CA2874548A1 - Cyclosporin a analogs - Google Patents
Cyclosporin a analogs Download PDFInfo
- Publication number
- CA2874548A1 CA2874548A1 CA2874548A CA2874548A CA2874548A1 CA 2874548 A1 CA2874548 A1 CA 2874548A1 CA 2874548 A CA2874548 A CA 2874548A CA 2874548 A CA2874548 A CA 2874548A CA 2874548 A1 CA2874548 A1 CA 2874548A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- compound
- methylamino
- cyclosporin
- hydroxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical class CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims abstract description 602
- 238000000034 method Methods 0.000 claims abstract description 123
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims abstract description 63
- 206010013774 Dry eye Diseases 0.000 claims abstract description 48
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 45
- 239000000203 mixture Substances 0.000 claims abstract description 36
- 150000001875 compounds Chemical class 0.000 claims description 723
- 150000001408 amides Chemical class 0.000 claims description 466
- 229930105110 Cyclosporin A Natural products 0.000 claims description 337
- 108010036949 Cyclosporine Proteins 0.000 claims description 337
- 229960001265 ciclosporin Drugs 0.000 claims description 335
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 144
- 125000000623 heterocyclic group Chemical group 0.000 claims description 95
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 64
- 125000000217 alkyl group Chemical group 0.000 claims description 49
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 48
- 206010061218 Inflammation Diseases 0.000 claims description 43
- -1 guanidinyl Chemical group 0.000 claims description 43
- 230000004054 inflammatory process Effects 0.000 claims description 43
- 239000000243 solution Substances 0.000 claims description 36
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 35
- 125000003118 aryl group Chemical group 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 35
- 208000024891 symptom Diseases 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 24
- 150000001412 amines Chemical class 0.000 claims description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 208000010217 blepharitis Diseases 0.000 claims description 18
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 18
- 238000001356 surgical procedure Methods 0.000 claims description 18
- DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical compound S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 claims description 17
- 208000002205 allergic conjunctivitis Diseases 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- 208000036142 Viral infection Diseases 0.000 claims description 15
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 15
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- 230000009385 viral infection Effects 0.000 claims description 15
- 201000010099 disease Diseases 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 13
- 206010046851 Uveitis Diseases 0.000 claims description 13
- 150000001299 aldehydes Chemical class 0.000 claims description 13
- 230000001684 chronic effect Effects 0.000 claims description 13
- 210000004175 meibomian gland Anatomy 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
- 201000004700 rosacea Diseases 0.000 claims description 12
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- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
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- 229910052717 sulfur Inorganic materials 0.000 claims description 11
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- 125000002757 morpholinyl group Chemical group 0.000 claims description 10
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
- 238000001704 evaporation Methods 0.000 claims description 8
- 239000000706 filtrate Substances 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 8
- 125000002950 monocyclic group Chemical group 0.000 claims description 8
- 125000003367 polycyclic group Chemical group 0.000 claims description 8
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- 206010023332 keratitis Diseases 0.000 claims description 7
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 7
- 239000000047 product Substances 0.000 claims description 7
- 229940124530 sulfonamide Drugs 0.000 claims description 7
- 150000003456 sulfonamides Chemical class 0.000 claims description 7
- 208000018464 vernal keratoconjunctivitis Diseases 0.000 claims description 7
- 238000005406 washing Methods 0.000 claims description 7
- 208000009299 Benign Mucous Membrane Pemphigoid Diseases 0.000 claims description 6
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 6
- 208000005100 Herpetic Keratitis Diseases 0.000 claims description 6
- 206010072139 Ocular rosacea Diseases 0.000 claims description 6
- 206010073938 Ophthalmic herpes simplex Diseases 0.000 claims description 6
- 241001621636 Pterygia Species 0.000 claims description 6
- ONCCWDRMOZMNSM-FBCQKBJTSA-N compound Z Chemical compound N1=C2C(=O)NC(N)=NC2=NC=C1C(=O)[C@H]1OP(O)(=O)OC[C@H]1O ONCCWDRMOZMNSM-FBCQKBJTSA-N 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
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- 150000002576 ketones Chemical class 0.000 claims description 6
- 208000015200 ocular cicatricial pemphigoid Diseases 0.000 claims description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 5
- 108010021119 Trichosanthin Proteins 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 5
- 229910052731 fluorine Chemical group 0.000 claims description 5
- FVIZARNDLVOMSU-UHFFFAOYSA-N ginsenoside K Natural products C1CC(C2(CCC3C(C)(C)C(O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O FVIZARNDLVOMSU-UHFFFAOYSA-N 0.000 claims description 5
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- SFFSGPCYJCMDJM-UHFFFAOYSA-N 2-[2-(3-oxo-1,2-benzoselenazol-2-yl)ethyl]-1,2-benzoselenazol-3-one Chemical compound [se]1C2=CC=CC=C2C(=O)N1CCN1C(=O)C(C=CC=C2)=C2[se]1 SFFSGPCYJCMDJM-UHFFFAOYSA-N 0.000 claims description 4
- 206010052779 Transplant rejections Diseases 0.000 claims description 4
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 claims description 4
- 239000011737 fluorine Chemical group 0.000 claims description 4
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 206010042033 Stevens-Johnson syndrome Diseases 0.000 claims description 3
- 231100000168 Stevens-Johnson syndrome Toxicity 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 3
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 claims description 2
- 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 claims description 2
- 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims description 2
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 claims description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000005513 benzoazaindolyl group Chemical group 0.000 claims description 2
- 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 125000003838 furazanyl group Chemical group 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000005945 imidazopyridyl group Chemical group 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- 150000003951 lactams Chemical class 0.000 claims description 2
- 150000002596 lactones Chemical class 0.000 claims description 2
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- 125000004095 oxindolyl group Chemical group N1(C(CC2=CC=CC=C12)=O)* 0.000 claims description 2
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000005936 piperidyl group Chemical group 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 125000006085 pyrrolopyridyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 claims description 2
- 125000001984 thiazolidinyl group Chemical group 0.000 claims description 2
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- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 2
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- ZTQSADJAYQOCDD-UHFFFAOYSA-N ginsenoside-Rd2 Natural products C1CC(C2(CCC3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC(C(C(O)C1O)O)OC1COC1OCC(O)C(O)C1O ZTQSADJAYQOCDD-UHFFFAOYSA-N 0.000 claims 1
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- C—CHEMISTRY; METALLURGY
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- C07K7/645—Cyclosporins; Related peptides
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Ophthalmology & Optometry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261654388P | 2012-06-01 | 2012-06-01 | |
| US61/654,388 | 2012-06-01 | ||
| PCT/US2013/043266 WO2013181339A2 (en) | 2012-06-01 | 2013-05-30 | Cyclosporin a analogs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2874548A1 true CA2874548A1 (en) | 2013-12-05 |
Family
ID=48577956
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2874548A Abandoned CA2874548A1 (en) | 2012-06-01 | 2013-05-30 | Cyclosporin a analogs |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US9266927B2 (enExample) |
| EP (2) | EP2855508B1 (enExample) |
| JP (1) | JP2015519368A (enExample) |
| CN (1) | CN104487449A (enExample) |
| AU (1) | AU2013267435B2 (enExample) |
| CA (1) | CA2874548A1 (enExample) |
| TW (1) | TW201408702A (enExample) |
| WO (1) | WO2013181339A2 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9890198B2 (en) | 2010-12-03 | 2018-02-13 | S&T Global Inc. | Cyclosporin derivatives and uses thereof |
| WO2014138437A1 (en) | 2013-03-08 | 2014-09-12 | Allergan, Inc. | Steroid conjugates |
| WO2016112321A1 (en) | 2015-01-08 | 2016-07-14 | Allergan, Inc. | Cyclosporin derivatives wherein the mebmt sidechain has been cyclized |
| WO2016160362A1 (en) | 2015-03-31 | 2016-10-06 | Allergan, Inc. | Cyclosporins modified on the mebmt sidechain by heterocyclic rings |
| US10738084B2 (en) | 2015-06-30 | 2020-08-11 | Sentry Therapeutics Limited | Macrocycles |
| CN118324867A (zh) * | 2016-05-17 | 2024-07-12 | 美国科技环球有限公司 | 新型环孢菌素衍生物及其用途 |
| US20230041197A1 (en) | 2018-06-20 | 2023-02-09 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with an immunomodulator |
| IL278473A (en) | 2020-11-03 | 2022-06-01 | Yeda Res & Dev | Methods for diagnosing and determining treatment in multiple myeloma |
| CN115028679B (zh) * | 2022-08-11 | 2022-11-15 | 深圳湾实验室 | 一种具有Cyclophilin A降解活性的PROTAC化合物及其制备方法与应用 |
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-
2013
- 2013-05-30 AU AU2013267435A patent/AU2013267435B2/en not_active Ceased
- 2013-05-30 EP EP13727787.7A patent/EP2855508B1/en active Active
- 2013-05-30 US US13/905,491 patent/US9266927B2/en active Active
- 2013-05-30 EP EP17184903.7A patent/EP3263587A1/en not_active Withdrawn
- 2013-05-30 CA CA2874548A patent/CA2874548A1/en not_active Abandoned
- 2013-05-30 WO PCT/US2013/043266 patent/WO2013181339A2/en not_active Ceased
- 2013-05-30 JP JP2015515175A patent/JP2015519368A/ja active Pending
- 2013-05-30 CN CN201380038907.0A patent/CN104487449A/zh active Pending
- 2013-05-31 TW TW102119527A patent/TW201408702A/zh unknown
-
2015
- 2015-08-12 US US14/824,392 patent/US20160039880A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP2015519368A (ja) | 2015-07-09 |
| HK1208874A1 (en) | 2016-03-18 |
| EP2855508A2 (en) | 2015-04-08 |
| US20160039880A1 (en) | 2016-02-11 |
| US20130324480A1 (en) | 2013-12-05 |
| CN104487449A (zh) | 2015-04-01 |
| EP2855508B1 (en) | 2018-02-14 |
| WO2013181339A3 (en) | 2014-03-13 |
| AU2013267435B2 (en) | 2017-11-09 |
| AU2013267435A1 (en) | 2014-12-18 |
| US9266927B2 (en) | 2016-02-23 |
| TW201408702A (zh) | 2014-03-01 |
| WO2013181339A2 (en) | 2013-12-05 |
| EP3263587A1 (en) | 2018-01-03 |
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