JP2016501851A5 - - Google Patents
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- JP2016501851A5 JP2016501851A5 JP2015543111A JP2015543111A JP2016501851A5 JP 2016501851 A5 JP2016501851 A5 JP 2016501851A5 JP 2015543111 A JP2015543111 A JP 2015543111A JP 2015543111 A JP2015543111 A JP 2015543111A JP 2016501851 A5 JP2016501851 A5 JP 2016501851A5
- Authority
- JP
- Japan
- Prior art keywords
- polypeptide
- amide
- salt
- ester
- amino acid
- 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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- 108090000765 processed proteins & peptides Proteins 0.000 claims description 69
- 229920001184 polypeptide Polymers 0.000 claims description 66
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 66
- 150000001408 amides Chemical class 0.000 claims description 43
- 150000003839 salts Chemical class 0.000 claims description 42
- 150000002148 esters Chemical class 0.000 claims description 40
- 150000008574 D-amino acids Chemical group 0.000 claims description 26
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 206010007556 Cardiac failure acute Diseases 0.000 claims description 6
- SNDPXSYFESPGGJ-SCSAIBSYSA-N D-2-aminopentanoic acid Chemical compound CCC[C@@H](N)C(O)=O SNDPXSYFESPGGJ-SCSAIBSYSA-N 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 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 4
- SNDPXSYFESPGGJ-UHFFFAOYSA-N 2-aminopentanoic acid Chemical compound CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 claims description 4
- 229940123338 Aldosterone synthase inhibitor Drugs 0.000 claims description 4
- 101800000407 Brain natriuretic peptide 32 Proteins 0.000 claims description 4
- 229940127291 Calcium channel antagonist Drugs 0.000 claims description 4
- ROHFNLRQFUQHCH-RXMQYKEDSA-N D-leucine Chemical compound CC(C)C[C@@H](N)C(O)=O ROHFNLRQFUQHCH-RXMQYKEDSA-N 0.000 claims description 4
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 claims description 4
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 claims description 4
- 239000000480 calcium channel blocker Substances 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 4
- FXHCFPUEIDRTMR-UHFFFAOYSA-N hydron;1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid;chloride Chemical compound Cl.C1=CC=C2CNC(C(=O)O)CC2=C1 FXHCFPUEIDRTMR-UHFFFAOYSA-N 0.000 claims description 4
- 239000003112 inhibitor Substances 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 108091008803 APLNR Proteins 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 206010003658 Atrial Fibrillation Diseases 0.000 claims description 3
- 206010059027 Brugada syndrome Diseases 0.000 claims description 3
- 206010007558 Cardiac failure chronic Diseases 0.000 claims description 3
- 208000031229 Cardiomyopathies Diseases 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 206010016807 Fluid retention Diseases 0.000 claims description 3
- 206010020772 Hypertension Diseases 0.000 claims description 3
- 208000008589 Obesity Diseases 0.000 claims description 3
- 208000005764 Peripheral Arterial Disease Diseases 0.000 claims description 3
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims description 3
- 206010042496 Sunburn Diseases 0.000 claims description 3
- 208000032109 Transient ischaemic attack Diseases 0.000 claims description 3
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 3
- 230000008484 agonism Effects 0.000 claims description 3
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 3
- 206010003119 arrhythmia Diseases 0.000 claims description 3
- 230000006793 arrhythmia Effects 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 208000004104 gestational diabetes Diseases 0.000 claims description 3
- 230000000302 ischemic effect Effects 0.000 claims description 3
- 235000020824 obesity Nutrition 0.000 claims description 3
- 201000011461 pre-eclampsia Diseases 0.000 claims description 3
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 3
- 208000037803 restenosis Diseases 0.000 claims description 3
- 201000010875 transient cerebral ischemia Diseases 0.000 claims description 3
- 230000009529 traumatic brain injury Effects 0.000 claims description 3
- 206010047302 ventricular tachycardia Diseases 0.000 claims description 3
- NRCSJHVDTAAISV-QMMMGPOBSA-N (2s)-2-amino-3-(3,4-dichlorophenyl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(Cl)C(Cl)=C1 NRCSJHVDTAAISV-QMMMGPOBSA-N 0.000 claims description 2
- 125000001431 2-aminoisobutyric acid group Chemical group [#6]C([#6])(N*)C(*)=O 0.000 claims description 2
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical group OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 claims description 2
- MVEOHWRUBFWKJY-UHFFFAOYSA-N 7-hydroxynaphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(O)=CC=C21 MVEOHWRUBFWKJY-UHFFFAOYSA-N 0.000 claims description 2
- 102000005666 Apolipoprotein A-I Human genes 0.000 claims description 2
- 108010059886 Apolipoprotein A-I Proteins 0.000 claims description 2
- 101800002247 Brain natriuretic peptide 45 Proteins 0.000 claims description 2
- BWKMGYQJPOAASG-SECBINFHSA-N D-1,2,3,4-Tetrahydroisoquinoline-3-carboxylic acid Chemical compound C1=CC=C2CN[C@@H](C(=O)O)CC2=C1 BWKMGYQJPOAASG-SECBINFHSA-N 0.000 claims description 2
- XUJNEKJLAYXESH-UWTATZPHSA-N D-Cysteine Chemical compound SC[C@@H](N)C(O)=O XUJNEKJLAYXESH-UWTATZPHSA-N 0.000 claims description 2
- LRQKBLKVPFOOQJ-RXMQYKEDSA-N D-norleucine Chemical group CCCC[C@@H](N)C(O)=O LRQKBLKVPFOOQJ-RXMQYKEDSA-N 0.000 claims description 2
- 102000002045 Endothelin Human genes 0.000 claims description 2
- 108050009340 Endothelin Proteins 0.000 claims description 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-Tyrosine Natural products OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 2
- HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical compound [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 claims description 2
- 125000003798 L-tyrosyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 claims description 2
- 102000003979 Mineralocorticoid Receptors Human genes 0.000 claims description 2
- 108090000375 Mineralocorticoid Receptors Proteins 0.000 claims description 2
- 102000003743 Relaxin Human genes 0.000 claims description 2
- 108090000103 Relaxin Proteins 0.000 claims description 2
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 claims description 2
- 235000004279 alanine Nutrition 0.000 claims description 2
- FUOOLUPWFVMBKG-UHFFFAOYSA-N alpha-amino-isobutyric acid Natural products CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 claims description 2
- QWCKQJZIFLGMSD-UHFFFAOYSA-N alpha-aminobutyric acid Chemical compound CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 claims description 2
- 239000002333 angiotensin II receptor antagonist Substances 0.000 claims description 2
- 239000005557 antagonist Substances 0.000 claims description 2
- 230000003178 anti-diabetic effect Effects 0.000 claims description 2
- 230000003579 anti-obesity Effects 0.000 claims description 2
- 239000003146 anticoagulant agent Substances 0.000 claims description 2
- 229940127219 anticoagulant drug Drugs 0.000 claims description 2
- 239000003472 antidiabetic agent Substances 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
- 210000004899 c-terminal region Anatomy 0.000 claims description 2
- 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 claims description 2
- 229940125881 cholesteryl ester transfer protein inhibitor Drugs 0.000 claims description 2
- 239000002934 diuretic Substances 0.000 claims description 2
- 230000001882 diuretic effect Effects 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000002308 endothelin receptor antagonist Substances 0.000 claims description 2
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 claims description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 2
- HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 claims description 2
- HPNRHPKXQZSDFX-OAQDCNSJSA-N nesiritide Chemical compound C([C@H]1C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)CNC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CO)C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1N=CNC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 HPNRHPKXQZSDFX-OAQDCNSJSA-N 0.000 claims description 2
- 229960001267 nesiritide Drugs 0.000 claims description 2
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 239000003087 receptor blocking agent Substances 0.000 claims description 2
- 239000002461 renin inhibitor Substances 0.000 claims description 2
- 229940086526 renin-inhibitors Drugs 0.000 claims description 2
- 229960004441 tyrosine Drugs 0.000 claims description 2
- ORQXBVXKBGUSBA-QMMMGPOBSA-N β-cyclohexyl-alanine Chemical compound OC(=O)[C@@H](N)CC1CCCCC1 ORQXBVXKBGUSBA-QMMMGPOBSA-N 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims 4
- 102000008100 Human Serum Albumin Human genes 0.000 claims 3
- 108091006905 Human Serum Albumin Proteins 0.000 claims 3
- 125000005647 linker group Chemical group 0.000 claims 3
- 125000003118 aryl group Chemical group 0.000 claims 2
- WCZSMQWMSBJQMP-UHFFFAOYSA-N 1-(4-phenoxyphenyl)piperidine Chemical compound C1CCCCN1C(C=C1)=CC=C1OC1=CC=CC=C1 WCZSMQWMSBJQMP-UHFFFAOYSA-N 0.000 description 1
- 230000009787 cardiac fibrosis Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- -1 salt ester Chemical class 0.000 description 1
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261728395P | 2012-11-20 | 2012-11-20 | |
| US61/728,395 | 2012-11-20 | ||
| US201361781397P | 2013-03-14 | 2013-03-14 | |
| US61/781,397 | 2013-03-14 | ||
| US201361858251P | 2013-07-25 | 2013-07-25 | |
| US61/858,251 | 2013-07-25 | ||
| PCT/US2013/070742 WO2014081702A2 (en) | 2012-11-20 | 2013-11-19 | Synthetic linear apelin mimetics for the treatment of heart failure |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018122192A Division JP2018172410A (ja) | 2012-11-20 | 2018-06-27 | 心不全治療用の合成鎖状アペリン模倣物 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016501851A JP2016501851A (ja) | 2016-01-21 |
| JP2016501851A5 true JP2016501851A5 (https=) | 2016-12-28 |
| JP6444882B2 JP6444882B2 (ja) | 2018-12-26 |
Family
ID=49876968
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015543111A Expired - Fee Related JP6444882B2 (ja) | 2012-11-20 | 2013-11-19 | 心不全治療用の合成鎖状アペリン模倣物 |
| JP2018122192A Pending JP2018172410A (ja) | 2012-11-20 | 2018-06-27 | 心不全治療用の合成鎖状アペリン模倣物 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018122192A Pending JP2018172410A (ja) | 2012-11-20 | 2018-06-27 | 心不全治療用の合成鎖状アペリン模倣物 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US10005829B2 (https=) |
| EP (1) | EP2922559B1 (https=) |
| JP (2) | JP6444882B2 (https=) |
| CN (1) | CN105007928B (https=) |
| AR (1) | AR093559A1 (https=) |
| ES (1) | ES2705323T3 (https=) |
| TW (1) | TW201425339A (https=) |
| UY (1) | UY35144A (https=) |
| WO (1) | WO2014081702A2 (https=) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9683018B2 (en) | 2013-07-25 | 2017-06-20 | Novartis Ag | Disulfide cyclic polypeptides for the treatment of heart failure |
| JP6505691B2 (ja) | 2013-07-25 | 2019-04-24 | ノバルティス アーゲー | 心不全治療用の環状アペリン誘導体 |
| US10588980B2 (en) | 2014-06-23 | 2020-03-17 | Novartis Ag | Fatty acids and their use in conjugation to biomolecules |
| EP3157942B1 (en) | 2014-06-23 | 2020-06-17 | Novartis AG | Site specific protein modifications |
| WO2016102648A1 (en) * | 2014-12-23 | 2016-06-30 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Metabolically stable apelin analogs in the treatment of disease mediated by the apelin receptor |
| ES2930077T3 (es) * | 2016-02-15 | 2022-12-07 | Inst Nat Sante Rech Med | Apelina para su uso en el tratamiento de la disfunción cognitiva posoperatoria |
| JOP20190245A1 (ar) | 2017-04-20 | 2019-10-15 | Novartis Ag | أنظمة توصيل إطلاق مستدام تتضمن روابط بلا أثر لنقطة الربط |
| EP3649146B1 (en) | 2017-07-03 | 2024-06-26 | The Governors of the University of Alberta | Apelin peptides and uses thereof |
| CN109771634A (zh) * | 2017-07-11 | 2019-05-21 | 南华大学 | 含有apelin 12环肽的药物组合物及用途 |
| US10905738B2 (en) * | 2018-07-05 | 2021-02-02 | Biozeus Desenvolvimento De Produtos Biofarmacêuticos | Synthetic peptides, prodrugs, pharmaceutical compositions and uses |
| CN114269367A (zh) * | 2019-08-15 | 2022-04-01 | 科巴公司 | 治疗性肽 |
| CN114099642A (zh) * | 2021-11-12 | 2022-03-01 | 南通大学 | 基因Apln在制备治疗与细胞成血管有关疾病药物中的应用 |
| WO2026007693A1 (zh) * | 2024-07-05 | 2026-01-08 | 浙江大学 | Apelin-13多肽突变体 |
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-
2013
- 2013-11-18 UY UY0001035144A patent/UY35144A/es unknown
- 2013-11-19 WO PCT/US2013/070742 patent/WO2014081702A2/en not_active Ceased
- 2013-11-19 ES ES13811648T patent/ES2705323T3/es active Active
- 2013-11-19 TW TW102142121A patent/TW201425339A/zh unknown
- 2013-11-19 JP JP2015543111A patent/JP6444882B2/ja not_active Expired - Fee Related
- 2013-11-19 US US14/440,198 patent/US10005829B2/en not_active Expired - Fee Related
- 2013-11-19 EP EP13811648.8A patent/EP2922559B1/en not_active Not-in-force
- 2013-11-19 CN CN201380070626.3A patent/CN105007928B/zh not_active Expired - Fee Related
- 2013-11-20 AR ARP130104278A patent/AR093559A1/es unknown
-
2018
- 2018-06-27 JP JP2018122192A patent/JP2018172410A/ja active Pending
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