Gliptins are go
Creators & Contributors
Looking at the DrugBank collection of DPPIV inhibitors for a previous post involved checking the three approved "gliptins". This relatively new class of protease inhibitor drugs for diabetes seem to be crossing or coming up to the FDA finish line thick and fast (altought it is ranked 25th of all research targets by compound numbers ) I was therefore intrigued to notice yet a 4th crop up in the ChEMBL blog of the latest INNs.
So what was this new one ? The first pops against PubChem Compound were negative on both name and code name. Next pop was Google that surprisingly also suggested gliptin number 5.
This got me wondering how many "declared" gliptins were there ? Going back the ChEMBL link opened up the USAN rather than the WHO INN. While there were no live links in the PDF there was a structure rendering and an IUPAC. I just copied and pasted that string into OPSIN and it did the buissness.
Reassuringly, I confirmed the same rendering as the USAN PDF and popping the SMILES into the PubChem structure search gives the same structure, CID 15983988 but there is also a "flat" version (no stereochemistry) as CID 11360300. Both of these had Thomson Pharma as primary SID sources from 2006, suggestive of patent extraction. This was confirmed via SureChem patent links to ChemSpider 13115365. There were seven US granted patents counted but you can only link out to the first three for free. One of these seems to be in the patent family of the Takeda first-filing and it was rather neat to put the Mw 357 from the PubChem entry in "find" and whack (flat) trelagliptin as "example 34" (Mw in green) below.
Having closed that circle I moved on to Teneligliptin. This hits straight through to CID 11949652, but the INN in this case was picked up by KEGG not MeSH. Here again ChemSpider 10123963 links to a SureChem patent from Mitshubishi. There were no Mw in examples this time but you can spot the lead in the claims.
From a cheminformatics and SAR point of view finding the filings for a single structure from the free links shown above might not have particular ulitity but you may see the complete set of exemplars and often with quanitative SAR data across the series. The ChemSpider open SureChem links are effectively teasers but the individual sign up does not seem too bad for 11 million extracted structures including Medline.
Continuing with Googling Teneligliptin came up with the same struture at Chemblink that I had never heard of but it also confirmed the compound as having code name MP513 from the Mitshubishi portfolio. Having got five gliptin structures and wondering if that was the lot I suddenly realized I'd missed the glaringly obvious, in this case MeSH "Pharmacological Action" ; "Dipeptidyl-Peptidase IV Inhibitors". Bingo! this gave no less than 17 CIDs. Along with some salt forms and research compounds this included vildagliptin CID 24848920 , alogliptin CID 11450633 , sitagliptin CID 4369359, linagliptin CID 10096344 and saxagliptin CID 11243969. With the two above that makes seven INNs-to-structures, not a bad haul for one blog post.
Additional details
Description
Looking at the DrugBank collection of DPPIV inhibitors for a previous post involved checking the three approved "gliptins". This relatively new class of protease inhibitor drugs for diabetes seem to be crossing or coming up to the FDA finish line thick and fast (altought it is ranked 25th of all research targets by compound numbers ) I was therefore
Identifiers
- UUID
- 37727f1e-807c-4238-b0d1-53f7259c50f2
- GUID
- tag:blogger.com,1999:blog-2155351992730855318.post-5818111007502075292
- URL
- https://cdsouthan.blogspot.com/2011/08/glyptins-to-go.html
Dates
- Issued
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2011-08-17T23:25:00
- Updated
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2012-09-05T00:23:10