ES2566387T3 - Compuestos heterocíclicos condensados de pirid-2-ilo, y composiciones y usos de los mismos - Google Patents

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Publication number

ES2566387T3

ES2566387T3 ES08727238.1T ES08727238T ES2566387T3 ES 2566387 T3 ES2566387 T3 ES 2566387T3 ES 08727238 T ES08727238 T ES 08727238T ES 2566387 T3 ES2566387 T3 ES 2566387T3

Authority

ES

Spain

Prior art keywords

substituted

pyridin

unsubstituted

compound according

compound

Prior art date

2007-04-02

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.)

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• 239000000203 mixture Substances 0.000 title claims description 114
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 title description 10
• 150000002391 heterocyclic compounds Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 265
• -1 azido, carbamoyl Chemical group 0.000 claims abstract description 141
• 125000003118 aryl group Chemical group 0.000 claims abstract description 75
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 67
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 58
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 52
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 38
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 31
• 150000003839 salts Chemical class 0.000 claims abstract description 23
• 125000002252 acyl group Chemical group 0.000 claims abstract description 21
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 21
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims abstract description 21
• 239000012453 solvate Substances 0.000 claims abstract description 20
• 125000004442 acylamino group Chemical group 0.000 claims abstract description 19
• 125000004404 heteroalkyl group Chemical group 0.000 claims abstract description 19
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 18
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 18
• 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 17
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 14
• 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 13
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 12
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 11
• 125000003396 thiol group Chemical group [H]S* 0.000 claims abstract description 11
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 10
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims abstract description 10
• 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 9
• 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 7
• 125000001475 halogen functional group Chemical group 0.000 claims abstract description 7
• 125000005553 heteroaryloxy group Chemical group 0.000 claims abstract description 7
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims abstract description 3
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract 3
• 238000000034 method Methods 0.000 claims description 106
• 238000011282 treatment Methods 0.000 claims description 40
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 38
• 239000008194 pharmaceutical composition Substances 0.000 claims description 34
• 239000001257 hydrogen Substances 0.000 claims description 33
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 28
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• 201000010099 disease Diseases 0.000 claims description 23
• 230000036407 pain Effects 0.000 claims description 22
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 22
• 229910052731 fluorine Inorganic materials 0.000 claims description 16
• 229910052801 chlorine Inorganic materials 0.000 claims description 15
• 208000035475 disorder Diseases 0.000 claims description 15
• 125000004104 aryloxy group Chemical group 0.000 claims description 14
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• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
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• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 8
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• 208000004296 neuralgia Diseases 0.000 claims description 8
• 208000009935 visceral pain Diseases 0.000 claims description 8
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• 208000003251 Pruritus Diseases 0.000 claims description 7
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 7
• 208000037765 diseases and disorders Diseases 0.000 claims description 7
• 230000002265 prevention Effects 0.000 claims description 7
• 125000003107 substituted aryl group Chemical group 0.000 claims description 7
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• 201000000980 schizophrenia Diseases 0.000 claims description 6
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 5
• JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims description 5
• 108010081348 HRT1 protein Hairy Proteins 0.000 claims description 5
• 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims description 5
• 206010019233 Headaches Diseases 0.000 claims description 5
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• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
• 231100000869 headache Toxicity 0.000 claims description 5
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 5
• 230000002757 inflammatory effect Effects 0.000 claims description 5
• 230000004054 inflammatory process Effects 0.000 claims description 5
• 230000007803 itching Effects 0.000 claims description 5
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• 201000008482 osteoarthritis Diseases 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
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• 208000019454 Feeding and Eating disease Diseases 0.000 claims description 4
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• 229910006069 SO3H Inorganic materials 0.000 claims description 4
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• 208000008548 Tension-Type Headache Diseases 0.000 claims description 4
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• 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 4
• 235000014632 disordered eating Nutrition 0.000 claims description 4
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• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
• 208000019116 sleep disease Diseases 0.000 claims description 4
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
• 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 4
• 230000002485 urinary effect Effects 0.000 claims description 4
• COHPLRFPNJNJIX-GOSISDBHSA-N (2s)-2-(6-methoxypyridin-3-yl)-2-[[6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-yl]amino]ethanol Chemical compound C1=NC(OC)=CC=C1[C@@H](CO)NC1=NC=NC2=C1CN(C=1N=CC(C)=CC=1)CC2 COHPLRFPNJNJIX-GOSISDBHSA-N 0.000 claims description 3
• WPBBTBJCOJRQNE-QGZVFWFLSA-N (2s)-2-[[6-(5-chloropyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-yl]amino]-2-(6-methoxypyridin-3-yl)ethanol Chemical compound C1=NC(OC)=CC=C1[C@@H](CO)NC1=NC=NC2=C1CN(C=1N=CC(Cl)=CC=1)CC2 WPBBTBJCOJRQNE-QGZVFWFLSA-N 0.000 claims description 3
• PUIPLPMBTAVSBG-GOSISDBHSA-N (3r)-3-(6-methoxypyridin-3-yl)-3-[[6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-yl]amino]propan-1-ol Chemical compound C1=NC(OC)=CC=C1[C@@H](CCO)NC1=NC=NC2=C1CN(C=1N=CC(C)=CC=1)CC2 PUIPLPMBTAVSBG-GOSISDBHSA-N 0.000 claims description 3
• XNAFMMCWOUXFDU-CQSZACIVSA-N 6-(5-methylpyridin-2-yl)-n-[(1r)-1-(2-methylpyrimidin-5-yl)ethyl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N([C@H](C)C=1C=NC(C)=NC=1)C(C=1C2)=NC=NC=1CCN2C1=CC=C(C)C=N1 XNAFMMCWOUXFDU-CQSZACIVSA-N 0.000 claims description 3
• 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 3
• 208000020925 Bipolar disease Diseases 0.000 claims description 3
• 206010069632 Bladder dysfunction Diseases 0.000 claims description 3
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
• 208000034347 Faecal incontinence Diseases 0.000 claims description 3
• 208000014540 Functional gastrointestinal disease Diseases 0.000 claims description 3
• 206010020751 Hypersensitivity Diseases 0.000 claims description 3
• 208000036110 Neuroinflammatory disease Diseases 0.000 claims description 3
• 206010033645 Pancreatitis Diseases 0.000 claims description 3
• 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 3
• 201000004681 Psoriasis Diseases 0.000 claims description 3
• 206010039085 Rhinitis allergic Diseases 0.000 claims description 3
• 201000009961 allergic asthma Diseases 0.000 claims description 3
• 208000026935 allergic disease Diseases 0.000 claims description 3
• 201000010105 allergic rhinitis Diseases 0.000 claims description 3
• 201000007637 bowel dysfunction Diseases 0.000 claims description 3
• 210000000481 breast Anatomy 0.000 claims description 3
• 229910052794 bromium Inorganic materials 0.000 claims description 3
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
• 230000003001 depressive effect Effects 0.000 claims description 3
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 3
• 206010014599 encephalitis Diseases 0.000 claims description 3
• 208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 3
• 230000009610 hypersensitivity Effects 0.000 claims description 3
• 208000002551 irritable bowel syndrome Diseases 0.000 claims description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
• 201000006370 kidney failure Diseases 0.000 claims description 3
• 125000002757 morpholinyl group Chemical group 0.000 claims description 3
• 201000006417 multiple sclerosis Diseases 0.000 claims description 3
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
• 230000003959 neuroinflammation Effects 0.000 claims description 3
• 210000002307 prostate Anatomy 0.000 claims description 3
• 230000000241 respiratory effect Effects 0.000 claims description 3
• 208000014001 urinary system disease Diseases 0.000 claims description 3
• SSNDZSZPTDFBHC-LJQANCHMSA-N (3r)-3-(6-methylpyridin-3-yl)-3-[[6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-yl]amino]propan-1-ol Chemical compound N1=CC(C)=CC=C1N1CC2=C(N[C@H](CCO)C=3C=NC(C)=CC=3)N=CN=C2CC1 SSNDZSZPTDFBHC-LJQANCHMSA-N 0.000 claims description 2
• SGUGDZUWFAUPNY-QGZVFWFLSA-N (3r)-3-[[6-(5-chloropyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-yl]amino]-3-(6-methoxypyridin-3-yl)propan-1-ol Chemical compound C1=NC(OC)=CC=C1[C@@H](CCO)NC1=NC=NC2=C1CN(C=1N=CC(Cl)=CC=1)CC2 SGUGDZUWFAUPNY-QGZVFWFLSA-N 0.000 claims description 2
• JYXGOVPRQNIYKV-QGZVFWFLSA-N (3r)-3-[[6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-yl]amino]-3-[6-(trifluoromethyl)pyridin-3-yl]propan-1-ol Chemical compound N1=CC(C)=CC=C1N1CC2=C(N[C@H](CCO)C=3C=NC(=CC=3)C(F)(F)F)N=CN=C2CC1 JYXGOVPRQNIYKV-QGZVFWFLSA-N 0.000 claims description 2
• 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
• VCVJHUNWPOOPQN-GFCCVEGCSA-N 6-(5-chloropyridin-2-yl)-n-[(1r)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N([C@H](C)C=1C=NC(=CC=1)C(F)(F)F)C(C=1C2)=NC=NC=1CCN2C1=CC=C(Cl)C=N1 VCVJHUNWPOOPQN-GFCCVEGCSA-N 0.000 claims description 2
• ICLOKAIXSUXTKZ-CQSZACIVSA-N 6-(5-methylpyridin-2-yl)-n-[(1r)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N([C@H](C)C=1C=NC(=CC=1)C(F)(F)F)C(C=1C2)=NC=NC=1CCN2C1=CC=C(C)C=N1 ICLOKAIXSUXTKZ-CQSZACIVSA-N 0.000 claims description 2
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• MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 2
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
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• 230000036772 blood pressure Effects 0.000 claims description 2
• 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
• 125000005945 imidazopyridyl group Chemical group 0.000 claims description 2
• 125000001041 indolyl group Chemical group 0.000 claims description 2
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
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• CMEYRTUYGFNHBD-HXUWFJFHSA-N 6-(5-chloropyridin-2-yl)-n-[(r)-cyclopropyl-[6-(trifluoromethyl)pyridin-3-yl]methyl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=NC(C(F)(F)F)=CC=C1[C@@H](C1CC1)NC1=NC=NC2=C1CN(C=1N=CC(Cl)=CC=1)CC2 CMEYRTUYGFNHBD-HXUWFJFHSA-N 0.000 claims 1
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• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 89
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• 239000000243 solution Substances 0.000 description 70
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• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 32
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