CA2767895C - Opsin-binding ligands, compositions and methods of use - Google Patents

Opsin-binding ligands, compositions and methods of use Download PDF

Info

Publication number
CA2767895C
CA2767895C CA2767895A CA2767895A CA2767895C CA 2767895 C CA2767895 C CA 2767895C CA 2767895 A CA2767895 A CA 2767895A CA 2767895 A CA2767895 A CA 2767895A CA 2767895 C CA2767895 C CA 2767895C
Authority
CA
Canada
Prior art keywords
compound
opsin
trimethylcyclohex
pharmaceutically acceptable
hydrogen
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.)
Expired - Fee Related
Application number
CA2767895A
Other languages
English (en)
French (fr)
Other versions
CA2767895A1 (en
Inventor
David S. Garvey
Gregory J. Larosa
Jeremy Robert Greenwood
Mark L. Brewer
Judd Berman
Jamie B. Cote
Tan Quach
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bikam Pharmaceuticals Inc
Original Assignee
Bikam Pharmaceuticals Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Bikam Pharmaceuticals Inc filed Critical Bikam Pharmaceuticals Inc
Publication of CA2767895A1 publication Critical patent/CA2767895A1/en
Application granted granted Critical
Publication of CA2767895C publication Critical patent/CA2767895C/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
    • C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
    • C—CHEMISTRY; METALLURGY
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • C07B59/002—Heterocyclic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • C07C233/10—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to carbon atoms of an unsaturated carbon skeleton containing rings other than six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/04—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms
    • C07C275/06—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an acyclic and saturated carbon skeleton
    • C07C275/14—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an acyclic and saturated carbon skeleton being further substituted by nitrogen atoms not being part of nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • 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
    • C—CHEMISTRY; METALLURGY
    • 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
    • C07D207/14—Nitrogen atoms not forming part of a nitro radical
    • 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
    • C07D211/06—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 no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—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 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
    • C07D211/38—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/06—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members
    • C07D241/08—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
    • C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
    • C07D243/08—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
    • C07D295/182—Radicals derived from carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
    • C07D295/182—Radicals derived from carboxylic acids
    • C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
    • C07D295/194—Radicals derived from thio- or thiono carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
    • C07D295/205—Radicals derived from carbonic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
    • C07D295/26—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/05—Isotopically modified compounds, e.g. labelled
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Steroid Compounds (AREA)
  • Peptides Or Proteins (AREA)
CA2767895A 2009-06-16 2010-06-16 Opsin-binding ligands, compositions and methods of use Expired - Fee Related CA2767895C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US26875709P 2009-06-16 2009-06-16
US61/268,757 2009-06-16
PCT/US2010/001739 WO2010147653A1 (en) 2009-06-16 2010-06-16 Opsin-binding ligands, compositions and methods of use

Publications (2)

Publication Number Publication Date
CA2767895A1 CA2767895A1 (en) 2010-12-23
CA2767895C true CA2767895C (en) 2017-12-12

Family

ID=43356669

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2767895A Expired - Fee Related CA2767895C (en) 2009-06-16 2010-06-16 Opsin-binding ligands, compositions and methods of use

Country Status (20)

Country Link
US (2) US9562022B2 (h)
EP (2) EP2442644B1 (h)
KR (3) KR20170041282A (h)
CN (1) CN102480943A (h)
AU (1) AU2010260535B2 (h)
CA (1) CA2767895C (h)
CY (1) CY1118221T1 (h)
DK (1) DK2442644T3 (h)
EA (1) EA021747B1 (h)
ES (1) ES2610429T3 (h)
HR (1) HRP20161477T1 (h)
HU (1) HUE031705T2 (h)
IN (1) IN2012DN00352A (h)
LT (1) LT2442644T (h)
PL (1) PL2442644T3 (h)
PT (1) PT2442644T (h)
SI (1) SI2442644T1 (h)
SM (2) SMT201600388T1 (h)
WO (1) WO2010147653A1 (h)
ZA (1) ZA201200226B (h)

Families Citing this family (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2069390A4 (en) * 2006-07-27 2009-12-30 Univ Florida OPSIN STABILIZING COMPOUNDS AND METHODS OF USE
IN2012DN00352A (h) 2009-06-16 2015-08-21 Bikam Pharmaceuticals Inc
WO2012134971A2 (en) * 2011-03-25 2012-10-04 Bikam Pharmaceuticals, Inc. Opsin-binding ligands, compositions and methods of use
BR112013032199A2 (pt) * 2011-06-14 2017-12-12 Bikam Pharmaceuticals Inc ligantes de ligação à opsina, composições e métodos de utilização
US9499464B2 (en) 2011-10-19 2016-11-22 Bikam Pharmaceuticals, Inc. Opsin-binding ligands, compositions and methods of use
CA2862807A1 (en) 2011-11-30 2013-06-06 Bikam Pharmaceuticals, Inc. Opsin-binding ligands, compositions and methods of use
EP2785178B1 (en) * 2011-12-01 2019-05-01 Bikam Pharmaceuticals, Inc. Opsin-binding ligands, compositions and methods of use
WO2014153235A2 (en) 2013-03-14 2014-09-25 Epizyme, Inc. Arginine methyltransferase inhibitors and uses thereof
EP2970136A1 (en) 2013-03-14 2016-01-20 Epizyme, Inc. Arginine methyl transferase inhibtors and uses thereof
WO2014153172A1 (en) 2013-03-14 2014-09-25 Epizyme, Inc. Pyrazole derivatives as prmt1 inhibitors and uses thereof
EP2970135B1 (en) 2013-03-14 2018-07-18 Epizyme, Inc. Pyrazole derivatives as prmt1 inhibitors and uses thereof
CA2903264A1 (en) 2013-03-14 2014-11-06 Epizyme, Inc. Pyrazole derivatives as arginine methyltransferase inhibitors and uses thereof
WO2014153226A1 (en) 2013-03-14 2014-09-25 Epizyme, Inc. Arginine methyltransferase inhibitors and uses thereof
US9120757B2 (en) 2013-03-14 2015-09-01 Epizyme, Inc. Arginine methyltransferase inhibitors and uses thereof
US9790219B2 (en) 2014-03-13 2017-10-17 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing CFTR activity
EP3116870A1 (en) 2014-03-13 2017-01-18 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing cftr activity
EP3157917B1 (en) 2014-06-19 2020-03-18 Proteostasis Therapeutics, Inc. Compounds, compositions and methods of increasing cftr activity
US10738011B2 (en) 2014-12-23 2020-08-11 Proteostasis Therapeutics, Inc. Derivatives of 5-(hetero)arylpyrazol-3-carboxylic amide or 1-(hetero)aryltriazol-4-carboxylic amide useful for the treatment of inter alia cystic fibrosis
CA2971850A1 (en) 2014-12-23 2016-06-30 Proteostasis Therapeutics, Inc. Derivatives of 5-phenyl- or 5-heteroarylthiazol-2-carboxylic amide useful for the treatment of inter alia cystic fibrosis
MA41253A (fr) 2014-12-23 2017-10-31 Proteostasis Therapeutics Inc Composés, compositions et procédés pour augmenter l'activité du cftr
CA2971835A1 (en) 2014-12-23 2016-06-30 Proteostasis Therapeutics, Inc. Derivatives of 3-heteroarylisoxazol-5-carboxylic amide useful for the treatment of inter alia cystic fibrosis
AU2016297886B2 (en) 2015-07-24 2020-12-10 Proteostasis Therapeutics, Inc. Compounds, compositions and methods of increasing CFTR activity
CN108430994B (zh) 2015-10-06 2022-04-12 蛋白质平衡治疗股份有限公司 用于调节cftr的化合物、组合物和方法
MX386698B (es) 2016-04-07 2025-03-19 Proteostasis Therapeutics Inc Atomos de silicona que contienen analogos de ivacaftor
AU2017280206A1 (en) 2016-06-21 2019-01-17 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing CFTR activity
JOP20190245A1 (ar) 2017-04-20 2019-10-15 Novartis Ag أنظمة توصيل إطلاق مستدام تتضمن روابط بلا أثر لنقطة الربط
US11344488B2 (en) 2017-10-16 2022-05-31 Takasago International Corporation Cool-sensation imparter composition containing 2,2,6-trimethylcyclohexanecarboxylic acid derivative
TW202027794A (zh) 2018-10-03 2020-08-01 瑞士商諾華公司 血管生成素樣３多肽之持續遞送
EP4183449A1 (en) 2021-11-17 2023-05-24 Samsara Therapeutics Inc. Autophagy inducing compounds and uses thereof

Family Cites Families (109)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3022291A (en) * 1962-02-20 cuhno
US3416530A (en) 1966-03-02 1968-12-17 Richard A. Ness Eyeball medication dispensing tablet
US3854480A (en) 1969-04-01 1974-12-17 Alza Corp Drug-delivery system
US3773919A (en) 1969-10-23 1973-11-20 Du Pont Polylactide-drug mixtures
US3850611A (en) * 1970-03-25 1974-11-26 Fujisawa Pharmaceutical Co Method for inhibiting plant growth with quaternary ammonium salts
US3828777A (en) 1971-11-08 1974-08-13 Alza Corp Microporous ocular device
BE802469A (fr) * 1972-07-20 1974-01-18 Wilkinson Sword Ltd Perfectionnements apportes et/ou relatifs a des composes exercant un effet refrigerant physiologique et compositions contenant ceux-ci
US3832253A (en) 1973-03-21 1974-08-27 Baxter Laboratories Inc Method of making an inflatable balloon catheter
US4014335A (en) 1975-04-21 1977-03-29 Alza Corporation Ocular drug delivery device
US4244890A (en) 1977-12-14 1981-01-13 Scm Corporation Cyclic terpenoid amines, their preparation and uses
US4263428A (en) 1978-03-24 1981-04-21 The Regents Of The University Of California Bis-anthracycline nucleic acid function inhibitors and improved method for administering the same
DE2830764A1 (de) 1978-07-13 1980-01-31 Basf Ag Acetanilide
US4300557A (en) 1980-01-07 1981-11-17 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Method for treating intraocular malignancies
ATE12348T1 (de) 1980-11-10 1985-04-15 Gersonde Klaus Prof Dr Verfahren zur herstellung von lipid-vesikeln durch ultraschallbehandlung, anwendung des verfahrens und vorrichtung zur durchfuehrung des verfahrens.
US4327725A (en) 1980-11-25 1982-05-04 Alza Corporation Osmotic device with hydrogel driving member
IE52535B1 (en) 1981-02-16 1987-12-09 Ici Plc Continuous release pharmaceutical compositions
US4485045A (en) 1981-07-06 1984-11-27 Research Corporation Synthetic phosphatidyl cholines useful in forming liposomes
EP0088046B1 (de) 1982-02-17 1987-12-09 Ciba-Geigy Ag Lipide in wässriger Phase
DE3218121A1 (de) 1982-05-14 1983-11-17 Leskovar, Peter, Dr.-Ing., 8000 München Arzneimittel zur tumorbehandlung
US4667014A (en) 1983-03-07 1987-05-19 Syntex (U.S.A.) Inc. Nonapeptide and decapeptide analogs of LHRH, useful as LHRH antagonists
EP0102324A3 (de) 1982-07-29 1984-11-07 Ciba-Geigy Ag Lipide und Tenside in wässriger Phase
US4452775A (en) 1982-12-03 1984-06-05 Syntex (U.S.A.) Inc. Cholesterol matrix delivery system for sustained release of macromolecules
CA1200416A (en) 1983-05-13 1986-02-11 Societe Des Produits Nestle S.A. Food process
US4544545A (en) 1983-06-20 1985-10-01 Trustees University Of Massachusetts Liposomes containing modified cholesterol for organ targeting
HUT35524A (en) 1983-08-02 1985-07-29 Hoechst Ag Process for preparing pharmaceutical compositions containing regulatory /regulative/ peptides providing for the retarded release of the active substance
EP0350973B1 (de) 1983-09-26 1997-11-05 Udo Dr. Ehrenfeld Mittel und Erzeugnis für die Diagnose und Therapie von Tumoren sowie zur Behandlung von Schwächen der zelligen und humoralen Immunabwehr
EP0143949B1 (en) 1983-11-01 1988-10-12 TERUMO KABUSHIKI KAISHA trading as TERUMO CORPORATION Pharmaceutical composition containing urokinase
EP0177742B1 (fr) 1984-09-12 1990-03-07 Firmenich Sa Composés azotés, leur préparation et leur utilisation à titre de produits de dèpart pour la préparation de cétones décaliniques
US5147647A (en) 1986-10-02 1992-09-15 Sohrab Darougar Ocular insert for the fornix
US5322691A (en) 1986-10-02 1994-06-21 Sohrab Darougar Ocular insert with anchoring protrusions
US5075109A (en) 1986-10-24 1991-12-24 Southern Research Institute Method of potentiating an immune response
US4997652A (en) 1987-12-22 1991-03-05 Visionex Biodegradable ocular implants
US4853224A (en) 1987-12-22 1989-08-01 Visionex Biodegradable ocular implants
US4894388A (en) 1988-12-22 1990-01-16 Monsanto Company Glycosidase inhibitors and use thereof
DE3905050A1 (de) 1989-02-18 1990-08-30 Lohmann Therapie Syst Lts Therapeutisches system zur verzoegerten und gesteuerten transdermalen oder transmucosalen verabreichung von wirkstoffen (ii)
US4946450A (en) 1989-04-18 1990-08-07 Biosource Genetics Corporation Glucan/collagen therapeutic eye shields
US5103008A (en) 1989-08-17 1992-04-07 Monsanto Company Compound, N-butyl-deoxynojirimycin-6-phosphate
US5043273A (en) 1989-08-17 1991-08-27 Monsanto Company Phosphorylated glycosidase inhibitor prodrugs
US5164188A (en) 1989-11-22 1992-11-17 Visionex, Inc. Biodegradable ocular implants
JPH04167172A (ja) 1990-10-31 1992-06-15 Nec Corp ベクトルプロセッサ
US5290892A (en) 1990-11-07 1994-03-01 Nestle S.A. Flexible intraocular lenses made from high refractive index polymers
US5378475A (en) 1991-02-21 1995-01-03 University Of Kentucky Research Foundation Sustained release drug delivery devices
US5770592A (en) 1991-11-22 1998-06-23 Alcon Laboratories, Inc. Prevention and treatment of ocular neovascularization using angiostatic steroids
US5679666A (en) 1991-11-22 1997-10-21 Alcon Laboratories, Inc. Prevention and treatment of ocular neovascularization by treatment with angiostatic steroids
US5178635A (en) 1992-05-04 1993-01-12 Allergan, Inc. Method for determining amount of medication in an implantable device
FR2690846B1 (fr) 1992-05-05 1995-07-07 Aiache Jean Marc Forme galenique pour administration oculaire et procede de preparation.
US5672659A (en) 1993-01-06 1997-09-30 Kinerton Limited Ionic molecular conjugates of biodegradable polyesters and bioactive polypeptides
WO1995003009A1 (en) 1993-07-22 1995-02-02 Oculex Pharmaceuticals, Inc. Method of treatment of macular degeneration
US5443505A (en) 1993-11-15 1995-08-22 Oculex Pharmaceuticals, Inc. Biocompatible ocular implants
US5455351A (en) 1993-12-13 1995-10-03 Abbott Laboratories Retroviral protease inhibiting piperazine compounds
US5516522A (en) 1994-03-14 1996-05-14 Board Of Supervisors Of Louisiana State University Biodegradable porous device for long-term drug delivery with constant rate release and method of making the same
CA2190121A1 (en) 1994-03-15 1995-09-21 Edith Mathiowitz Polymeric gene delivery system
US5710165A (en) 1994-07-06 1998-01-20 Synthelabo Use of polyamine antagonists for the treatment of glaucoma
US5844102A (en) 1994-07-07 1998-12-01 University Of Maryland Baltimore County Glycohydrolase inhibitors, their preparation and use thereof
US5595760A (en) 1994-09-02 1997-01-21 Delab Sustained release of peptides from pharmaceutical compositions
AUPM897594A0 (en) 1994-10-25 1994-11-17 Daratech Pty Ltd Controlled release container
CA2204789C (en) 1994-11-10 2002-11-12 Paul Ashton Implantable refillable controlled release device to deliver drugs directly to an internal portion of the body
US5725493A (en) 1994-12-12 1998-03-10 Avery; Robert Logan Intravitreal medicine delivery
US5869079A (en) 1995-06-02 1999-02-09 Oculex Pharmaceuticals, Inc. Formulation for controlled release of drugs by combining hydrophilic and hydrophobic agents
US5773019A (en) 1995-09-27 1998-06-30 The University Of Kentucky Research Foundation Implantable controlled release device to deliver drugs directly to an internal portion of the body
US5743274A (en) 1996-03-18 1998-04-28 Peyman; Gholam A. Macular bandage for use in the treatment of subretinal neovascular members
US5824073A (en) 1996-03-18 1998-10-20 Peyman; Gholam A. Macular indentor for use in the treatment of subretinal neovascular membranes
US5904144A (en) 1996-03-22 1999-05-18 Cytotherapeutics, Inc. Method for treating ophthalmic diseases
US6299895B1 (en) 1997-03-24 2001-10-09 Neurotech S.A. Device and method for treating ophthalmic diseases
US6270954B1 (en) 1996-04-10 2001-08-07 The Regents Of The University Of California Correction of genetic defects using chemical chaperones
JP2000509971A (ja) 1996-04-10 2000-08-08 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア 化学的シャペローンを用いる遺伝的欠陥の修正
WO1998001121A1 (fr) * 1996-07-05 1998-01-15 Shionogi & Co., Ltd. Antagoniste des canaux calciques de type p/q
DE19638486A1 (de) 1996-09-20 1998-03-26 Basf Ag Hetaroylderivate
WO1999007418A2 (en) 1997-08-11 1999-02-18 Allergan Sales, Inc. Sterile bioerodible implant device with improved biocompatability and method
US5902598A (en) 1997-08-28 1999-05-11 Control Delivery Systems, Inc. Sustained release drug delivery devices
US6146366A (en) 1998-11-03 2000-11-14 Ras Holding Corp Device for the treatment of macular degeneration and other eye disorders
US6492333B1 (en) 1999-04-09 2002-12-10 Osteoscreen, Inc. Treatment of myeloma bone disease with proteasomal and NF-κB activity inhibitors
US6562836B1 (en) 1999-05-24 2003-05-13 Queen's University Of Kingston Methods and compounds for inhibiting amyloid deposits
US6416777B1 (en) 1999-10-21 2002-07-09 Alcon Universal Ltd. Ophthalmic drug delivery device
US6331313B1 (en) 1999-10-22 2001-12-18 Oculex Pharmaceticals, Inc. Controlled-release biocompatible ocular drug delivery implant devices and methods
WO2001040227A1 (fr) * 1999-12-03 2001-06-07 Ono Pharmaceutical Co., Ltd. Derives triazaspiro[5.5]undecane et medicaments contenant ces derives en tant que principe actif
US6656912B2 (en) 2000-01-20 2003-12-02 Washington University In St. Louis Methods to treat α1-antitrypsin deficiency
AU2001247848A1 (en) 2000-03-31 2001-10-15 Michigan State University Process for the preparation of 1,5-dideoxy-1,5-imino hexitols from oximes or imines
US6375972B1 (en) 2000-04-26 2002-04-23 Control Delivery Systems, Inc. Sustained release drug delivery devices, methods of use, and methods of manufacturing thereof
US6818203B2 (en) * 2000-08-11 2004-11-16 Schering Aktiengesellschaft Use of perfluoroalkyl-containing metal complexes as contrast media in MR-imaging for visualization of plaque, tumors and necroses
WO2002053128A2 (en) 2001-01-03 2002-07-11 Bausch & Lomb Incorporated Sustained release drug delivery devices with multiple agents
GB0118752D0 (en) 2001-08-01 2001-09-26 Pfizer Ltd Process for the production of quinazolines
EP1430042A2 (en) 2001-09-25 2004-06-23 SmithKline Beecham Corporation Bicyclic heterocycles as rxr ligands
US6976584B2 (en) 2002-06-26 2005-12-20 Bausch & Lomb Incorporated Package for surgical implant
US20040131648A1 (en) * 2002-10-24 2004-07-08 The Procter & Gamble Company Nuclear hormone receptor compounds, products and methods employing same
US20050048099A1 (en) 2003-01-09 2005-03-03 Allergan, Inc. Ocular implant made by a double extrusion process
EP2857036B1 (en) 2003-01-31 2016-12-21 Mount Sinai School of Medicine of New York University Combination therapy for treating protein deficiency disorders
EP1610772A4 (en) 2003-03-14 2008-06-18 Univ Washington RETINOID REPLACEMENT AND OPSIN AGONISTS AND METHOD OF USE THEREOF
WO2004108867A2 (en) 2003-06-02 2004-12-16 Flexitral, Inc. Cyclohexene carboamides and carbothioamides
CL2004001996A1 (es) 2003-08-08 2005-05-06 Eyetech Pharmaceuticals Inc Aptameros anti-vegf (factor de crecimiento endotelial vascular) con bloqueo nucleotidico 5'-5' o 3'-3' invertido, composicion que lo contiene, util para trastornos de neovascularizacion.
WO2005087210A2 (en) 2004-03-17 2005-09-22 Lars Michael Larsen Prevention of retinopathy by inhibition of the visual cycle
CA2571049C (en) 2004-06-18 2016-08-09 University Of Washington Retinal derivatives and methods for the use thereof for the treatment of visual disorders
EP2025336A1 (en) 2004-06-23 2009-02-18 Sirion Therapeutics, Inc. Retinyl derivatives for treating ophtalmic conditions
JP2008515778A (ja) 2004-08-18 2008-05-15 シリオン セラピューティクス， インコーポレイテッド 眼の状態を１３−シス−レチニル誘導体で処置するための組み合わせ方法、組成物および治療
US20080275133A1 (en) 2004-09-30 2008-11-06 University Of Calfornia-San Francisco Local Administration of Retinoids to Treat Deficiencies in Dark Adaptation
CA2588384A1 (en) 2004-11-23 2006-06-22 Ptc Therapeutics, Inc. Tetrahydrocarbazoles as active agents for inhibiting vegf production by translational control
EP1858499A4 (en) 2005-02-24 2010-03-03 Univ Washington METHOD FOR TREATING DEGENERATIVE NETWORK DISEASE
GB0506133D0 (en) * 2005-03-24 2005-05-04 Sterix Ltd Compound
CA2627319A1 (en) 2005-11-30 2007-06-07 Prakash Jagtap Purine derivatives and methods of use thereof
AU2007277035A1 (en) 2006-07-27 2008-01-31 University Of Florida Research Foundation, Inc. Compositions and methods for treating or preventing ophthalmic light toxicity
EP2069391A4 (en) * 2006-07-27 2009-12-30 Univ Florida COMPOSITIONS AND METHODS FOR TREATING AND / OR PREVENTING OPHTHALMOLOGICAL DISEASES
EP2069390A4 (en) 2006-07-27 2009-12-30 Univ Florida OPSIN STABILIZING COMPOUNDS AND METHODS OF USE
MY156662A (en) 2007-11-01 2016-03-15 Acucela Inc Amine derivative compounds for treating ophthalmic diseases and disorders
WO2009086303A2 (en) * 2007-12-21 2009-07-09 University Of Rochester Method for altering the lifespan of eukaryotic organisms
US20110015442A1 (en) 2008-03-17 2011-01-20 Toshiya Takahashi Sulfone compound and method for producing the same
US8674137B2 (en) 2008-10-22 2014-03-18 Acucela Inc. Compounds for treating ophthalmic diseases and disorders
WO2010074746A1 (en) 2008-12-23 2010-07-01 Bikam Pharmaceuticals, Inc. Methods of use for opsin binding ligands
IN2012DN00352A (h) 2009-06-16 2015-08-21 Bikam Pharmaceuticals Inc
BR112013032199A2 (pt) 2011-06-14 2017-12-12 Bikam Pharmaceuticals Inc ligantes de ligação à opsina, composições e métodos de utilização

Also Published As

Publication number Publication date
KR20120112351A (ko) 2012-10-11
CY1118221T1 (el) 2017-06-28
SI2442644T1 (sl) 2017-01-31
KR101921288B1 (ko) 2018-11-22
EA021747B1 (ru) 2015-08-31
EP3100723A1 (en) 2016-12-07
EP2442644A4 (en) 2013-05-22
PT2442644T (pt) 2016-11-09
ZA201200226B (en) 2013-06-26
KR20170041282A (ko) 2017-04-14
WO2010147653A1 (en) 2010-12-23
US20170037018A1 (en) 2017-02-09
KR20180099944A (ko) 2018-09-05
US20110003784A1 (en) 2011-01-06
AU2010260535B2 (en) 2015-08-20
KR101726358B1 (ko) 2017-04-26
EP3100723B1 (en) 2019-06-12
DK2442644T3 (en) 2016-10-10
SMT201600388T1 (it) 2017-03-08
EP2442644A1 (en) 2012-04-25
SMT201600388B (it) 2017-03-08
AU2010260535A1 (en) 2012-02-02
US9562022B2 (en) 2017-02-07
HRP20161477T1 (hr) 2016-12-16
ES2610429T3 (es) 2017-04-27
EA201270018A1 (ru) 2012-07-30
EP2442644B1 (en) 2016-08-10
CA2767895A1 (en) 2010-12-23
PL2442644T3 (pl) 2017-02-28
HUE031705T2 (en) 2017-07-28
IN2012DN00352A (h) 2015-08-21
CN102480943A (zh) 2012-05-30
LT2442644T (lt) 2016-12-12

Similar Documents

Publication Publication Date Title
CA2767895C (en) Opsin-binding ligands, compositions and methods of use
WO2011155983A1 (en) Opsin-binding ligands, compositions and methods of use
AU2016234993B2 (en) Opsin-binding ligands, compositions and methods of use
AU2015258306B2 (en) Opsin-binding ligands, compositions and methods of use
US20170137398A1 (en) Opsin-binding ligands, compositions and methods of use
HK1231770B (en) Opsin-binding ligands, compositions and methods of use
HK1231770A1 (en) Opsin-binding ligands, compositions and methods of use
WO2010074746A1 (en) Methods of use for opsin binding ligands
WO2012134971A2 (en) Opsin-binding ligands, compositions and methods of use
AU2017201135A1 (en) Opsin-binding ligands, compositions and methods of use

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20150409

MKLA Lapsed

Effective date: 20220301

MKLA Lapsed

Effective date: 20200831