OA13050A - 5,7-diaminopyrazolo [4,3-D] pyrimidines useful in the treatment of hypertension. - Google Patents

Info

Publication number

OA13050A

OA13050A OA1200500306A OA1200500306A OA13050A OA 13050 A OA13050 A OA 13050A OA 1200500306 A OA1200500306 A OA 1200500306A OA 1200500306 A OA1200500306 A OA 1200500306A OA 13050 A OA13050 A OA 13050A

Authority

OA

OAPI

Prior art keywords

nmr

400mhz

lrms

pyrazolo

formula

Prior art date

2003-04-29

Links

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• Global Dossier
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• 238000011282 treatment Methods 0.000 title claims description 22
• 206010020772 Hypertension Diseases 0.000 title description 24
• ZTAWTRPFJHKMRU-UHFFFAOYSA-N 7-deaza-8-aza-2,6-diaminopurine Chemical class NC1=NC(N)=C2NN=CC2=N1 ZTAWTRPFJHKMRU-UHFFFAOYSA-N 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 316
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 216
• 238000000034 method Methods 0.000 claims description 109
• -1 Ci-C6alkoxy Chemical group 0.000 claims description 108
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 91
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 73
• 229910052757 nitrogen Inorganic materials 0.000 claims description 67
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 58
• 229910052760 oxygen Inorganic materials 0.000 claims description 58
• 239000001301 oxygen Substances 0.000 claims description 58
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 54
• 239000005864 Sulphur Substances 0.000 claims description 52
• 125000006413 ring segment Chemical group 0.000 claims description 44
• 229910052739 hydrogen Inorganic materials 0.000 claims description 43
• 239000001257 hydrogen Substances 0.000 claims description 40
• 239000002253 acid Substances 0.000 claims description 35
• 125000005842 heteroatom Chemical group 0.000 claims description 34
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 33
• 125000000217 alkyl group Chemical group 0.000 claims description 33
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 33
• 125000001072 heteroaryl group Chemical group 0.000 claims description 33
• 125000002950 monocyclic group Chemical group 0.000 claims description 29
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
• 125000001188 haloalkyl group Chemical group 0.000 claims description 28
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 28
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 27
• 125000005843 halogen group Chemical group 0.000 claims description 18
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 17
• 239000003795 chemical substances by application Substances 0.000 claims description 14
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
• 150000003839 salts Chemical class 0.000 claims description 14
• 229920006395 saturated elastomer Polymers 0.000 claims description 14
• 125000003545 alkoxy group Chemical group 0.000 claims description 13
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
• 239000003112 inhibitor Substances 0.000 claims description 12
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 11
• 125000004122 cyclic group Chemical group 0.000 claims description 11
• 230000000694 effects Effects 0.000 claims description 10
• 125000005347 halocycloalkyl group Chemical group 0.000 claims description 10
• 125000003367 polycyclic group Chemical group 0.000 claims description 10
• 201000010099 disease Diseases 0.000 claims description 9
• UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 claims description 8
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• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 8
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• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
• 125000003118 aryl group Chemical group 0.000 claims description 7
• 125000004429 atom Chemical group 0.000 claims description 7
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 7
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
• UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 claims description 6
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• 125000004043 oxo group Chemical group O=* 0.000 claims description 6
• AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 claims description 6
• 239000002464 receptor antagonist Substances 0.000 claims description 6
• 229940044551 receptor antagonist Drugs 0.000 claims description 6
• RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 claims description 6
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 5
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 5
• 230000005764 inhibitory process Effects 0.000 claims description 5
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
• 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 4
• 239000002160 alpha blocker Substances 0.000 claims description 4
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 4
• 239000002934 diuretic Substances 0.000 claims description 4
• 229940030606 diuretics Drugs 0.000 claims description 4
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
• 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 4
• HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 claims description 4
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 4
• 125000004076 pyridyl group Chemical group 0.000 claims description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 3
• METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 claims description 3
• TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 claims description 3
• JIVPVXMEBJLZRO-CQSZACIVSA-N 2-chloro-5-[(1r)-1-hydroxy-3-oxo-2h-isoindol-1-yl]benzenesulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC([C@@]2(O)C3=CC=CC=C3C(=O)N2)=C1 JIVPVXMEBJLZRO-CQSZACIVSA-N 0.000 claims description 3
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 3
• IUVMAUQEZFTTFB-YUMQZZPRSA-N Atagabalin Chemical compound C[C@H]1CC(CN)(CC(O)=O)C[C@@H]1C IUVMAUQEZFTTFB-YUMQZZPRSA-N 0.000 claims description 3
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 3
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• 102000007637 Soluble Guanylyl Cyclase Human genes 0.000 claims description 3
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