CLOBETASOL


Status
Molecule Category	Free-form
ATC	D07AD01


Active Pharmaceutical Ingredients Bioactive chemicals	Exact Similarity SubStructure	Threshold (%) >= 70

Structure


InChI Key	FCSHDIVRCWTZOX-DVTGEIKXSA-N
Smiles	C[C@H]1C[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@]2(C)[C@@]1(O)C(=O)CCl
InChI	InChI=1S/C22H28ClFO4/c1-12-8-16-15-5-4-13-9-14(25)6-7-19(13,2)21(15,24)17(26)10-20(16,3)22(12,28)18(27)11-23/h6-7,9,12,15-17,26,28H,4-5,8,10-11H2,1-3H3/t12-,15-,16-,17-,19-,20-,21-,22-/m0/s1

Reference

Journal : Bioorg. Med. Chem. Lett.

Title : Structure-activity relationships of 6-(aminomethylphenoxy)-benzoxaborole derivatives as anti-inflammatory agent.

PubMed ID : 23411072

DOI : 10.1016/j.bmcl.2013.01.072

Year : 2013

Volume : 23

Issue : 6

First Page : 1680

Last Page : 1683

Authors : Akama T, Virtucio C, Dong C, Kimura R, Zhang YK, Nieman JA, Sharma R, Lu X, Sales M, Singh R, Wu A, Fan XQ, Liu L, Plattner JJ, Jarnagin K, Freund YR.

Abstract : A series of novel 6-(aminomethylphenoxy)benzoxaborole analogs was synthesized for the investigation of the structure-activity relationship of the inhibition of TNF-alpha, IL-1beta, and IL-6, from lipopolysaccharide stimulated peripheral blood mononuclear cells. Compounds 9d and 9e showed potent activity against all three cytokines with IC50 values between 33 and 83nM. Chloro substituted analog 9e (AN3485) is considered to be a promising lead for novel anti-inflammatory agent with a favorable pharmacokinetic profile.

Reference

Journal : Bioorg. Med. Chem. Lett.

Title : Structure-activity relationships of 6-(aminomethylphenoxy)-benzoxaborole derivatives as anti-inflammatory agent.

PubMed ID : 23411072

DOI : 10.1016/j.bmcl.2013.01.072

Year : 2013

Volume : 23

Issue : 6

First Page : 1680

Last Page : 1683

Authors : Akama T, Virtucio C, Dong C, Kimura R, Zhang YK, Nieman JA, Sharma R, Lu X, Sales M, Singh R, Wu A, Fan XQ, Liu L, Plattner JJ, Jarnagin K, Freund YR.

Reference

Journal : Bioorg. Med. Chem. Lett.

Title : Structure-activity relationships of 6-(aminomethylphenoxy)-benzoxaborole derivatives as anti-inflammatory agent.

PubMed ID : 23411072

DOI : 10.1016/j.bmcl.2013.01.072

Year : 2013

Volume : 23

Issue : 6

First Page : 1680

Last Page : 1683

Authors : Akama T, Virtucio C, Dong C, Kimura R, Zhang YK, Nieman JA, Sharma R, Lu X, Sales M, Singh R, Wu A, Fan XQ, Liu L, Plattner JJ, Jarnagin K, Freund YR.

Reference

Journal : Bioorg. Med. Chem. Lett.

Title : Structure-activity relationships of 6-(aminomethylphenoxy)-benzoxaborole derivatives as anti-inflammatory agent.

PubMed ID : 23411072

DOI : 10.1016/j.bmcl.2013.01.072

Year : 2013

Volume : 23

Issue : 6

First Page : 1680

Last Page : 1683

Authors : Akama T, Virtucio C, Dong C, Kimura R, Zhang YK, Nieman JA, Sharma R, Lu X, Sales M, Singh R, Wu A, Fan XQ, Liu L, Plattner JJ, Jarnagin K, Freund YR.

Reference

Journal : Bioorg Med Chem Lett

Title : Discovery of the potent non-steroidal glucocorticoid receptor modulator BAY 1003803 as clinical candidate.

PubMed ID : 32631518

DOI : 10.1016/j.bmcl.2020.127298

Year : 2020

Volume : 30

Issue : 16

First Page : 127298

Last Page : 127298

Authors : Berger M, May E, Rehwinkel H, Schäcke H, Neuhaus R, Rottmann A, Zollner TM, Jaroch S.

Abstract : We report on the discovery of the new clinical candidate BAY 1003803 as glucocorticoid receptor agonist for the topical treatment of psoriasis or severe atopic dermatitis. In the course of optimizing the amino alcohol series as a highly potent new non-steroidal lead structure, considerations were made as to how physicochemical properties and safety concerns relate to structural motifs. BAY 1003803 demonstrates strong anti-inflammatory activity in vitro paired with a pharmacokinetic profile suitable for topical application.

Reference

Journal : Bioorg Med Chem Lett

Title : Discovery of the potent non-steroidal glucocorticoid receptor modulator BAY 1003803 as clinical candidate.

PubMed ID : 32631518

DOI : 10.1016/j.bmcl.2020.127298

Year : 2020

Volume : 30

Issue : 16

First Page : 127298

Last Page : 127298

Authors : Berger M, May E, Rehwinkel H, Schäcke H, Neuhaus R, Rottmann A, Zollner TM, Jaroch S.

Reference

Journal : Bioorg Med Chem Lett

Title : Discovery of the potent non-steroidal glucocorticoid receptor modulator BAY 1003803 as clinical candidate.

PubMed ID : 32631518

DOI : 10.1016/j.bmcl.2020.127298

Year : 2020

Volume : 30

Issue : 16

First Page : 127298

Last Page : 127298

Authors : Berger M, May E, Rehwinkel H, Schäcke H, Neuhaus R, Rottmann A, Zollner TM, Jaroch S.

Reference

Journal : Bioorg Med Chem Lett

Title : Discovery of the potent non-steroidal glucocorticoid receptor modulator BAY 1003803 as clinical candidate.

PubMed ID : 32631518

DOI : 10.1016/j.bmcl.2020.127298

Year : 2020

Volume : 30

Issue : 16

First Page : 127298

Last Page : 127298

Authors : Berger M, May E, Rehwinkel H, Schäcke H, Neuhaus R, Rottmann A, Zollner TM, Jaroch S.

Reference

Journal : Bioorg Med Chem Lett

Title : Discovery of the potent non-steroidal glucocorticoid receptor modulator BAY 1003803 as clinical candidate.

PubMed ID : 32631518

DOI : 10.1016/j.bmcl.2020.127298

Year : 2020

Volume : 30

Issue : 16

First Page : 127298

Last Page : 127298

Authors : Berger M, May E, Rehwinkel H, Schäcke H, Neuhaus R, Rottmann A, Zollner TM, Jaroch S.

Assay Description	Organism	Bioactivity
Antiinflammatory activity in human PBMCs assessed as inhibition of LPS-induced IL6 release at 100 uM incubated for 15 mins prior to LPS challenge measured after 24 hrs by HTRF assay relative to control	Homo sapiens	80.0 %
Antiinflammatory activity in human PBMCs assessed as inhibition of LPS-induced IL1-beta release at 100 uM incubated for 15 mins prior to LPS challenge measured after 24 hrs by HTRF assay relative to control	Homo sapiens	80.0 %
Antiinflammatory activity in human PBMCs assessed as inhibition of LPS-induced TNFalpha release at 100 uM incubated for 15 mins prior to LPS challenge measured after 24 hrs by HTRF assay relative to control	Homo sapiens	80.0 %
Antiinflammatory activity in human PBMCs assessed as inhibition of LPS-induced TNFalpha release incubated for 15 mins prior to LPS challenge measured after 24 hrs by HTRF assay	Homo sapiens	7.0 nM
Inhibition of LPS-induced TNFalpha release in human PBMC cells	Homo sapiens	0.23 nM
Inhibition of LPS-induced IL12p40 release in human PBMC cells	Homo sapiens	0.14 nM
Inhibition of PHA-induced IL2 release in human PBMC cells	Homo sapiens	0.14 nM
Inhibition of PHA-induced IFNgamma release in human PBMC cells	Homo sapiens	0.16 nM
Inhibition of PHA-induced IL4 release in human PBMC cells	Homo sapiens	0.07 nM

CONTENTS

Structure