JP2015524476A5 - - Google Patents
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- JP2015524476A5 JP2015524476A5 JP2015526672A JP2015526672A JP2015524476A5 JP 2015524476 A5 JP2015524476 A5 JP 2015524476A5 JP 2015526672 A JP2015526672 A JP 2015526672A JP 2015526672 A JP2015526672 A JP 2015526672A JP 2015524476 A5 JP2015524476 A5 JP 2015524476A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- chr
- och
- alkylene
- compound according
- Prior art date
- 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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- 125000000217 alkyl group Chemical group 0.000 claims description 221
- 150000001875 compounds Chemical class 0.000 claims description 73
- 125000002947 alkylene group Chemical group 0.000 claims description 24
- 239000003814 drug Substances 0.000 claims description 8
- 239000005541 ACE inhibitor Substances 0.000 claims description 6
- 239000002792 enkephalinase inhibitor Substances 0.000 claims description 6
- 239000003112 inhibitor Substances 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 102100030988 Angiotensin-converting enzyme Human genes 0.000 claims description 5
- 206010019280 Heart failures Diseases 0.000 claims description 5
- 206010020772 Hypertension Diseases 0.000 claims description 5
- 230000009977 dual effect Effects 0.000 claims description 5
- 208000017169 kidney disease Diseases 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 108020001621 Natriuretic Peptide Proteins 0.000 claims description 4
- 102000004571 Natriuretic peptide Human genes 0.000 claims description 4
- 239000000674 adrenergic antagonist Substances 0.000 claims description 4
- 239000002333 angiotensin II receptor antagonist Substances 0.000 claims description 4
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 4
- 239000003146 anticoagulant agent Substances 0.000 claims description 4
- 239000003119 guanylate cyclase activator Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000000692 natriuretic peptide Substances 0.000 claims description 4
- 239000002464 receptor antagonist Substances 0.000 claims description 4
- 229940044551 receptor antagonist Drugs 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- 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 3
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 claims description 3
- QZDDFQLIQRYMBV-UHFFFAOYSA-N 2-[3-nitro-2-(2-nitrophenyl)-4-oxochromen-8-yl]acetic acid Chemical compound OC(=O)CC1=CC=CC(C(C=2[N+]([O-])=O)=O)=C1OC=2C1=CC=CC=C1[N+]([O-])=O QZDDFQLIQRYMBV-UHFFFAOYSA-N 0.000 claims description 2
- 108010005094 Advanced Glycation End Products Proteins 0.000 claims description 2
- 229940123338 Aldosterone synthase inhibitor Drugs 0.000 claims description 2
- 102400000345 Angiotensin-2 Human genes 0.000 claims description 2
- 101800000733 Angiotensin-2 Proteins 0.000 claims description 2
- 102100035765 Angiotensin-converting enzyme 2 Human genes 0.000 claims description 2
- 108090000975 Angiotensin-converting enzyme 2 Proteins 0.000 claims description 2
- 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 claims description 2
- 229940122155 Bradykinin receptor antagonist Drugs 0.000 claims description 2
- 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 claims description 2
- 229940127291 Calcium channel antagonist Drugs 0.000 claims description 2
- 229940119334 Chymase inhibitor Drugs 0.000 claims description 2
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 claims description 2
- 229940097420 Diuretic Drugs 0.000 claims description 2
- 229940122783 Endothelin converting-enzyme inhibitor Drugs 0.000 claims description 2
- 229940118365 Endothelin receptor antagonist Drugs 0.000 claims description 2
- 229940127406 Estrogen Receptor Agonists Drugs 0.000 claims description 2
- 229940102550 Estrogen receptor antagonist Drugs 0.000 claims description 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 2
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 claims description 2
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims description 2
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical class O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 2
- 102000003840 Opioid Receptors Human genes 0.000 claims description 2
- 108090000137 Opioid Receptors Proteins 0.000 claims description 2
- 229940127473 Prostaglandin Receptor Agonists Drugs 0.000 claims description 2
- 102000007637 Soluble Guanylyl Cyclase Human genes 0.000 claims description 2
- 108010007205 Soluble Guanylyl Cyclase Proteins 0.000 claims description 2
- 229940123445 Tricyclic antidepressant Drugs 0.000 claims description 2
- 239000012190 activator Substances 0.000 claims description 2
- 229940121359 adenosine receptor antagonist Drugs 0.000 claims description 2
- 239000000048 adrenergic agonist Substances 0.000 claims description 2
- 239000000951 adrenergic alpha-1 receptor antagonist Substances 0.000 claims description 2
- 239000000332 adrenergic beta-1 receptor antagonist Substances 0.000 claims description 2
- 229940126157 adrenergic receptor agonist Drugs 0.000 claims description 2
- 239000002170 aldosterone antagonist Substances 0.000 claims description 2
- 229940083712 aldosterone antagonist Drugs 0.000 claims description 2
- 102000004305 alpha Adrenergic Receptors Human genes 0.000 claims description 2
- 108090000861 alpha Adrenergic Receptors Proteins 0.000 claims description 2
- 239000003098 androgen Substances 0.000 claims description 2
- 239000000400 angiotensin II type 1 receptor blocker Substances 0.000 claims description 2
- 229950006323 angiotensin ii Drugs 0.000 claims description 2
- 229940125364 angiotensin receptor blocker Drugs 0.000 claims description 2
- 239000005557 antagonist Substances 0.000 claims description 2
- 230000001142 anti-diarrhea Effects 0.000 claims description 2
- 229940127219 anticoagulant drug Drugs 0.000 claims description 2
- 239000003472 antidiabetic agent Substances 0.000 claims description 2
- 229940125708 antidiabetic agent Drugs 0.000 claims description 2
- 239000003793 antidiarrheal agent Substances 0.000 claims description 2
- 229940125714 antidiarrheal agent Drugs 0.000 claims description 2
- 239000000030 antiglaucoma agent Substances 0.000 claims description 2
- 239000003965 antinociceptive agent Substances 0.000 claims description 2
- 229960004676 antithrombotic agent Drugs 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 102000012740 beta Adrenergic Receptors Human genes 0.000 claims description 2
- 108010079452 beta Adrenergic Receptors Proteins 0.000 claims description 2
- 239000003152 bradykinin antagonist Substances 0.000 claims description 2
- 239000000480 calcium channel blocker Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000003601 chymase inhibitor Substances 0.000 claims description 2
- 229960005156 digoxin Drugs 0.000 claims description 2
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 claims description 2
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 claims description 2
- 239000002934 diuretic Substances 0.000 claims description 2
- 230000001882 diuretic effect Effects 0.000 claims description 2
- 239000003136 dopamine receptor stimulating agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000002857 endothelin converting enzyme inhibitor Substances 0.000 claims description 2
- 239000002308 endothelin receptor antagonist Substances 0.000 claims description 2
- 239000000262 estrogen Substances 0.000 claims description 2
- 229940011871 estrogen Drugs 0.000 claims description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 2
- 230000000407 monoamine reuptake Effects 0.000 claims description 2
- 229940035363 muscle relaxants Drugs 0.000 claims description 2
- 239000003158 myorelaxant agent Substances 0.000 claims description 2
- 239000002840 nitric oxide donor Substances 0.000 claims description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 2
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 claims description 2
- 150000003180 prostaglandins Chemical class 0.000 claims description 2
- 239000000296 purinergic P1 receptor antagonist Substances 0.000 claims description 2
- 239000000018 receptor agonist Substances 0.000 claims description 2
- 229940044601 receptor agonist Drugs 0.000 claims description 2
- 239000002461 renin inhibitor Substances 0.000 claims description 2
- 229940086526 renin-inhibitors Drugs 0.000 claims description 2
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 claims description 2
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 claims description 2
- 239000003195 sodium channel blocking agent Substances 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 239000003029 tricyclic antidepressant agent Substances 0.000 claims description 2
- 229960005486 vaccine Drugs 0.000 claims description 2
- 239000002536 vasopressin receptor antagonist Substances 0.000 claims description 2
- IFWBKJFCPSEDNJ-CJAUYULYSA-N (2s,4r)-5-[4-(5-chloro-2-fluorophenyl)phenyl]-2-(ethoxymethyl)-2-methyl-4-[(3-oxo-1,2-oxazole-5-carbonyl)amino]pentanoic acid Chemical compound C([C@H](C[C@@](C)(COCC)C(O)=O)NC(=O)C=1ONC(=O)C=1)C(C=C1)=CC=C1C1=CC(Cl)=CC=C1F IFWBKJFCPSEDNJ-CJAUYULYSA-N 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- 239000000203 mixture Substances 0.000 description 16
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 239000007821 HATU Substances 0.000 description 5
- 238000002953 preparative HPLC Methods 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102000003729 Neprilysin Human genes 0.000 description 4
- 108090000028 Neprilysin Proteins 0.000 description 4
- -1 alkylene morpholinium Chemical compound 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 229940125904 compound 1 Drugs 0.000 description 3
- FXKFFTMLFPWYFH-RDGPPVDQSA-N (4s,7s,12br)-7-[[(2s)-2-acetylsulfanyl-3-methylbutanoyl]amino]-6-oxo-2,3,4,7,8,12b-hexahydro-1h-pyrido[2,1-a][2]benzazepine-4-carboxylic acid Chemical compound O=C1[C@@H](NC(=O)[C@@H](SC(C)=O)C(C)C)CC2=CC=CC=C2[C@H]2CCC[C@@H](C(O)=O)N21 FXKFFTMLFPWYFH-RDGPPVDQSA-N 0.000 description 2
- XJEVZVWMLSOJJV-UHFFFAOYSA-N 3-ethoxy-1h-pyrazole-5-carboxylic acid Chemical compound CCOC1=CC(C(O)=O)=NN1 XJEVZVWMLSOJJV-UHFFFAOYSA-N 0.000 description 2
- FSTWEXGBKCPRAJ-AEFFLSMTSA-N C[C@](C[C@@H](CC1=CC=C(C=C1)C2=CC(=CC=C2)Cl)N)(C(=O)O)O Chemical compound C[C@](C[C@@H](CC1=CC=C(C=C1)C2=CC(=CC=C2)Cl)N)(C(=O)O)O FSTWEXGBKCPRAJ-AEFFLSMTSA-N 0.000 description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 229960002680 enalaprilat Drugs 0.000 description 2
- LZFZMUMEGBBDTC-QEJZJMRPSA-N enalaprilat (anhydrous) Chemical compound C([C@H](N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 LZFZMUMEGBBDTC-QEJZJMRPSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- YFAHICISBQLBQH-OALUTQOASA-N (2s)-3-(1h-indol-3-yl)-2-[[1-[[(2s)-4-methyl-2-sulfanylpentanoyl]amino]cyclopentanecarbonyl]amino]propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C(=O)C1(NC(=O)[C@@H](S)CC(C)C)CCCC1 YFAHICISBQLBQH-OALUTQOASA-N 0.000 description 1
- BOAUMKBGSVYOEB-ZHRRBRCNSA-N (2s,4r)-5-[4-(2-fluorophenyl)phenyl]-2-(hydroxymethyl)-2-methyl-4-(2h-triazole-4-carbonylamino)pentanoic acid Chemical compound C([C@H](C[C@](CO)(C)C(O)=O)NC(=O)C=1NN=NC=1)C(C=C1)=CC=C1C1=CC=CC=C1F BOAUMKBGSVYOEB-ZHRRBRCNSA-N 0.000 description 1
- LJEPCHNLNDLQGW-NLFFAJNJSA-N (2s,4r)-5-[4-(3-chlorophenyl)phenyl]-2-(methoxymethyl)-4-[(3-methoxy-1,2-oxazole-5-carbonyl)amino]-2-methylpentanoic acid Chemical compound C([C@H](C[C@@](C)(COC)C(O)=O)NC(=O)C=1ON=C(OC)C=1)C(C=C1)=CC=C1C1=CC=CC(Cl)=C1 LJEPCHNLNDLQGW-NLFFAJNJSA-N 0.000 description 1
- ZWBWIQRYNATOPM-GCJKJVERSA-N (2s,4r)-5-[4-(3-fluorophenyl)phenyl]-2-(hydroxymethyl)-2-methyl-4-(2h-triazole-4-carbonylamino)pentanoic acid Chemical compound C([C@H](C[C@](CO)(C)C(O)=O)NC(=O)C=1N=NNC=1)C(C=C1)=CC=C1C1=CC=CC(F)=C1 ZWBWIQRYNATOPM-GCJKJVERSA-N 0.000 description 1
- OTNYMWVQTODFDY-BCHFMIIMSA-N (2s,4r)-5-[4-(5-chloro-2-fluorophenyl)phenyl]-2-(hydroxymethyl)-2-methyl-4-[(5-propan-2-yl-1h-pyrazole-3-carbonyl)amino]pentanoic acid Chemical compound N1C(C(C)C)=CC(C(=O)N[C@H](CC=2C=CC(=CC=2)C=2C(=CC=C(Cl)C=2)F)C[C@@](C)(CO)C(O)=O)=N1 OTNYMWVQTODFDY-BCHFMIIMSA-N 0.000 description 1
- OVBFMEVBMNZIBR-UHFFFAOYSA-N -2-Methylpentanoic acid Natural products CCCC(C)C(O)=O OVBFMEVBMNZIBR-UHFFFAOYSA-N 0.000 description 1
- TYXFDFMUHPWCDX-WMZOPIPTSA-N 2-[(3s)-2-oxo-3-[[(2s)-3-phenyl-2-sulfanylpropanoyl]amino]-4,5-dihydro-3h-1-benzazepin-1-yl]acetic acid Chemical compound C([C@H](S)C(=O)N[C@H]1CCC2=CC=CC=C2N(C1=O)CC(=O)O)C1=CC=CC=C1 TYXFDFMUHPWCDX-WMZOPIPTSA-N 0.000 description 1
- HFBWRCZRDIVAMQ-UHFFFAOYSA-N 3-acetyl-1h-pyrazole-5-carboxylic acid Chemical compound CC(=O)C=1C=C(C(O)=O)NN=1 HFBWRCZRDIVAMQ-UHFFFAOYSA-N 0.000 description 1
- WHBIWWYTGXQXSD-UHFFFAOYSA-N 3-ethyl-1,2-oxazole-5-carboxylic acid Chemical compound CCC=1C=C(C(O)=O)ON=1 WHBIWWYTGXQXSD-UHFFFAOYSA-N 0.000 description 1
- WMMGHBYADJNEOC-UHFFFAOYSA-N 3-methoxy-1,2-oxazole-5-carboxylic acid Chemical compound COC=1C=C(C(O)=O)ON=1 WMMGHBYADJNEOC-UHFFFAOYSA-N 0.000 description 1
- CMIRWXFQPVROKZ-UHFFFAOYSA-N 5h-2-benzazepine-4-carboxylic acid Chemical compound C1C(C(=O)O)=CN=CC2=CC=CC=C21 CMIRWXFQPVROKZ-UHFFFAOYSA-N 0.000 description 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical group C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 1
- LRVXKVGCLKMFDL-FNICBLQJSA-N ClC=1C=CC(=C(C1)C1=CC=C(C=C1)C[C@H](C([C@](C(=O)O)(C)O)C)NC(=O)C1=NNC(=C1)OCC)F Chemical compound ClC=1C=CC(=C(C1)C1=CC=C(C=C1)C[C@H](C([C@](C(=O)O)(C)O)C)NC(=O)C1=NNC(=C1)OCC)F LRVXKVGCLKMFDL-FNICBLQJSA-N 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- 108010007859 Lisinopril Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229960004530 benazepril Drugs 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000006638 cyclopentyl carbonyl group Chemical group 0.000 description 1
- 229960000873 enalapril Drugs 0.000 description 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 229960002394 lisinopril Drugs 0.000 description 1
- RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 229960003401 ramipril Drugs 0.000 description 1
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261680804P | 2012-08-08 | 2012-08-08 | |
| US61/680,804 | 2012-08-08 | ||
| US201361774163P | 2013-03-07 | 2013-03-07 | |
| US61/774,163 | 2013-03-07 | ||
| PCT/US2013/053956 WO2014025891A1 (en) | 2012-08-08 | 2013-08-07 | Neprilysin inhibitors |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017020923A Division JP2017105817A (ja) | 2012-08-08 | 2017-02-08 | ネプリライシン阻害剤 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2015524476A JP2015524476A (ja) | 2015-08-24 |
| JP2015524476A5 true JP2015524476A5 (enExample) | 2016-09-01 |
| JP6092390B2 JP6092390B2 (ja) | 2017-03-08 |
Family
ID=48998730
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015526672A Active JP6092390B2 (ja) | 2012-08-08 | 2013-08-07 | ネプリライシン阻害剤 |
| JP2017020923A Withdrawn JP2017105817A (ja) | 2012-08-08 | 2017-02-08 | ネプリライシン阻害剤 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI2651896T1 (sl) | 2010-12-15 | 2015-11-30 | Theravance Biopharma R&D Ip, Llc | Inhibitorji neprilizina |
| CN103261168B (zh) | 2010-12-15 | 2015-08-05 | 施万生物制药研发Ip有限责任公司 | 脑啡肽酶抑制剂 |
| AU2012217615B2 (en) | 2011-02-17 | 2016-09-29 | Theravance Biopharma R&D Ip, Llc | Substituted aminobutyric derivatives as neprilysin inhibitors |
| US8449890B2 (en) | 2011-02-17 | 2013-05-28 | Theravance, Inc. | Neprilysin inhibitors |
| ES2653215T3 (es) | 2011-05-31 | 2018-02-06 | Theravance Biopharma R&D Ip, Llc | Inhibidores de neprilisina |
| TWI560172B (en) | 2011-11-02 | 2016-12-01 | Theravance Biopharma R&D Ip Llc | Neprilysin inhibitors |
| AR089955A1 (es) * | 2012-02-15 | 2014-10-01 | Theravance Inc | Proceso para preparar compuestos de acido 4-amino-5-bifenil-4-il-2-hidroximetil-2-metil-pentanoico |
| ES2710932T3 (es) | 2012-06-08 | 2019-04-29 | Theravance Biopharma R&D Ip Llc | Inhibidores de neprilisina |
| US9126956B2 (en) | 2012-08-08 | 2015-09-08 | Theravance Biopharma R&D Ip, Llc | Neprilysin inhibitors |
| HUE034210T2 (hu) | 2013-03-05 | 2018-02-28 | Theravance Biopharma R&D Ip Llc | Neprilizininhibitorok |
| EP3099668B1 (en) * | 2014-01-30 | 2022-05-04 | Theravance Biopharma R&D IP, LLC | 5-biphenyl-4-heteroarylcarbonylamino-pentanoic acid derivatives as neprilysin inhibitors |
| MX2016009760A (es) | 2014-01-30 | 2016-11-08 | Theravance Biopharma R&D Ip Llc | Inhibidores de neprilisina. |
| CN107074744B (zh) * | 2014-12-03 | 2019-06-18 | 上海翰森生物医药科技有限公司 | Nep抑制剂结晶型游离酸、钙盐多晶型及其制备方法和应用 |
| WO2016130650A1 (en) | 2015-02-11 | 2016-08-18 | Theravance Biopharma R&D Ip, Llc | (2s, 4r)-5-(5'-chloro-2'-fluorobiphenyl-4-yl)-2-ethoxyoxalylamino)-2-hydroxymethyl-2-methylpentanoic acid as neprilysin inhibitor |
| RU2715241C2 (ru) | 2015-02-19 | 2020-02-26 | ТЕРЕВАНС БАЙОФАРМА Ар энд Ди АйПи, ЭлЭлСи | (2r,4r)-5-(5′-хлор-2′-фторбифенил-4-ил)-2-гидрокси-4-[(5-метилоксазол-2-карбонил)амино]пентановая кислота |
| TWI731943B (zh) * | 2016-03-08 | 2021-07-01 | 美商施萬生物製藥研發Ｉｐ有限責任公司 | 結晶型（2s，4r）－5－（5’－氯－2’－氟－［1，1’－聯苯］－4－基）－2－（乙氧基甲基）－4－（3－羥基異㗁唑－5－甲醯胺基）－2－甲基戊酸及其用途 |
| CN105753741A (zh) * | 2016-04-26 | 2016-07-13 | 常州制药厂有限公司 | 一种抗心衰药物Sacubitril中间体的制备方法 |
| CN107903191A (zh) * | 2017-12-04 | 2018-04-13 | 武汉药明康德新药开发有限公司 | 2‑NH‑Boc‑3‑(3`,4`‑二甲基‑[1,1`‑联苯]‑4)丙酸的制法 |
| UY38072A (es) | 2018-02-07 | 2019-10-01 | Novartis Ag | Compuestos derivados de éster butanoico sustituido con bisfenilo como inhibidores de nep, composiciones y combinaciones de los mismos |
| WO2020110008A1 (en) | 2018-11-27 | 2020-06-04 | Novartis Ag | Cyclic pentamer compounds as proprotein convertase subtilisin/kexin type 9 (pcsk9) inhibitors for the treatment of metabolic disorder |
| JP7657151B2 (ja) | 2018-11-27 | 2025-04-04 | ノバルティス アーゲー | 代謝性障害の処置のためのプロタンパク質コンバターゼスブチリシン／ケキシン９型（ｐｃｓｋ９）阻害剤としての環状ペプチド |
| UY38485A (es) | 2018-11-27 | 2020-06-30 | Novartis Ag | Compuestos tetrámeros cíclicos como inhibidores de proproteína convertasa subtilisina/kexina tipo 9 (pcsk9), método de tratamiento, uso y su preparación |
| RU2736511C1 (ru) * | 2020-01-24 | 2020-11-17 | Автономная некоммерческая образовательная организация высшего образования "Сколковский институт науки и технологий" | Производные бифенила, обладающие биологической активностью, фармацевтические композиции и способы лечения на основе этих соединений и их применение |
| WO2023084449A1 (en) | 2021-11-12 | 2023-05-19 | Novartis Ag | Diaminocyclopentylpyridine derivatives for the treatment of a disease or disorder |
| KR102485499B1 (ko) * | 2022-07-15 | 2023-01-09 | 오가노이드사이언스 주식회사 | 신장 질환의 치료 또는 예방용 조성물 |
Family Cites Families (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4189604A (en) | 1975-07-22 | 1980-02-19 | Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai | Bestatin |
| US4206232A (en) | 1976-05-10 | 1980-06-03 | E. R. Squibb & Sons, Inc. | Relieving hypertension with carboxyalkylacylamino acids |
| IL58849A (en) | 1978-12-11 | 1983-03-31 | Merck & Co Inc | Carboxyalkyl dipeptides and derivatives thereof,their preparation and pharmaceutical compositions containing them |
| FR2480747A1 (fr) | 1980-04-17 | 1981-10-23 | Roques Bernard | Derives d'acides amines et leur application therapeutique |
| US4906615A (en) | 1980-12-18 | 1990-03-06 | Schering Corporation | Substituted dipeptides as inhibitors of enkephalinases |
| US4722810A (en) | 1984-08-16 | 1988-02-02 | E. R. Squibb & Sons, Inc. | Enkephalinase inhibitors |
| US4939261A (en) | 1984-06-08 | 1990-07-03 | Ciba-Geigy Corporation | N-substituted butyramide derivatives useful for treatment of conditions responsive to inhibition of enkephalinase |
| EP0225292A3 (en) | 1985-12-06 | 1988-11-30 | Ciba-Geigy Ag | Certain n-substituted butyramide derivatives |
| US4929641B1 (en) | 1988-05-11 | 1994-08-30 | Schering Corp | Mercapto-acylamino acid antihypertensives |
| KR880007441A (ko) | 1986-12-11 | 1988-08-27 | 알렌 제이.스피겔 | 스피로-치환된 글루타르아미드 이뇨제 |
| FR2623498B1 (fr) | 1987-11-24 | 1990-04-06 | Bioprojet Soc Civ | Nouveaux composes enantiomeres derives d'amino-acides, leur procede de preparation et leurs applications therapeutiques |
| GB8820844D0 (en) | 1988-09-05 | 1988-10-05 | Pfizer Ltd | Therapeutic agents |
| US5599951A (en) | 1989-09-15 | 1997-02-04 | Societe Civile Bioprojet | Amino acid derivatives, the process for their preparation and their applications to therapy |
| US5294632A (en) | 1991-05-01 | 1994-03-15 | Ciba-Geigy Corporation | Phosphono/biaryl substituted dipetide derivatives |
| US5155100A (en) | 1991-05-01 | 1992-10-13 | Ciba-Geigy Corporation | Phosphono/biaryl substituted dipeptide derivatives |
| US5217996A (en) | 1992-01-22 | 1993-06-08 | Ciba-Geigy Corporation | Biaryl substituted 4-amino-butyric acid amides |
| US5508272A (en) | 1993-06-15 | 1996-04-16 | Bristol-Myers Squibb Company | Compounds containing a fused bicycle ring and processes therefor |
| DE19510566A1 (de) | 1995-03-23 | 1996-09-26 | Kali Chemie Pharma Gmbh | Benzazepin-, Benzoxazepin- und Benzothiazepin-N-essigsäurederivate sowie Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel |
| AU5687396A (en) | 1995-04-21 | 1996-11-07 | Novarits Ag | N-aroylamino acid amides as endothelin inhibitors |
| US6660756B2 (en) | 2001-03-28 | 2003-12-09 | Pfizer Inc. | N-phenpropylcyclopentyl-substituted glutaramide derivatives as inhibitors of neutral endopeptidase |
| GB0119305D0 (en) | 2001-04-12 | 2001-10-03 | Aventis Pharma Gmbh | Mercaptoacetylamide derivatives,a process for their preparation and their use |
| WO2006027680A1 (en) | 2004-09-10 | 2006-03-16 | Pfizer Limited | 3-(1-carbamoylcyclohexyl) propionic acid derivatives as inhibitors of neutral endopeptidase enzyme |
| AR057882A1 (es) | 2005-11-09 | 2007-12-26 | Novartis Ag | Compuestos de accion doble de bloqueadores del receptor de angiotensina e inhibidores de endopeptidasa neutra |
| WO2007106708A2 (en) | 2006-03-10 | 2007-09-20 | Novartis Ag | Combinations of the angiotensin ii antagonist valsartan and the nep inhibitor daglutril |
| ES2602566T3 (es) | 2007-01-12 | 2017-02-21 | Novartis Ag | Proceso para preparar ácido 5-bifenil-4-amino-2-metil pentanoico |
| TWI448284B (zh) | 2007-04-24 | 2014-08-11 | Theravance Inc | 雙效抗高血壓劑 |
| AR070176A1 (es) | 2008-01-17 | 2010-03-17 | Novartis Ag | Procesos de sintesis de inhibidores de nep, compuestos intermediarios y uso de los mismos en la sintesis |
| PL2435409T3 (pl) * | 2009-05-28 | 2015-01-30 | Novartis Ag | Podstawione pochodne aminopropionowe jako inhibitory neprylizyny |
| CA2763565A1 (en) * | 2009-05-28 | 2010-12-02 | Novartis Ag | Substituted aminobutyric derivatives as neprilysin inhibitors |
| JP5447204B2 (ja) * | 2009-06-15 | 2014-03-19 | 東洋インキＳｃホールディングス株式会社 | （メタ）アクリロイル基を有するウレタン樹脂及び該ウレタン樹脂を含有する活性エネルギー線硬化性接着剤、並びに太陽電池用裏面保護シート |
| JO2967B1 (en) | 2009-11-20 | 2016-03-15 | نوفارتس ايه جي | Acetic acid derivatives of carbamoyl methyl amino are substituted as new NEP inhibitors |
| ES2550485T3 (es) | 2010-01-22 | 2015-11-10 | Novartis Ag | Intermedios de inhibidores de la endopeptidasa neutra y método de preparación de los mismos |
| US8673974B2 (en) | 2010-11-16 | 2014-03-18 | Novartis Ag | Substituted amino bisphenyl pentanoic acid derivatives as NEP inhibitors |
| US8993631B2 (en) | 2010-11-16 | 2015-03-31 | Novartis Ag | Method of treating contrast-induced nephropathy |
| CN103261168B (zh) | 2010-12-15 | 2015-08-05 | 施万生物制药研发Ip有限责任公司 | 脑啡肽酶抑制剂 |
| SI2651896T1 (sl) * | 2010-12-15 | 2015-11-30 | Theravance Biopharma R&D Ip, Llc | Inhibitorji neprilizina |
| US8449890B2 (en) | 2011-02-17 | 2013-05-28 | Theravance, Inc. | Neprilysin inhibitors |
| AU2012217615B2 (en) * | 2011-02-17 | 2016-09-29 | Theravance Biopharma R&D Ip, Llc | Substituted aminobutyric derivatives as neprilysin inhibitors |
| ES2699773T3 (es) | 2011-05-31 | 2019-02-12 | Theravance Biopharma R&D Ip Llc | Inhibidores de neprilisina |
| CA2835281A1 (en) | 2011-05-31 | 2012-12-06 | Theravance, Inc. | Neprilysin inhibitors |
| ES2653215T3 (es) | 2011-05-31 | 2018-02-06 | Theravance Biopharma R&D Ip, Llc | Inhibidores de neprilisina |
| TWI560172B (en) | 2011-11-02 | 2016-12-01 | Theravance Biopharma R&D Ip Llc | Neprilysin inhibitors |
| AR089955A1 (es) * | 2012-02-15 | 2014-10-01 | Theravance Inc | Proceso para preparar compuestos de acido 4-amino-5-bifenil-4-il-2-hidroximetil-2-metil-pentanoico |
| CA2871292A1 (en) | 2012-05-31 | 2013-12-05 | Theravance Biopharma R&D Ip, Llc | Nitric oxide donor neprilysin inhibitors |
| ES2710932T3 (es) | 2012-06-08 | 2019-04-29 | Theravance Biopharma R&D Ip Llc | Inhibidores de neprilisina |
| LT2864292T (lt) | 2012-06-08 | 2017-07-10 | Theravance Biopharma R&D Ip, Llc | Neprilizino inhibitoriai |
| US9126956B2 (en) | 2012-08-08 | 2015-09-08 | Theravance Biopharma R&D Ip, Llc | Neprilysin inhibitors |
| MX2016009760A (es) | 2014-01-30 | 2016-11-08 | Theravance Biopharma R&D Ip Llc | Inhibidores de neprilisina. |
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