WO2016210190A1 - Ionizable compounds and compositions and uses thereof - Google Patents
Ionizable compounds and compositions and uses thereof Download PDFInfo
- Publication number
- WO2016210190A1 WO2016210190A1 PCT/US2016/039114 US2016039114W WO2016210190A1 WO 2016210190 A1 WO2016210190 A1 WO 2016210190A1 US 2016039114 W US2016039114 W US 2016039114W WO 2016210190 A1 WO2016210190 A1 WO 2016210190A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- alkyl
- compound
- aminoalkyl
- hydroxyalkyl
- independently
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 560
- 239000000203 mixture Substances 0.000 title claims abstract description 327
- 239000013543 active substance Substances 0.000 claims abstract description 41
- 239000002105 nanoparticle Substances 0.000 claims abstract description 27
- 239000003814 drug Substances 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 336
- 125000003342 alkenyl group Chemical group 0.000 claims description 154
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 146
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 137
- 150000002632 lipids Chemical class 0.000 claims description 133
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 63
- 125000003545 alkoxy group Chemical group 0.000 claims description 50
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 49
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 41
- 239000003381 stabilizer Substances 0.000 claims description 29
- 230000005847 immunogenicity Effects 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 108091030071 RNAI Proteins 0.000 claims description 10
- 230000009368 gene silencing by RNA Effects 0.000 claims description 10
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 9
- 102000040650 (ribonucleotides)n+m Human genes 0.000 claims description 9
- 108020004459 Small interfering RNA Proteins 0.000 claims description 9
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
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- 101100347612 Arabidopsis thaliana VIII-B gene Proteins 0.000 claims description 6
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- 108091027967 Small hairpin RNA Proteins 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 125000004185 ester group Chemical group 0.000 claims description 4
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
- 125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims description 3
- 125000005191 hydroxyalkylamino group Chemical group 0.000 claims description 3
- 239000000758 substrate Substances 0.000 claims description 3
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- 208000024891 symptom Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 11
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- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 258
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 147
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- 239000000047 product Substances 0.000 description 104
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 94
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- 238000002360 preparation method Methods 0.000 description 64
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 49
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- 239000000306 component Substances 0.000 description 38
- -1 lipid compounds Chemical class 0.000 description 37
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 37
- 239000000377 silicon dioxide Substances 0.000 description 33
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 29
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 24
- 0 *CC(N(*)*)=O Chemical compound *CC(N(*)*)=O 0.000 description 21
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- 229910052786 argon Inorganic materials 0.000 description 16
- 239000007789 gas Substances 0.000 description 16
- 239000007787 solid Substances 0.000 description 15
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- 239000007864 aqueous solution Substances 0.000 description 12
- 238000010936 aqueous wash Methods 0.000 description 12
- 238000000605 extraction Methods 0.000 description 12
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- 125000006355 carbonyl methylene group Chemical group [H]C([H])([*:2])C([*:1])=O 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 210000002966 serum Anatomy 0.000 description 10
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
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- 239000000706 filtrate Substances 0.000 description 9
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 9
- 230000002452 interceptive effect Effects 0.000 description 8
- 229920001223 polyethylene glycol Polymers 0.000 description 8
- 150000001721 carbon Chemical group 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 7
- 229920001427 mPEG Polymers 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- SNKAWJBJQDLSFF-NVKMUCNASA-N 1,2-dioleoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC SNKAWJBJQDLSFF-NVKMUCNASA-N 0.000 description 6
- LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 description 6
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- 125000006364 carbonyl oxy methylene group Chemical group [H]C([H])([*:2])OC([*:1])=O 0.000 description 6
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 6
- 238000005538 encapsulation Methods 0.000 description 6
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 6
- OYHQOLUKZRVURQ-UHFFFAOYSA-M octadeca-9,12-dienoate Chemical compound CCCCCC=CCC=CCCCCCCCC([O-])=O OYHQOLUKZRVURQ-UHFFFAOYSA-M 0.000 description 6
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- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 4
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
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- 125000002669 linoleoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- GDJLJNFNXINTHS-RGMNGODLSA-N methyl (2s)-2-amino-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CNC(=O)OC(C)(C)C GDJLJNFNXINTHS-RGMNGODLSA-N 0.000 description 1
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- 239000000312 peanut oil Substances 0.000 description 1
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- NKZVILXYMBJHBC-UHFFFAOYSA-J pentacalcium hydroxide phosphate Chemical compound P(=O)([O-])([O-])[O-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[OH-].[Ca+2] NKZVILXYMBJHBC-UHFFFAOYSA-J 0.000 description 1
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- CJIVCSBYIRBJSG-UHFFFAOYSA-N pyrrolidine-3,3-diol Chemical compound OC1(O)CCNC1 CJIVCSBYIRBJSG-UHFFFAOYSA-N 0.000 description 1
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- NLQLSVXGSXCXFE-UHFFFAOYSA-N sitosterol Natural products CC=C(/CCC(C)C1CC2C3=CCC4C(C)C(O)CCC4(C)C3CCC2(C)C1)C(C)C NLQLSVXGSXCXFE-UHFFFAOYSA-N 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L sodium sulphate Substances [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
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- LGJMUZUPVCAVPU-HRJGVYIJSA-N stigmastanol Chemical compound C([C@@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CC[C@@H](CC)C(C)C)[C@@]2(C)CC1 LGJMUZUPVCAVPU-HRJGVYIJSA-N 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- VSWJMEOTFCYQNI-ZPPAUJSGSA-N trimethyl-[3-[[(9Z,12Z)-octadeca-9,12-dienoyl]-[2-[(9Z,12Z)-octadeca-9,12-dienoyl]oxyethyl]amino]propyl]azanium Chemical compound C[N+](CCCN(C(CCCCCCC\C=C/C\C=C/CCCCC)=O)CCOC(CCCCCCC\C=C/C\C=C/CCCCC)=O)(C)C VSWJMEOTFCYQNI-ZPPAUJSGSA-N 0.000 description 1
- WBIJWCAGCBRBMS-UHFFFAOYSA-N trimethyl-[3-[tetradecanoyl(2-tetradecanoyloxyethyl)amino]propyl]azanium Chemical compound C[N+](CCCN(C(CCCCCCCCCCCCC)=O)CCOC(CCCCCCCCCCCCC)=O)(C)C WBIJWCAGCBRBMS-UHFFFAOYSA-N 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- CGSJXLIKVBJVRY-XTGBIJOFSA-N zymosterol Chemical compound C([C@@]12C)C[C@H](O)C[C@@H]1CCC1=C2CC[C@]2(C)[C@@H]([C@@H](CCC=C(C)C)C)CC[C@H]21 CGSJXLIKVBJVRY-XTGBIJOFSA-N 0.000 description 1
Classifications
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- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
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- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/16—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
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- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
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- C07C237/08—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
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- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/50—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the nitrogen atom of at least one of the carboxamide groups quaternised
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- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
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- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/12—Oxygen or sulfur atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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- C07D211/82—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/86—Oxygen atoms
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- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
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-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Definitions
- This invention relates to the fields of biopharmaceuticals and therapeutics. More particularly, this invention relates to compounds, compositions and methods for providing nanoparticles to deliver and distribute active agents or drug compounds to cells, tissues, organs, and subjects.
- Therapeutic agents such as drug compounds, nucleic acid molecules and other active agents operate by uptake into cells, tissues, and organs of a subject.
- one way to carry out transfection of nucleic acids is to encapsulate the active molecules in a lipid nanoparticle.
- Drawbacks of this methodology include potential toxicity in various modalities of delivery, such as intravenous injection, and low rates of cell penetration.
- nanoparticles for active agents There is a continuing need for lipid-like molecules and compositions for efficient transfection and distribution of nucleic acid molecules and other agents to cells and subjects.
- This invention relates to molecules and compositions thereof for use in biopharmaceuticals and therapeutics. More particularly, this invention relates to compounds, compositions and methods for providing nanoparticles to deliver and distribute active agents or drug compounds to cells, tissues, organs, and subjects.
- This invention provides a range of ionizable compounds.
- the ionizable compounds of this invention can be used to form nanoparticles to deliver and distribute active agents.
- Embodiments of this invention include a broad range of compounds having lipid-like or liposome-forming properties.
- a compound may have the structure shown in
- n and m are each independently from 1 to 2; and R 4 and R 5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- R 3 is selected from
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxy alkoxy, and aminoalkyl;
- each R 7 is independently selected from H, alkyl, and hydroxyalkyl
- each R 8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R 8 may form a ring;
- q is from zero to four;
- Q is O or R 7 ;
- p is from 1 to 4.
- a compound can have the structure shown in
- n and m are each independently from 1 to 2; and R 4 and R 5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- R 3 is a C( 12-20) alkyl group or a C( 12-20) alkenyl group that is substituted with a carboxylic acid or ester group.
- a compound may have the structure shown in
- n and m are each independently from 1 to 2; and R 4 and R 5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- R 3 is selected from alkyl, hydroxyalkyl, alkoxyalkoxy, and carboxyalkyl;
- R 6 is selected from R 7 2 , N + HR 7 2 and N + R 7 3 ;
- R 7 is selected from H, alkyl, hydroxyalkyl.
- a compound of this invention may have the structure shown in Formula
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- R is selected from
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxy alkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl
- each R 8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R 8 may form a ring;
- q is from zero to four;
- Q is O or R 7 ;
- p is from 1 to 4.
- a compound can have the structure shown in
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- Z is S or O
- R 3 is selected from
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl
- p is from 1 to 4.
- a compound may have the structure shown in Formula
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- p is from 1 to 4.
- R 3 is selected from
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxy alkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl
- each R 8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R 8 may form a ring;
- q is from zero to four;
- a com ound of this invention can have the structure shown in Formula VI
- R 2 and R 4 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- R 3 is selected from aminoalkyl, quaternary aminoalkyl.
- a compound of this invention can have the structure shown in Formula VII
- n and m are each independently from 1 to 2; and R 4 and R 5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- R 3 is selected from H, alkyl, aminoalkyl, quaternary aminoalkyl, hydroxyalkyl, alkoxyalkyl, alkoxyalkoxy alkyl.
- a compound may have the structure shown in Formula
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- R 3 is selected from
- R is selected from
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl
- each R 8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R 8 may form a ring;
- q is from zero to four;
- Q is O or R 7 .
- a compound may have the structure shown in Formula
- n and m are each independently from 1 to 2;
- R 4 and R 5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- Z is N, O;
- R 3 is selected from
- alkyl hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl
- p is from 1 to 4.
- a compound can have the structure shown in
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- p is from 1 to 4.
- R' is selected from
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxy alkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl
- each R 8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R 8 may form a ring;
- q is from zero to four;
- a compound of this disclosure can have the structure shown in Formula X Formula X
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- R 3 is selected from
- a compound may have the structure shown in
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- Z is O or H
- p is from 1 to 4.
- R 3 is selected from
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxy alkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl; each R is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R 8 may form a ring;
- q is from zero to four;
- Q is O or R 7 .
- compositions containing an ionizable compound above and a pharmaceutically acceptable carrier may contain nanoparticles.
- This disclosure includes pharmaceutical compositions comprising an ionizable compound above, an active agent, and a pharmaceutically acceptable carrier.
- the ionizable compound may be from 15 mol% to 40 mol% of the lipids of the composition.
- the composition may comprise nanoparticles.
- An active agent of this disclosure may be one or more RNAi molecules.
- An active agent may be one or more RNAi molecules selected from small interfering RNAs (siRNA), double stranded RNAs (dsRNA) that are Dicer substrates, microRNAs (miRNA), short hairpin RNAs (shRNA), DNA-directed RNAs (ddRNA), Piwi- interacting RNAs (piRNA), repeat associated siRNAs (rasiRNA), and modified forms thereof.
- siRNA small interfering RNAs
- dsRNA double stranded RNAs
- shRNA short hairpin RNAs
- ddRNA DNA-directed RNAs
- piRNA Piwi- interacting RNAs
- rasiRNA repeat associated siRNAs
- An active agent of this disclosure may be one or more active
- this invention includes compositions for use in distributing an active agent for treating a condition or disease in a subject, the composition comprising an ionizable compound above, a structural lipid, a stabilizer lipid, and a lipid for reducing immunogenicity of the composition.
- the active agent can be one or more RNAi molecules and the composition may comprise nanoparticles that encapsulate the RNAi molecules.
- compositions containing an ionizable compound and one or more pharmaceutically acceptable excipients.
- a composition of this invention can be a nanoparticle composed, at least in part, of an ionizable compound.
- Compounds of this invention can be used to make compositions for use in distributing an active agent in a subject, where the composition includes an ionizable compound.
- a composition of this invention can be used in distributing an active agent for treating a condition or disease in a subject.
- a composition for use in distributing an active agent for treating a condition or disease in a subject can include an ionizable compound, a structural lipid, and a lipid for reducing immunogenicity of the composition.
- FIG. 1 shows a scheme for the preparation of Compound A6.
- FIG. 2 shows a scheme for the preparation of Compound AB.
- FIG. 3 shows a scheme for the preparation of Compound A4.
- FIG. 4 shows a scheme for the preparation of Compound B8.
- FIG. 5 shows a scheme for the preparation of Compound A9.
- FIG. 6 shows a scheme for the preparation of Compound AA.
- FIG. 7 shows a scheme for the preparation of Compound A5.
- FIG. 8 shows a scheme for the preparation of Compound Al .
- FIG. 9 shows a scheme for the preparation of Compound D22.
- FIG. 10 shows a scheme for the preparation of Compounds A7 and A8.
- FIG. 11 shows a scheme for the preparation of Compounds C3 and C2.
- FIG. 12 shows a scheme for the preparation of Compound DD.
- FIG. 13 shows a scheme for the preparation of Compound E4.
- FIG. 14 shows a scheme for the preparation of Compound CA.
- FIG. 15 shows a scheme for the preparation of Compound Dl .
- FIG. 16 shows a scheme for the preparation of Compound D7.
- FIG. 17 shows a scheme for the preparation of Compound F6.
- FIG. 18 shows a scheme for the preparation of Compounds F5 and F7.
- FIG. 19 shows a scheme for the preparation of Compounds F8 and F9.
- FIG. 20 shows a scheme for the preparation of Compounds C25 and C24.
- FIG. 21 shows a scheme for the preparation of Compound D16.
- FIG. 22 shows a scheme for the preparation of Compound D17.
- FIG. 23 shows a scheme for the preparation of Compound D18.
- FIG. 24 shows a scheme for the preparation of Compound D19.
- FIG. 25 shows a scheme for the preparation of Compound D20.
- FIG. 26 shows a scheme for the preparation of Compound D21.
- FIG. 27 shows a scheme for the preparation of Compound E37.
- FIG. 28 shows a scheme for the preparation of Compounds E38 and E39.
- FIG. 29 shows a scheme for the preparation of Compound E40.
- FIG. 30 shows a scheme for the preparation of Compound A23.
- FIG. 31 shows a scheme for the preparation of Compound A24.
- FIG. 32 shows a scheme for the preparation of Compound A25.
- This invention provides a range of ionizable molecules that are amphiphiles with lipid-like properties.
- the ionizable compounds of this invention can be used in delivering therapeutic agents to cells, tissues or organs, organisms, and subjects.
- this invention provides compounds for forming lipid nanoparticles for encapsulating and delivering active agents such as nucleic acid molecules to cells and subjects.
- This invention can provide a composition for use in distributing an active agent in cells, tissues or organs, organisms, and subjects, where the composition includes one or more of the ionizable molecules of this invention.
- compositions of this invention may include one or more of the ionizable molecules, along with a structural lipid, and one or more lipids for reducing
- An ionizable molecule of this invention can be any mol% of a composition of this invention.
- compositions of this invention may include one or more of the ionizable molecules, along with a structural lipid, and one or more lipids for reducing
- compositions of this invention may include one or more of the ionizable molecules, along with a structural lipid, one or more stabilizer lipids, and one or more lipids for reducing immunogenicity of the composition.
- a component of a formulation can be a single compound, or can be a combination of one or more suitable lipid compounds.
- a stabilizer lipid can refer to a single stabilizer lipid, or to a combination of one or more suitable stabilizer lipids.
- the ionizable compounds of a composition of this invention can be from
- the ionizable molecules of a composition can be from 55 mol% to 65 mol% of the lipid components of the composition. In further embodiments, the ionizable molecules of a composition can be about 60 mol% of the lipid components of the composition.
- the structural lipid of a composition of this invention can be from 20 mol% to 50 mol% of the lipid components of the composition. In certain embodiments, the structural lipid of a composition can be from 35 mol% to 45 mol% of the lipid components of the composition.
- the one or more lipids for reducing immunogenicity of the composition can be from a total of 1 mol% to 8 mol% of the lipid components of the composition. In certain embodiments, the one or more lipids for reducing immunogenicity of the composition can be from a total of 1 mol% to 5 mol% of the lipid components of the composition.
- a composition of this invention can further include a cationic lipid, which can be from 5 mol% to 25 mol% of the lipid components of the composition.
- a composition of this invention can further include a cationic lipid, which can be from 5 mol% to 15 mol% of the lipid components of the composition.
- the molar ratio of the concentrations of the cationic lipid to the ionizable molecules of a composition of this invention can be from 5:80 to 25:50.
- the entirety of the lipid components may include one or more of the ionizable compound molecular components, a structural lipid, and one or more lipids for reducing immunogenicity of the composition.
- the ionizable molecules of a composition of this invention can be from 15 mol% to 40 mol% of the lipid components of the composition. In certain embodiments, the ionizable molecules of a composition can be from 20 mol% to 35 mol% of the lipid components of the composition. In further embodiments, the ionizable molecules of a composition can be from 25 mol% to 30 mol% of the lipid components of the
- the structural lipid of a composition of this invention can be from 25 mol% to 40 mol% of the lipid components of the composition. In certain embodiments, the structural lipid of a composition can be from 30 mol% to 35 mol% of the lipid components of the composition.
- the sum of the stabilizer lipids of a composition of this invention can be from 25 mol% to 40% mol% of the lipid components of the composition. In certain embodiments, the sum of the stabilizer lipids of a composition can be from 30 mol% to 40 mol% of the lipid components of the composition.
- a composition of this invention can include two or more stabilizer lipids, where each of the stabilizer lipids individually can be from 5 mol% to 35 mol% of the lipid components of the composition. In certain embodiments, a composition of this invention can include two or more stabilizer lipids, where each of the stabilizer lipids individually can be from 10 mol% to 30 mol% of the lipid components of the composition.
- the sum of the one or more stabilizer lipids can be from 25 mol% to 40 mol% of the lipids of the composition, wherein each of the stabilizer lipids individually can be from 5 mol% to 35% mol%.
- the sum of the one or more stabilizer lipids can be from 30 mol% to 40 mol% of the lipids of the composition, wherein each of the stabilizer lipids individually can be from 10 mol% to 30% mol%.
- the one or more lipids for reducing immunogenicity of the composition can be from a total of 1 mol% to 8 mol% of the lipid components of the composition. In certain embodiments, the one or more lipids for reducing immunogenicity of the composition can be from a total of 1 mol% to 5 mol% of the lipid components of the composition.
- a composition of this invention can further include a cationic lipid, which can be from 5 mol% to 25 mol% of the lipid components of the composition.
- a composition of this invention can further include a cationic lipid, which can be from 5 mol% to 15 mol% of the lipid components of the composition.
- the molar ratio of the concentrations of the cationic lipid to the ionizable molecules of a composition of this invention can be from 5:35 to 25: 15.
- the entirety of the lipid components of a composition may include one or more of the ionizable compound molecular components, a structural lipid, one or more lipids for reducing immunogenicity of the composition, and one or more stabilizer lipids.
- three lipid-like components i.e. one or more ionizable molecules, a structural lipid, and one or more lipids for reducing
- immunogenicity of the composition can be 100% of the lipid components of the composition.
- a cationic lipid can be included.
- compositions of this invention are shown in Table 1.
- Table 1 Compositions of lipid components (each in mol% of total)
- lipid-like components i.e. one or more ionizable molecules, a structural lipid, and one or more lipids for reducing
- immunogenicity of the composition and one or more stabilizer lipids can be 100% of the lipid components of the composition.
- compositions of this invention are shown in Table 2.
- Table 2 Compositions of lipid components (each in mol% of total)
- aspects of this invention can provide a range of compositions for use in distributing an active agent to various organs or tissues of a subject.
- compositions of this invention can contain an ionizable lipid, a structural lipid, and a lipid for reducing immunogenicity of the composition.
- compositions of this invention can contain an ionizable lipid, a structural lipid, one or more stabilizer lipids, and a lipid for reducing immunogenicity of the composition.
- compositions of this invention may provide a surprisingly selective biodistribution of the active agent to a particular organ or tissue.
- composition of this invention can provide a surprisingly selective biodistribution of the active agent to the lung of a subject.
- composition of this invention can provide a surprisingly selective biodistribution of the active agent to the liver of a subject.
- a composition of this invention can provide a surprisingly selective biodistribution of the active agent to the colon of a subject. [00100] In some embodiments, a composition of this invention can provide a surprisingly selective biodistribution of the active agent to the pancreas of a subject.
- the ratio of the distribution of the active agent to the lung over the distribution of the active agent to the subject's liver can be at least 1.5.
- the ratio of the distribution of the active agent to the lung to the distribution of the active agent to the subject's liver can be at least 5.
- the ionizable compounds of this invention can have lipid-like properties, for example, as amphiphiles.
- Examples of an ionizable molecule include compounds having the structure shown in Formula I Formula I
- n and m are each independently from 1 to 2; and R 4 and R 5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- R 3 is selected from 1-azetidines, 1 -pyrrolidines, 1-piperidines, 4-morpholines, and 1 4-piperazines wherein the rings can be substituted at any carbon atom position,
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxy alkoxy, and aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl;
- each R 8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R 8 may form a ring;
- q is from zero to four;
- Q is O or R 7 ;
- p is from 1 to 4.
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a CQ4-18) alkyl group, or a CQ4-18) alkenyl group.
- R 4 and R 5 are independently for each occurrence a C(16-18) alkyl group, or a C(16-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- p is 1, 2, 3 or 4.
- q is 0, 1, 2, 3 or 4.
- examples of an ionizable molecule include compounds havin the structure shown in Formula I Formula I
- n and m are each independently from 1 to 2; and R 4 and R 5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- R 3 is selected from
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxy alkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl
- Q is O or R 7 .
- each of the alkenyl groups can have from one to two double bonds.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- examples of an ionizable molecule include compounds havin the structure shown in Formula I Formula I
- n and m are each independently from 1 to 2; and R 4 and R 5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- R 3 is selected from
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxy alkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl
- Q is O or R 7 .
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a CQ4-18) alkyl group, or a CQ4-18) alkenyl group. [00118] In some embodiments, R 4 and R 5 are independently for each occurrence a C(16-18) alkyl group, or a C(16-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- n and m can be each independently from 3 to 6.
- examples of an ionizable molecule include compounds havin the structure shown in Formula I Formula I
- n and m are each independently from 1 to 2; and R 4 and R 5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- R 3 is selected from
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl.
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a CQ4-18) alkyl group, or a CQ4-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- examples of an ionizable molecule include compounds havin the structure shown in Formula I Formula I
- n and m are each independently from 1 to 2; and R 4 and R 5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- R 3 is selected from
- each R 6 is independently hydroxyl
- each R 7 is independently selected from H, alkyl.
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a
- Examples of an ionizable compound include the following compound Al :
- Examples of an ionizable compound include the following compound A2:
- Examples of an ionizable compound include the following compound A3 :
- Examples of an ionizable compound include the following compound A4:
- Examples of an ionizable compound include the following compound A5:
- an ionizable compound examples include the following compound A6:
- Examples of an ionizable compound include the following compound A7:
- Examples of an ionizable compound include the following compound A8:
- Examples of an ionizable compound include the following compound A9:
- an ionizable compound examples include the following compound AA:
- Examples of an ionizable compound include the following compound AB:
- Examples of an ionizable compound include the following compound AC:
- Examples of an ionizable compound include the following compound AD:
- Examples of an ionizable compound include the following compound AE:
- Examples of an ionizable compound include the following compound AF:
- Examples of an ionizable compound include the following compound Bl :
- Examples of an ionizable compound include the following compound B2:
- Examples of an ionizable compound include the following compound B3 :
- Examples of an ionizable compound include the following compound B4:
- Examples of an ionizable compound include the following compound B5 :
- Examples of an ionizable compound include the following compound B6: 00149] Examples of an ionizable compound include the following compound B7:
- Examples of an ionizable molecule include compounds having the structure shown in Formula II Formula II
- n and m are each independently from 1 to 2; and R 4 and R 5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- R 3 is a C( 12-20) alkyl group or a C( 12-20) alkenyl group that is substituted with a carboxylic acid or ester group.
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a CQ4-18) alkyl group, or a CQ4-18) alkenyl group.
- R 3 is a CQ4-18) alkyl group, or a C(14-18) alkenyl group that is substituted with a carboxylic acid or ester group.
- Examples of an ionizable compound include the following compound B8:
- Examples of an ionizable compound include the following compound B9:
- Examples of an ionizable compound include the following compound BA:
- Examples of an ionizable compound include the following compound BB:
- examples of an ionizable compound include compounds having the structure shown in Formula III Formula III
- n and m are each independently from 1 to 2; and R 4 and R 5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- R 3 is selected from alkyl, hydroxyalkyl, alkoxyalkoxy, and carboxyalkyl;
- R 6 is selected from R 7 2 , N + HR 7 2 and N + R 7 3 ;
- R 7 is selected from H, alkyl, hydroxyalkyl, and aminoalkyl.
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a CQ4-18) alkyl group, or a CQ4-18) alkenyl group.
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a C(16-18) alkyl group, or a C(16-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- Examples of an ionizable compound include the following compound BC:
- Examples of an ionizable compound include the following compound BD:
- Examples of an ionizable compound include the following compound BE :
- each of the alkenyl groups can have from one to two double bonds.
- Examples of an ionizable compound include compounds having the structure shown in Formula IV
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- R 3 is selected from 1-azetidines, 1 -pyrrolidines, 1-piperidines, 4-morpholines, and 1 4-piperazines wherein the rings can be substituted at any carbon atom position,
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl;
- each R 8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R 8 may form a ring;
- q is from zero to four;
- Q is O or R 7 ;
- p is from 1 to 4.
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a CQ4-18) alkyl group, or a CQ4-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- R 4 and R 5 are independently for each occurrence a C(16-18) alkyl group, or a C(16-18) alkenyl group.
- p is 1, 2, 3 or 4.
- q is 0, 1, 2, 3 or 4.
- Examples of an ionizable compound include compounds having the structure shown in Formula IV Formula IV
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- R J is selected from
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl
- each R 8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R 8 may form a ring;
- q is from zero to four;
- p is from 1 to 4.
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a CQ4-18) alkyl group, or a CQ4-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- R 4 and R 5 are independently for each occurrence a C(16-18) alkyl group, or a C(16-18) alkenyl group.
- p is 1, 2, 3 or 4.
- q is 0, 1, 2, 3 or 4.
- Examples of an ionizable compound include compounds having the structure shown in Formula IV
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- R 3 is selected from
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a CQ4-18) alkyl group, or a CQ4-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- Examples of an ionizable compound include compounds having the structure shown in Formula IV
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- R 3 is selected from
- each R 6 is independently selected from H, hydroxyl, hydroxyalkyl, aminoalkyl;
- each R 7 is independently selected from H, alkyl
- p is from 1 to 4.
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a CQ4-18) alkyl group, or a CQ4-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- Examples of an ionizable compound include the following compound BF:
- Examples of an ionizable compound include the following compound CI :
- Examples of an ionizable compound include the following compound C3 :
- Examples of an ionizable compound include the following compound C4:
- Examples of an ionizable compound include the following compound C5:
- Examples of an ionizable compound include the following compound C6:
- Examples of an ionizable compound include the following compound C7:
- Examples of an ionizable compound include the following compound C8:
- Examples of an ionizable compound include the following compound C9:
- Examples of an ionizable compound include the following compound CA:
- Examples of an ionizable compound include the following compound CB:
- Examples of an ionizable compound include the following compound CC:
- Examples of an ionizable compound include the following compound CD:
- Examples of an ionizable compound include the following compound CE:
- Examples of an ionizable compound include the following compound Dl :
- Examples of an ionizable compound include the following compound D2:
- ionizable compound include the following compound D3 :
- Examples of an ionizable compound include the following compound D4:
- n ionizable compound include the following compound D5:
- Examples of an ionizable compound include the following compound D6: 00212] Examples of an ionizable compound include the following compound D7:
- Examples of an ionizable compound include compounds having the structure shown in Formula IV-B
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- Z is S or O
- R 3 is selected from
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxy alkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl;
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a CQ4-18) alkyl group, or a CQ4-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- R 4 and R 5 are independently for each occurrence a C(16-18) alkyl group, or a C(16-18) alkenyl group.
- p is 1, 2, 3 or 4.
- Examples of an ionizable compound include the following compound D8:
- Examples of an ionizable compound include the following compound D9:
- Examples of an ionizable compound include the following compound DA: 00222] Examples of an ionizable compound include the following compound DB:
- Examples of an ionizable compound include the following compound DD:
- Examples of an ionizable compound include the following compound DE:
- Examples of an ionizable compound include the following compound DF:
- Examples of an ionizable compound include the following compound E4:
- Embodiments of this invention include compounds having the structure shown in Formula V Formula V
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- p is from 1 to 4.
- R 3 is selected from 1-azetidines, 1 -pyrrolidines, 1-piperidines, 4-morpholines, and 1 4-piperazines wherein the rings can be substituted at any carbon atom position,
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl
- each R 8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R 8 may form a ring;
- q is from zero to four;
- Q is O or R 7 .
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a C(14-18) alkyl group, or a C(14-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- R 4 and R 5 are independently for each occurrence a C(16-18) alkyl group, or a C(16-18) alkenyl group.
- p is 1, 2, 3 or 4.
- q is 0, 1, 2, 3 or 4.
- Embodiments of this invention include compounds having the stmcture
- R 4 and R 5 are independently for occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- p is from 1 to 4.
- R 3 is selected from
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl;
- Q is O or R 7 .
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a C(14-18) alkyl group, or a C(14-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- Examples of an ionizable compound include the following compound E5:
- Examples of an ionizable compound include the following compound E7:
- Examples of an ionizable compound include the following compound E8:
- Examples of an ionizable compound include the following compound E9:
- Examples of an ionizable compound include the following compound EA:
- Examples of an ionizable compound include the following compound EB:
- Examples of an ionizable compound include the following compound EC:
- Examples of an ionizable compound include the following compound ED:
- Examples of an ionizable compound include the following compound EE:
- Examples of an ionizable compound include the following compound EF:
- Examples of an ionizable compound include the following compound Fl :
- Examples of an ionizable compound include the following compound F2:
- Examples of an ionizable compound include compounds having the structure shown in Formula VI
- R 2 and R 4 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- R 3 is selected from aminoalkyl, quaternary aminoalkyl.
- each of the alkenyl groups can have from one to two double bonds.
- R 2 and R 4 are independently for each occurrence a C(14-18) alkyl group, or a C(14-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- Examples of an ionizable compound include the following compound F5:
- Examples of an ionizable compound include the following compound F6:
- Examples of an ionizable compound include the following compound F7:
- Examples of an ionizable compound include the following compound F8:
- Examples of an ionizable compound include the following compound F9:
- Examples of an ionizable compound include compounds having the structure shown in Formula VII
- n and m are each independently from 1 to 2; and R 4 and R 5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- R 3 is selected from H, alkyl, aminoalkyl, quaternary aminoalkyl, hydroxyalkyl, alkoxyalkyl, alkoxyalkoxy alkyl.
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a CQ4-18) alkyl group, or a CQ4-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- Examples of an ionizable compound include the following compound FA:
- Examples of an ionizable compound include the following compound FB:
- Examples of an ionizable compound include the following compound FC:
- each of the alkenyl groups can have from one to two double bonds.
- a compound can have the structure shown in
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- R' is selected from
- R 10 is selected from 1-azetidines, 1 -pyrrolidines, 1 -piped dines, 4-morpholines, and 1 4-piperazines wherein the rings can be substituted at any carbon atom position,
- R 9 is selected from
- alkyl hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl;
- each R 8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R 8 may form a ring;
- q is from zero to four;
- p is from 1 to 4.
- Q is O or R 7 .
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a CQ4-18) alkyl group, or a CQ4-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- R 4 and R 5 are independently for each occurrence a C(16-18) alkyl group, or a C(16-18) alkenyl group.
- p is 1, 2, 3 or 4.
- q is 0, 1, 2, 3 or 4.
- a compound in certain embodiments, can have the structure shown in
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- R is selected from
- R 9 is selected from
- alkyl hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl
- each R 8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R 8 may form a ring;
- p is from 1 to 4.
- q is from zero to four;
- Q is O or R 7 .
- a compound can have the structure shown in Formula VIII
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- R 3 is selected from
- R 10 is selected from
- R 9 is selected from
- alkyl hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl
- each R 8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R 8 may form a ring;
- p is from 1 to 4.
- q is from zero to four;
- Q is O or R 7 .
- a compound can have the structure shown in Formula VIII
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group; wherein R is selected from
- R is selected from
- R 9 is selected from
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxy alkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl
- Q is O or R 7 .
- a compound can have the structure shown in Formula VIII
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- R 3 is selected from
- R 10 is selected from
- R 9 is selected from
- alkyl hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl
- Q is O or R 7 .
- Examples of an ionizable compound include the following compound FD:
- Examples of an ionizable compound include the following compound FE:
- Examples of an ionizable compound include the following compound FF:
- Examples of an ionizable compound include the following compound Al l :
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound A14:
- Examples of an ionizable compound include the following compound A15:
- Examples of an ionizable compound include the following compound A16: [00295] Examples of an ionizable compound include the following compound A18:
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound A20:
- Examples of an ionizable compound include the following compound A21 : [00299] Examples of an ionizable compound include the following compound A22:
- Examples of an ionizable compound include the following compound A23 :
- Examples of an ionizable compound include the following compound A24:
- Examples of an ionizable compound include the following compound A25:
- each of the alkenyl groups can have from one to two double bonds.
- a compound can have the structure shown in Formula VIII-B
- n and m are each independently from 1 to 2;
- R 4 and R 5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- Z is N, O;
- R 3 is selected from
- alk l hydroxyalkyl, alkoxy, alkox alkoxy, aminoalkyl; independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl;
- p is from 1 to 4.
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a CQ4-18) alkyl group, or a CQ4-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- Examples of an ionizable compound include the following compound Bl l :
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound B14:
- a compound can have the stmcture shown in Formula IX
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- p is from 1 to 4.
- R 3 is selected from 1-azetidines, 1 -pyrrolidines, 1-piperidines, 4-morpholines, and 1 4-piperazines wherein the rings can be substituted at any carbon atom position,
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl;
- each R 8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R 8 may form a ring;
- q is from zero to four;
- Q is O or R 7 .
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a CQ4-18) alkyl group, or a CQ4-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- R 4 and R 5 are independently for each occurrence a C(16-18) alkyl group, or a C(16-18) alkenyl group.
- p is 1, 2, 3 or 4.
- q is 0, 1, 2, 3 or 4.
- a compound can have the structure shown in Formula IX
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- p is from 1 to 4.
- R 3 is selected from
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl
- each R 8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R 8 may form a ring;
- q is from zero to four.
- R 4 and R 5 are independently for each occurrence a CQ4-18) alkyl group, or a CQ4-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- a compound can have the structure shown in Formula IX
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- p is from 1 to 4.
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl
- each R 8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R 8 may form a ring;
- q is from zero to four.
- R 4 and R 5 are independently for each occurrence a CQ4-18) alkyl group, or a CQ4-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- Examples of an ionizable compound include the following compound Cl l :
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound C20:
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound C25:
- a compound can have the structure shown in Formula X Formula X
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- R 3 is selected from
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a C(14-18) alkyl group, or a CQ4-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- Examples of an ionizable compound include the following compound Dl l :
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound D14:
- Embodiments of this invention include compounds having the structure shown in Formula XI Formula XI
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- Z is O or H
- p is from 1 to 4.
- R 3 is selected from 1-azetidines, 1 -pyrrolidines, 1-piperidines, 4-morpholines, and 1 4-piperazines wherein the rings can be substituted at any carbon atom position,
- n also be selected from amino and aminoalkyl groups which can be substituted
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl;
- each R 8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R 8 may form a ring;
- q is from zero to four;
- Q is O or R 7 .
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a CQ4-18) alkyl group, or a C(14-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- R 4 and R 5 are independently for each occurrence a C(16-18) alkyl group, or a C(16-18) alkenyl group.
- p is 1, 2, 3 or 4.
- q is 0, 1, 2, 3 or 4.
- Embodiments of this invention include compounds having the stmcture
- R 4 and R 5 are independently for each occurrence a C( 12-20) alkyl group, or a C( 12-20) alkenyl group;
- Z is O or H
- p is from 1 to 4.
- R 3 is selected from
- each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxy alkoxy, aminoalkyl;
- each R 7 is independently selected from H, alkyl
- each R 8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R 8 may form a ring;
- each of the alkenyl groups can have from one to two double bonds.
- R 4 and R 5 are independently for each occurrence a C(14-18) alkyl group, or a C(14-18) alkenyl group.
- alkyl, hydroxyalkyl, and aminoalkyl refer to C(l-6)alkyl, hydroxyl[C(l-6)alkyl], and amino[C(l-6)alkyl].
- Examples of an ionizable compound include the following compound El l :
- Examples of an ionizable compound include the following compound E12:
- Examples of an ionizable compound include the following compound E13 :
- Examples of an ionizable compound include the following compound E14:
- Examples of an ionizable compound include the following compound E15 :
- Examples of an ionizable compound include the following compound E16:
- Examples of an ionizable compound include the following compound E17:
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound E22:
- Examples of an ionizable compound include the following compound E23 :
- Examples of an ionizable compound include the following compound E24
- Examples of an ionizable compound include the following compound E25
- Examples of an ionizable compound include the following compound E26: Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound E37
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of an ionizable compound include the following compound
- Examples of structural lipids include cholesterols, sterols, and steroids.
- Examples of structural lipids include cholanes, cholestanes, ergostanes, campestanes, poriferastanes, stigmastanes, gorgostanes, lanostanes, gonanes, estranes, androstanes, pregnanes, and cycloartanes.
- Examples of structural lipids include sterols and zoosterols such as cholesterol, lanosterol, zymosterol, zymostenol, desmosterol, stigmastanol,
- Examples of structural lipids include pegylated cholesterols, and cholestane 3-oxo-(Cl-22)acyl compounds, for example, cholesteryl acetate, cholesteryl arachidonate, cholesteryl butyrate, cholesteryl hexanoate, cholesteryl myristate, cholesteryl palmitate, cholesteryl behenate, cholesteryl stearate, cholesteryl caprylate, cholesteryl n-decanoate, cholesteryl dodecanoate, cholesteryl nervonate, cholesteryl pelargonate, cholesteryl n-valerate, cholesteryl oleate, cholesteryl elaidate, cholesteryl erucate, cholesteryl heptanoate, cholesteryl linolelaidate, and cholesteryl linoleate.
- cholesteryl acetate cholesteryl arachidonate, cholesteryl but
- Examples of structural lipids include sterols such as phytosterols, beta- sitosterol, campesterol, ergosterol, brassicasterol, delta-7-stigmasterol, and delta-7- avenasterol.
- sterols such as phytosterols, beta- sitosterol, campesterol, ergosterol, brassicasterol, delta-7-stigmasterol, and delta-7- avenasterol.
- Stabilizer lipids such as phytosterols, beta- sitosterol, campesterol, ergosterol, brassicasterol, delta-7-stigmasterol, and delta-7- avenasterol.
- Examples of stabilizer lipids include zwitterionic lipids.
- stabilizer lipids include compounds such as phospholipids.
- Examples of phospholipids include phosphatidylcholine,
- phosphatidylethanolamine phosphatidylserine, phosphatidylinositol, phosphatidic acid, palmitoyloleoyl phosphatidylcholine, lysophosphatidylcholine,
- stabilizer lipids include phosphatidyl ethanolamine compounds and phosphatidyl choline compounds.
- stabilizer lipids include l,2-dioleoyl-s «-Glycero-3- Phosphocholine (DOPC).
- stabilizer lipids include diphytanoyl phosphatidyl ethanolamine (DPhPE) and l,2-Diphytanoyl-s «-Glycero-3-Phosphocholine (DPhPC).
- DPhPE diphytanoyl phosphatidyl ethanolamine
- DPhPC l,2-Diphytanoyl-s «-Glycero-3-Phosphocholine
- stabilizer lipids include l,2-distearoyl-sn-glycero-3- phosphocholine (DSPC), l,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2- dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), and l,2-dioleoyl-sn-glycero-3- phosphoethanolamine (DOPE).
- Examples of stabilizer lipids include 1,2-dilauroyl-sn-glycerol (DLG); 1,2-dimyristoyl-sn-glycerol (DMG); 1,2-dipalmitoyl-sn-glycerol (DPG); 1,2-distearoyl- sn-glycerol (DSG); l,2-diarachidoyl-sn-glycero-3-phosphocholine (DAPC);
- DMG 1,2-dimyristoyl-sn-glycerol
- DPG 1,2-dipalmitoyl-sn-glycerol
- DSG 1,2-distearoyl- sn-glycerol
- DAPC l,2-diarachidoyl-sn-glycero-3-phosphocholine
- DPePC l,2-dilauroyl-sn-glycero-3-phosphoethanolamine
- DLPE 1,2-dimyristoyl-sn- glycero-3-phosphoethanolamine
- DMPE 1,2-dimyristoyl-sn- glycero-3-phosphoethanolamine
- DSPE l,2-distearoyl-sn-glycero-3- phosphoethanolamine
- POPC palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine
- P-Lyso-PC l-palmitoyl-2-lyso-sn-glycero- 3-phosphocholine
- S- Lyso-PC l-Stearoyl-2-lyso-sn-glycero-3-phosphocholine
- Examples of lipids for reducing immunogenicity include polymeric compounds and polymer-lipid conjugates.
- Examples of lipids for reducing immunogenicity include pegylated lipids having polyethyleneglycol (PEG) regions.
- PEG regions can be of any molecular mass.
- a PEG region can have a molecular mass of 200, 300, 350, 400, 500, 550, 750, 1000, 1500, 2000, 3000, 3500, 4000 or 5000 Da.
- Examples of lipids for reducing immunogenicity include compounds having a methoxypolyethyleneglycol region.
- Examples of lipids for reducing immunogenicity include compounds having a carbonyl-methoxypolyethyleneglycol region.
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Abstract
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Priority Applications (9)
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RU2018102536A RU2776478C2 (en) | 2015-06-24 | 2016-06-23 | Ionized compounds and compositions and their use |
EP20163284.1A EP3686184A3 (en) | 2015-06-24 | 2016-06-23 | Ionizable compounds and compositions and uses thereof |
CA2990668A CA2990668A1 (en) | 2015-06-24 | 2016-06-23 | Ionizable compounds and compositions and uses therefof |
ES16815348T ES2828717T3 (en) | 2015-06-24 | 2016-06-23 | Ionizable Compounds and Compositions and Uses Thereof |
EP16815348.4A EP3313449B1 (en) | 2015-06-24 | 2016-06-23 | Ionizable compounds and compositions and uses thereof |
KR1020187002177A KR102659774B1 (en) | 2015-06-24 | 2016-06-23 | Ionizable compounds and compositions and uses thereof |
CN201680037092.8A CN107708739A (en) | 2015-06-24 | 2016-06-23 | Ionizable compound, composition and their purposes |
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KR102659774B1 (en) | 2024-04-23 |
RU2018102536A3 (en) | 2019-11-08 |
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EP3686184A2 (en) | 2020-07-29 |
CN107708739A (en) | 2018-02-16 |
RU2018102536A (en) | 2019-07-24 |
US20190127318A1 (en) | 2019-05-02 |
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ES2828717T3 (en) | 2021-05-27 |
US20220242820A1 (en) | 2022-08-04 |
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JP6480025B2 (en) | 2019-03-06 |
AU2016281685A1 (en) | 2018-01-18 |
JP2018524330A (en) | 2018-08-30 |
CA2990668A1 (en) | 2016-12-29 |
EP3313449B1 (en) | 2020-09-23 |
EP3313449A1 (en) | 2018-05-02 |
EP3686184A3 (en) | 2020-08-26 |
US20160376229A1 (en) | 2016-12-29 |
TW201713614A (en) | 2017-04-16 |
US11384051B2 (en) | 2022-07-12 |
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AU2016281685B2 (en) | 2021-08-12 |
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