WO1999045926B1 - Condensed heterocyclic compounds as anti-inflammatory and immunomodulatory agents - Google Patents

Condensed heterocyclic compounds as anti-inflammatory and immunomodulatory agents

Info

Publication number
WO1999045926B1
WO1999045926B1 PCT/GB1999/000580 GB9900580W WO9945926B1 WO 1999045926 B1 WO1999045926 B1 WO 1999045926B1 GB 9900580 W GB9900580 W GB 9900580W WO 9945926 B1 WO9945926 B1 WO 9945926B1
Authority
WO
WIPO (PCT)
Prior art keywords
aryl
optionally substituted
alkyl
salts
inflammatory
Prior art date
Application number
PCT/GB1999/000580
Other languages
French (fr)
Other versions
WO1999045926A1 (en
Inventor
Patrick Vivian Richard Shannon
Thomas Eichholtz
David Linstead
Philip Masdin
Richard Skinner
Original Assignee
Univ Cardiff
Patrick Vivian Richard Shannon
Thomas Eichholtz
David Linstead
Philip Masdin
Richard Skinner
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 Univ Cardiff, Patrick Vivian Richard Shannon, Thomas Eichholtz, David Linstead, Philip Masdin, Richard Skinner filed Critical Univ Cardiff
Priority to AU26328/99A priority Critical patent/AU2632899A/en
Publication of WO1999045926A1 publication Critical patent/WO1999045926A1/en
Publication of WO1999045926B1 publication Critical patent/WO1999045926B1/en

Links

Classifications

    • 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
    • A61K31/403—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 condensed with carbocyclic rings, e.g. carbazole
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4245—Oxadiazoles
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates to use of a compound of formula (1) as an immunomodulatory or anti-inflammatory drug or for use in the treatment of a therapeutic indication in which inhibition of dehydro-orate dehydrogenase (DHODH) is beneficial and salts and physiologically functional salts thereof, wherein X, R?5, R6, A, Z1 and Z2¿ have the meanings given in Claim 1.

Claims

AMENDED CLAIMS[received by the International Bureau on 17 September 1999 (17.09.99); original claim 1 amended; remaining claims unchanged ( 1 page)]
1. Use of a compound of formula (1) in the manufacture of a medicament for use as an immunomodulatory or anti-inflammatory drug or for use in the treatment of a therapeutic indication in which inhibition of dihydro-orate dehydrogenase (DHODH) is beneficial:-
Figure imgf000003_0001
and salts and physiologically functional salts thereof,
wherein X is O, S, SO, SO2, CH2, CO or NR7, wherein R7 is H or the following groups which may be optionally substituted: cyloalkyl, cycloalkenyl, alkyl, alkenyl, alkynyl, aryl, aralkyl, acyl, aroyl, sulphonyl, alkylsulphonyl, arylsulphonyl or COOR;
R5 and R6 are independently selected from H, hydroxy, nitro, amino, halo, cyano, CHO, COR8, CO2R8 and the following groups which may be optionally substituted: alkyl, aryl, aryloxy, aralkyloxy, alkoxy, aralkyl, wherein R is optionally substituted alkyl and aryl;
A is:
Figure imgf000003_0002
wherein R1 is COR8, CHO, CH2OH, CH2OR8, CONH2, COOR8, CONHR8, CONR8R8, CONHNR8R8, COO(CH2)nNR8R8, CSOR8, CSSR8, COSR8, CSNHR8, CSNR8 R8,
PCT/GB1999/000580 1998-02-27 1999-02-25 Condensed heterocyclic compounds as anti-inflammatory and immunomodulatory agents WO1999045926A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU26328/99A AU2632899A (en) 1998-02-27 1999-02-25 Condensed heterocyclic compounds as anti-inflammatory and immunomodulatory agents

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9804343.3A GB9804343D0 (en) 1998-02-27 1998-02-27 Chemical compounds
GB9804343.3 1998-02-27

Publications (2)

Publication Number Publication Date
WO1999045926A1 WO1999045926A1 (en) 1999-09-16
WO1999045926B1 true WO1999045926B1 (en) 1999-11-04

Family

ID=10827805

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1999/000580 WO1999045926A1 (en) 1998-02-27 1999-02-25 Condensed heterocyclic compounds as anti-inflammatory and immunomodulatory agents

Country Status (3)

Country Link
AU (1) AU2632899A (en)
GB (1) GB9804343D0 (en)
WO (1) WO1999045926A1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9108961B2 (en) 2010-05-17 2015-08-18 Forum Pharmaceuticals, Inc. Crystalline form of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride
US9486441B2 (en) 2008-04-21 2016-11-08 Signum Biosciences, Inc. Compounds, compositions and methods for making the same
US9585877B2 (en) 2012-05-08 2017-03-07 Forum Pharmaceuticals, Inc. Methods of maintaining, treating or improving cognitive function

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003006424A1 (en) 2001-07-10 2003-01-23 4Sc Ag Novel compounds as anti-inflammatory, immunomodulatory and anti-proliferatory agents
DE10164139A1 (en) 2001-12-27 2003-07-10 Bayer Ag 2-heteroaryl carboxamides
SI1578741T1 (en) 2002-12-23 2011-11-30 4Sc Ag Aromatic compounds as anti-inflammatory, immunomodulatory and anti-proliferatory agents
ES2319596B1 (en) 2006-12-22 2010-02-08 Laboratorios Almirall S.A. NEW DERIVATIVES OF THE AMINO-NICOTINIC AND AMINO-ISONICOTINIC ACIDS.
EP2100881A1 (en) 2008-03-13 2009-09-16 Laboratorios Almirall, S.A. Pyrimidyl- or pyridinylaminobenzoic acid derivatives
UY31272A1 (en) 2007-08-10 2009-01-30 Almirall Lab NEW DERIVATIVES OF AZABIFENILAMINOBENZOIC ACID
EP2135610A1 (en) 2008-06-20 2009-12-23 Laboratorios Almirall, S.A. Combination comprising DHODH inhibitors and methotrexate
EP2239256A1 (en) 2009-03-13 2010-10-13 Almirall, S.A. Sodium salt of 5-cyclopropyl-2-{[2-(2,6-difluorophenyl)pyrimidin-5-yl]amino}benzoic acid as DHODH inhibitor
EP2228367A1 (en) 2009-03-13 2010-09-15 Almirall, S.A. Addition salts of amines containing hydroxyl and/or carboxylic groups with amino nicotinic acid derivatives as DHODH inhibitors
EP2230232A1 (en) 2009-03-13 2010-09-22 Almirall, S.A. Addition salts of tromethamine with azabiphenylaminobenzoic acid derivatives as DHODH inhibitors
EP2314577A1 (en) 2009-10-16 2011-04-27 Almirall, S.A. Process for manufacturing 2-[(3,5-difluoro-3'-methoxy-1,1'-biphenyl-4-yl)amino]nicotinic acid
US8686048B2 (en) 2010-05-06 2014-04-01 Rhizen Pharmaceuticals Sa Immunomodulator and anti-inflammatory compounds
UA108760C2 (en) 2010-07-01 2015-06-10 Calcium salts of the compound as anti-inflammatory, immunomodulatory and antiproliferative agents
EP2672963A4 (en) 2011-02-08 2015-06-24 Childrens Medical Center Methods for treatment of melanoma
WO2018136009A1 (en) 2017-01-20 2018-07-26 Aslan Pharmaceuticals Pte Ltd Combination therapy
IL307422A (en) 2018-03-16 2023-12-01 Immunic Ag Calcium salt polymorph inhibitors of dihydroorotate dehydrogenase and processes for preparing same

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9215361D0 (en) * 1992-07-20 1992-09-02 Wellcome Found Heterocyclic compounds
GB9401921D0 (en) * 1994-02-01 1994-03-30 Wellcome Found Heterocyclic compounds
GB9401994D0 (en) * 1994-02-02 1994-03-30 Wellcome Found Heterocyclic compounds
GB9413758D0 (en) * 1994-07-07 1994-08-24 Wellcome Found Heterocyclic compounds

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9486441B2 (en) 2008-04-21 2016-11-08 Signum Biosciences, Inc. Compounds, compositions and methods for making the same
US9108961B2 (en) 2010-05-17 2015-08-18 Forum Pharmaceuticals, Inc. Crystalline form of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride
US9273044B2 (en) 2010-05-17 2016-03-01 Forum Pharmaceuticals, Inc. Crystalline form of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate
US9550767B2 (en) 2010-05-17 2017-01-24 Forum Pharmaceuticals, Inc. Crystalline form of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate
US9585877B2 (en) 2012-05-08 2017-03-07 Forum Pharmaceuticals, Inc. Methods of maintaining, treating or improving cognitive function

Also Published As

Publication number Publication date
WO1999045926A1 (en) 1999-09-16
GB9804343D0 (en) 1998-04-22
AU2632899A (en) 1999-09-27

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