CA2905237A1 - Small molecule modulators of pcsk9 and methods of use thereof - Google Patents
Small molecule modulators of pcsk9 and methods of use thereof Download PDFInfo
- Publication number
- CA2905237A1 CA2905237A1 CA2905237A CA2905237A CA2905237A1 CA 2905237 A1 CA2905237 A1 CA 2905237A1 CA 2905237 A CA2905237 A CA 2905237A CA 2905237 A CA2905237 A CA 2905237A CA 2905237 A1 CA2905237 A1 CA 2905237A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- substituted
- alkyl
- phenyl
- amino
- 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.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 42
- 150000003384 small molecules Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 440
- 239000000203 mixture Substances 0.000 claims abstract description 155
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 69
- 150000003839 salts Chemical class 0.000 claims abstract description 45
- 201000010099 disease Diseases 0.000 claims abstract description 37
- 208000035475 disorder Diseases 0.000 claims abstract description 28
- 239000012453 solvate Substances 0.000 claims abstract description 20
- 238000008214 LDL Cholesterol Methods 0.000 claims abstract description 19
- 108010028554 LDL Cholesterol Proteins 0.000 claims abstract description 14
- -1 2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0 2,6]decan-4-yl Chemical group 0.000 claims description 147
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 92
- 125000003118 aryl group Chemical group 0.000 claims description 88
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 71
- 125000001072 heteroaryl group Chemical group 0.000 claims description 42
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 35
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 30
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 125000004001 thioalkyl group Chemical group 0.000 claims description 26
- 125000004122 cyclic group Chemical group 0.000 claims description 24
- 125000000623 heterocyclic group Chemical group 0.000 claims description 23
- 125000001424 substituent group Chemical group 0.000 claims description 23
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 19
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 17
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- 125000001931 aliphatic group Chemical group 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
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- 125000001188 haloalkyl group Chemical group 0.000 claims description 10
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 9
- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 claims description 8
- 150000001413 amino acids Chemical group 0.000 claims description 8
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
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- 239000003937 drug carrier Substances 0.000 claims description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 7
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 7
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- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 125000002653 sulfanylmethyl group Chemical group [H]SC([H])([H])[*] 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000003107 substituted aryl group Chemical group 0.000 claims description 5
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 4
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- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 3
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 3
- WYKHSBAVLOPISI-UHFFFAOYSA-N 2-phenyl-1,3-thiazole Chemical compound C1=CSC(C=2C=CC=CC=2)=N1 WYKHSBAVLOPISI-UHFFFAOYSA-N 0.000 claims description 2
- VQGHOUODWALEFC-UHFFFAOYSA-N 2-phenylpyridine Chemical compound C1=CC=CC=C1C1=CC=CC=N1 VQGHOUODWALEFC-UHFFFAOYSA-N 0.000 claims description 2
- CHJJHGSNNPEDNJ-UHFFFAOYSA-N 3-phenyl-1,2,5-oxadiazole Chemical compound C1=NON=C1C1=CC=CC=C1 CHJJHGSNNPEDNJ-UHFFFAOYSA-N 0.000 claims description 2
- XTXZCNATVCIKTR-UHFFFAOYSA-N 5-methyl-4-phenyl-1h-pyrazole Chemical compound N1N=CC(C=2C=CC=CC=2)=C1C XTXZCNATVCIKTR-UHFFFAOYSA-N 0.000 claims description 2
- OEDUIFSDODUDRK-UHFFFAOYSA-N 5-phenyl-1h-pyrazole Chemical compound N1N=CC=C1C1=CC=CC=C1 OEDUIFSDODUDRK-UHFFFAOYSA-N 0.000 claims description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 2
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 2
- CDNZEVWFGTWVJC-UHFFFAOYSA-N pyridine;1,2-thiazole Chemical compound C=1C=NSC=1.C1=CC=NC=C1 CDNZEVWFGTWVJC-UHFFFAOYSA-N 0.000 claims description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 306
- 210000004027 cell Anatomy 0.000 description 165
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 125
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 122
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 108
- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene chloride Substances ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 96
- 238000005160 1H NMR spectroscopy Methods 0.000 description 93
- 238000006243 chemical reaction Methods 0.000 description 80
- 102000000853 LDL receptors Human genes 0.000 description 79
- 108010001831 LDL receptors Proteins 0.000 description 79
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 72
- 238000001819 mass spectrum Methods 0.000 description 70
- 239000000543 intermediate Substances 0.000 description 67
- 238000004293 19F NMR spectroscopy Methods 0.000 description 65
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- 239000007821 HATU Substances 0.000 description 53
- 238000003756 stirring Methods 0.000 description 51
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 50
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 50
- 230000000694 effects Effects 0.000 description 48
- 230000002829 reductive effect Effects 0.000 description 45
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 44
- XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 40
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 38
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 37
- 230000001965 increasing effect Effects 0.000 description 36
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 35
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
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- 238000002360 preparation method Methods 0.000 description 16
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 16
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- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 description 1
- 125000000565 sulfonamide group Chemical group 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
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- DLYMUMPBWDXPBA-DRLKCWBASA-N tert-butyl n-[(2s)-1-[[(2s)-1-[[(2s)-1-[(6-amino-1,1,1-trifluoro-2-hydroxy-6-oxohexan-3-yl)amino]-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound NC(=O)CCC(C(O)C(F)(F)F)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)C)CC1=CC=CC=C1 DLYMUMPBWDXPBA-DRLKCWBASA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
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- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
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- 229940124597 therapeutic agent Drugs 0.000 description 1
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- 125000006407 thiazinanyl group Chemical group 0.000 description 1
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- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 230000000929 thyromimetic effect Effects 0.000 description 1
- 229950004437 tiqueside Drugs 0.000 description 1
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
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- XYNPYHXGMWJBLV-OFMODGJOSA-N tomatidine Natural products O[C@@H]1C[C@H]2[C@@](C)([C@@H]3[C@H]([C@H]4[C@@](C)([C@H]5[C@@H](C)[C@]6(O[C@H]5C4)NC[C@@H](C)CC6)CC3)CC2)CC1 XYNPYHXGMWJBLV-OFMODGJOSA-N 0.000 description 1
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- 230000002110 toxicologic effect Effects 0.000 description 1
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- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
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- 230000009261 transgenic effect Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
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- 125000001425 triazolyl group Chemical group 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
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- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
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- 239000003981 vehicle Substances 0.000 description 1
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- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
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- 239000011709 vitamin E Substances 0.000 description 1
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- 229910052727 yttrium Inorganic materials 0.000 description 1
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- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0827—Tripeptides containing heteroatoms different from O, S, or N
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0806—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/081—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing O or S as heteroatoms, e.g. Cys, Ser
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Vascular Medicine (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Crystallography & Structural Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361792249P | 2013-03-15 | 2013-03-15 | |
| US61/792,249 | 2013-03-15 | ||
| PCT/CA2014/050255 WO2014139008A1 (en) | 2013-03-15 | 2014-03-14 | Small molecule modulators of pcsk9 and methods of use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2905237A1 true CA2905237A1 (en) | 2014-09-18 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2905237A Abandoned CA2905237A1 (en) | 2013-03-15 | 2014-03-14 | Small molecule modulators of pcsk9 and methods of use thereof |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20160031935A1 (enExample) |
| EP (1) | EP2961765A4 (enExample) |
| JP (1) | JP2016511274A (enExample) |
| KR (1) | KR20150132362A (enExample) |
| CN (1) | CN105431447A (enExample) |
| AU (1) | AU2014231330A1 (enExample) |
| BR (1) | BR112015023761A2 (enExample) |
| CA (1) | CA2905237A1 (enExample) |
| HK (1) | HK1222864A1 (enExample) |
| WO (1) | WO2014139008A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3160513B1 (en) | 2014-06-30 | 2020-02-12 | Glykos Finland Oy | Saccharide derivative of a toxic payload and antibody conjugates thereof |
| EP3182971A4 (en) | 2014-08-21 | 2018-04-25 | SRX Cardio, LLC | Composition and methods of use of small molecules as binding ligands for the modulation of proprotein convertase subtilisin/kexin type 9(pcsk9) protein activity |
| US20170290806A1 (en) * | 2014-09-08 | 2017-10-12 | Temple University-Of The Commonwealth System Of Higher Education | PCSK9 Inhibitors and Methods of Use Thereof |
| MX384944B (es) * | 2015-03-20 | 2025-03-14 | Univ Aarhus | Inhibidores de pcsk9 para el tratamiento de trastornos del metabolismo de lipoproteínas". |
| JP2019525947A (ja) | 2016-06-01 | 2019-09-12 | エムスリー・バイオテクノロジー・インコーポレイテッドＭ３ Ｂｉｏｔｅｃｈｎｏｌｏｇｙ， Ｉｎｃ． | 化合物 |
| JP7110124B2 (ja) | 2016-06-24 | 2022-08-01 | エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト | 心血管疾患を治療するための組成物及び方法 |
| GB2567210B (en) | 2017-10-06 | 2020-01-15 | Rolls Royce Plc | A bladed disk |
| CN109096247A (zh) * | 2018-08-15 | 2018-12-28 | 上海罕道医药科技有限公司 | 一种3h双吖丙啶基双取代吡啶衍生物的制备方法 |
| CN119060040A (zh) | 2019-01-18 | 2024-12-03 | 阿斯利康(瑞典)有限公司 | Pcsk9抑制剂及其使用方法 |
| LV15544A (lv) * | 2019-07-01 | 2021-01-20 | Latvijas Organiskās Sintēzes Institūts | Jauni borskābi saturoši peptidomimētiķi kā malārijas serīna proteāzes inhibitori |
| WO2024163598A2 (en) * | 2023-01-31 | 2024-08-08 | Brandeis University | Peptides comprising thioester groups, including depsipeptide thioesters, methods of making, and use thereof |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998013461A1 (en) * | 1996-09-24 | 1998-04-02 | The Procter & Gamble Company | Liquid laundry detergent compositions containing proteolytic enzyme and protease inhibitors |
| GB9623908D0 (en) * | 1996-11-18 | 1997-01-08 | Hoffmann La Roche | Amino acid derivatives |
| US6358491B1 (en) * | 1999-08-27 | 2002-03-19 | Berlex Laboratories, Inc. | Somatostatin analogs |
| WO2003092605A2 (en) * | 2002-04-30 | 2003-11-13 | Trustees Of Tufts College | Protease inhibitors |
| PE20090145A1 (es) * | 2007-04-13 | 2009-04-23 | Novartis Ag | Moleculas de enlace de la pro-proteina convertasa-subtilisina/quexina tipo 9 (pcsk9) |
| AR079344A1 (es) * | 2009-12-22 | 2012-01-18 | Lilly Co Eli | Analogo peptidico de oxintomodulina, composicion farmaceutica que lo comprende y uso para preparar un medicamento util para tratar diabetes no insulinodependiente y/u obesidad |
| AU2011223795B2 (en) * | 2010-03-01 | 2015-11-05 | Onyx Therapeutics, Inc. | Compounds for immunoproteasome inhibition |
| CN104254518A (zh) * | 2012-02-16 | 2014-12-31 | 阿奇克斯制药公司 | 线性肽抗生素 |
-
2014
- 2014-03-14 AU AU2014231330A patent/AU2014231330A1/en not_active Abandoned
- 2014-03-14 HK HK16110987.6A patent/HK1222864A1/zh unknown
- 2014-03-14 CN CN201480026888.4A patent/CN105431447A/zh active Pending
- 2014-03-14 EP EP14765405.7A patent/EP2961765A4/en not_active Withdrawn
- 2014-03-14 JP JP2015561865A patent/JP2016511274A/ja active Pending
- 2014-03-14 KR KR1020157029032A patent/KR20150132362A/ko not_active Withdrawn
- 2014-03-14 BR BR112015023761A patent/BR112015023761A2/pt active Search and Examination
- 2014-03-14 CA CA2905237A patent/CA2905237A1/en not_active Abandoned
- 2014-03-14 WO PCT/CA2014/050255 patent/WO2014139008A1/en not_active Ceased
- 2014-03-14 US US14/776,701 patent/US20160031935A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU2014231330A1 (en) | 2015-10-01 |
| EP2961765A4 (en) | 2016-11-09 |
| EP2961765A1 (en) | 2016-01-06 |
| BR112015023761A2 (pt) | 2017-07-18 |
| WO2014139008A1 (en) | 2014-09-18 |
| HK1222864A1 (zh) | 2017-07-14 |
| JP2016511274A (ja) | 2016-04-14 |
| KR20150132362A (ko) | 2015-11-25 |
| US20160031935A1 (en) | 2016-02-04 |
| CN105431447A (zh) | 2016-03-23 |
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| Date | Code | Title | Description |
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| FZDE | Discontinued |
Effective date: 20190314 |