Ciluprevir: Difference between revisions

Ciluprevir
Clinical data
Routes of; administration	By mouth
ATC code	None;
Legal status
Legal status	Development terminated;
Pharmacokinetic data
Protein binding	>99.1%
Identifiers
	IUPAC name (2R,6S,12Z,13aS,14aR,16aS)-6-[(Cyclopentyloxycarbonyl)amino]-2-({7-methoxy-2-[(propan-2-ylamino)-1,3-thiazol-4-yl]quinolin- 4-yl}oxy)-5,16-dioxo-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a(5H)-carboxylic acid;
CAS Number	300832-84-2;
PubChem CID	9853710;
ChemSpider	8029420;
UNII	75C8DU40T0;
ChEMBL	ChEMBL297884;
CompTox Dashboard (EPA)	DTXSID50870316 ;
Chemical and physical data
Formula	C40H50N6O8S
Molar mass	774.93 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C2N[C@]7(C(=O)O)C[C@H]7/C=C\CCCCC[C@H](NC(=O)OC1CCCC1)C(=O)N6[C@H]2C[C@@H](Oc3cc(nc4c3ccc(OC)c4)c5nc(sc5)NC(C)C)C6;
	InChI InChI=1S/C40H50N6O8S/c1-23(2)41-38-43-32(22-55-38)31-19-34(28-16-15-26(52-3)17-30(28)42-31)53-27-18-33-35(47)45-40(37(49)50)20-24(40)11-7-5-4-6-8-14-29(36(48)46(33)21-27)44-39(51)54-25-12-9-10-13-25/h7,11,15-17,19,22-25,27,29,33H,4-6,8-10,12-14,18,20-21H2,1-3H3,(H,41,43)(H,44,51)(H,45,47)(H,49,50)/b11-7-/t24-,27-,29+,33+,40-/m1/s1; Key:PJZPDFUUXKKDNB-KNINVFKUSA-N;

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Revision as of 10:19, 25 February 2017

Ciluprevir was a drug used experimentally in the treatment of hepatitis C. It is manufactured by Boehringer Ingelheim and developed under the research code of BILN 2061. It was the first-in-class NS3/4A protease inhibitor to enter clinical development and tested in human.^[2] Ciluprevir is a potent competitive reversible inhibitor of NS3/4A protease from HCV genotype 1a (K_i = 0.3 nM) and 1b (K_i = 0.66 nM). It shows good selectivity for NS3 protease against representative serine and cysteine proteases, human leukocyte elastase and cathepsin B (IC₅₀ > 30 μM).^[1]

Its development was halted in phase Ib clinical trials because of toxicity in animals. However, ciluprevir scaffold was exploited to design new macrocyclic inhibitors such as simeprevir (TMC-435) and danoprevir.^[3]

References

^ ^a ^b Tan, Seng-Lai; He, Yupeng, eds. (2011). Hepatitis C: Antiviral Drug Discovery and Development. Norfolk, UK: Caister Academic Press. p. 199. ISBN 978-1-904455-78-3. {{cite book}}: |access-date= requires |url= (help)
^ Tan, Seng-Lai, ed. (2006). "6. HCV NS3-4A Serine Protease". Hepatitis C Viruses: Genomes and Molecular Biology. Norfolk (UK): Horizon Bioscience. ISBN 978-1-904933-20-5.
^ Chatel-Chaix, L; Baril, M; Lamarre, D (August 2010). "Hepatitis C Virus NS3/4A Protease Inhibitors: A Light at the End of the Tunnel". Viruses. 2 (8): 1752–65. doi:10.3390/v2081752. PMC 3185733. PMID 21994705. {{cite journal}}: |access-date= requires |url= (help)CS1 maint: unflagged free DOI (link)

This antiinfective drug article is a stub. You can help Wikipedia by expanding it.

[Tan-1] Tan, Seng-Lai; He, Yupeng, eds. (2011). Hepatitis C: Antiviral Drug Discovery and Development. Norfolk, UK: Caister Academic Press. p. 199. ISBN 978-1-904455-78-3. {{cite book}}: |access-date= requires |url= (help)

[2] Tan, Seng-Lai, ed. (2006). "6. HCV NS3-4A Serine Protease". Hepatitis C Viruses: Genomes and Molecular Biology. Norfolk (UK): Horizon Bioscience. ISBN 978-1-904933-20-5.

[3] Chatel-Chaix, L; Baril, M; Lamarre, D (August 2010). "Hepatitis C Virus NS3/4A Protease Inhibitors: A Light at the End of the Tunnel". Viruses. 2 (8): 1752–65. doi:10.3390/v2081752. PMC 3185733. PMID 21994705. {{cite journal}}: |access-date= requires |url= (help)CS1 maint: unflagged free DOI (link)

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[2]

[3]

@@ Line 1: / Line 1: @@
 {{Drugbox
-| IUPAC_name = (1''S'',4''R'',6''S'',7''Z'',14''S'',18''R'')-14- {[(cyclopentyloxy)carbonyl]amino}-18-[(7-methoxy-2- {2-[(propan-2-yl)amino]-1,3-thiazol-4-yl}quinolin-4- yl)oxy]-2,15-dioxo-3,16- diazatricyclo[14.3.0.0<sup>{4,6}</sup>]nonadec-7-ene-4- carboxylic acid
+| IUPAC_name = (2''R'',6''S'',12''Z'',13a''S'',14a''R'',16a''S'')-6-[(Cyclopentyloxycarbonyl)amino]-2-({7-methoxy-2-[(propan-2-ylamino)-1,3-thiazol-4-yl]quinolin- 4-yl}oxy)-5,16-dioxo-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[''e'']pyrrolo[1,2-''a''][1,4]diazacyclopentadecine-14a(5''H'')-carboxylic acid
 | image = Ciluprevir.svg
 | alt =
 | caption =
 <!--Clinical data-->
 | tradename =
 | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
-| pregnancy_US = <!-- A / B            / C / D / X -->
+| pregnancy_US = <!-- A / B / C / D / X -->
 | pregnancy_category =
 | legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
 | legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
 | legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM -->
 | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
-| legal_status = Investigational
+| legal_status = Development terminated
-| routes_of_administration =
+| routes_of_administration = [[Oral administration|By mouth]]
 <!--Pharmacokinetic data-->
 | bioavailability =
+| protein_bound = >99.1%<ref name = "Tan">{{cite book|editor1-last=Tan|editor1-first=Seng-Lai|editor2-last=He|editor2-first=Yupeng|title=Hepatitis C: Antiviral Drug Discovery and Development|date=2011|publisher=Caister Academic Press|location=Norfolk, UK|isbn=978-1-904455-78-3|page=199|accessdate=25 February 2017}}</ref>
-| protein_bound =
 | metabolism =
 | elimination_half-life =
 | excretion =
 <!--Identifiers-->
 | CAS_number = 300832-84-2
 | ATCvet =
-| ATC_prefix = none
+| ATC_prefix = None
 | ATC_suffix =
 | DrugBank =
@@ Line 44: / Line 44: @@
 }}
-'''Ciluprevir''' is used experimentally in the treatment of [[hepatitis C]]. It is manufactured by [[Boehringer Ingelheim]] Pharma GmbH & Co.&nbsp;kg and developed under the research code of '''BILN-2061'''. It is targeted against [[NS2-3 protease]].<ref>{{cite journal | pmid = 16789888 | year = 2005 | last1 = Abbenante | first1 = G | last2 = Fairlie | first2 = DP | title = Protease inhibitors in the clinic | volume = 1 | issue = 1 | pages = 71–104 | journal = Medicinal chemistry | doi=10.2174/1573406053402569}}</ref>
+'''Ciluprevir''' was a drug used experimentally in the treatment of [[hepatitis C]]. It is manufactured by [[Boehringer Ingelheim]] and developed under the research code of '''BILN 2061'''. It was the first-in-class [[NS3 (HCV)|NS3]]/[[NS4A|4A]] protease inhibitor to enter clinical development and tested in human.<ref>{{cite book | editor1-last = Tan | editor1-first = Seng-Lai | title = Hepatitis C Viruses: Genomes and Molecular Biology | date = 2006 | publisher = Horizon Bioscience | location = Norfolk (UK) | isbn = 978-1-904933-20-5 | url = https://www.ncbi.nlm.nih.gov/books/NBK1613/ | chapter = 6. HCV NS3-4A Serine Protease}}</ref> Ciluprevir is a potent competitive reversible inhibitor of NS3/4A protease from HCV genotype 1a (K<sub>i</sub> = 0.3 nM) and 1b (K<sub>i</sub> = 0.66 nM). It shows good selectivity for NS3 protease against representative serine and cysteine proteases, human leukocyte elastase and cathepsin B ([[IC50|IC<sub>50</sub>]] > 30 ''μ''M).<ref name = "Tan" />
+Its development was halted in phase Ib clinical trials because of toxicity in animals. However, ciluprevir scaffold was exploited to design new macrocyclic inhibitors such as [[simeprevir]] (TMC-435) and [[danoprevir]].<ref>{{cite journal | last1 = Chatel-Chaix | first1 = L | last2 = Baril | first2 = M | last3 = Lamarre | first3 = D | title = Hepatitis C Virus NS3/4A Protease Inhibitors: A Light at the End of the Tunnel | journal = Viruses | date = August 2010 | volume = 2 | issue = 8 | pages = 1752–65 | doi = 10.3390/v2081752 | pmid = 21994705 | accessdate = 25 February 2017 | pmc = 3185733}}</ref>
 ==References==
 {{reflist}}
+{{RNA antivirals}}
-[[Category:Protease inhibitors]]
+[[Category:Abandoned drugs]]
+[[Category:NS3/4A protease inhibitor]]
 {{antiinfective-drug-stub}}