Darglitazone: Difference between revisions
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{{short description|Chemical compound}} |
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{{Drugbox |
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| width = 260 |
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<!--Clinical data--> |
<!--Clinical data--> |
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| tradename = |
| tradename = |
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| legal_status = |
| legal_status = Development terminated |
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<!--Identifiers--> |
<!--Identifiers--> |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 141200-24-0 |
| CAS_number = 141200-24-0 |
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| PubChem = 60870 |
| PubChem = 60870 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 55624 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = AVP9C03Z3K |
| UNII = AVP9C03Z3K |
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| ChemSpiderID = 54854 |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChI = 1S/C23H20N2O4S/c1-14-18(24-22(29-14)17-5-3-2-4-6-17)11-12-19(26)16-9-7-15(8-10-16)13-20-21(27)25-23(28)30-20/h2-10,20H,11-13H2,1H3,(H,25,27,28) |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey = QQKNSPHAFATFNQ-UHFFFAOYSA-N |
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<!--Chemical data--> |
<!--Chemical data--> |
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| C=23 | H=20 | N=2 | O=4 | S=1 |
| C=23 | H=20 | N=2 | O=4 | S=1 |
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| molecular_weight = 420.481 g/mol |
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| smiles = CC1=C(N=C(O1)C2=CC=CC=C2)CCC(=O)C3=CC=C(C=C3)CC4C(=O)NC(=O)S4 |
| smiles = CC1=C(N=C(O1)C2=CC=CC=C2)CCC(=O)C3=CC=C(C=C3)CC4C(=O)NC(=O)S4 |
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'''Darglitazone''' is a member of the thiazolidinedione class of drugs and an agonist of [[Peroxisome proliferator-activated receptor gamma|peroxisome proliferator-activated receptor-γ]] (PPAR-γ), an orphan member of the nuclear receptor superfamily of transcription factors. It has a variety of insulin-sensitizing effects, such as improving glycemic and lipidemic control, and |
'''Darglitazone''' (previously known as '''CP 86325-2''') is a member of the {{w|thiazolidinedione}} class of drugs and an agonist of [[Peroxisome proliferator-activated receptor gamma|peroxisome proliferator-activated receptor-γ]] (PPAR-γ), an orphan member of the nuclear receptor superfamily of transcription factors. It has a variety of insulin-sensitizing effects, such as improving glycemic and lipidemic control, and was researched by [[Pfizer]] as a treatment of metabolic disorders such as {{w|Diabetes mellitus type 2|type 2 diabetes mellitus}}.<ref>{{cite journal | vauthors = Hulin B, Clark DA, Goldstein SW, McDermott RE, Dambek PJ, Kappeler WH, Lamphere CH, Lewis DM, Rizzi JP | display-authors = 6 | title = Novel thiazolidine-2,4-diones as potent euglycemic agents | journal = Journal of Medicinal Chemistry | volume = 35 | issue = 10 | pages = 1853–64 | date = May 1992 | pmid = 1588563 | doi = 10.1021/jm00088a022 }}</ref> |
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Its development was terminated on November 08, 1999.<ref>{{cite web |title=Drug Profile: Darglitazone |url=http://adisinsight.springer.com/drugs/800003002| work = Adis Insight |publisher=Springer Nature Switzerland AG |access-date=28 November 2015}}</ref> |
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==Synthesis== |
==Synthesis== |
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[[File:Darglitazone.png|thumb|left|Synthesis of darglitazone]]<br /><br /><br /><br /><br /><br /> |
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The first step in the construction of the terminal side chain in the first glitazones comprises a reaction of [[benzaldehyde]] with the mono-[[oxime]] from [[diacetyl]] to afford the corresponding benzoxazole N-oxide. Reaction of that intermediate with phosphorus oxychloride leads to the chlorination of the adjacent methyl group in a version of the [[Amine_oxide#Reactions|Plonovski reaction]] to afford the choromethyl derivative. This is then used to alkylate the carbanion from the substituted acetoacetate. Heating the first-obtained product in a strong acid leads to the [[hydrolysis]] of the [[ester]]. The resulting β-ketoacid loses [[carbon dioxide]] under reaction conditions; the acetal hydrolyses also to reveal the free [[aldehyde]]. [[Aldol condensation]] of this last intermediate in the presence of a [[base (chemistry)|base]] with readily available [[thiazolidinedione]] links the two fragments. The double bond in the first-formed product is then reduced catalytically to afford darglitazone. |
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[[File:Darglitazone.png|500px]] |
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{{reflist}} |
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{{Oral hypoglycemics}} |
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{{PPAR modulators}} |
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{{Cite journal|doi=10.1021/jm00088a022|title=Novel thiazolidine-2,4-diones as potent euglycemic agents|pmid=1588563|year=1992|last1=Hulin|first1=Bernard|last2=Clark|first2=David A.|last3=Goldstein|first3=Steven W.|last4=McDermott|first4=Ruth E.|last5=Dambek|first5=Paul J.|last6=Kappeler|first6=Werner H.|last7=Lamphere|first7=Charles H.|last8=Lewis|first8=Diana M.|last9=Rizzi|first9=James P.|journal=Journal of Medicinal Chemistry|volume=35|issue=10|pages=1853}} |
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[[Category:Oxazoles]] |
[[Category:Oxazoles]] |
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[[Category:Thiazolidinediones]] |
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