WO1999034804A1 - Agonistes de recepteur d'adenosine a¿2a? - Google Patents

Agonistes de recepteur d'adenosine a¿2a? Download PDF

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Publication number
WO1999034804A1
WO1999034804A1 PCT/US1999/000366 US9900366W WO9934804A1 WO 1999034804 A1 WO1999034804 A1 WO 1999034804A1 US 9900366 W US9900366 W US 9900366W WO 9934804 A1 WO9934804 A1 WO 9934804A1
Authority
WO
WIPO (PCT)
Prior art keywords
rolipram
alkyl
groups
adenosine receptor
type
Prior art date
Application number
PCT/US1999/000366
Other languages
English (en)
Inventor
Joel M. Linden
Gail W. Sullivan
Ian Sarembock
W. Michael Sheld
Original Assignee
The University Of Virginia Patent Foundation
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 University Of Virginia Patent Foundation filed Critical The University Of Virginia Patent Foundation
Priority to EP99901368A priority Critical patent/EP1044004A1/fr
Priority to AU21082/99A priority patent/AU2108299A/en
Priority to JP2000527253A priority patent/JP2002500188A/ja
Priority to CA002317093A priority patent/CA2317093A1/fr
Publication of WO1999034804A1 publication Critical patent/WO1999034804A1/fr

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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • 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

Definitions

  • Figure 3 illustrates the synergistic effect of WRC-0474[SHA 211] and rolipram in inhibiting TNF ⁇ -stimulated adherent PMN superoxide release;
  • each of R 5 and R 6 independently may be hydrogen, C 3.7 -cycloalkyl, or any of the meanings of R 1 , provided that R 5 and R 6 are not both hydrogen;
  • R 18 and R 19 each are alike or different and are hydrocarbon radicals having up to 18 carbon atoms with at least one being other than methyl, a heterocychc ring, or alkyl of 1-5 carbon atoms which is substituted by one or more of halogen atoms, hydroxy, carboxy, alkoxy, alkoxycarbonyl or an amino group or amino.
  • alkyl groups examples include hydroxy groups, e.g., 2-hydroxyethyl or 3-hydroxypropyl; carboxy groups, e.g., carboxymethyl or carboxyethyl; alkoxy groups, wherein each alkoxy group contains 1-5 carbon atoms, e.g., ethoxymethyl, isopropoxymethyl, 2- methoxyethyl, 2-isopropoxyethyl, 2-butoxyethyl, 2-isobutyoxyethyl, and 3- pentoxypropyl.
  • alkoxycarbonyl of 1-5 carbon atoms in the alkoxy group are alkoxycarbonyl of 1-5 carbon atoms in the alkoxy group.
  • the compound of formula (I) may be administered in the form of a pharmaceutically acceptable salt.
  • salts include acid addition salts.
  • Preferred pharmaceutically acceptable addition salts include salts of mineral acids, for example, hydrochloric acid, sulfuric acid, nitric acid, and the like; salts of monobasic carboxylic acids, such as, for example, acetic acid, propionic acid, and the like; salts of dibasic carboxylic acids, such as maleic acid, fumaric acid, oxalic acid, and the like; and salts of tribasic carboxylic acids, such as carboxysuccinic acid, citric acid, and the like.
  • the amount of active agent per oral dosage unit usually is 0.1-20 mg, preferably 0.5-10 mg.
  • the daily dosage is usually 0.1- 50 mg, preferably 1-30 mg p.o.
  • the amount of active agent per dosage unit is usually 0.005-10 mg, preferably 0.01-5 mg.
  • the daily dosage is usually 0.01-20 mg, preferably 0.02-5 mg i.v. or i.m.
  • dosage levels and their related procedures would be consistent with those known in the art, such as those dosage levels and procedures described in U.S. Patent No. 5,565,462 to Eitan et al., which is incorporated herein by reference.
  • the dosage of the A 2A adenosine receptor agonist may be reduced by a factor of 5 to 10 from the dosage used when no Type IV phosphodiesterase inhibitor is administered. This reduces the possibility of side effects.
  • the present invention will now be described in more detail in the context of the coadministration of WRC-0470, WRC-0474[SHA 211], WRC-0090 or WRC-0018 and rolipram. However, it is to be understood that the present invention may be practiced with other compounds of formula (I) and other Type IV phosphodiesterase inhibitors of formula (V).
  • Adenoviral- mediated gene transfer affords several advantages over other techniques.
  • gene expression is only transient, and has been observed for 7-14 days with diminution or loss of expression by 28 days. Lack of persistence may result form host immune cytolytic responses directed against infected cells.
  • the inflammatory response generated by the present generation of adenovims results in neointimal lesion formation and may thus offset the benefit of a therapeutic gene.

Abstract

L'invention concerne des agonistes de récepteurs d'adénosine A2A combinés avec du rolipram, leurs dérivés ou d'autres inhibiteurs de phosphodiestérase (PDE) type IV qui sont efficaces pour le traitement de maladies inflammatoires.
PCT/US1999/000366 1998-01-08 1999-01-07 Agonistes de recepteur d'adenosine a¿2a? WO1999034804A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP99901368A EP1044004A1 (fr) 1998-01-08 1999-01-07 Agonistes de recepteur d'adenosine a 2a?
AU21082/99A AU2108299A (en) 1998-01-08 1999-01-07 A2A adenosine receptor agonists
JP2000527253A JP2002500188A (ja) 1998-01-08 1999-01-07 Ａ２ａアデノシンレセプター作動因子
CA002317093A CA2317093A1 (fr) 1998-01-08 1999-01-07 Agonistes de recepteur d'adenosine a2a

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US393098A 1998-01-08 1998-01-08
US09/003,930 1998-01-08

Publications (1)

Publication Number Publication Date
WO1999034804A1 true WO1999034804A1 (fr) 1999-07-15

Family

ID=21708282

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/000366 WO1999034804A1 (fr) 1998-01-08 1999-01-07 Agonistes de recepteur d'adenosine a¿2a?

Country Status (5)

Country Link
EP (1) EP1044004A1 (fr)
JP (1) JP2002500188A (fr)
AU (1) AU2108299A (fr)
CA (1) CA2317093A1 (fr)
WO (1) WO1999034804A1 (fr)

Cited By (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000072799A2 (fr) * 1999-05-27 2000-12-07 The University Of Virginia Patent Foundation Methode et compositions permettant de traiter la reponse inflammatoire
WO2001081346A2 (fr) * 2000-04-25 2001-11-01 Icos Corporation Inhibiteurs de la phosphatidyl-inositol 3-kinase delta humaine
US6326359B1 (en) * 1998-10-16 2001-12-04 Pfizer Inc Adenosine A2A receptor agonists as antiinflammatory agents
WO2001093909A2 (fr) * 2000-06-06 2001-12-13 Glaxo Group Limited Procede de traitement du cancer
WO2002000676A1 (fr) * 2000-06-27 2002-01-03 Pfizer Limited Derives de purine
US6339072B2 (en) 1997-06-18 2002-01-15 Discovery Therapeutics Inc. Compositions and methods for preventing restenosis following revascularization procedures
US6514949B1 (en) 1994-07-11 2003-02-04 University Of Virginia Patent Foundation Method compositions for treating the inflammatory response
US6624158B2 (en) 2000-09-15 2003-09-23 Pfizer Inc Purine derivatives
WO2003086408A1 (fr) * 2002-04-10 2003-10-23 University Of Virginia Patent Foundation Utilisation d'agonistes du recepteur d'adenosine a2a dans le traitement de maladies inflammatoires
US6667300B2 (en) 2000-04-25 2003-12-23 Icos Corporation Inhibitors of human phosphatidylinositol 3-kinase delta
WO2004078184A1 (fr) * 2003-03-07 2004-09-16 Cambridge Biotechnology Ltd Utilisation d'agonistes de recepteur d'adenosine en therapie
US6921753B2 (en) 2000-06-27 2005-07-26 Pfizer Inc Purine derivatives
US7214665B2 (en) 2001-10-01 2007-05-08 University Of Virginia Patent Foundation 2-propynyl adenosine analogs having A2A agonist activity and compositions thereof
US7226913B2 (en) 1999-02-01 2007-06-05 University Of Virginia Patent Foundation Pharmaceutical compositions having A2A adenosine receptor agonist activity
EP1802316A2 (fr) * 2004-09-20 2007-07-04 Inotek Pharmaceuticals Corporation Dérivés de la purine et leurs procédés d'utilisation
US7378400B2 (en) 1999-02-01 2008-05-27 University Of Virginia Patent Foundation Method to reduce an inflammatory response from arthritis
US7427606B2 (en) * 1999-02-01 2008-09-23 University Of Virginia Patent Foundation Method to reduce inflammatory response in transplanted tissue
US7442687B2 (en) 2004-08-02 2008-10-28 The University Of Virginia Patent Foundation 2-polycyclic propynyl adenosine analogs having A2A agonist activity
US7576069B2 (en) 2004-08-02 2009-08-18 University Of Virginia Patent Foundation 2-polycyclic propynyl adenosine analogs having A2A agonist activity
US7605143B2 (en) 2004-08-02 2009-10-20 University Of Virginia Patent Foundation 2-propynyl adenosine analogs with modified 5′-ribose groups having A2A agonist activity
EP2178370A1 (fr) * 2007-07-17 2010-04-28 Combinatorx, Incorporated Combinaisons pour le traitement des troubles prolifératifs des lymphocytes b
US7759321B2 (en) 2003-03-07 2010-07-20 Cambridge Biotechnology Ltd Compounds for the treatment of pain
US7932260B2 (en) 2004-05-13 2011-04-26 Icos Corporation Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta
US8252766B2 (en) 2002-12-09 2012-08-28 Cbt Development Limited Use of spongosine for the treatment of pain
US8440677B2 (en) 2009-03-24 2013-05-14 Gilead Calistoga Llc Atropisomers of 2-purinyl-3-tolyl-quinazolinone derivatives and methods of use
US8691829B2 (en) 2009-07-21 2014-04-08 Gilead Calistoga Llc Treatment of liver disorders with PI3K inhibitors
US8865730B2 (en) 2012-03-05 2014-10-21 Gilead Calistoga Llc Polymorphic forms of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one
US9238070B2 (en) 2008-11-13 2016-01-19 Gilead Calistoga Llc Therapies for hematologic malignancies
US9492449B2 (en) 2008-11-13 2016-11-15 Gilead Calistoga Llc Therapies for hematologic malignancies
US9505796B2 (en) 2006-03-21 2016-11-29 Crozet Medical Gmbh Phosphorylated A2A receptor agonists
US9567337B2 (en) 2013-12-20 2017-02-14 Gilead Calistoga Llc Process methods for phosphatidylinositol 3-kinase inhibitors
US9708327B2 (en) 2013-12-20 2017-07-18 Gilead Calistoga Llc Polymorphic forms of a hydrochloride salt of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one
US11021467B2 (en) 2014-06-13 2021-06-01 Gilead Sciences, Inc. Phosphatidylinositol 3-kinase inhibitors

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BUSTER B(A) ET AL: "The effect of adenosine receptor agonists on neutrophil pleocytosis and blood-brain barrier pathophysiology in experimental bacterial meningitis.", ABSTRACTS OF THE INTERSCIENCE CONFERENCE ON ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 37TH INTERSCIENCE CONFERENCE ON ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 37, pages 39, XP002104913 *
SULLIVAN GW ET AL: "The specific type IV phosphodiesterase inhibitor rolipram combined with adenosine reduces tumor necrosis factor-alpha-primed neutrophil oxidative activity.", INT J IMMUNOPHARMACOL;17(10):793-803 1995, XP002104914 *
WALKER BA ET AL: "Adenosine A2a receptor activation delays apoptosis in human neutrophils.", J IMMUNOL, MAR 15 1997, 158 (6) P2926-31, UNITED STATES, XP002104915 *

Cited By (73)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6514949B1 (en) 1994-07-11 2003-02-04 University Of Virginia Patent Foundation Method compositions for treating the inflammatory response
US6339072B2 (en) 1997-06-18 2002-01-15 Discovery Therapeutics Inc. Compositions and methods for preventing restenosis following revascularization procedures
US6372723B1 (en) 1997-06-18 2002-04-16 Discovery Therapeutics, Inc. Compositions and methods for preventing restenosis following revascularization procedures
US6326359B1 (en) * 1998-10-16 2001-12-04 Pfizer Inc Adenosine A2A receptor agonists as antiinflammatory agents
US7378400B2 (en) 1999-02-01 2008-05-27 University Of Virginia Patent Foundation Method to reduce an inflammatory response from arthritis
US7226913B2 (en) 1999-02-01 2007-06-05 University Of Virginia Patent Foundation Pharmaceutical compositions having A2A adenosine receptor agonist activity
US7427606B2 (en) * 1999-02-01 2008-09-23 University Of Virginia Patent Foundation Method to reduce inflammatory response in transplanted tissue
WO2000072799A3 (fr) * 1999-05-27 2001-07-12 Univ Virginia Methode et compositions permettant de traiter la reponse inflammatoire
WO2000072799A2 (fr) * 1999-05-27 2000-12-07 The University Of Virginia Patent Foundation Methode et compositions permettant de traiter la reponse inflammatoire
US8637533B2 (en) 2000-04-25 2014-01-28 Icos Corporation Inhibitors of human phosphatidylinositol 3-kinase delta
US6800620B2 (en) 2000-04-25 2004-10-05 Icos Inhibitors of human phosphatidylinositol 3-kinase delta
US6518277B1 (en) 2000-04-25 2003-02-11 Icos Corporation Inhibitors of human phosphatidylinositol 3-kinase delta
US10695349B2 (en) 2000-04-25 2020-06-30 Icos Corporation Inhibitors of human phosphatidylinositol 3-kinase delta
US8653077B2 (en) 2000-04-25 2014-02-18 Icos Corporation Inhibitors of human phosphatidylinositol 3-kinase delta
US6667300B2 (en) 2000-04-25 2003-12-23 Icos Corporation Inhibitors of human phosphatidylinositol 3-kinase delta
US9487772B2 (en) 2000-04-25 2016-11-08 Icos Corporation Inhibitors of human phosphatidylinositol 3-kinase delta
EP2223922A3 (fr) * 2000-04-25 2011-04-27 ICOS Corporation Inhibiteurs delta de phosphatidyl-inositol 3-kinase humaine
US10010550B2 (en) 2000-04-25 2018-07-03 Icos Corporation Inhibitors of human phosphatidylinositol 3-kinase delta
US10398695B2 (en) 2000-04-25 2019-09-03 Icos Corporation Inhibitors of human phosphatidylinositol 3-kinase delta
US6949535B2 (en) 2000-04-25 2005-09-27 Icos Corporation Inhibitors of human phosphatidyl-inositol 3-kinase delta
EA008241B1 (ru) * 2000-04-25 2007-04-27 Айкос Корпорейшн Ингибиторы фосфатидилинозитол-3-киназы дельта человека
WO2001081346A3 (fr) * 2000-04-25 2002-03-21 Icos Corp Inhibiteurs de la phosphatidyl-inositol 3-kinase delta humaine
US8138195B2 (en) 2000-04-25 2012-03-20 Icos Corporation Inhibitors of human phosphatidylinositol 3-kinase delta
WO2001081346A2 (fr) * 2000-04-25 2001-11-01 Icos Corporation Inhibiteurs de la phosphatidyl-inositol 3-kinase delta humaine
WO2001093909A3 (fr) * 2000-06-06 2002-12-05 Glaxo Group Ltd Procede de traitement du cancer
WO2001093909A2 (fr) * 2000-06-06 2001-12-13 Glaxo Group Limited Procede de traitement du cancer
US7238676B2 (en) 2000-06-27 2007-07-03 Pfizer Inc. Purine derivatives
US6921753B2 (en) 2000-06-27 2005-07-26 Pfizer Inc Purine derivatives
AP1372A (en) * 2000-06-27 2005-02-21 Pfizer Purine derivatives.
WO2002000676A1 (fr) * 2000-06-27 2002-01-03 Pfizer Limited Derives de purine
US6624158B2 (en) 2000-09-15 2003-09-23 Pfizer Inc Purine derivatives
US7214665B2 (en) 2001-10-01 2007-05-08 University Of Virginia Patent Foundation 2-propynyl adenosine analogs having A2A agonist activity and compositions thereof
WO2003086408A1 (fr) * 2002-04-10 2003-10-23 University Of Virginia Patent Foundation Utilisation d'agonistes du recepteur d'adenosine a2a dans le traitement de maladies inflammatoires
US8252766B2 (en) 2002-12-09 2012-08-28 Cbt Development Limited Use of spongosine for the treatment of pain
WO2004078184A1 (fr) * 2003-03-07 2004-09-16 Cambridge Biotechnology Ltd Utilisation d'agonistes de recepteur d'adenosine en therapie
US7759321B2 (en) 2003-03-07 2010-07-20 Cambridge Biotechnology Ltd Compounds for the treatment of pain
US7790698B2 (en) 2003-03-07 2010-09-07 Cambridge Biotechnology Ltd Use of adenosine receptor agonists in therapy
US7932260B2 (en) 2004-05-13 2011-04-26 Icos Corporation Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta
US8980901B2 (en) 2004-05-13 2015-03-17 Icos Corporation 5-fluoro-3-phenyl-2[1-(9H-purin-6-ylamino)propyl]-3H-quinazolin-4-one and 6-fluoro-3-phenyl-2-[1-(9H-purin-6-ylamino)ethyl]-3H-quinazolin-4-one as inhibitors of human phosphatidylinositol 3-kinase delta
US10336756B2 (en) 2004-05-13 2019-07-02 Icos Corporation (S)-2-(1-aminopropyl)-5-fluoro-3-phenylquinazolin-4(3H)-one precursor of a quinazolinone as inhibitor of human phosphatidylinositol 3-kinase delta
US9149477B2 (en) 2004-05-13 2015-10-06 Icos Corporation 5-fluoro-3-phenyl-2-[1-(9h-purin-6-ylamino)propyl]-3h-quinazolin-4-one as an inhibitor of human phosphatidylinositol 3-kinase delta
US8207153B2 (en) 2004-05-13 2012-06-26 Icos Corporation Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta
US8993583B2 (en) 2004-05-13 2015-03-31 Icos Corporation 5-fluoro-3-phenyl-2-[1-(9H-purin-6-ylamino)propyl]-3H-quinazolin-4-one and 6-fluoro-3-phenyl-2-[1-(9H-purin-6-ylamino)ethyl]-3H-quinazolin-4-one as inhibitors of human phosphatidylinositol 3-kinase delta
US10906907B2 (en) 2004-05-13 2021-02-02 Icos Corporation Tert-butyl (s)-(1-(5-fluoro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)propyl)carbamate precursor of a quinazolinone inhibitor of human phosphatidylinositol 3-kinase delta and a process for preparing thereof
USRE44599E1 (en) 2004-05-13 2013-11-12 Icos Corporation Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta
USRE44638E1 (en) 2004-05-13 2013-12-10 Icos Corporation Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta
US7989431B2 (en) 2004-08-02 2011-08-02 University Of Virginia Patent Foundation 2-propynyl adenosine analogs with modified 5′-ribose groups having A2A agonist activity
US7576069B2 (en) 2004-08-02 2009-08-18 University Of Virginia Patent Foundation 2-polycyclic propynyl adenosine analogs having A2A agonist activity
US7442687B2 (en) 2004-08-02 2008-10-28 The University Of Virginia Patent Foundation 2-polycyclic propynyl adenosine analogs having A2A agonist activity
US7605143B2 (en) 2004-08-02 2009-10-20 University Of Virginia Patent Foundation 2-propynyl adenosine analogs with modified 5′-ribose groups having A2A agonist activity
EP1802316A2 (fr) * 2004-09-20 2007-07-04 Inotek Pharmaceuticals Corporation Dérivés de la purine et leurs procédés d'utilisation
US7863253B2 (en) 2004-09-20 2011-01-04 Inotek Pharmaceuticals Corporation Purine Derivatives and methods of use thereof
EP1802316A4 (fr) * 2004-09-20 2010-08-25 Inotek Pharmaceuticals Corp Dérivés de la purine et leurs procédés d'utilisation
US8133880B2 (en) 2004-09-20 2012-03-13 Inotek Pharmaceuticals Corporation Purine derivatives and methods of use thereof
US9505796B2 (en) 2006-03-21 2016-11-29 Crozet Medical Gmbh Phosphorylated A2A receptor agonists
EP2178370A4 (fr) * 2007-07-17 2011-01-12 Zalicus Inc Combinaisons pour le traitement des troubles prolifératifs des lymphocytes b
EP2178370A1 (fr) * 2007-07-17 2010-04-28 Combinatorx, Incorporated Combinaisons pour le traitement des troubles prolifératifs des lymphocytes b
US9238070B2 (en) 2008-11-13 2016-01-19 Gilead Calistoga Llc Therapies for hematologic malignancies
US10154998B2 (en) 2008-11-13 2018-12-18 Gilead Calistoga Llc Therapies for hematologic malignancies
US9492449B2 (en) 2008-11-13 2016-11-15 Gilead Calistoga Llc Therapies for hematologic malignancies
US8440677B2 (en) 2009-03-24 2013-05-14 Gilead Calistoga Llc Atropisomers of 2-purinyl-3-tolyl-quinazolinone derivatives and methods of use
US8691829B2 (en) 2009-07-21 2014-04-08 Gilead Calistoga Llc Treatment of liver disorders with PI3K inhibitors
US9469643B2 (en) 2012-03-05 2016-10-18 Gilead Calistoga, LLC. Polymorphic forms of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one
US10730879B2 (en) 2012-03-05 2020-08-04 Gilead Calistoga Llc Polymorphic forms of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one
US8865730B2 (en) 2012-03-05 2014-10-21 Gilead Calistoga Llc Polymorphic forms of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one
US10059677B2 (en) 2013-12-20 2018-08-28 Gilead Calistoga Llc Process for preparing phosphatidylinositol 3-kinase inhibitors and intermediates thereof
US10047060B2 (en) 2013-12-20 2018-08-14 Gilead Calistoga Llc Process methods for phosphatidylinositol 3-kinase inhibitors
US9708327B2 (en) 2013-12-20 2017-07-18 Gilead Calistoga Llc Polymorphic forms of a hydrochloride salt of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one
US10414737B2 (en) 2013-12-20 2019-09-17 Gilead Sciences, Inc. Process methods for phosphatidylinositol 3-kinase inhibitors
US10442805B2 (en) 2013-12-20 2019-10-15 Gilead Calistoga Llc Polymorphic forms of a hydrochloride salt of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one
US9567337B2 (en) 2013-12-20 2017-02-14 Gilead Calistoga Llc Process methods for phosphatidylinositol 3-kinase inhibitors
US10954199B2 (en) 2013-12-20 2021-03-23 Gilead Sciences, Inc. Process methods for phosphatidylinositol 3-kinase inhibitors
US11021467B2 (en) 2014-06-13 2021-06-01 Gilead Sciences, Inc. Phosphatidylinositol 3-kinase inhibitors

Also Published As

Publication number Publication date
AU2108299A (en) 1999-07-26
JP2002500188A (ja) 2002-01-08
EP1044004A1 (fr) 2000-10-18
CA2317093A1 (fr) 1999-07-15

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