[go: up one dir, main page]

WO2010029048A1 - Dérivés de 1,2,5-thiadiazole utiles en tant qu’adjuvants immunologiques - Google Patents

Dérivés de 1,2,5-thiadiazole utiles en tant qu’adjuvants immunologiques Download PDF

Info

Publication number
WO2010029048A1
WO2010029048A1 PCT/EP2009/061580 EP2009061580W WO2010029048A1 WO 2010029048 A1 WO2010029048 A1 WO 2010029048A1 EP 2009061580 W EP2009061580 W EP 2009061580W WO 2010029048 A1 WO2010029048 A1 WO 2010029048A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
compound
cells
compounds
independently represent
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.)
Ceased
Application number
PCT/EP2009/061580
Other languages
English (en)
Inventor
Anna Ranghetti
Federica Mainoldi
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.)
Sekmed Srl
Original Assignee
Sekmed Srl
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 Sekmed Srl filed Critical Sekmed Srl
Publication of WO2010029048A1 publication Critical patent/WO2010029048A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/10—1,2,5-Thiadiazoles; Hydrogenated 1,2,5-thiadiazoles

Definitions

  • the reaction is carried out according to conventional procedures for the chemistry of amides, preferably using a suitable peptide coupling reagent such as TBTU, 2-(1 H)- benzotriazole-1-yl)-1 ,1 ,3,3-tetramethyluronium tetrafluoroborate in the presence of N-hydroxybenzotriazole in a suitable solvent.
  • a suitable peptide coupling reagent such as TBTU, 2-(1 H)- benzotriazole-1-yl)-1 ,1 ,3,3-tetramethyluronium tetrafluoroborate
  • compositions containing a compound of formula (I) or a salt thereof in admixture with a pharmaceutically acceptable carrier are a further object of the present invention.
  • the compounds of formula (I) as well as pharmaceutical compositions containing them can be used also in combination with vaccines, as adjuvants.
  • the immune potentiator activity of the compounds of formula (I) has been tested in vitro and in vivo.
  • the experiments carried out to exploit DC properties showed that the compounds of formula (I) are capable of positively influence DC functionality, therefore usable as adjuvants.
  • the compounds object of the present invention are a class of small molecules, easy to synthesize at very low cost.
  • the compounds of formula (I) are able to activate
  • the compounds of formula (I) favour the production of molecules that create an environment unfavourable for the maintenance and propagation of allergic responses, their administration during the manifestation of an allergic reaction can be envisaged to reduce the symptoms.
  • the compounds of formula (I), object of the present invention are a class of small molecules with immune potentiator effects able to favour the development of immune responses considered to be protective against viral or bacterial infections. This particular property can be exploited to improve the efficacy of currently used vaccine formulations and to produce new vaccine formulations. In order to better illustrate the present invention without limiting it, the following examples are now given.
  • OVA ovalbumin
  • Immature D1 cells were cultured in Iscove's modified Dulbecco's medium (Sigma Chemical Co., Saint Louis, MO) supplemented with 10% FCS (Invitrogen Life Technologies, Carlsbad, CA) and 30% R1 medium, i.e. granulocyte-macrophage colony-stimulating factor-transfected NIH-3T3 fibroblast conditioned medium. Before stimulation, loosely adherent D1 cells were detached using 2 mM EDTA and washed once. The cells were then plated at a density of 1 x 106 cells/ml in 35 mm Petri dishes. NK cell purifica tion .
  • NK cells were positively selected from splenocytes. 108 cells were stained with biotinylated anti-pan-NK-cell (DX5) antibody (20 ⁇ g/ml), washed and incubated with streptavidin MicroBeads (Miltenyi Biotech, Bergisch Gladbach, Germany). Cells were then positively selected with MS columns, according to the manufacturer's recommendations. NK cells were used when more than 95% were NK1.1 positive.
  • DC activation and NK-DC co-cultures D1 cells were resuspended in IMDM complete medium plated in 24 well plates (2.5x10 5 cells/well). Cells were treated with the molecule. In some cases, after 0.5 hours NK cells (5x10 5 cells/well) were added directly to the culture. 18 hours after DC activation, clarified supernatants were tested for IL2 or IFN ⁇ production. Mice immunization.
  • mice were immunized at day 0 and at day 15 with 2 sc injections (50 ⁇ l each site). Total amount of antigen: 20 ⁇ g Ovalbumin. Compound X: 250 ⁇ g or 25 ⁇ g per mouse. IgGI and lgG2a serum levels.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention porte sur les composés de la formule (I), dans laquelle R1, R2, R3 et R4 ont les significations rapportées dans la description, qui s’utilisent en tant qu’adjuvants immunologiques. Ils peuvent être utilisés en tant qu'adjuvants pour des vaccins.
PCT/EP2009/061580 2008-09-09 2009-09-07 Dérivés de 1,2,5-thiadiazole utiles en tant qu’adjuvants immunologiques Ceased WO2010029048A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP08163973 2008-09-09
EP08163973.4 2008-09-09

Publications (1)

Publication Number Publication Date
WO2010029048A1 true WO2010029048A1 (fr) 2010-03-18

Family

ID=41381635

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2009/061580 Ceased WO2010029048A1 (fr) 2008-09-09 2009-09-07 Dérivés de 1,2,5-thiadiazole utiles en tant qu’adjuvants immunologiques

Country Status (1)

Country Link
WO (1) WO2010029048A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105121404A (zh) * 2013-03-15 2015-12-02 豪夫迈·罗氏有限公司 作为RORc调节剂的芳基磺酰胺和氨基磺酸衍生物
CN106661009A (zh) * 2014-04-28 2017-05-10 江苏康缘药业股份有限公司 抗肠病毒71噻二唑烷衍生物
CN113851716A (zh) * 2021-09-24 2021-12-28 珠海市赛纬电子材料股份有限公司 非水电解液及其锂离子电池

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1566380A1 (fr) * 2002-11-22 2005-08-24 Mitsubishi Pharma Corporation Composes d'isoquinolinone et leur utilisation a des fins medicinales

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1566380A1 (fr) * 2002-11-22 2005-08-24 Mitsubishi Pharma Corporation Composes d'isoquinolinone et leur utilisation a des fins medicinales

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 2007, FUKUSHIMA, HIROSHI ET AL: "Preparation of imidazolidinone derivatives as 11.beta.-HSD1 inhibitors", XP002559376, retrieved from STN Database accession no. 2007:1110441 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105121404A (zh) * 2013-03-15 2015-12-02 豪夫迈·罗氏有限公司 作为RORc调节剂的芳基磺酰胺和氨基磺酸衍生物
CN106661009A (zh) * 2014-04-28 2017-05-10 江苏康缘药业股份有限公司 抗肠病毒71噻二唑烷衍生物
JP2017513914A (ja) * 2014-04-28 2017-06-01 ジアンス カニョン ファーマシューティカル カンパニー リミテッド 抗エンテロウイルス７１チアジアゾリジン誘導体
US9988361B2 (en) * 2014-04-28 2018-06-05 Jiangsu Kanion Pharmaceutical Co., Ltd. Anti-enterovirus 71 thiadiazolidine derivative
CN113851716A (zh) * 2021-09-24 2021-12-28 珠海市赛纬电子材料股份有限公司 非水电解液及其锂离子电池

Similar Documents

Publication Publication Date Title
JP7104096B2 (ja) 脂質付加された免疫反応調節化合物の組成物、製剤及び方法
JP7010286B2 (ja) グアニジノ基で置換された縮合［１，２］イミダゾ［４，５－ｃ］環状化合物
CN108290845B (zh) 嘧啶化合物
JP6956070B2 (ja) グアニジン置換イミダゾ［４，５−ｃ］環状化合物
HK1197068A1 (en) Methods for preparation of glycosphingolipids and uses thereof
EA023536B1 (ru) Производные оксоаденина, конъюгированные с фосфо- или фосфонолипидами
JP2010537961A5 (fr)
CN105339346B (zh) Neoseptin：小分子佐剂
Hussein et al. Double conjugation strategy to incorporate lipid adjuvants into multiantigenic vaccines
JP6956071B2 (ja) 置換グアニジン基を含有するイミダゾ［４，５−ｃ］環状化合物
JP2021515755A (ja) Ｎ−１分枝基を有する置換イミダゾ［４，５−ｃ］キノリン化合物
US10576147B2 (en) Muramyl peptide derivative compound, synthesis and uses thereof
WO2010029048A1 (fr) Dérivés de 1,2,5-thiadiazole utiles en tant qu’adjuvants immunologiques
JP2021514000A (ja) ジアリールトレハロース化合物及びその使用
EP1711174B1 (fr) Compositions d'adjuvants
RU2008137968A (ru) Иммуномодулирующие и противоопухолевые пептиды
CN108884132B (zh) 胞壁酰肽衍生物化合物、其合成及其用途
CN111094285B (zh) 新型咪唑喹啉化合物及其制备方法和用途
EP3177601B1 (fr) Adjuvants à petites molécules indépendants du tlr
JP2021506891A (ja) 免疫応答調節剤として使用するための分岐鎖連結基を有するアミド置換イミダゾ［４，５−ｃ］キノリン化合物
WO2010041097A1 (fr) Nouveaux adjuvants de vaccin
TW202426444A (zh) 免疫調節劑及免疫調節劑結合物
EP4169513A1 (fr) Composition d'adjuvant comprenant des agonistes du sting
JP2021524474A (ja) Ｎ−１分枝状シクロアルキル置換イミダゾ［４，５−ｃ］キノリン化合物、組成物、及び方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 09782718

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 09782718

Country of ref document: EP

Kind code of ref document: A1