`
`October 1 ,1999
`
`Competitive Update: Nothing new to report
`
`Current FTE’s: 3
`
`Monthly Summary: None
`
`The goal of the program is to discover small molecule inhibitors of dipeptidyl peptidase IV (DP4) for
`use in the treatment and prevention of diabetes. Inhibition of DP4 should prevent the degradation of
`GLP—1 and potentiate its action in vivo. BMS-356379 was previously identified as a novel and
`proprietary inhibitor with an inhibitory constant of 28 nM vs pig kindey DP4. Rat oral bioavailability of
`this compound is in progress as well as studies related to in vitro metabolism and P450 inhibition.
`it
`was recently demonstrated that the Caco~2 permeability of this compound is 114 mnfsec, which would
`predict good oral absorption. The cyano substituted cyclopropanated pyrroiidine precursor is currently
`being scaled up for future analoging in this series. In an attempt to uncover other suitable chemotypes
`related to BMS~356379,
`the generation of additional cyclopropanated analogs are in progress.
`In
`contrast to BMS-356379 (a 4,5—fused analog),
`the 2,3—fused anaiog BMS—378736 exhibited only
`marginal activity in the screening assay (20% inhibition @ 10 uM) while the related 3,4-fused analog,
`EMS-378738 (X = H) exhibited significant potency in this screen (80% inhibition @ 10 uM). Ki values
`will be determine shortly. Efforts are currently directed towards generation of the related cyano
`derivative (X = ON) in hopes of further enhancing potency with this chemotype.
`
`Me
`
`H2N
`
`Me
`
`N
`
`‘
`
`0
`
`CN
`
`BMS-356379
`DFL4 screen:
`BLQI R'|ih=|l3§8C_3FH§|0 UM
`
`raj}
`
`Me
`
`HZN
`
`Me
`
`N
`
`_’
`‘If?
`CN
`
`0
`
`3Ms_373735
`DP4 screen:
`20% lnhlb. @ ‘E0 uM
`
`Me
`
`HZN
`
`Me
`
`Nx
`
`0
`
`X
`
`BMS-378738 (X = H)
`DP4 screen:
`30% inhib_ @ 10 "M
`
`Page 1 of 1
`
`Astraleneca Exhibit 2185
`Mylan V. Astraleneca
`IPR2015-013-l0
`
`AstraZeneca Exhibit 2185
`Mylan v. AstraZeneca
`IPR2015-01340
`
`Page 1 of 1
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
