Evidence map›Paper›PMID 30034600›Full record

ArticleACS medicinal chemistry letters2018

Discovery of MK-8318, a Potent and Selective CRTh2 Receptor Antagonist for the Treatment of Asthma.

Xianhai Huang, Jason Brubaker, Wei Zhou, Purakkattle J Biju, Li Xiao, Ning Shao, Ying Huang, Li Dong, Zhidan Liu, Rema Bitar and 21 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS medicinal chemistry letters, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

1 citing paper in PubMed, 11 citations in OpenAlex.

  1. 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

31 authors at 1 institution in 1 country.

Xianhai HuangDiscovery Chemistry, In Vitro Pharmacology, Drug Metabolism and Pharmacokinetics, and Process Chemistry, Merck Research Laboratory, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Jason BrubakerDiscovery Chemistry and Immunology, Merck Research Laboratory, 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Wei ZhouDiscovery Chemistry, In Vitro Pharmacology, Drug Metabolism and Pharmacokinetics, and Process Chemistry, Merck Research Laboratory, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Purakkattle J BijuDiscovery Chemistry, In Vitro Pharmacology, Drug Metabolism and Pharmacokinetics, and Process Chemistry, Merck Research Laboratory, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Li XiaoDiscovery Chemistry, In Vitro Pharmacology, Drug Metabolism and Pharmacokinetics, and Process Chemistry, Merck Research Laboratory, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Ning ShaoDiscovery Chemistry, In Vitro Pharmacology, Drug Metabolism and Pharmacokinetics, and Process Chemistry, Merck Research Laboratory, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Ying HuangDiscovery Chemistry, In Vitro Pharmacology, Drug Metabolism and Pharmacokinetics, and Process Chemistry, Merck Research Laboratory, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Li DongDiscovery Chemistry, In Vitro Pharmacology, Drug Metabolism and Pharmacokinetics, and Process Chemistry, Merck Research Laboratory, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Zhidan LiuDiscovery Chemistry, In Vitro Pharmacology, Drug Metabolism and Pharmacokinetics, and Process Chemistry, Merck Research Laboratory, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Rema BitarDiscovery Chemistry, In Vitro Pharmacology, Drug Metabolism and Pharmacokinetics, and Process Chemistry, Merck Research Laboratory, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Alexei BuevichDiscovery Chemistry, In Vitro Pharmacology, Drug Metabolism and Pharmacokinetics, and Process Chemistry, Merck Research Laboratory, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Joon JungDiscovery Chemistry and Immunology, Merck Research Laboratory, 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Scott L PetersonDiscovery Chemistry and Immunology, Merck Research Laboratory, 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
John W ButcherDiscovery Chemistry and Immunology, Merck Research Laboratory, 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Joshua CloseDiscovery Chemistry and Immunology, Merck Research Laboratory, 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Michelle MartinezDiscovery Chemistry and Immunology, Merck Research Laboratory, 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Rachel N MacCossDiscovery Chemistry and Immunology, Merck Research Laboratory, 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Hongjun ZhangDiscovery Chemistry and Immunology, Merck Research Laboratory, 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Scott CrawfordDiscovery Chemistry and Immunology, Merck Research Laboratory, 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Kevin D McCormickDiscovery Chemistry, In Vitro Pharmacology, Drug Metabolism and Pharmacokinetics, and Process Chemistry, Merck Research Laboratory, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Robert AslanianDiscovery Chemistry, In Vitro Pharmacology, Drug Metabolism and Pharmacokinetics, and Process Chemistry, Merck Research Laboratory, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Ravi NargundDiscovery Chemistry, In Vitro Pharmacology, Drug Metabolism and Pharmacokinetics, and Process Chemistry, Merck Research Laboratory, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Craig CorrellDiscovery Chemistry and Immunology, Merck Research Laboratory, 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Francois GervaisDiscovery Chemistry and Immunology, Merck Research Laboratory, 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Hongchen QiuDiscovery Chemistry, In Vitro Pharmacology, Drug Metabolism and Pharmacokinetics, and Process Chemistry, Merck Research Laboratory, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Xiaoxin YangDiscovery Chemistry, In Vitro Pharmacology, Drug Metabolism and Pharmacokinetics, and Process Chemistry, Merck Research Laboratory, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Charles GarlisiDiscovery Chemistry, In Vitro Pharmacology, Drug Metabolism and Pharmacokinetics, and Process Chemistry, Merck Research Laboratory, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Diane RindgenDiscovery Chemistry, In Vitro Pharmacology, Drug Metabolism and Pharmacokinetics, and Process Chemistry, Merck Research Laboratory, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Kevin M MaloneyDiscovery Chemistry, In Vitro Pharmacology, Drug Metabolism and Pharmacokinetics, and Process Chemistry, Merck Research Laboratory, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Phieng SiliphaivanhDiscovery Chemistry and Immunology, Merck Research Laboratory, 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Anandan PalaniDiscovery Chemistry, In Vitro Pharmacology, Drug Metabolism and Pharmacokinetics, and Process Chemistry, Merck Research Laboratory, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Merck & Co., Inc., Rahway, NJ, USA (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A novel series of tricyclic tetrahydroquinolines were identified as potent and selective CRTh2 receptor antagonists. The agonism and antagonism switch was achieved through structure-based drug design (SBDD) using a CRTh2 receptor homologue model. The challenge of very low exposures in pharmacokinetic studies was overcome by exhaustive medicinal chemistry lead optimization through focused SAR studies on the tricyclic core. Further optimization resulted in the identification of the preclinical candidate 4-(cyclopropyl((3

Identifiers

PMID30034600
PMCPMC6047040
OpenAlexW2809507578

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.