JP2015524476A5 - - Google Patents
Download PDFInfo
- Publication number
- 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.)
- Granted
Links
- 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 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 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 |
|---|---|---|---|
| JP2017020923A Withdrawn JP2017105817A (ja) | 2012-08-08 | 2017-02-08 | ネプリライシン阻害剤 |
Country Status (32)
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2817368C (en) | 2010-12-15 | 2019-12-31 | Theravance, Inc. | Neprilysin inhibitors |
| ES2548887T3 (es) | 2010-12-15 | 2015-10-21 | Theravance Biopharma R&D Ip, Llc | Inhibidores de neprilisina |
| AU2012217615B2 (en) | 2011-02-17 | 2016-09-29 | Theravance Biopharma R&D Ip, Llc | Substituted aminobutyric derivatives as neprilysin inhibitors |
| ES2564275T3 (es) | 2011-02-17 | 2016-03-21 | Theravance Biopharma R&D Ip, Llc | Derivados aminobutíricos sustituidos como inhibidores de neprilisina |
| 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 |
| CN104470521B (zh) | 2012-06-08 | 2017-04-12 | 施万生物制药研发Ip有限责任公司 | 脑啡肽酶抑制剂 |
| HUE031301T2 (hu) | 2012-08-08 | 2017-07-28 | Theravance Biopharma R&D Ip Llc | Neprilizin inhibitorok |
| HUE034210T2 (hu) | 2013-03-05 | 2018-02-28 | Theravance Biopharma R&D Ip Llc | Neprilizininhibitorok |
| CA2934898A1 (en) | 2014-01-30 | 2015-08-06 | Theravance Biopharma R&D Ip, Llc | 5-biphenyl-4-heteroarylcarbonylamino-pentanoic acid derivatives as neprilysin inhibitors |
| AU2015210983B2 (en) | 2014-01-30 | 2018-10-04 | Theravance Biopharma R&D Ip, Llc | Neprilysin inhibitors |
| WO2016086798A1 (zh) * | 2014-12-03 | 2016-06-09 | 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 |
| EP3256446B1 (en) | 2015-02-11 | 2022-05-18 | Theravance Biopharma R&D IP, LLC | (2s,4r)-5-(5'-chloro-2'-fluorobiphenyl-4-yl)-4-(ethoxyoxalylamino)-2-hydroxymethyl-2-methylpentanoic acid as neprilysin inhibitor |
| AU2016220348B2 (en) | 2015-02-19 | 2019-10-17 | Theravance Biopharma R&D Ip, Llc | (2R,4R)-5-(5'-chloro-2'-fluorobiphenyl-4-yl)-2-hydroxy-4-[(5-methyloxazole-2-carbonyl)amino]pentanoic acid |
| EP3408260B1 (en) | 2016-03-08 | 2021-05-05 | Theravance Biopharma R&D IP, LLC | Crystalline (2s,4r)-5-(5'-chloro-2-fluoro-[1,1'-biphenyl]-4-yl)-2-(ethoxymethyl)-4-(3-hydroxyisoxazole-5-carboxamido)-2-methylpentanoic acid and uses thereof |
| 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 |
| 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 |
| JP2022507958A (ja) | 2018-11-27 | 2022-01-18 | ノバルティス アーゲー | 代謝障害の治療用のプロタンパク質転換酵素サブチリシン／ケキシン９型（ｐｃｓｋ９）阻害薬としての環状四量体化合物 |
| 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 |
| WO1996033170A1 (en) | 1995-04-21 | 1996-10-24 | 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 |
| PE20091364A1 (es) | 2008-01-17 | 2009-10-13 | Novartis Ag | Proceso para la preparacion de inhibidores de nep |
| CA2763565A1 (en) | 2009-05-28 | 2010-12-02 | Novartis Ag | Substituted aminobutyric derivatives as neprilysin inhibitors |
| ES2602902T3 (es) | 2009-05-28 | 2017-02-22 | Novartis Ag | Derivados aminopropiónicos sustituidos como inhibidores de neprilisina |
| CN102459393B (zh) * | 2009-06-15 | 2014-10-01 | 东洋油墨Sc控股株式会社 | 聚氨酯树脂、活性能量线固化性粘合剂及太阳能电池用背面保护片 |
| JO2967B1 (en) | 2009-11-20 | 2016-03-15 | نوفارتس ايه جي | Acetic acid derivatives of carbamoyl methyl amino are substituted as new NEP inhibitors |
| CN104262228B (zh) | 2010-01-22 | 2017-01-18 | 诺华股份有限公司 | 中性内肽酶抑制剂中间体和其制备方法 |
| US8993631B2 (en) | 2010-11-16 | 2015-03-31 | Novartis Ag | Method of treating contrast-induced nephropathy |
| US8673974B2 (en) | 2010-11-16 | 2014-03-18 | Novartis Ag | Substituted amino bisphenyl pentanoic acid derivatives as NEP inhibitors |
| CA2817368C (en) * | 2010-12-15 | 2019-12-31 | Theravance, Inc. | Neprilysin inhibitors |
| ES2548887T3 (es) | 2010-12-15 | 2015-10-21 | Theravance Biopharma R&D Ip, Llc | Inhibidores de neprilisina |
| AU2012217615B2 (en) * | 2011-02-17 | 2016-09-29 | Theravance Biopharma R&D Ip, Llc | Substituted aminobutyric derivatives as neprilysin inhibitors |
| ES2564275T3 (es) | 2011-02-17 | 2016-03-21 | Theravance Biopharma R&D Ip, Llc | Derivados aminobutíricos sustituidos como inhibidores de neprilisina |
| ES2699773T3 (es) | 2011-05-31 | 2019-02-12 | Theravance Biopharma R&D Ip Llc | Inhibidores de neprilisina |
| ES2653215T3 (es) | 2011-05-31 | 2018-02-06 | Theravance Biopharma R&D Ip, Llc | Inhibidores de neprilisina |
| ES2642883T3 (es) | 2011-05-31 | 2017-11-20 | 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 |
| CN104470521B (zh) | 2012-06-08 | 2017-04-12 | 施万生物制药研发Ip有限责任公司 | 脑啡肽酶抑制剂 |
| EP2864292B1 (en) | 2012-06-08 | 2017-04-12 | Theravance Biopharma R&D IP, LLC | Neprilysin inhibitors |
| HUE031301T2 (hu) | 2012-08-08 | 2017-07-28 | Theravance Biopharma R&D Ip Llc | Neprilizin inhibitorok |
| AU2015210983B2 (en) | 2014-01-30 | 2018-10-04 | Theravance Biopharma R&D Ip, Llc | Neprilysin inhibitors |
-
2013
- 2013-08-07 HU HUE13750454A patent/HUE031301T2/hu unknown
- 2013-08-07 AU AU2013299642A patent/AU2013299642B2/en active Active
- 2013-08-07 PL PL13750454T patent/PL2882716T3/pl unknown
- 2013-08-07 SG SG11201500845UA patent/SG11201500845UA/en unknown
- 2013-08-07 US US13/961,269 patent/US9126956B2/en active Active
- 2013-08-07 EP EP13750454.4A patent/EP2882716B9/en active Active
- 2013-08-07 CA CA2879697A patent/CA2879697C/en active Active
- 2013-08-07 BR BR112015002821-7A patent/BR112015002821B1/pt active IP Right Grant
- 2013-08-07 SI SI201330556A patent/SI2882716T1/sl unknown
- 2013-08-07 AR ARP130102816A patent/AR092073A1/es not_active Application Discontinuation
- 2013-08-07 NZ NZ704741A patent/NZ704741A/en not_active IP Right Cessation
- 2013-08-07 WO PCT/US2013/053956 patent/WO2014025891A1/en not_active Application Discontinuation
- 2013-08-07 MX MX2015001711A patent/MX366149B/es active IP Right Grant
- 2013-08-07 LT LTEP13750454.4T patent/LT2882716T/lt unknown
- 2013-08-07 RS RS20170240A patent/RS55797B1/sr unknown
- 2013-08-07 KR KR1020157003174A patent/KR102104954B1/ko active Active
- 2013-08-07 HR HRP20170088TT patent/HRP20170088T1/hr unknown
- 2013-08-07 PT PT137504544T patent/PT2882716T/pt unknown
- 2013-08-07 ES ES13750454.4T patent/ES2615275T3/es active Active
- 2013-08-07 MY MYPI2015000065A patent/MY172924A/en unknown
- 2013-08-07 SM SM20170134T patent/SMT201700134T1/it unknown
- 2013-08-07 JP JP2015526672A patent/JP6092390B2/ja active Active
- 2013-08-07 RU RU2015107751A patent/RU2650114C2/ru active
- 2013-08-07 ME MEP-2017-51A patent/ME02626B/me unknown
- 2013-08-07 DK DK13750454.4T patent/DK2882716T3/en active
- 2013-08-07 CN CN201380042178.6A patent/CN104520277B/zh active Active
- 2013-08-08 TW TW102128546A patent/TWI603958B/zh active
-
2015
- 2015-01-13 IL IL236698A patent/IL236698A/en active IP Right Grant
- 2015-01-27 CO CO15016031A patent/CO7180201A2/es unknown
- 2015-01-28 ZA ZA2015/00654A patent/ZA201500654B/en unknown
- 2015-02-06 PH PH12015500260A patent/PH12015500260A1/en unknown
- 2015-07-29 US US14/812,095 patent/US9670186B2/en active Active
-
2017
- 2017-02-08 JP JP2017020923A patent/JP2017105817A/ja not_active Withdrawn
- 2017-02-24 CY CY20171100263T patent/CY1118681T1/el unknown
- 2017-04-26 US US15/497,508 patent/US9873685B2/en active Active
- 2017-10-23 IL IL255206A patent/IL255206A0/en active IP Right Grant
- 2017-12-14 US US15/841,749 patent/US10189823B2/en active Active
-
2018
- 2018-12-04 US US16/209,112 patent/US10570120B2/en active Active
-
2020
- 2020-01-10 US US16/739,525 patent/US11124502B2/en active Active
-
2021
- 2021-08-16 US US17/445,096 patent/US11634413B2/en active Active
-
2023
- 2023-02-23 US US18/173,573 patent/US11919888B2/en active Active
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2015524476A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | ||
| FI108136B (fi) | Menetelmä terapeuttisesti käyttökelpoisen 6-merkaptoasetyyliamino-5-oksopyrrolo[2,1-a][2]bentsatsepiini- ja 7-merkaptoasetyyli-amino-6-oksopyrido-ja-[1,4]atsatsino-, [1,4]oksatsino- ja tiatsino[3,4-a][2]bentsatsepiinijohdannaisten valmistamiseksi | |
| EP2632465B1 (en) | Inhibitors of the renal outer medullary potassium channel | |
| US8288385B2 (en) | 6-(3-aza-bicyclo[3.1.0]hex-3-yl)-2-phenyl-pyrimidines | |
| ES3032633T3 (en) | Heterocyclic apelin receptor (apj) agonists and uses thereof | |
| KR20180090852A (ko) | 개선된 아펠린 수용체(apj) 효능제 및 이의 용도 | |
| CZ20013254A3 (cs) | Heterocyklické aromatické sloučeniny pouľitelné jako stimulátory sekrece růstového hormonu | |
| EP2804851A1 (en) | Therapeutically active compounds and their methods of use | |
| WO2015154673A1 (en) | Novel prodrugs and combinations for treatment of hypertension and cardiovascular diseases | |
| PH12014502573B1 (en) | Substituted pyrrolidines as factor xia inhibitors for the treatment thromboembolic diseases | |
| EP2875021A1 (en) | Beta amino acid derivatives as integrin antagonists | |
| JP2014508755A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | ||
| JP2014505734A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | ||
| JP2015525215A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | ||
| JP2015523988A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | ||
| US20020119992A1 (en) | Thrombin inhibitors | |
| PT91426A (pt) | Processo para a preparacao de composicoes farmaceuticas antiviricas incorporando derivados de acido alfa-aminoboronico | |
| CZ20022352A3 (cs) | 4-pyridinyl-N-acyl-L-fenylalaniny | |
| WO2017117538A1 (en) | Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists | |
| JP2010513274A (ja) | アンジオテンシンｉｉ受容体拮抗薬 | |
| US11634428B2 (en) | Deuterated angiotensin-converting enzyme-2 (ACE-2) inhibitors | |
| US6172256B1 (en) | Chiral-β-amino acid compounds and derivatives thereof | |
| WO2006104008A1 (ja) | ウレア誘導体、それを含有する医薬組成物およびそれらの医薬用途 | |
| CN104496969B (zh) | 一种用于肾素-血管紧张素-醛固酮系统双重抑制剂的化合物 | |
| HUT51292A (en) | Process for production of amin-methil-peptides and medical compositions containinh them as active substance |