@misc{
 title = {Aminopyrimidine compounds as polo-like kinase 1 inhibitors and their preparation, pharmaceutical compositions and use for treatment of cancer},
 type = {misc},
 year = {2006},
 keywords = {aminopyrimidine prepn polo like kinase inhibitor p,treatment cancer plk1 inhibitor aminopyridine prep},
 pages = {151 pp.},
 publisher = {Amgen, Inc., USA .},
 revision = {WO 2006066172 A1},
 id = {c957bb4a-492a-3105-8a85-e73a6629e21e},
 created = {2015-10-01T17:18:19.000Z},
 file_attached = {false},
 profile_id = {64f7fb50-d000-335d-a02d-06c5f340a97a},
 last_modified = {2023-08-25T17:51:16.417Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Smith2006},
 source_type = {Patent},
 notes = {CAPLUS AN 2006:605439(Patent)},
 private_publication = {false},
 abstract = {The invention relates to aminopyrimidine compds. of formula I, which are useful for treating diseases mediated by polo-like kinase 1 (Plk1). The invention also relates to the therapeutic use of such aminopyrimidine compds. and compns. thereof in treating disease states assocd. with abnormal cell growth and unwanted cell proliferation. Compds. of formula I wherein X1 is CR1 or N; X2 is CH or N; Y is O, S, CHR7 or NR7; W is CN, (un)substituted imidazolidine, (un)substituted imidazoline, or (un)substituted tetrahydropyrimidine; R1 and R2 are independently H, halo, CN, (un)substituted C1-6 alkyl, (un)substituted alkyl(hetero)aryl, etc.; R3 is H, OH, halo, NO2, NH2, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, or (hetero)aryl; R4 and R7 are independently H or C1-6 alkyl; n is an integer from 1 to 6; and their pharmaceutically acceptable salts, hydrates and stereoisomers are claimed. Example compd. II was prepd. by substitution of 4-(5-bromothien-2-yl)-2-chloropyrimidine with 1-(2-aminoethyl)imidazolidin-2-one. Addnl. 464 example compds. were prepd. in this invention. All the invention compds. were evaluated for their human polo-like kinase 1 inhibitory activity. From the assay, it was detd. that all the example compds. exhibited plk1 activity with IC50 values less than 1 μM. [on SciFinder(R)]},
 bibtype = {misc},
 author = {Smith, Adrian Leonard and Brennan, Paul Edward and Demorin, Frenel Fils and Liu, Gang and Paras, Nick A and Retz, Daniel Martin}
}

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The invention also relates to the therapeutic use of such aminopyrimidine compds. and compns. thereof in treating disease states assocd. with abnormal cell growth and unwanted cell proliferation. Compds. of formula I wherein X1 is CR1 or N; X2 is CH or N; Y is O, S, CHR7 or NR7; W is CN, (un)substituted imidazolidine, (un)substituted imidazoline, or (un)substituted tetrahydropyrimidine; R1 and R2 are independently H, halo, CN, (un)substituted C1-6 alkyl, (un)substituted alkyl(hetero)aryl, etc.; R3 is H, OH, halo, NO2, NH2, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, or (hetero)aryl; R4 and R7 are independently H or C1-6 alkyl; n is an integer from 1 to 6; and their pharmaceutically acceptable salts, hydrates and stereoisomers are claimed. Example compd. II was prepd. by substitution of 4-(5-bromothien-2-yl)-2-chloropyrimidine with 1-(2-aminoethyl)imidazolidin-2-one. Addnl. 464 example compds. were prepd. in this invention. All the invention compds. were evaluated for their human polo-like kinase 1 inhibitory activity. From the assay, it was detd. that all the example compds. exhibited plk1 activity with IC50 values less than 1 μM. 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The invention also relates to the therapeutic use of such aminopyrimidine compds. and compns. thereof in treating disease states assocd. with abnormal cell growth and unwanted cell proliferation. Compds. of formula I wherein X1 is CR1 or N; X2 is CH or N; Y is O, S, CHR7 or NR7; W is CN, (un)substituted imidazolidine, (un)substituted imidazoline, or (un)substituted tetrahydropyrimidine; R1 and R2 are independently H, halo, CN, (un)substituted C1-6 alkyl, (un)substituted alkyl(hetero)aryl, etc.; R3 is H, OH, halo, NO2, NH2, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, or (hetero)aryl; R4 and R7 are independently H or C1-6 alkyl; n is an integer from 1 to 6; and their pharmaceutically acceptable salts, hydrates and stereoisomers are claimed. Example compd. II was prepd. by substitution of 4-(5-bromothien-2-yl)-2-chloropyrimidine with 1-(2-aminoethyl)imidazolidin-2-one. Addnl. 464 example compds. were prepd. in this invention. 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