MD4425C1 - Alcoxipirazoli în calitate de activatori ai guanilat-ciclazei solubile - Google Patents

Info

Publication number

MD4425C1

MD4425C1 MDA20150019A MD20150019A MD4425C1 MD 4425 C1 MD4425 C1 MD 4425C1 MD A20150019 A MDA20150019 A MD A20150019A MD 20150019 A MD20150019 A MD 20150019A MD 4425 C1 MD4425 C1 MD 4425C1

Authority

MD

Moldova

Prior art keywords

compound

electrospray

mmol

alkyl

compound according

Prior art date

2012-09-07

Links

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• 102000007637 Soluble Guanylyl Cyclase Human genes 0.000 title claims abstract description 11
• 108010007205 Soluble Guanylyl Cyclase Proteins 0.000 title claims abstract description 11
• -1 Alkoxy pyrazoles Chemical class 0.000 title claims description 141
• 239000003119 guanylate cyclase activator Substances 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 480
• 238000000034 method Methods 0.000 claims abstract description 209
• 150000003839 salts Chemical class 0.000 claims abstract description 50
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 26
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 24
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 24
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 20
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 17
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 17
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 15
• 229910052801 chlorine Inorganic materials 0.000 claims abstract description 14
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 14
• 229910052731 fluorine Inorganic materials 0.000 claims abstract description 13
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 10
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 10
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 6
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 5
• 239000001301 oxygen Substances 0.000 claims abstract description 5
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 31
• 201000010099 disease Diseases 0.000 claims description 16
• 208000035475 disorder Diseases 0.000 claims description 15
• 229910052799 carbon Inorganic materials 0.000 claims description 11
• 125000003118 aryl group Chemical group 0.000 claims description 10
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• 208000010228 Erectile Dysfunction Diseases 0.000 claims description 9
• 201000001881 impotence Diseases 0.000 claims description 9
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
• 229910052736 halogen Inorganic materials 0.000 claims description 7
• 150000002367 halogens Chemical class 0.000 claims description 7
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• 125000001072 heteroaryl group Chemical group 0.000 claims description 6
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• 230000003213 activating effect Effects 0.000 claims description 5
• 208000027866 inflammatory disease Diseases 0.000 claims description 5
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 5
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 5
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 4
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• 208000018737 Parkinson disease Diseases 0.000 claims description 4
• 125000003545 alkoxy group Chemical group 0.000 claims description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
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• 208000021722 neuropathic pain Diseases 0.000 claims description 4
• 125000003566 oxetanyl group Chemical group 0.000 claims description 4
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• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 4
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• 206010020853 Hypertonic bladder Diseases 0.000 claims description 3
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• 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 3
• 230000000747 cardiac effect Effects 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 125000002883 imidazolyl group Chemical group 0.000 claims description 3
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
• 208000020629 overactive bladder Diseases 0.000 claims description 3
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
• 125000004076 pyridyl group Chemical group 0.000 claims description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
• 125000000335 thiazolyl group Chemical group 0.000 claims description 3
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• 208000033679 diabetic kidney disease Diseases 0.000 claims description 2
• 230000003389 potentiating effect Effects 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims 1
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• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract description 4
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 2
• 125000000753 cycloalkyl group Chemical group 0.000 abstract description 2
• 238000004949 mass spectrometry Methods 0.000 description 261
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• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 92
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• 235000019439 ethyl acetate Nutrition 0.000 description 90
• 238000006243 chemical reaction Methods 0.000 description 86
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• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 32
• 238000010898 silica gel chromatography Methods 0.000 description 32
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
• 238000002360 preparation method Methods 0.000 description 30
• 239000012044 organic layer Substances 0.000 description 29
• 239000012267 brine Substances 0.000 description 28
• 238000004587 chromatography analysis Methods 0.000 description 28
• 239000011734 sodium Substances 0.000 description 28
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
• 238000004809 thin layer chromatography Methods 0.000 description 27
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 26
• 239000001913 cellulose Substances 0.000 description 26
• 229920002678 cellulose Polymers 0.000 description 26
• 238000003756 stirring Methods 0.000 description 26
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 25
• 239000000706 filtrate Substances 0.000 description 25
• 239000000047 product Substances 0.000 description 25
• 239000012043 crude product Substances 0.000 description 24
• 239000002904 solvent Substances 0.000 description 24
• 239000012141 concentrate Substances 0.000 description 23
• 235000008504 concentrate Nutrition 0.000 description 23
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
• 238000010992 reflux Methods 0.000 description 22
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 21
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 21
• 239000012190 activator Substances 0.000 description 21
• 239000002253 acid Substances 0.000 description 19
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
• 238000010828 elution Methods 0.000 description 18
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 18
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• 229910052796 boron Inorganic materials 0.000 description 16
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