Evidence map›Paper›PMID 24900813›Full record

ArticleACS medicinal chemistry letters2014

Novel Peptidomimetic Hepatitis C Virus NS3/4A Protease Inhibitors Spanning the P2-P1' Region.

Anna K Lampa, Sara M Bergman, Sofia S Gustafsson, Hiba Alogheli, Eva B Akerblom, Gunnar G Lindeberg, Richard M Svensson, Per Artursson, U Helena Danielson, Anders Karlén and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS medicinal chemistry letters, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
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

11 authors.

Anna K LampaDepartment of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University , BMC, Box 574, SE-751 23 Uppsala, Sweden.
Sara M BergmanDepartment of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University , BMC, Box 574, SE-751 23 Uppsala, Sweden.
Sofia S GustafssonDepartment of Chemistry-BMC, Uppsala University , BMC, Box 576, SE-751 23 Uppsala, Sweden.
Hiba AlogheliDepartment of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University , BMC, Box 574, SE-751 23 Uppsala, Sweden.
Eva B AkerblomDepartment of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University , BMC, Box 574, SE-751 23 Uppsala, Sweden.
Gunnar G LindebergDepartment of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University , BMC, Box 574, SE-751 23 Uppsala, Sweden.
Richard M SvenssonDepartment of Pharmacy, Uppsala University , Box 580, SE-751 23 Uppsala, Sweden ; The Uppsala University Drug Optimization and Pharmaceutical Profiling Platform, Uppsala University , a Node of the Chemical Biology Consortium Sweden (CBCS), Box 580, SE-751 23 Uppsala, Sweden.
Per ArturssonDepartment of Pharmacy, Uppsala University , Box 580, SE-751 23 Uppsala, Sweden ; The Uppsala University Drug Optimization and Pharmaceutical Profiling Platform, Uppsala University , a Node of the Chemical Biology Consortium Sweden (CBCS), Box 580, SE-751 23 Uppsala, Sweden.
U Helena DanielsonDepartment of Chemistry-BMC, Uppsala University , BMC, Box 576, SE-751 23 Uppsala, Sweden.
Anders KarlénDepartment of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University , BMC, Box 574, SE-751 23 Uppsala, Sweden.
Anja SandströmDepartment of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University , BMC, Box 574, SE-751 23 Uppsala, Sweden.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Herein, novel hepatitis C virus NS3/4A protease inhibitors based on a P2 pyrimidinyloxyphenylglycine in combination with various regioisomers of an aryl acyl sulfonamide functionality in P1 are presented. The P1' 4-(trifluoromethyl)phenyl side chain was shown to be particularly beneficial in terms of inhibitory potency. Several inhibitors with K i-values in the nanomolar range were developed and included identification of promising P3-truncated inhibitors spanning from P2-P1'. Of several different P2 capping groups that were evaluated, a preference for the sterically congested Boc group was revealed. The inhibitors were found to retain inhibitory potencies for A156T, D168V, and R155K variants of the protease. Furthermore, in vitro pharmacokinetic profiling showed several beneficial effects on metabolic stability as well as on apparent intestinal permeability from both P3 truncation and the use of the P1' 4-(trifluoromethyl)phenyl side chain.

Indexed as

HCVNS3peptidomimeticsphenylglycineprotease inhibitors

Identifiers

PMID24900813
PMCPMC4027635

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.