CA3046357A1 - Methods of making substituted porphyrin pharmaceutical compounds and compositions - Google Patents
Methods of making substituted porphyrin pharmaceutical compounds and compositions Download PDFInfo
- Publication number
- CA3046357A1 CA3046357A1 CA3046357A CA3046357A CA3046357A1 CA 3046357 A1 CA3046357 A1 CA 3046357A1 CA 3046357 A CA3046357 A CA 3046357A CA 3046357 A CA3046357 A CA 3046357A CA 3046357 A1 CA3046357 A1 CA 3046357A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- formula
- composition
- pyridyl
- porphyrins
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 170
- 239000000203 mixture Substances 0.000 title claims abstract description 117
- 238000000034 method Methods 0.000 title claims abstract description 55
- 150000004032 porphyrins Chemical class 0.000 title abstract description 36
- -1 pyridyl porphyrins Chemical class 0.000 claims description 58
- 239000000243 solution Substances 0.000 claims description 53
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 51
- 150000001450 anions Chemical group 0.000 claims description 45
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 43
- 239000011259 mixed solution Substances 0.000 claims description 40
- 239000007788 liquid Substances 0.000 claims description 36
- 239000007864 aqueous solution Substances 0.000 claims description 29
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 24
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 22
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 22
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 20
- 239000011572 manganese Substances 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
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- LLLXGCKPGCZALY-UHFFFAOYSA-N 2-butoxyethyl 4-methylbenzenesulfonate Chemical compound CCCCOCCOS(=O)(=O)C1=CC=C(C)C=C1 LLLXGCKPGCZALY-UHFFFAOYSA-N 0.000 claims description 10
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 10
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- XTAZYLNFDRKIHJ-UHFFFAOYSA-N n,n-dioctyloctan-1-amine Chemical compound CCCCCCCCN(CCCCCCCC)CCCCCCCC XTAZYLNFDRKIHJ-UHFFFAOYSA-N 0.000 claims description 10
- 238000001914 filtration Methods 0.000 claims description 9
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- GVNNKCCHSQVNGZ-UHFFFAOYSA-N [Mn].N1C=2C=C(N=3)C=CC=3C=C(N3)C=CC3=CC(=N3)C=CC3=CC1=CC=2C1=CC=CC=N1 Chemical class [Mn].N1C=2C=C(N=3)C=CC=3C=C(N3)C=CC3=CC(=N3)C=CC3=CC1=CC=2C1=CC=CC=N1 GVNNKCCHSQVNGZ-UHFFFAOYSA-N 0.000 claims description 8
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- XOGDUYVYKGKZAC-UHFFFAOYSA-N 23-(2-butoxyethyl)-12-pyridin-2-yl-21H-porphyrin Chemical compound C1=CC(C=C2NC(=CC3=NC(=C4)C=C3)C=C2)=NC1=CC=1N(CCOCCCC)C4=CC=1C1=CC=CC=N1 XOGDUYVYKGKZAC-UHFFFAOYSA-N 0.000 abstract description 3
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- DJTWWKVWRNNVRB-UHFFFAOYSA-N 23-pyridin-2-yl-21H-porphyrin Chemical class C1=C(N=2)C=CC=2C=C(N2)C=CC2=CC(=N2)C=CC2=CC2=CC=C1N2C1=CC=CC=N1 DJTWWKVWRNNVRB-UHFFFAOYSA-N 0.000 description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 16
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 16
- VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000009472 formulation Methods 0.000 description 15
- 230000007246 mechanism Effects 0.000 description 15
- 125000004076 pyridyl group Chemical group 0.000 description 15
- 125000005490 tosylate group Chemical group 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 14
- 239000012535 impurity Substances 0.000 description 14
- 230000000875 corresponding effect Effects 0.000 description 13
- 238000004128 high performance liquid chromatography Methods 0.000 description 13
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical class [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 13
- 239000002002 slurry Substances 0.000 description 13
- 238000006263 metalation reaction Methods 0.000 description 12
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- 102000019197 Superoxide Dismutase Human genes 0.000 description 11
- 108010012715 Superoxide dismutase Proteins 0.000 description 11
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- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
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- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 7
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Classifications
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- C—CHEMISTRY; METALLURGY
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- 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
- C07D487/22—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 four or more hetero rings
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F13/00—Compounds containing elements of Groups 7 or 17 of the Periodic Table
- C07F13/005—Compounds without a metal-carbon linkage
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B47/00—Formation or introduction of functional groups not provided for in groups C07B39/00 - C07B45/00
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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- Nitrogen Condensed Heterocyclic Rings (AREA)
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| US201662436743P | 2016-12-20 | 2016-12-20 | |
| US62/436,743 | 2016-12-20 | ||
| PCT/US2017/067263 WO2018118891A1 (en) | 2016-12-20 | 2017-12-19 | Methods of making substituted porphyrin pharmaceutical compounds and compositions |
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| CA3046357A1 true CA3046357A1 (en) | 2018-06-28 |
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| CA3046357A Abandoned CA3046357A1 (en) | 2016-12-20 | 2017-12-19 | Methods of making substituted porphyrin pharmaceutical compounds and compositions |
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| MX (1) | MX2019007301A (enExample) |
| WO (1) | WO2018118891A1 (enExample) |
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| CN110621377A (zh) * | 2017-04-04 | 2019-12-27 | 贝奥密美体合资有限公司 | 治疗和/或预防与放射和/或化疗暴露有关的副作用的方法、组合物以及试剂盒 |
| CN111417400B (zh) * | 2017-09-29 | 2022-12-02 | 杜克大学 | 氟取代的卟啉化合物、包含其的药物组合物及其制备和使用方法 |
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| US6127356A (en) * | 1993-10-15 | 2000-10-03 | Duke University | Oxidant scavengers |
| ATE312103T1 (de) * | 1999-01-25 | 2005-12-15 | Nat Jewish Med & Res Center | Substituierte porphyrine und deren therapeutische verwendungen |
| WO2003103680A1 (en) * | 2002-06-07 | 2003-12-18 | Duke University | Substituted porphyrins |
| WO2005077269A1 (en) * | 2004-02-09 | 2005-08-25 | Duke University | Substituted porphyrins |
| US20110275606A1 (en) * | 2009-01-07 | 2011-11-10 | Duke University | Substituted porphyrins |
| WO2010138633A1 (en) * | 2009-05-26 | 2010-12-02 | Duke University | Method of providing neuroprotection using substituted porphyrins |
| WO2015112586A1 (en) * | 2014-01-22 | 2015-07-30 | Duke University | Methods of treating pruritus |
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- 2017-12-19 CA CA3046357A patent/CA3046357A1/en not_active Abandoned
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- 2017-12-19 EP EP17882736.6A patent/EP3558902A4/en not_active Withdrawn
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Also Published As
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|---|---|
| JP2020502280A (ja) | 2020-01-23 |
| US20190330220A1 (en) | 2019-10-31 |
| EP3558902A1 (en) | 2019-10-30 |
| KR20190098211A (ko) | 2019-08-21 |
| CN110291060A (zh) | 2019-09-27 |
| WO2018118891A1 (en) | 2018-06-28 |
| MX2019007301A (es) | 2019-10-30 |
| EP3558902A4 (en) | 2020-06-24 |
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