Sammanfattning

Screening of an in-house library of compounds identified 12-thiazole abietanes as a new class of reversible inhibitors of the human metabolic serine hydrolase. Further optimization of the first hit compound lead to the 2-methylthiazole derivative 18, with an IC50 value of 3.4 +/- 0.2 mu M and promising selectivity. ABHD16A has been highlighted as a new target for inflammation-mediated pain, although selective inhibitors of hABHD16A (human ABHD16A) have not yet been reported. Our study presents abietane-type diterpenoids as an attractive starting point for the design of selective ABHD16A inhibitors, which will contribute toward understanding the significance of hABHD16A inhibition in vivo.

Originalspråkengelska
TidskriftACS Medicinal Chemistry Letters
Volym9
Utgåva12
Sidor (från-till)1269-1273
Antal sidor9
ISSN1948-5875
DOI
StatusPublicerad - 13 dec 2018
MoE-publikationstypA1 Tidskriftsartikel-refererad

Vetenskapsgrenar

  • 317 Farmaci
  • 116 Kemi

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title = "Discovery of 12-thiazole abietanes as selective inhibitors of the human metabolic serine hydrolase hABHD16A",
abstract = "Screening of an in-house library of compounds identified 12-thiazole abietanes as a new class of reversible inhibitors of the human metabolic serine hydrolase. Further optimization of the first hit compound lead to the 2-methylthiazole derivative 18, with an IC50 value of 3.4 +/- 0.2 mu M and promising selectivity. ABHD16A has been highlighted as a new target for inflammation-mediated pain, although selective inhibitors of hABHD16A (human ABHD16A) have not yet been reported. Our study presents abietane-type diterpenoids as an attractive starting point for the design of selective ABHD16A inhibitors, which will contribute toward understanding the significance of hABHD16A inhibition in vivo.",
keywords = "dehydroabietic acid, hABHD16A inhibitor, lysophosphatidylserine, metabolic serine hydrolase, 317 Pharmacy, 116 Chemical sciences",
author = "Ahonen, {Tiina Johanna} and Savinainen, {Juha R.} and Yli-Kauhaluoma, {Jari Tapani} and Kalso, {Eija Anneli} and Laitinen, {Jarmo T.} and Moreira, {V{\^a}nia M.}",
year = "2018",
month = "12",
day = "13",
doi = "10.1021/acsmedchemlett.8b00442",
language = "English",
volume = "9",
pages = "1269--1273",
journal = "ACS Medicinal Chemistry Letters",
issn = "1948-5875",
publisher = "American Chemical Society",
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Discovery of 12-thiazole abietanes as selective inhibitors of the human metabolic serine hydrolase hABHD16A. / Ahonen, Tiina Johanna; Savinainen, Juha R.; Yli-Kauhaluoma, Jari Tapani; Kalso, Eija Anneli; Laitinen, Jarmo T.; Moreira, Vânia M.

I: ACS Medicinal Chemistry Letters, Vol. 9, Nr. 12, 13.12.2018, s. 1269-1273.

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

TY - JOUR

T1 - Discovery of 12-thiazole abietanes as selective inhibitors of the human metabolic serine hydrolase hABHD16A

AU - Ahonen, Tiina Johanna

AU - Savinainen, Juha R.

AU - Yli-Kauhaluoma, Jari Tapani

AU - Kalso, Eija Anneli

AU - Laitinen, Jarmo T.

AU - Moreira, Vânia M.

PY - 2018/12/13

Y1 - 2018/12/13

N2 - Screening of an in-house library of compounds identified 12-thiazole abietanes as a new class of reversible inhibitors of the human metabolic serine hydrolase. Further optimization of the first hit compound lead to the 2-methylthiazole derivative 18, with an IC50 value of 3.4 +/- 0.2 mu M and promising selectivity. ABHD16A has been highlighted as a new target for inflammation-mediated pain, although selective inhibitors of hABHD16A (human ABHD16A) have not yet been reported. Our study presents abietane-type diterpenoids as an attractive starting point for the design of selective ABHD16A inhibitors, which will contribute toward understanding the significance of hABHD16A inhibition in vivo.

AB - Screening of an in-house library of compounds identified 12-thiazole abietanes as a new class of reversible inhibitors of the human metabolic serine hydrolase. Further optimization of the first hit compound lead to the 2-methylthiazole derivative 18, with an IC50 value of 3.4 +/- 0.2 mu M and promising selectivity. ABHD16A has been highlighted as a new target for inflammation-mediated pain, although selective inhibitors of hABHD16A (human ABHD16A) have not yet been reported. Our study presents abietane-type diterpenoids as an attractive starting point for the design of selective ABHD16A inhibitors, which will contribute toward understanding the significance of hABHD16A inhibition in vivo.

KW - dehydroabietic acid

KW - hABHD16A inhibitor

KW - lysophosphatidylserine

KW - metabolic serine hydrolase

KW - 317 Pharmacy

KW - 116 Chemical sciences

U2 - 10.1021/acsmedchemlett.8b00442

DO - 10.1021/acsmedchemlett.8b00442

M3 - Article

VL - 9

SP - 1269

EP - 1273

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

SN - 1948-5875

IS - 12

ER -