DK2268607T5 - Peptidnukleinsyrederivater med god cellepenetrering og krafig affinitet for nukleinsyre - Google Patents
Peptidnukleinsyrederivater med god cellepenetrering og krafig affinitet for nukleinsyre Download PDFInfo
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- DK2268607T5 DK2268607T5 DK09719041.7T DK09719041T DK2268607T5 DK 2268607 T5 DK2268607 T5 DK 2268607T5 DK 09719041 T DK09719041 T DK 09719041T DK 2268607 T5 DK2268607 T5 DK 2268607T5
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- 238000000034 method Methods 0.000 claims description 38
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- 150000002431 hydrogen Chemical class 0.000 claims description 35
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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 1
- GPTXCAZYUMDUMN-UHFFFAOYSA-N tert-butyl n-(2-hydroxyethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCO GPTXCAZYUMDUMN-UHFFFAOYSA-N 0.000 description 1
- XDJCYKMWJCYQJM-UHFFFAOYSA-N tert-butyl n-(3-hydroxypropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCO XDJCYKMWJCYQJM-UHFFFAOYSA-N 0.000 description 1
- QIKPEQVGXKJLEY-UHFFFAOYSA-N tert-butyl n-(3-prop-2-ynoxypropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCOCC#C QIKPEQVGXKJLEY-UHFFFAOYSA-N 0.000 description 1
- PDAFIZPRSXHMCO-ZCFIWIBFSA-N tert-butyl n-[(2r)-1-hydroxypropan-2-yl]carbamate Chemical compound OC[C@@H](C)NC(=O)OC(C)(C)C PDAFIZPRSXHMCO-ZCFIWIBFSA-N 0.000 description 1
- VULKFBHOEKTQSF-UHFFFAOYSA-N tert-butyl n-[2-(2-aminoethoxy)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCOCCN VULKFBHOEKTQSF-UHFFFAOYSA-N 0.000 description 1
- NROTZNAWFRRNIS-UHFFFAOYSA-N tert-butyl n-[2-[2-[(6-oxo-3,7-dihydropurin-2-yl)amino]ethoxy]ethyl]carbamate Chemical compound O=C1NC(NCCOCCNC(=O)OC(C)(C)C)=NC2=C1N=CN2 NROTZNAWFRRNIS-UHFFFAOYSA-N 0.000 description 1
- LPHXDOGUEPNTJE-UHFFFAOYSA-N tert-butyl n-[3-(2-aminoethoxy)propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCOCCN LPHXDOGUEPNTJE-UHFFFAOYSA-N 0.000 description 1
- ISGDRUJSNRUSDS-UHFFFAOYSA-N tert-butyl n-[3-(prop-2-ynylamino)propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNCC#C ISGDRUJSNRUSDS-UHFFFAOYSA-N 0.000 description 1
- PSOHUKLWHXJGLR-UHFFFAOYSA-N tert-butyl n-[3-[(6-amino-7h-purin-2-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(N)=C2NC=NC2=N1 PSOHUKLWHXJGLR-UHFFFAOYSA-N 0.000 description 1
- IVPCGNMZUWWJMC-UHFFFAOYSA-N tert-butyl n-[3-[(6-oxo-3,7-dihydropurin-2-yl)amino]propyl]carbamate Chemical compound O=C1NC(NCCCNC(=O)OC(C)(C)C)=NC2=C1N=CN2 IVPCGNMZUWWJMC-UHFFFAOYSA-N 0.000 description 1
- USFPINLPPFWTJW-UHFFFAOYSA-N tetraphenylphosphonium Chemical compound C1=CC=CC=C1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 USFPINLPPFWTJW-UHFFFAOYSA-N 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108010062760 transportan Proteins 0.000 description 1
- PBKWZFANFUTEPS-CWUSWOHSSA-N transportan Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(N)=O)[C@@H](C)CC)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CN)[C@@H](C)O)C1=CC=C(O)C=C1 PBKWZFANFUTEPS-CWUSWOHSSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/16—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/001—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof by chemical synthesis
- C07K14/003—Peptide-nucleic acids (PNAs)
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Biophysics (AREA)
- Animal Behavior & Ethology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biotechnology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Virology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Claims (16)
1. Peptidnukleinsyrederivat med formlen I eller et farmaceutisk acceptabelt salt deraf:
Formel I hvor, n er et heltal lig med eller større end 5; SI, S2, .... Sn-1, Sn, TI, T2, ..., Tn-1 og Tn uafhængigt repræsenterer hydrogen, deuterium, substitueret eller ikke-substitueret alkyl, eller en substitueret eller ikke-substitueret arylradikal; X og Y uafhængigt repræsenterer hydrogen, deuterium, substitueret eller ikke-substitueret alkyl, substitueret eller ikke-substitueret acyl, substitueret eller ikke-substitueret sulfonyl, eller en substitueret eller ikke-substitueret arylradikal; Z repræsenterer hydroxy, substitueret eller ikke-substitueret alkyloxy, substitueret eller ikke-substitueret aryloxy, en substitueret eller ikke-substitueret aminoradikal; Bl, B2, ..., Bn-1, og Bn er uafhængigt udvalgt fra naturlige nukleobaser indbefattende adenin, thymin, guanin, cytosin og uracil, og unaturlige nukleobaser; og mindst én af Bl, B2, ..., Bn-1 og Bn er uafhængigt udvalgt fra unaturlige nukleobaser repræsenteret ved formel II, formel III eller formel IV:
Formel II Formel III Formel IV hvor, RI, R2, R3, R4, R5 og R6 er uafhængigt udvalgt fra substitueret eller ikke-substitueret alkyl og en hydrogenradikal; og LI, L2 og L3 er en ko valent linker repræsenteret ved formel V, der forbinder en basisk aminogruppe med delen, der er ansvarlig for nukleobaseparringsegenskabeme:
Formel V hvor, Q1 og Qm er en substitueret eller ikke-substitueret methylen- (-CH2-) radikal, og Qm er direkte bundet til den basiske aminogruppe; Q2, Q3,..., og Om-1 er uafhængigt udvalgt fra substitueret eller ikke-substitueret methylen, oxygen (-O-), svovl (-S-), og en substitueret eller ikke-substitueret aminoradikal [-N(H)-, eller -N(substituent)-]; og m er et heltal fra 2 til 15.
2. Peptidnukleinsyrederivat ifølge krav 1 eller et farmaceutisk acceptabelt salt deraf: hvor, n er et heltal fra 5 til 30; SI, S2, ..., Sn-1, Sn, TI, T2, ..., Tn-1, og Tn er en hydrogenradikal; X og Y er uafhængigt udvalgt fra hydrogen, substitueret eller ikke-substitueret alkyl, substitueret eller ikke-substitueret acyl, en substitueret eller ikke-substitueret sulfonylradikal; Z repræsenterer hydroxy, substitueret eller ikke-substitueret alkyloxy, substitueret eller ikke-substitueret aryloxy, en substitueret eller ikke-substitueret aminoradikal; Bl, B2, ..., Bn-1 og Bn er uafhængigt udvalgt fra naturlige nukleobaser indbefattende adenin, thymin, guanin, cytosin og uracil, og unaturlige nukleobaser; og mindst én af Bl, B2,..., Bn-1 og Bn er uafhængigt udvalgt fra unaturlige nukleobaser repræsenteret ved formel II, formel III eller formel IV.
3. Peptidnukleinsyrederivat ifølge krav 1 eller et farmaceutisk acceptabelt salt deraf: hvor, n er et heltal fra 8 til 25; SI, S2,..., Sn-1, Sn, TI, T2,.... Tn-1, og Tn er en hydrogenradikal; X og Y er uafhængigt udvalgt fra hydrogen, substitueret eller ikke-substitueret alkyl, en substitueret eller ikke-substitueret acylradikal; Z repræsenterer hydroxy, eller en substitueret eller ikke-substitueret aminoradikal; Bl, B2, ..., Bn-1, og Bn er uafhængigt udvalgt fra naturlige nukleobaser indbefattende adenin, thymin, guanin, cytosin og uracil, og unaturlige nukleobaser; mindst to af Bl, B2,..., Bn-1, og Bn er uafhængigt udvalgt fra unaturlige nukleobaser repræsenteret ved formel II, formel III eller formel IV; RI, R2, R3, R4, R5 og R6 er uafhængigt udvalgt fra substitueret eller ikke-substitueret alkyl og en hydrogenradikal; Q1 og Qm er en substitueret eller ikke-substitueret methylenradikal, og Qm er direkte bundet til den basiske aminogruppe; Q2, Q3,og Qm-1 er uafhængigt udvalgt fra substitueret eller ikke-substitueret methylen, oxygen og en aminoradikal; og m er et heltal fra 2 til 12.
4. Peptidnukleinsyrederivat ifølge krav 1 eller et farmaceutisk acceptabelt salt deraf: hvor, n er et heltal fra 10 til 25; SI, S2, ..., Sn-1, Sn, TI, T2, ..., Tn-1, og Tn er en hydrogenradikal; X og Y er uafhængigt udvalgt fra hydrogen, og en substitueret eller ikke-substitueret acylradikal; Z repræsenterer hydroxy, eller en substitueret eller ikke-substitueret aminoradikal; Bl, B2, ..., Bn-1 og Bn er uafhængigt udvalgt fra naturlige nukleobaser indbefattende adenin, thymin, guanin, cytosin og uracil, og unaturlige nukleobaser; mindst tre af Bl, B2, ..., Bn-1, og Bn er uafhængigt udvalgt fra unaturlige nukleobaser repræsenteret ved formel II, formel III eller formel IV; RI, R2, R3, R4, R5 og R6 er uafhængigt udvalgt fra substitueret eller ikke-substitueret alkyl og en hydrogenradikal; Q1 og Qm er en methylenradikal, og Qm er direkte bundet til den basiske aminogruppe; Q2, Q3, ..., og Qm-1 er uafhængigt udvalgt fra methylen, oxygen og en aminoradikal; og m er et heltal fra 2 til 10.
5. Peptidnukleinsyrederivat ifølge krav 1 eller et farmaceutisk acceptabelt salt deraf: hvor, n er et heltal fra 10 til 20; SI, S2, ..., Sn-1, Sn, TI, T2, ..., Tn-1 og Tn er en hydrogenradikal; X og Y er uafhængigt udvalgt fra hydrogen og en substitueret eller ikke-substitueret acylradikal; Z repræsenterer hydroxy eller en substitueret eller ikke-substitueret aminoradikal; Bl, B2, ..., Bn-1, og Bn er uafhængigt udvalgt fra naturlige nukleobaser indbefattende adenin, thymin, guanin, cytosin og uracil, og unaturlige nukleobaser; mindst tre af Bl, B2, ..., Bn-1, og Bn er uafhængigt udvalgt fra unaturlige nukleobaser repræsenteret ved formel II, formel III eller formel IV; RI, R3, og R5 er en hydrogenradikal, og R2, R4 og R6 er uafhængigt repræsenterer hydrogen, eller substitueret eller ikke-substitueret amindinradikal; Q1 og Qm er en methylenradikal, og Qm er direkte bundet til den basiske aminogruppe; Q2, Q3, ..., og Qm-1 er uafhængigt udvalgt fra methylen, oxygen og en aminoradikal; og m er et heltal fra 2 til 10.
6. Peptidnukleinsyrederivat ifølge krav 1 eller et farmaceutisk acceptabelt salt deraf: hvor, n er et heltal fra 10 til 20; SI, S2, ..., Sn-1, Sn, TI, T2, ..., Tn-1, og Tn er en hydrogenradikal; X og Y er uafhængigt udvalgt fra hydrogen, og en substitueret eller ikke-substitueret acylradikal; Z repræsenterer hydroxy, eller en substitueret eller ikke-substitueret aminoradikal; Bl, B2, ..., bn-1, og Bn er uafhængigt udvalgt fra adenin, thymin, guanin, cytosin og uracil, og unaturlige nukleobaser; mindst tre af Bl, B2, ..., Bn-1, og Bn er uafhængigt udvalgt fra unaturlige nukleobaser repræsenteret ved formel II, formel III eller formel IV; RI, R3 og R5 er en hydrogenradikal, og R2, R4, og R6 uafhængigt repræsenterer hydrogen, eller amidinylradikal; Q1 og Qm er en methylenradikal, og Qm er direkte bundet til den basiske aminogruppe; Q2, Q3, ..., og Qm-1 er uafhængigt udvalgt fra methylen og en oxygenradikal; og m er et heltal fra 2 til 8.
7. Peptidnukleinsyrederivat ifølge krav 1 eller et farmaceutisk acceptabelt salt deraf: hvor, n er et heltal fra 8 til 20; SI, S2, ..., Sn-1, Sn, TI, T2, Tn-1, og Tn er en hydrogenradikal; X er en hydrogenradikal; Y repræsenterer hydrogen, eller en substitueret eller ikke-substitueret acylradikal; Z repræsenterer hydroxy, eller en substitueret eller ikke-substitueret aminoradikal; Bl, B2, ..., Bn-1, og Bn er uafhængigt udvalgt fra adenin, thymin, guanin, cytosin og unaturlige nukleobaser; mindst tre af Bl, B2,..., Bn-1, og Bn er uafhængigt udvalgt fra unaturlige nukleobaser repræsenteret ved formel II, formel III eller formel IV; RI, R3, og R5 er en hydrogenradikal, og R2, R4, og R6 uafhængigt repræsenterer hydrogen eller amidinylradikal; LI repræsenterer -(CH2)2-0-(CH2)2-, -CH2-0-(CH2)2-, eller -CH2-0-(CH2)3- hvor den højre ende er direkte bundet til den basiske aminogruppe; og L2 og L3 er uafhængigt udvalgt fra -(CH2)2-0-(CH2)2-, -(CH2)3-0-(CH2)2-, - (CH2)2-0-(CH2)3-, -(CH2)2-, -(CH2)3-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2)7-, og - (CH2)8- hvor den højre ende er direkte bundet til den basiske aminogruppe.
8. Farmaceutisk sammensætning, der indeholder en terapeutisk effektiv mængde af peptidnukleinsyrederivat ifølge et hvilket som helst af kravene 1 ~D7 eller et farmaceutisk acceptabelt salt deraf til et terapeutisk formål.
9. Fremgangsmåde til anvendelse af peptidnukleinsyrederivat ifølge et hvilket som helst af kravene 1 ~ □ 7 eller et salt deraf til et diagnostisk formål.
10. Fremgangsmåde til anvendelse af peptidnukleinsyrederivat ifølge et hvilket som helst af kravene 1 ~ □ 7 eller et salt deraf til in vitro modulering af cellulært proteinekspression.
11. Forbindelse med formlen VI:
Formel VI hvor, R7 er hydrogen, N-succinyl, eller en substitueret eller ikke-substitueret alkylradikal; PI er udvalgt fra hydrogen, t-butoxycarbonyl, (9H-fluoren-9-yl)methoxy-carbonyl, substitueret eller ikke-substitueret benzyloxycarbonyl, og en substitueret eller ikke-substitueret arylsulfonylradikal; P2 er udvalgt fra hydrogen, t-butoxycarbonyl, (9H-fluoren-9-yl)methoxy-carbonyl, substitueret eller ikke-substitueret benzyloxycarbonyl, substitueret alkyloxycarbonyl, substitueret eller ikke-substitueret alkyl, amidinyl, l,3-bis(t-butoxycarbonyl) amidinyl, l,3-bis-(benzyloxycarbonyl)amidinylradikal; og LI er en linker repræsenteret ved formel V:
Formel V hvor, Q1 og Qm er en substitueret eller ikke-substitueret methylenradikal, og Qm er direkte bundet til aminoradikalen; Q2, Q3,..., og Qm-1 er uafhængigt udvalgt fra substitueret eller ikke-substitueret methylen, oxygen, svovl og en substitueret eller ikke-substitueret aminoradikal; og m er et heltal fra 2 til 15.
12. Forbindelse med formlen VII:
Formel VII hvor, R8 er hydrogen, N-succinyl, eller en substitueret eller ikke-substitueret alkylradikal; PI er udvalgt fra hydrogen, t-butoxycarbonyl, (9H-fluoren-9-yl)methoxy-carbonyl, substitueret eller ikke-substitueret benzyloxycarbonyl, og en substitueret eller ikke-substitueret arylsulfonylradikal; P2 er udvalgt fra hydrogen, t-butoxycarbonyl, (9H-fluoren-9-yl)methoxy-carbonyl, substitueret eller ikke-substitueret benzyloxycarbonyl, substitueret alkyloxycarbonyl, substitueret eller ikke-substitueret alkyl, amidinyl, l,3-bis(t-butoxycarbonyl) amidinyl, l,3-bis-(benzyl-oxycarbonyl)amidinylradikal; P3 er udvalgt fra hydrogen, t-butoxycarbonyl, (9H-fluoren-9-yl)methoxy-carbonyl, en substitueret eller ikke-substitueret benzyloxycarbonylradikal; P4 er udvalgt fra hydrogen, og en t-butoxycarbonylradikal; og L2 er en linker repræsenteret ved formel V:
Formel V hvor, Q1 og Qm er en substitueret eller ikke-substitueret methylenradikal, og Qm er direkte bundet til aminoradikalen; Q2, Q3,..., og Qm-1 er uafhængigt udvalgt fra substitueret eller ikke-substitueret methylen, oxygen, svovl og en substitueret eller ikke-substitueret aminoradikal; og m er et heltal fra 2 til 15.
13. Forbindelse med formlen VIII:
Formel VIII hvor, R9 er hydrogen, N-succinyl, eller en substitueret eller ikke-substitueret alkylradikal; PI er udvalgt fra hydrogen, t-butoxycarbonyl, (9H-fluoren-9-yl)methoxy-carbonyl, substitueret eller ikke-substitueret benzyloxycarbonyl, og en substitueret eller ikke-substitueret arylsulfonylradikal; P2 er udvalgt fra hydrogen, t-butoxycarbonyl, (9H-fluoren-9-yl)methoxy-carbonyl, substitueret eller ikke-substitueret benzyloxycarbonyl, substitueret alkyloxycarbonyl, substitueret eller ikke-substitueret alkyl, amidinyl, l,3-bis(t-butoxycarbonyl) amidinyl, l,3-bis-(benzyl-oxycarbonyl)amidinylradikal; og L3 er en linker repræsenteret ved formel V:
Formel V hvor, Q1 og Qm er en substitueret eller ikke-substitueret methylenradikal, og Qm er direkte bundet til aminoradikalen; Q2, Q3,..., og Qm-1 er uafhængigt udvalgt fra substitueret eller ikke-substitueret methylen, oxygen, svovl og en substitueret eller ikke-substitueret aminoradikal; og m er et heltal fra 2 til 15.
14. Forbindelse med formlen IX:
Formel IX hvor, RIO er hydroxy, substitueret eller ikke-substitueret alkyloxy, eller en substitueret eller ikke-substitueret aminoradikal; P2 er udvalgt fra hydrogen, t-butoxycarbonyl, (9H-fluoren-9-yl)methoxy-carbonyl, substitueret eller ikke-substitueret benzyloxycarbonyl, substitueret alkyloxycarbonyl, substitueret eller ikke-substitueret alkyl, amidinyl, l,3-bis(t-butoxycarbonyl) amidinyl, l,3-bis-(benzyloxycarbonyl)amidinylradikal; og LI er en linker repræsenteret ved formel V:
Formel V hvor, Q1 og Qm er en substitueret eller ikke-substitueret methylenradikal, og Qm er direkte bundet til aminoradikalen; Q2, Q3,..., og Qm-1 er uafhængigt udvalgt fra substitueret eller ikke-substitueret methylen, oxygen, svovl og en substitueret eller ikke-substitueret aminoradikal; og m er et heltal fra 2 til 15.
15. Forbindelse med formlen X:
Formel X hvor, RI 1 er hydroxy, substitueret eller ikke-substitueret alkyloxy, eller en substitueret eller ikke-substitueret aminoradikal; P2 er udvalgt fra hydrogen, t-butoxycarbonyl, (9H-fluoren-9-yl)methoxy-carbonyl, substitueret eller ikke-substitueret benzyloxycarbonyl, substitueret alkyloxycarbonyl, substitueret eller ikke-substitueret alkyl, amidinyl, l,3-bis(t-butoxycarbonyl) amidinyl, l,3-bis-(benzyl-oxycarbonyl)amidinylradikal; P3 er udvalgt fra hydrogen, t-butoxycarbonyl, (9H-fluoren-9-yl)methoxy-carbonyl, en substitueret eller ikke-substitueret benzyloxycarbonylradikal; P4 er udvalgt fra hydrogen, og en t-butoxycarbonylradikal; og L2 er en linker repræsenteret ved formel V:
Formel V hvor, Q1 og Qm er en substitueret eller ikke-substitueret methylenradikal, og Qm er direkte bundet til aminoradikalen; Q2, Q3 og Qm-1 er uafhængigt udvalgt fra substitueret eller ikke-substitueret methylen, oxygen, svovl og en substitueret eller ikke-substitueret aminoradikal; og m er et heltal fra 2 til 15.
16. Forbindelse med formlen XI:
Formel XI hvor, RI 2 er hydroxy, substitueret eller ikke-substitueret alkyloxy, eller en substitueret eller ikke-substitueret aminoradikal; P2 er udvalgt fra hydrogen, t-butoxycarbonyl, (9H-fluoren-9-yl)methoxy-carbonyl, substitueret eller ikke-substitueret benzyloxycarbonyl, substitueret alkyloxycarbonyl, substitueret eller ikke-substitueret alkyl, amidinyl, l,3-bis(t-butoxycarbonyl) amidinyl, l,3-bis-(benzyl-oxycarbonyl)amidinylradikal; og L3 er en linker repræsenteret ved formel V:
Formel V hvor, Q1 og Qm er en substitueret eller ikke-substitueret methylenradikal, og Qm er direkte bundet til aminoradikalen; Q2, Q3,..., og Qm-1 er uafhængigt udvalgt fra substitueret eller ikke-substitueret methylen, oxygen, svovl og en substitueret eller ikke-substitueret aminoradikal; og m er et heltal fra 2 til 15.
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| PH12012500732A1 (en) * | 2009-10-16 | 2020-10-19 | Melinta Therapeutics Inc | Antimicrobial compounds and methods of making and using the same |
| BR112012008759A2 (pt) | 2009-10-16 | 2020-08-25 | Rib-X Pharmaceuticals, Inc. | compostos antimicrobianos e métodos de fabricação e uso dos mesmos |
| ES2675798T3 (es) * | 2009-10-16 | 2018-07-12 | Melinta Therapeutics, Inc. | Compuestos antimicrobianos y métodos para fabricar y usar los mismos |
| MX339000B (es) | 2009-10-16 | 2016-05-09 | Melinta Therapeutics Inc | Compuestos antimicrobianos y metodos para fabricar y utilizar los mismos. |
| CN103958514B (zh) | 2011-04-15 | 2018-07-03 | 梅琳塔治疗公司 | 抗微生物化合物及制备和使用所述化合物的方法 |
| CN103031337A (zh) * | 2012-09-28 | 2013-04-10 | 北京吉利奥生物科技发展有限公司 | 一种小核酸分子快递技术 |
| WO2015035421A1 (en) | 2013-09-09 | 2015-03-12 | Melinta Therapeutics, Inc. | Antimicrobial compounds and methods of making and using the same |
| EP3039025A4 (en) | 2013-09-09 | 2017-05-31 | Melinta Therapeutics, Inc. | Antimicrobial compounds and methods of making and using the same |
| JP2018507881A (ja) | 2015-03-11 | 2018-03-22 | メリンタ セラピューティクス，インコーポレイテッド | 抗微生物化合物ならびにこれらを作製および使用する方法 |
| EP3365375A4 (en) * | 2015-10-20 | 2019-09-04 | Sorrento Therapeutics, Inc. | INTRACELLULAR ADMINISTRATION COMPOUNDS |
| JP2019515041A (ja) | 2016-05-06 | 2019-06-06 | メリンタ セラピューティクス、 インコーポレイテッドＭｅｌｉｎｔａ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． | 抗菌剤ならびにそれを作製および使用する方法 |
| SG11201900153XA (en) * | 2016-08-08 | 2019-02-27 | Olipass Corp | Androgen receptor antisense oligonucleotides |
| CN109996807B (zh) * | 2016-09-16 | 2023-07-28 | 奥利通公司 | Scn9a反义寡核苷酸 |
| RU2753517C2 (ru) * | 2016-10-11 | 2021-08-17 | Олипасс Корпорейшн | Антисмысловые олигонуклеотиды к hif-1-альфа |
| JP7060216B2 (ja) | 2016-11-16 | 2022-04-26 | アカデミシュ ジーケンハウス ライデン ハー．オー．デー．エン． ルムク | 多様な選択された臓器又は組織をターゲティングするための物質 |
| WO2018122610A1 (en) * | 2016-12-30 | 2018-07-05 | Olipass Corporation | Exon skipping by peptide nucleic acid derivatives |
| KR102483119B1 (ko) * | 2017-01-06 | 2023-01-02 | 올리패스 주식회사 | Snap25 안티센스 올리고뉴클레오타이드 |
| BR112019014689A2 (pt) | 2017-01-24 | 2020-02-18 | Olipass Corporation | Inibidor da dor antissenso de scn9a |
| KR20190011181A (ko) * | 2017-07-24 | 2019-02-01 | 올리패스 주식회사 | 티로시나아제 안티센스 올리고뉴클레오티드 |
| WO2019022434A1 (en) * | 2017-07-24 | 2019-01-31 | Olipass Corporation | ANTISENSE OLIGONUCLEOTIDES OF TYROSINASE |
| TWI832851B (zh) * | 2018-05-18 | 2024-02-21 | 韓商奧利通公司 | 基質金屬蛋白酶-1之反義寡核苷酸 |
| KR102304280B1 (ko) | 2018-08-14 | 2021-09-23 | 올리패스 주식회사 | 아세틸코에이카복실라제2 안티센스 올리고뉴클레오티드 |
| EP3999523A4 (en) * | 2019-07-18 | 2023-08-16 | Olipass Corporation | MELANOPHILIN ANTISENSE OLIGONUCLEOTIDES |
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| KR20240172540A (ko) * | 2023-06-01 | 2024-12-10 | 주식회사 기프티드엠에스 | 세포 투과가 가능한 펩타이드-핵산 올리고머를 유효성분으로 포함하는 코로나바이러스 감염 질환 예방 또는 치료용 약학적 조성물 |
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