;1.3- Dipropil-8-[6-(6-piridilmetilamino)-3-piridil]xantina;1.3- Dipropil-8-(6-(4-metilpiperazino)-3-piridil)xantina;1.3- Dipropil-8-[6-(3-piridilmetilamino)-3-piridil]xantina;1.3- Dipropil-8-[6-(2-metilbenzilamino)-3-piridil]xantina;19/07/2018, pág. 21/271.3- Dipropil-8-[6-[2-(3,4-dimetoxifenil)etilamino]-3-piridil]xantina;1.3- Dipropil-8-[6-[(N-propilcarbamoil), metilamino]-3-piridil]xantina;1.3- Dipropil-8-[6-(3-pentilamino)-3-piridil]xantina;1.3- Dipropil-8-[6-(2,2-difeniletilamino)-3-piridil]xantina;1.3- Dipropil-8-[6-[2-(1-etilpirrolidinometilamino)]-3-piridil]xantina;1.3- Dipropil-8-[6-(3-metoxibenzilamino)-3-piridil]xantina;1.3- Dipropil-8-[6-[(N-fenilcarbamoil)metilamino]-3-piridil]xantina;1.3- Dipropil-8-[6-(furfurilamino)-3-piridil]xantina;1.3- Dipropil-8-[6-[2-(4-metoxifenil)etilamino]-3-piridil]xantina;1.3- Dipropil-8-[6-(2-metoxibenzilamino)-3-piridil]xantina;1.3- Dipropil-8-[6-(propilamino)-3-piridil]xantina;1.3- Dipropil-8-[6-(ciclopentilamino)-3-piridil]xantina;1.3- Dipropil-8-[6-(ciclohexilamino)-3-piridil]xantina;1.3- Dipropil-7-etil-8-(6-cloro-3-piridil)xantina;1.3- Dipropil-7-(3-fluoropropil-8-(6-cloro-3-piridil)xantina;1.3- Dipropil-7-metil-8-(6-cloro-3-piridil)xantina;1.3- Dipropil-7-(2-bromoetil)-8-(6-cloro-3-piridil)xantina;1.3- Dipropil-8-[6-(2-tiofenometilamino)-3-piridil]xantina;1.3- Dipropil-8-[6-[(N-(4-metoxifenilcarbamoil)metilamino]-3-piridil]xantina;1.3- Dipropil-8-[6-[N-nicotinoilmetilamino]-3-piridil]xantina;1.3- Dipropil-8-[6-[(N-(4-fluorofenilcarbamoil)metilamino]-3-piridil]xantina;1.3- Dipropil-8-[6-[N-isonicotinoilmetilamino]-3-piridil]xantina;1.3- Dipropil-8-[6-[N-metoxicarbonilmetilamino]-3-piridil]xantina;1.3- Dipropil-8-[6-[N-fenilcarbamoil, N-(2-fenilcarbamoiloxietil)amino]-3-piridil] xantina;1.3- Dipropil-8-{6-[4-(N-fenilcarbamoil)]piperazino-3-piridil}xantina;1.3- Dipropil-8-{6-[4-(N-isonicotinoil)]piperazino-3-piridil}xantina;1-propil-3-(4-metoxifenil)etil-8-(6-cloro-3-piridil)xantina;1-Propil-3-(metoxifeniletil)-8-(6-piperazino-3-piridil)xantina;1.3- Dipropil-8-[6-(4-piridilamino)-3-piridil]xantina;1.3- Dipropil-8-{6-[4-(N-nicotinoil)]piperazino-3-piridil}xantina;1.3- Dipropil-8-[6-(hexahidro-1,4-diazaepin-1 -il)-3-piridil]xantina;19/07/2018, pág. 22/271.3- Dietil-8-(6-cloro-3-piridil)xantina;1.3- Dietil-8-(6-piperazino-3-piridil)xantina;1.3- Dietil-8-[6-[(N-fenilcarbamoil)metilamino]-3-piridil]xantina;1.3- Dietil-8-[6-[N-nicotinoiletilamino]-3-piridil]xantina;1.3- Dietil-8-(6-metilamino-3-piridil)xantina;1.3- Dietil-8-[6-[N-nicotinoilmetilamino]-3-piridil]xantina;1.3- Dietil-8-[6-[N-nicotinoilciclopropilamino]-3-piridil]xantina;1.3- Diciclopropilmetil-8-(6-metilaminopiridin-3-il)xantina;1-Propargil-3-metil-8-(6-metilamino-3-piridil)xantina;8-[6-(2,5-diaza-biciclo[2.2.2]oct-2-il)-piridin-3-il}-1,3-dipropil-3,7-dihidropurina-2,6-diona;1.3- Diciclopropilmetil-8-[6-[N-nicotinoilmetilamino]-3-piridil]xantina;1.3- Diciclopropilmetil-8-[6-[N-nicotinoiletilamino]-3-piridil]xantina;1.3- Dialil-8-(6-metilamino-3-piridil)xantina;1-Clopropilmetil-3-etil-8-(6-metilaminopiridin-3-il)xantina;1.3- Dietil-8-[6-(2-piridilmetilamino)-3-piridil]xantina;1.3- Dietil-8-[6-(3-piridilmetilamino)-3-piridil]xantina;1.3- Dietil-8-[6-(3-metoxibenzilamino)-3-piridil]xantina;1.3- Dipropil-8-[6-[2-(3-piridil)-etilamino]-3-piridil]xantina;1.3- Dietil-8-[6-[2-(3-piridil)-etilamino]-3-piridil]xantina;1.3- Dipropil-8-[6-[2-(2-piridil)-etilamino]-3-piridil]xantina;1.3- Dietil-8-[6-[2-(2-piridil)-etilamino]-3-piridil]xantina;1.3- Dietil-8-(6-pirrolidinilpirid-3-il)xantina;1.3- Dietil-8-[6-[2-(1-pirrolidinil)-etilamino]-3-piridil]xantina;1.3- Dipropil-8-(6-(2-metoxietil)amino-3-piridil)xantina;1.3- Dipropil-8-(6-(2-acetilaminoetil)amino-3-piridil)xantina;1.3- Dietil-8-(6-bromo-3-piridil)xantina;1.3- Dipropil-8-{6-[4-(2-piridil)-piperazino]-3-piridil}xantina;1.3- Dietil-8-{6-[4-(2-piridil)-piperazino]-3-piridil}xantina;1.3- Dietil-8-[6-(trans-2,5-dimetilpiperazino)-3-piridil]xantina;1.3- Dipropil-8-{6-[4-(2-pirimidinil)-piperazino]-3-piridil}xantina;1.3- Dietil-8-{6-[4-(2-pirimidinil)-piperazino]-3-piridil}xantina;19/07/2018, pág. 23/271.3- Dietil-8-(6-(2-metoxietil)amino-3-piridil)xantina;1 -Propargil, 3-metil-8-(6-Bromo-3-piridil)xantina;1.3- Dietil-8-[6-[N-nicotinoil, N-(2-metoxietil)amino]-3-piridil]xantina;1 -Propargil, 3-metil-8-(6-(2-metoxietil)-3-piridil)xantina;1.3- Dietil-8-[6-[N-isonicotinoil, N-(2-metoxietil)amino]-3-piridil]xantina;1 -(5-(1,3-Dietil-2,3,6,7-tetrahidro-2,6-dioxo-1 H-purin-8-il)piridin-2-il)-1 -(2metoxietil)-3-(piridina-4-il)uréia;1.3- Dimetil-8-(6-bromo-3-piridil)xantina;1.3- Dimetil-8-(6-metilamino-3-piridil)xantina;1.3- Dimetil-8-[6-[N-nicotinoilmetilamino]-3-piridil]xantina;1.3- Dipropil-8-[6-[N-nicotinoil, N-(2-metoxietil)amino]-3-piridil]xantina; 1-Propargil, 3-metil-8-[6-[N-nicotinoil, N-(2-metoxietil)amino]-3-piridil] xantina; 1-Propargil, 3-metil-8-[6-[N-nicotinoilmetilamino]-3-piridil]xantina;1.3- Dipropil-8-(2,6-dicloro-3-piridil)xantina;1.3- Dipropil-8-(2,6-dimetilamino-3-piridil)xantina;1.3- Dipropil-8-(2,6-di(2-metoxietil)-3-piridil)xantina;1.3- Dipropil-8-[2,6-di[N-nicotinoilmetilamino]-3-piridil]xantina;1.3- Dipropil-8-[2,6-di[N-nicotinoil, N-metoxietil]-3-piridil]xantina;1.3- Dietil-8-[6-[N-(2-pirazinacarbonil)metilamino]-3-piridil]xantina;1.3- Dietil-8-[6-[N-(isoxazol-5-carbonil)metilamino]-3-piridil]xantina;1.3- Dipropil-8-[6-[N-(2-pirazinacarbonil)metilamino]-3-piridil]xantina;1.3- Dipropil-8-[6-[N-(isoxazol-5-carbonil)metilamino]-3-piridil]xantina;1.3- Dipropil-8-[6-[N-(5-metilisoxazol-3-il-3-carbonil)metilamino]-3piridil]xantina;1.3- Dipropil-8-[6-[N-(2-cloro-6-metoxipiridinil-4-carbonil), N-metilamino]-3piridil]xantina;1.3- Dipropil-8-[6-[N-(N-óxido de isonicotinoil), N-metilamino]-3-piridil]xantina; 1-propil-3-(4-metoxifenil)etil-8-(6-metilamino-3-piridil)xantina;1.3- Dietil-8-[6-[N-(N-óxido de isonicotinoil), N-metilamino]-3-piridil]xantina;1.3- Dialil-8-(6-cloro-3-piridil)xantina;1-propil-3-(4-metoxifenil)etil-8-[6-(N-nicotinoilmetilamino)-3-piridil]xantina;1-propil-3-(4-metoxifenil)etil-8-[6-(N-(6-cloronicotinoil)metilamino)-319/07/2018, pág. 24/27 piridil]xantina;1.3- dialil-8-[6-(N-nicotinoilmetilamino)-3-piridil]xantina;1.3- dialil-8-[6-(N-(6-cloronicotinoil)metilamino)-3-piridil]xantina;1.3- dipropil-8-[6-(N-[6-(trifluorometil)nicotinoil]metilamino)-3-piridil]xantina;1.3- dietil-8-[6-(2-hidróxi-5-metil)benzaldeidohidrazono]-3-piridil]xantina;1.3- dietil-8-[6-(bromopiridina-3-carbaldeidohidrazono]-3-piridil]xantina; 1-Ciclopropil-3-etil-8-(6-metilamino-3-piridil)xantina; 1-Ciclopropil-3-propil-8-(6-metilamino-3-piridil)xantina; 1-Propil-3-ciclopropil-8-(6-metilamino-3-piridil)xantina; 1-Ciclopropil-3-propil-8-(6-(2-metoxietil)amino-3-piridil)xantina; 1-Ciclopropil-3-propil-8-[6-[N-nicotinoilmetilamino]-3-piridil]xantina;1.3- Dietil-8-[6-(N-(6-cloronicotinoil)metilamino)-3-piridil]xantina;1.3- Dipropil-8-(2-cloro-6-metoxietilamino-4-piridil)xantina;1.3- Dipropil-8-(2-cloro-6-metilamino-4-piridil)xantina;1.3- Dipropil-8-[2-[N-nicotinoil, N-(2-metoxietil)amino]-6-cloro-4-piridil)xantina;1.3- Dipropil-8-[2-[N-nicotinoil, N-metilamino]-6-cloro-4-piridil)xantina; 1-Ciclopropil-3-propil-8-[6-[N-(6-cloronicotinoil)metilamino]-3-piridil]xantina; 1-Etil-3-ciclopropil-8-(6-metilamino-3-piridil)xantina;1-Etil-3-ciclopropil-8-(6-(2-metoxietil)amino-3-piridil)xantina;1.3- Dietil-8-[6-hidrazino-3-piridil]xantina;1.3- Dietil-8-[6-(ciclopropilamino)-3-piridil]xantina;1.3- Dietil-8-[6-(ciclopropilmetilamino)-3-piridil]xantina;N'-[5-(1,3-dietil-2,6-dioxo-2,3,6,7-tetrahidro-1H-purin-8-il)-piridin-2-il]hidrazida;N-[5-(1,3-dietil-2,6-dioxo-2,3,6,7-tetrahidro-1 H-purin-8-il)-piridin-2-il]-N'(piridina-3-carbonil)-hidrazida;1.3- Dietil-8-[6-(etilamino)-3-piridil]xantina;1.3- Dietil-8-[6-[N-nicotinoilciclopropilmetilamino]-3-piridil]xantina; e 1-Ciclopropilmetil-3-etil-8-[6-[N-(6-cloronicotinoil)metilamino]-3-piridil]xantina; ou um sal farmaceuticamente aceitável do mesmo, opcionalmente na forma de um estereoisômero único ou mistura de estereoisômeros deste.
- 52. Composição farmacêutica, caracterizada pelo fato de que19/07/2018, pág. 25/27 compreende:(a) uma quantidade terapeuticamente eficaz de um composto como definido na reivindicação 1; e (b) um excipiente farmaceuticamente aceitável.
- 53. Composição farmacêutica, caracterizada pelo fato de que compreende:(a) uma quantidade terapeuticamente eficaz de um composto como definido na reivindicação 51; e (b) um excipiente farmaceuticamente aceitável.
- 54. Método terapêutico para prevenção ou tratamento de um sintoma ou condição patológica em um mamífero, onde a atividade de receptores de adenosina A2B está implicada e o antagonismo de sua ação é desejado, caracterizado pelo fato de que compreende administrar ao mamífero uma quantidade eficaz de um composto como definido na reivindicação 1.
- 55. Método para tratamento de asma, alergias, doenças alérgicas ou uma doença auto-imune, caracterizado pelo fato de que compreende administrar uma quantidade eficaz de um composto como definido na reivindicação 1, a um mamífero com necessidade de tal tratamento.
- 56. Método para tratamento de doenças diarréicas, resistência à insulina, diabetes, câncer, lesões de reperfusão/isquemia, retinopatia diabética ou retinopatia induzida por oxigênio hiperbárico, caracterizado pelo fato de que compreende administrar uma quantidade eficaz de um composto como definido na reivindicação 1, ou um sal farmaceuticamente aceitável do mesmo a um mamífero com necessidade de tal tratamento.
- 57. Método terapêutico para prevenção ou tratamento de um sintoma ou condição patológica em um mamífero, onde a atividade de receptores de adenosina A2B está implicada e o antagonismo de sua ação é desejado, caracterizado pelo fato de que compreende administrar ao mamífero uma quantidade eficaz de um composto como definido na reivindicação 1.
- 58. Uso de um composto como definido em qualquer uma das reivindicações 1-51, caracterizado pelo fato de que é na produção de um medicamento para o tratamento de asma, alergias, doenças alérgicas, uma19/07/2018, pág. 26/27 doença auto-imune, doenças diarréicas, resistência à insulina, diabetes, câncer, lesões de reperfusão/isquemia, retinopatia diabética ou retinopatia induzida por oxigênio hiperbárico em um mamífero, tal como um ser humano.Petição 870180062187, de 19/07/2018, pág. 27/27
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