Preparation of pyrazolo[1,5-a]pyrimidine carboxamides as atr kinase inhibitors.

Abstract

The present invention relates to compds. of formula I as inhibitors of atr protein kinase as well as processes for the prepn. of I and their intermediates useful as monotherapy for cancer or in combination with other cancer agents. Compds. of formula I [wherein R1 is independently C(J1)2CN, halo, M, etc.; R9 is independently H, C(J1)2CN, M, etc.; J1 is independently H, C1-2 alkyl, or two occurrences of J1, together with the carbon to which they are attached, form a 3-4 membered (un)substituted carbocyclic ring; M is a C1-8 aliph. chain wherein up to three methylene units are optionally O, C(O), S(O)n, etc.; n is 0, 1, or 2; R2 and R3 are independently H, halo, CN, etc.; R4 is, for example, a substituted piperidine, piperazine, azabicyclo[3.2.1]octane, etc.] or pharmaceutically acceptable salts or prodrugs thereof are claimed and exemplified. II was prepd. via deprotection of the corresponding BOC protected ester in 31% yield. I were screened for their ability to sensitize colorectal cancer cells to cisplatin where II demonstrated a sensitization value of <0.02 μM. [on SciFinder(R)]