Evidence map›Paper›PMID 26248802›Full record

ArticleBioorganic & medicinal chemistry letters2015

Boronic acid-containing aminopyridine- and aminopyrimidinecarboxamide CXCR1/2 antagonists: Optimization of aqueous solubility and oral bioavailability.

Aaron D Schuler, Courtney A Engles, Dean Y Maeda, Mark T Quinn, Liliya N Kirpotina, Winston N Wicomb, S Nicholas Mason, Richard L Auten, John A Zebala

Open access · greenAbstract read
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.6field-weighted citation impact, top 31% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Therapeutic inhibition of CXCR1/2: where do we stand?Internal and emergency medicine · 2023
    Review
  5. Review
  6. Discovery of 1,5-Dihydro-4ACS medicinal chemistry letters · 2021
    Article
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Aaron D SchulerSyntrix Biosystems, 215 Clay Street NW, Suite B-5, Auburn, WA 98001, United States. Electronic address: aschuler@syntrixbio.com.
Courtney A EnglesSyntrix Biosystems, 215 Clay Street NW, Suite B-5, Auburn, WA 98001, United States.
Dean Y MaedaSyntrix Biosystems, 215 Clay Street NW, Suite B-5, Auburn, WA 98001, United States.
Mark T QuinnDepartment of Microbiology and Immunology, Montana State University, 960 Technology Boulevard, Bozeman, MT 59717, United States.
Liliya N KirpotinaDepartment of Microbiology and Immunology, Montana State University, 960 Technology Boulevard, Bozeman, MT 59717, United States.
Winston N WicombInfectious Disease Research Institute, 1616 Eastlake Avenue East, Seattle, WA 98102, United States.
S Nicholas MasonDepartment of Pediatrics (Neonatal Medicine), DUMC Box 3373, Duke University, Durham, NC 27710, United States.
Richard L AutenDepartment of Pediatrics (Neonatal Medicine), DUMC Box 3373, Duke University, Durham, NC 27710, United States.
John A ZebalaSyntrix Biosystems, 215 Clay Street NW, Suite B-5, Auburn, WA 98001, United States.
Syntrix Biosystems (United States) · USDuke University · USMontana State University · USInfectious Disease Research Institute · US

Funding

Optimization of CXCR1/2 antagonist SX-576 for the treatment of BPD and COPDR44HL072614 · NHLBI · SYNTRIX BIOSYSTEMS, INC. · PI MAEDA, DEAN YOSHIMASA, ZEBALA, JOHN A · 2005 to 2014
$6.2M
Pilot Grants ProgramP30GM110732 · NIGMS · MONTANA STATE UNIVERSITY - BOZEMAN · PI QUINN, MARK T · 2014 to 2018
$5.4M
NHLBI NIH HHS R44 HL072614NHLBI NIH HHS R44HL072614NIGMS NIH HHS P30 GM110732
6 · The paper itself

Abstract

The chemokine receptors CXCR1 and CXCR2 are important pharmaceutical targets due to their key roles in inflammatory diseases and cancer progression. We have previously identified 2-[5-(4-fluoro-phenylcarbamoyl)-pyridin-2-ylsulfanylmethyl]-phenylboronic acid (SX-517) and 6-(2-boronic acid-5-trifluoromethoxy-benzylsulfanyl)-N-(4-fluoro-phenyl)-nicotinamide (SX-576) as potent non-competitive boronic acid-containing CXCR1/2 antagonists. Herein we report the synthesis and evaluation of aminopyridine and aminopyrimidine analogs of SX-517 and SX-576, identifying (2-{(benzyl)[(5-boronic acid-2-pyridyl)methyl]amino}-5-pyrimidinyl)(4-fluorophenylamino)formaldehyde as a potent chemokine antagonist with improved aqueous solubility and oral bioavailability.

Indexed as

Administration, OralBiological AvailabilityBoronic AcidsDose-Response Relationship, DrugHumansMolecular StructureNiacinamideReceptors, Interleukin-8AReceptors, Interleukin-8BSolubilityStructure-Activity RelationshipWater2-(5-(4-fluorophenylcarbamoyl)pyridin-2-ylsulfanylmethyl)phenylboronic acidBoronic AcidsNiacinamideReceptors, Interleukin-8AReceptors, Interleukin-8BSX-576WaterAntagonistAsthmaCOPDCXCR1CXCR2

Identifiers

PMID26248802
PMCPMC4564001
OpenAlexW982281751

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.