WO2016008946A1 - Novel compounds - Google Patents

Novel compounds Download PDF

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Publication number
WO2016008946A1
WO2016008946A1 PCT/EP2015/066203 EP2015066203W WO2016008946A1 WO 2016008946 A1 WO2016008946 A1 WO 2016008946A1 EP 2015066203 W EP2015066203 W EP 2015066203W WO 2016008946 A1 WO2016008946 A1 WO 2016008946A1
Authority
WO
WIPO (PCT)
Prior art keywords
amino
carboxyethyl
mmol
glutamine
thio
Prior art date
Application number
PCT/EP2015/066203
Other languages
English (en)
French (fr)
Inventor
Kingston Mills
Patrick Kelly
Jean-Gerard Tiraby
Thierry Lioux
Eric Perouzel
Original Assignee
The Provost, Fellows, Foundation Scholars, And The Other Members Of Board, Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth, Near Dublin
Invivogen Sas
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 The Provost, Fellows, Foundation Scholars, And The Other Members Of Board, Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth, Near Dublin, Invivogen Sas filed Critical The Provost, Fellows, Foundation Scholars, And The Other Members Of Board, Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth, Near Dublin
Priority to AU2015289178A priority Critical patent/AU2015289178A1/en
Priority to EP15736524.8A priority patent/EP3169698B1/en
Priority to CA2989065A priority patent/CA2989065A1/en
Priority to JP2017522733A priority patent/JP2017528514A/ja
Priority to US15/326,534 priority patent/US20170210778A1/en
Publication of WO2016008946A1 publication Critical patent/WO2016008946A1/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C07K5/0215—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing natural amino acids, forming a peptide bond via their side chain functional group, e.g. epsilon-Lys, gamma-Glu
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C237/12—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/57—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C323/58—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton
    • C07C323/59—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton with acylated amino groups bound to the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C07K5/06043—Leu-amino acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C07K5/06052—Val-amino acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic

Definitions

  • Prodrugs are any covalently bonded carriers that release a compound of formula (I) in vivo when such prodrug is administered to a patient.
  • Prodrugs are generally prepared by modifying functional groups in a way such that the modification is cleaved, either by routine manipulation or in vivo, yielding the parent compound.
  • Prodrugs include, for example, compounds of this invention wherein hydroxy, amine or sulfhydryl groups are bonded to any group that, when administered to a patient, cleaves to form the hydroxy, amine or sulfhydryl groups.
  • n 0 and X is sulphur.
  • the present invention provides a subset of compounds of formula (I), having formula (la) or a pharmaceutically acceptable salt thereof,
  • the present invention provides a subset of compounds of formula (I), of formula (lc) or a pharmaceutically acceptable salt thereof,
  • R7 is C1-C4 alkyl
  • chiral refers to molecules which have the property of non- superimposability on thei r m i rror image partner.
  • heteroatom as used herein means an atom of any element other than carbon or hydrogen. Preferred heteroatoms are nitrogen, oxygen, sulphur, phosphorus and selenium.
  • D amino acid or "D” and “L amino acid'Or “L” as used herein refer to absolute configuration of the amino acid, rather than a particular direction of rotation of plane-polarized light.
  • the usage herein is consistent with standard usage by those of skill in the art.
  • deprotection reaction processes include (a) catalytic hydrogenolysis using molecular hydrogen and palladium (H 2 /Pd) or catalytic transfer hydrogenolysis; (b) reduction with metallic sodium in liquid ammonia and (c) or reaction with strong acids using halogenated acids or hydrohalogenic acids, e.g. hydrobromic acid in acetic acid (HBr/AcOH) or liquid HF, BBr 3 /DCM, TFA/thioanisole and sulfonic acids.
  • halogenated acids or hydrohalogenic acids e.g. hydrobromic acid in acetic acid (HBr/AcOH) or liquid HF, BBr 3 /DCM, TFA/thioanisole and sulfonic acids.
  • the crude compounds or intermediates obtained according to the processes described herein can be subjected to purification.
  • Purification is carried out by any one of the methods known for this purpose, i.e. any conventional procedure involving extraction, precipitation, chromatography, electrophoresis, or the like.
  • HPLC high performance liquid chromatography
  • the elution can be carried using a water-acetonitrile-based solvent commonly employed for protein purification.
  • Compounds of formula (I) may be prepared by the general methods outlined hereinafter. In the following description, the groups X, W, R ⁇ , R2, R3, R4, R5, R7,
  • the sulfonyl reaction is conducted in accordance with standard methods of organic chemistry, see for example, Lieb. Ann. Chem. P. 641, 1990, with the appropriate sulfonyl chloride or bromide. This reaction is usually carried out in an inert organic solvent.
  • Ri6 is C1-C4 alkyl optionally substituted by Op , wherein p is a hydroxyl protecting group
  • R4 and m have the meanings defined in formula(I) or they are group or function with protecting groups thereof and P3 is a carboxy proctecting group, using the general methods described above for obtaining a peptide bond, following by removal of any protecting group.
  • Compounds of formula (IX) also known as mesolanthionine derivatives in which X represents a sulphur atom can be prepared from a compound of formula (XII),
  • R5 has the meanings of formula(I) or it is a protecting group thereof and P4 represents a nitrogen protecting group where Pi and P4 are orthogonal protections and D-amino acid derivatives of general formula (XIII),
  • reaction is conveniently carried out in an aprotic solvent such as dichloroethane, toluene and in the presence of a suitable lewis acid such as Boron trifluoride diethyl etherate.
  • aprotic solvent such as dichloroethane, toluene
  • a suitable lewis acid such as Boron trifluoride diethyl etherate.
  • the process consists in coupling, an aminoacid or a peptide of the general formula (XXII),

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Transplantation (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Peptides Or Proteins (AREA)
PCT/EP2015/066203 2014-07-16 2015-07-15 Novel compounds WO2016008946A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
AU2015289178A AU2015289178A1 (en) 2014-07-16 2015-07-15 Novel compounds
EP15736524.8A EP3169698B1 (en) 2014-07-16 2015-07-15 Novel compounds
CA2989065A CA2989065A1 (en) 2014-07-16 2015-07-15 Novel compounds
JP2017522733A JP2017528514A (ja) 2014-07-16 2015-07-15 新規化合物
US15/326,534 US20170210778A1 (en) 2014-07-16 2015-07-15 Novel compounds

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP14177268.1A EP2975046A1 (en) 2014-07-16 2014-07-16 Novel compounds
EP14177268.1 2014-07-16

Publications (1)

Publication Number Publication Date
WO2016008946A1 true WO2016008946A1 (en) 2016-01-21

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PCT/EP2015/066203 WO2016008946A1 (en) 2014-07-16 2015-07-15 Novel compounds

Country Status (6)

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US (1) US20170210778A1 (und)
EP (2) EP2975046A1 (und)
JP (1) JP2017528514A (und)
AU (1) AU2015289178A1 (und)
CA (1) CA2989065A1 (und)
WO (1) WO2016008946A1 (und)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10575469B2 (en) * 2016-07-14 2020-03-03 Cnh Industrial America Llc Net wrapping system
US11021514B2 (en) 2016-06-01 2021-06-01 Athira Pharma, Inc. Compounds
WO2021195372A1 (en) * 2020-03-26 2021-09-30 Nutrivert Llc Lipophilic enantiomers of desacetylglucosamine muramyl dipeptide with anti-inflammatory and growth promoting activity

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2089816A (en) * 1980-12-19 1982-06-30 Rhone Poulenc Sante Tri- tetra- and penta-peptides their preparation and compositions containing them
US20060194740A1 (en) 2005-02-25 2006-08-31 Ulevitch Richard J NOD1 as an anti-tumor agent
WO2007042273A2 (en) * 2005-10-14 2007-04-19 Thomas Frank Hofmann & Andreas Dunkel Kokumi flavour compounds and use
US7244557B2 (en) 2003-05-14 2007-07-17 Regents Of The University Of Michigan Method of screening modulators of Nod1 signaling
US7396812B2 (en) 2003-03-27 2008-07-08 Institut Pasteur Method for modulating Nod1 activity, use of a MTP related molecule for modulating Nod1 activity, and therapeutic applications thereof
WO2010072797A1 (en) 2008-12-22 2010-07-01 The Provost, Fellows and Scholars of The Holy and Undivided Trinity of Queen Elizabeth, Near Dublin Compounds and methods for the treatment of autoimmune and inflammatory disease
WO2012027455A1 (en) * 2010-08-24 2012-03-01 The University Of Toledo Glutathione-lanthionine compounds and methods related thereto

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2089816A (en) * 1980-12-19 1982-06-30 Rhone Poulenc Sante Tri- tetra- and penta-peptides their preparation and compositions containing them
US4401658A (en) 1980-12-19 1983-08-30 Rhone-Poulenc Sante Tri-, tetra, and penta-peptides, their preparation and compositions containing them
US7396812B2 (en) 2003-03-27 2008-07-08 Institut Pasteur Method for modulating Nod1 activity, use of a MTP related molecule for modulating Nod1 activity, and therapeutic applications thereof
US7244557B2 (en) 2003-05-14 2007-07-17 Regents Of The University Of Michigan Method of screening modulators of Nod1 signaling
US20060194740A1 (en) 2005-02-25 2006-08-31 Ulevitch Richard J NOD1 as an anti-tumor agent
US20090028795A1 (en) 2005-02-25 2009-01-29 Ulevitch Richard J NOD1 as an Anti-Tumor Agent
WO2007042273A2 (en) * 2005-10-14 2007-04-19 Thomas Frank Hofmann & Andreas Dunkel Kokumi flavour compounds and use
WO2010072797A1 (en) 2008-12-22 2010-07-01 The Provost, Fellows and Scholars of The Holy and Undivided Trinity of Queen Elizabeth, Near Dublin Compounds and methods for the treatment of autoimmune and inflammatory disease
WO2012027455A1 (en) * 2010-08-24 2012-03-01 The University Of Toledo Glutathione-lanthionine compounds and methods related thereto

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"Bioreversible Carriers in Drug Design", 1987, AMERICAN PHARMACEUTICAL ASSOCIATION AND PERGAMON PRESS
"Remington's Pharmaceutical Sciences", MACK PUBLISHING COMPANY
"Yuki Gosei 2", vol. 20, 1992, MARUZEN, article "Jikken Kagaku Koza", pages: 300
BERGE ET AL., J. PHARM, SCI., vol. 66, 1977, pages 1 - 19
BIGHLEY ET AL.: "Encyclopaedia of Pharmaceutical Technology", vol. 13, 1996, MARCEL DEKKER INC, pages: 453 - 497
BODANSKY ET AL.: "Peptide Synthesis", 1976, JOHN WILEY & SONS
CARPINO ET AL., J. AM. CHEM. SOC., vol. 92, no. 19, 1970, pages 5748 - 5749
CARPINO ET AL., J. ORG. CHEM., vol. 37, no. 22, 1972, pages 3404 - 3409
D. FLEISHER; S. RAMON; H. BARBRA: "Improved oral drug delivery: solubility limitations overcome by the use of prodrugs", ADVANCED DRUG DELIVERY REVIEWS, vol. 19, no. 2, 1996, pages 115 - 130, XP002478093, DOI: doi:10.1016/0169-409X(95)00103-E
GREENE, T.W.; WUTS, P.G.M: "Protective Groups in Organic Synthesis", 1991, WILEY
GREENE: "Protective Groups in Organic Synthesis", 2007, WILEY
HOUBEN-WEYL: "Methods of Organic Chemistry, Synthesis of Peptides and Peptidomimetics", vol. VOL E 22, 2002, GEORG THIEME VERLAG
LIEB. ANN. CHEM, 1990, pages 641
NOBUO IZUMIYA ET AL.: "Fundamentals and Experiments for Peptide Synthesis", 1985, MARUZEN CO., LTD.
P L GOULD, INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol. 33, 1986, pages 201 - 217
PAUL LLOYD- WILLIAMS; FERNANDO ALBERICIO; ERNEST GIRALT: "Chemical Approaches to the Synthesis of Peptides and Proteins", 1997, CRC PRESS
T. HIGUCHI; V. STELLA: "Prodrugs as Novel Delivery Systems", A.C.S. SYMPOSIUM SERIES, vol. 14
THEODORA W. GREENE: "Protective Groups in Organic Synthesis", 1999, JOHN WILEY & SONS

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11021514B2 (en) 2016-06-01 2021-06-01 Athira Pharma, Inc. Compounds
US10575469B2 (en) * 2016-07-14 2020-03-03 Cnh Industrial America Llc Net wrapping system
WO2021195372A1 (en) * 2020-03-26 2021-09-30 Nutrivert Llc Lipophilic enantiomers of desacetylglucosamine muramyl dipeptide with anti-inflammatory and growth promoting activity
AU2021241625B2 (en) * 2020-03-26 2025-04-24 Nutrivert Inc. Lipophilic enantiomers of desacetylglucosamine muramyl dipeptide with anti-inflammatory and growth promoting activity

Also Published As

Publication number Publication date
EP2975046A1 (en) 2016-01-20
JP2017528514A (ja) 2017-09-28
EP3169698B1 (en) 2018-12-05
AU2015289178A1 (en) 2017-02-16
CA2989065A1 (en) 2016-01-21
US20170210778A1 (en) 2017-07-27
EP3169698A1 (en) 2017-05-24

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