KinasePro

Kinase Chemistry – Just a year and a half behind the times.

Pfizer’s Jnk

Posted by kinasepro on November 15, 2007

SD’s got a series of Jnk1 inhibitors in WO/2007/125405:

COC1=CC=C(CC(NC2=NC=C(C=CC(C4=CN(C)N=C4)=C3)C3=C2)=O)C=C1

First half of the compounds look about like that one, and Jnk1 data is given…
Second half appear discretely in the claims and look more like Jnk3 inhibitors to me.

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3 Responses to “Pfizer’s Jnk”

  1. milkshake said

    My reading of the patent was that they had two series of compounds, both intended for their diabetes JNK1project – and for some reason they decided to stuff both of them in the same application.

    I think a natural explanation can be that they were pursuing both series in parallel at the beginning of their project but they got a cell potency only in the first series – which they then took forward. The compounds from the second series were put there to broaden the claim scope.

    I think the structure you posted is their main lead on which they did some conformationally-restricted analogs, perhaps to improve selectivity.

    I also suspect that the binding mode you guessed is not quite correct – that there are some induced-fit changes.

    Overall I think it is a solid work, not the prophetic bull you sometimes see in the patents.

  2. milkshake said

    I also think their lead compound has no methyl and the N-methylated analog is nearly inactive – if you compare the provisional document SAR table with the final one, you will notice that they mixed up data with % of inhibition (@1uM) with EC50. So I think the compound you depicted has 2% inh at 1uM. Please note this is the only N-alkylated compound they claim in the series, the rest has free NH

  3. kinasepro said

    Thanks for pointing this out. The pictured compound is example 4 in the PCT and listed at 0.8 % @ 1 uM which certainly changes the picture…

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