KinasePro

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

WO/2007/066185

Posted by kinasepro on June 14, 2007

>> Update: Its PF2341066

Polymorphs of a c-Met / HGFR inhibitor.

NC1=NC=C(C2=CN(C3CCNCC3)N=C2)C=C1O[C@@H](C4=C(Cl)C=CC(F)=C4Cl)C

WO/2007/066187 has some data, and the compound is originally from US2006046991; WO/2006/021881

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7 Responses to “WO/2007/066185”

  1. milkshake said

    Well this is bloody Sugen c-Met inhibitor. The Augouron c-Met compound sucked so they replaced them with ours.

  2. Wijit said

    Milkshake, was this series discovered by Sugen scientists then transferred to Pfizer, La Jolla, when Sugen was bought by Pfizer?

    From Sugen series: WO2006/021881, WO2006/021884, WO2006/021885, WO2006/021886?

    From Pfizer/Augouron Series: WO 2005/121125?

  3. milkshake said

    Yes, it was. I was there when it was discovered. It resulted from combing a high-throughput 3,5-aryl-ubstituted-2-aminopyridine hit with the X-ray of cocrystal of a indolinone-5-benzylsulfone compound. So it was a good example of a rational drug design. The advantage of this class of compounds (unlike the another class, the one that I worked on) was that the compounds worked quite well also in various muatnt forms of c-Met. You can tell it was from Sugen by looking on the author list, Jean Cui should be there.

  4. kinasepro said

    My bad. It makes me wonder how Agouron got the assignment, but I guess it’s just semantics since fizzer owned the lot of’m by the time they were filed. WO/2004/076412 is the earliest I can find, and its labeled a Sugen app.

    The pictured compound is likely PF-2341066 for which there is a Cancer Res

  5. Wijit said

    Thx. Looks like Sugen were way out in front in the c-MET inhibitor arena, too bad you got fizzered!

  6. How magic is the methyl? Doing something to the conformation preferences pehaps?

  7. milkshake said

    I forgot the SAR – it has been more than 4 years now and I was involved with the other Met series which were structurally unrelated. But I remember faintly that the compounds without the methyl were made right at the beginning, about 5-6 years ago. (I was working on VEGF/PDGF oxindole compounds at the time so did not watch Met too closely)

    The methyl does something important because you find it even in the earliest compounds – and I faintly remember the opposite enantiomer is no good. It could be could be the cell potency, metabolic stability, selectivity – be my guest.

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