CA2641501A1 - Nitrooxy-comprising derivatives of apraclonidine and brimodnidine as al pha2 -adrenergic receptor agonists - Google Patents
Nitrooxy-comprising derivatives of apraclonidine and brimodnidine as al pha2 -adrenergic receptor agonists Download PDFInfo
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- CA2641501A1 CA2641501A1 CA002641501A CA2641501A CA2641501A1 CA 2641501 A1 CA2641501 A1 CA 2641501A1 CA 002641501 A CA002641501 A CA 002641501A CA 2641501 A CA2641501 A CA 2641501A CA 2641501 A1 CA2641501 A1 CA 2641501A1
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- IEJXVRYNEISIKR-UHFFFAOYSA-N apraclonidine Chemical class ClC1=CC(N)=CC(Cl)=C1NC1=NCCN1 IEJXVRYNEISIKR-UHFFFAOYSA-N 0.000 title description 10
- 239000000048 adrenergic agonist Substances 0.000 title description 7
- 229940126157 adrenergic receptor agonist Drugs 0.000 title description 6
- 229910004679 ONO2 Inorganic materials 0.000 claims abstract description 15
- 208000010412 Glaucoma Diseases 0.000 claims abstract description 11
- 238000011282 treatment Methods 0.000 claims abstract description 8
- 208000022873 Ocular disease Diseases 0.000 claims abstract description 5
- 230000004410 intraocular pressure Effects 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 114
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 17
- 239000000243 solution Substances 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 239000002876 beta blocker Substances 0.000 claims description 5
- 229940097320 beta blocking agent Drugs 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 239000003489 carbonate dehydratase inhibitor Substances 0.000 claims description 3
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 239000001301 oxygen Chemical group 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 239000003981 vehicle Substances 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 239000000839 emulsion Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 239000011593 sulfur Chemical group 0.000 claims description 2
- 239000000725 suspension Substances 0.000 claims description 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 2
- 229940122072 Carbonic anhydrase inhibitor Drugs 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000011200 topical administration Methods 0.000 claims 1
- 230000000144 pharmacologic effect Effects 0.000 abstract description 5
- 239000000384 adrenergic alpha-2 receptor agonist Substances 0.000 abstract description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 56
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
- 125000006239 protecting group Chemical group 0.000 description 23
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- 238000000034 method Methods 0.000 description 19
- 239000012454 non-polar solvent Substances 0.000 description 14
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- 150000007529 inorganic bases Chemical class 0.000 description 13
- 239000002798 polar solvent Substances 0.000 description 13
- -1 dipevefrin Chemical compound 0.000 description 12
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 11
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- 125000001893 nitrooxy group Chemical group [O-][N+](=O)O* 0.000 description 10
- 150000003254 radicals Chemical class 0.000 description 9
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 8
- 229960002610 apraclonidine Drugs 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- XYLJNLCSTIOKRM-UHFFFAOYSA-N Alphagan Chemical compound C1=CC2=NC=CN=C2C(Br)=C1NC1=NCCN1 XYLJNLCSTIOKRM-UHFFFAOYSA-N 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
- 150000007513 acids Chemical class 0.000 description 7
- 229960003679 brimonidine Drugs 0.000 description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
- 0 C*1(CCN2COC(OCCC*)=O)C2=Nc(c(Cl)c2)c1cc2N Chemical compound C*1(CCN2COC(OCCC*)=O)C2=Nc(c(Cl)c2)c1cc2N 0.000 description 6
- 239000002841 Lewis acid Substances 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 102000030484 alpha-2 Adrenergic Receptor Human genes 0.000 description 6
- 108020004101 alpha-2 Adrenergic Receptor Proteins 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 150000007517 lewis acids Chemical class 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 6
- NYENCOMLZDQKNH-UHFFFAOYSA-K bis(trifluoromethylsulfonyloxy)bismuthanyl trifluoromethanesulfonate Chemical compound [Bi+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F NYENCOMLZDQKNH-UHFFFAOYSA-K 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- DISKGNKRAOTMPJ-UHFFFAOYSA-N 2-hydroxyethyl nitrate;2-nitrooxyethyl 2-[(5-bromoquinoxalin-6-yl)amino]-4,5-dihydroimidazole-1-carboxylate Chemical compound OCCO[N+]([O-])=O.[O-][N+](=O)OCCOC(=O)N1CCN=C1NC1=CC=C(N=CC=N2)C2=C1Br DISKGNKRAOTMPJ-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 206010030043 Ocular hypertension Diseases 0.000 description 4
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- UICJXEGPDXXFPO-UHFFFAOYSA-N 2-nitrooxyethyl carbonochloridate Chemical compound [O-][N+](=O)OCCOC(Cl)=O UICJXEGPDXXFPO-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 229910002651 NO3 Inorganic materials 0.000 description 3
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
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- 230000000694 effects Effects 0.000 description 3
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- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
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- TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 description 2
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- XZAMUZYWWLHHHB-UHFFFAOYSA-N 4-nitrooxybutyl carbonochloridate Chemical compound [O-][N+](=O)OCCCCOC(Cl)=O XZAMUZYWWLHHHB-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
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- 230000036543 hypotension Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- MVFCKEFYUDZOCX-UHFFFAOYSA-N iron(2+);dinitrate Chemical compound [Fe+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O MVFCKEFYUDZOCX-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229960001160 latanoprost Drugs 0.000 description 1
- GGXICVAJURFBLW-CEYXHVGTSA-N latanoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1CC[C@@H](O)CCC1=CC=CC=C1 GGXICVAJURFBLW-CEYXHVGTSA-N 0.000 description 1
- 208000018769 loss of vision Diseases 0.000 description 1
- 231100000864 loss of vision Toxicity 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 238000000324 molecular mechanic Methods 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 208000020911 optic nerve disease Diseases 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 229960001416 pilocarpine Drugs 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 210000001747 pupil Anatomy 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Substances ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 210000001585 trabecular meshwork Anatomy 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
- C07D233/50—Nitrogen atoms not forming part of a nitro radical with carbocyclic radicals directly attached to said nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/74—Quinazolines; Hydrogenated quinazolines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
- C07D239/76—N-oxides
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Ophthalmology & Optometry (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US76516606P | 2006-02-06 | 2006-02-06 | |
| US60/765,166 | 2006-02-06 | ||
| PCT/EP2007/051017 WO2007090793A1 (en) | 2006-02-06 | 2007-02-02 | Nitrooxy-comprising derivatives of apraclonidine and brimodnidine as al pha2 -adrenergic receptor agonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2641501A1 true CA2641501A1 (en) | 2007-08-16 |
Family
ID=37810330
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002641501A Abandoned CA2641501A1 (en) | 2006-02-06 | 2007-02-02 | Nitrooxy-comprising derivatives of apraclonidine and brimodnidine as al pha2 -adrenergic receptor agonists |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US7799784B2 (enExample) |
| EP (1) | EP1981852A1 (enExample) |
| JP (1) | JP2009525970A (enExample) |
| CA (1) | CA2641501A1 (enExample) |
| WO (1) | WO2007090793A1 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8062653B2 (en) | 2009-02-18 | 2011-11-22 | Bezwada Biomedical, Llc | Controlled release of nitric oxide and drugs from functionalized macromers and oligomers |
| EP2525793B1 (en) * | 2010-01-21 | 2018-09-05 | Allergan, Inc. | Alpha-2 adrenergic agonist having long duration of intraocular pressure-lowering effect |
| WO2013126156A1 (en) * | 2012-02-22 | 2013-08-29 | Bausch & Lomb Incorporated | Nitric oxide donating selective glucocorticoid receptor agonist compounds and ophthalmic compositions |
| CA2871292A1 (en) | 2012-05-31 | 2013-12-05 | Theravance Biopharma R&D Ip, Llc | Nitric oxide donor neprilysin inhibitors |
| WO2014144268A1 (en) * | 2013-03-15 | 2014-09-18 | University Of Maryland | Automated fruit and vegetable calyx or stem removal machine |
| WO2018175922A1 (en) | 2017-03-23 | 2018-09-27 | Graybug Vision, Inc. | Drugs and compositions for the treatment of ocular disorders |
| MX2019013363A (es) | 2017-05-10 | 2020-01-13 | Graybug Vision Inc | Microparticulas de liberacion extendida y suspensiones de las mismas para terapia medica. |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4517199A (en) * | 1981-11-20 | 1985-05-14 | Alcon Laboratories, Inc. | Method for lowering intraocular pressure using phenylimino-imidazoles |
| US5856329A (en) | 1995-06-28 | 1999-01-05 | Allergan | Method of using (2-imidazolin-2-ylamino) quinoxalines in treating ocular neural injury |
| PL380065A1 (pl) * | 2003-12-02 | 2006-12-11 | Nicox S.A. | Nitrooksypochodne karwedilolu i inne beta blokery jako leki przeciwko nadciśnieniu |
| JP2007513113A (ja) | 2003-12-02 | 2007-05-24 | ニコックス エス エイ | 抗高血圧薬剤のニトロオキシ誘導体 |
-
2007
- 2007-02-02 US US12/162,529 patent/US7799784B2/en not_active Expired - Fee Related
- 2007-02-02 CA CA002641501A patent/CA2641501A1/en not_active Abandoned
- 2007-02-02 JP JP2008552815A patent/JP2009525970A/ja not_active Withdrawn
- 2007-02-02 WO PCT/EP2007/051017 patent/WO2007090793A1/en not_active Ceased
- 2007-02-02 EP EP07726294A patent/EP1981852A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| WO2007090793A1 (en) | 2007-08-16 |
| US20080318965A1 (en) | 2008-12-25 |
| EP1981852A1 (en) | 2008-10-22 |
| JP2009525970A (ja) | 2009-07-16 |
| US7799784B2 (en) | 2010-09-21 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |