5-alkynyl-pyrimidines

Patent metadata

Field	Value
Publication number	US-9321771-B2
Application number	US-201314087179-A
Country	US
Kind code	B2
Filing date	Nov 22, 2013
Priority date	Jan 26, 2010
Publication date	Apr 26, 2016
Grant date	Apr 26, 2016

Abstract

The present invention encompasses compounds of general formula (1)

wherein

R 1 to R 3 are defined as in claim 1 , which are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation, and the use thereof for preparing a medicament having the above-mentioned properties.

First claim

The invention claimed is:

1. A method of treating a disease, wherein the disease is cancer selected from a group consisting of prostrate, breast and ovarian cancer, comprising administering an effective amount of a compound of formula 1 or a pharmaceutically acceptable salt thereof, to a patient in need thereof, wherein:

R 3 denotes a group selected from among 3-8 membered heterocycloalkyl, C 6-10 aryl and 5-12 membered heteroaryl, optionally substituted by one or more identical or different R 4 ; and
R 1 denotes a group selected from among C 6-10 aryl and 5-12 membered heteroaryl, optionally substituted by one or more identical or different R 5 and
R 2 denotes a group selected from among hydrogen, C 1-4 alkyl, C 3-8 cycloalkyl, 3-8 membered heteroalkyl, 3-8 membered heterocycloalkyl, —OR v , —SR v , —CF 3 , —CN, —NC and —NO 2 , and
each R 4 denotes a group selected from among R a and R b ; and
each R a independently of one another denotes hydrogen or a group selected from among C 1-6 alkyl, 2-6 membered heteroalkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, C 4-16 cycloalkylalkyl, C 6-10 aryl, C 7-16 arylalkyl, 5-12 membered heteroaryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl, R a optionally being substituted by one or more identical or different R b and/or R c4 ,
each R b denotes a suitable group and is selected independently of one another from among ═O, —OR c , C 1-3 haloalkyloxy, —OCF 3 , —OCHF 2 , ═S, —SR c , ═NR c , ═NOR c , ═NNR c R c1 , ═NN(R g )C(O)NR c R c1 , —NR c R c1 , —ONR c R c1 , —N(OR c )R c1 , —N(R g )NR c R c1 , halogen, —CF 3 , —CN, —NC, —OCN, —SCN, —NO, —NO 2 , ═N 2 , —N 3 , —S(O)R c , —S(O)OR c , —S(O) 2 R c , —S(O) 2 OR c , —S(O)NR c R c1 , —S(O) 2 NR c R c1 , —OS(O)R c , —OS(O) 2 R c , —OS(O) 2 OR c , —OS(O)NR c R c1 , —OS(O) 2 NR c R c1 , —C(O)R c , —C(O)OR c , —C(O)SR c , —C(O)NR c R c1 , —C(O)N(R g )NR c R c1 , —C(O)N(R g )OR c , —C(NR g )NR c R c1 , —C(NOH)R c , —C(NOH)NR c R c1 , —OC(O)R c , —OC(O)OR c , —OC(O)SR c , —OC(O)NR c R c1 , —OC(NR g )NR c R c1 , —SC(O)R c , —SC(O)OR c , —SC(O)NR c R c1 , —SC(NR g )NR c R c1 , —N(R g )C(O)R c , —N[C(O)R c ][C(O)R c1 ], —N(OR g )C(O)R c , —N(R g )C(NR g1 )R c , —N(R g )N(R g1 )C(O)R c , —N[C(O)R c2 ]NR c R c1 , —N(R g )C(S)R c , —N(R g )S(O)R c , —N(R g )S(O)OR c , —N(R g )S(O) 2 R c , —N[S(O) 2 R c ][S(O) 2 R c1 ], —N(R g )S(O) 2 OR c , —N(R g )S(O) 2 NR c R c1 , —N(R g )[S(O) 2 ] 2 R c , —N(R g )C(O)OR c , —N(R g )C(O)SR c , —N(R g )C(O)NR c R c1 , —N(R g )C(O)NR g1 NR c R c1 , —N(R g )N(R g1 )C(O)NR c R c1 , —N(R g )C(S)NR c R c1 , —[N(R g )C(O)] 2 R c , —N(R g )[C(O)] 2 R c , —N{[C(O)] 2 R c }{[C(O)] 2 R c1 }, —N(R g )[C(O)] 2 OR c , —N(R g )[C(O)] 2 NR c R c1 , —N{[C(O)] 2 OR c }{[C(O)] 2 OR c1 }, —N{[C(O)] 2 NR c R c1 }{[C(O)] 2 NR c2 R c3 }, —[N(R g )C(O)] 2 OR c , —N(R g )C(NR g1 )OR c , —N(R g )C(NOH)R c , —N(R g )C(NR g1 )SR c , —N(R g )C(NR g1 )NR c R c1 , —N(R g )C(═N—CN)NR c R c1 and —N═C(R g )NR c R c1 and
each R c , R d , R c2 , R c3 and R c4 independently of one another denotes hydrogen or a group selected from among C 1-6 alkyl, 2-6 membered heteroalkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, C 4-16 cycloalkylalkyl, C 6-10 aryl, C 7-16 arylalkyl, 5-12 membered hetero-aryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl, R c , R c1 , R c2 , R c3 and R c4 independently optionally being substituted by one or more identical or different R d and/or R e4 , where R c together with R g and/or R c1 and/or R c2 and/or R c3 or R c2 together with R c3 may form a 3-8 membered heterocyclalkyl residue via a shared C-, N- O- or S-atom, and
each R d denotes a suitable group and is selected independently of one another from among ═O, —OR e , C 1-3 haloalkyloxy, —OCF 3 , —OCHF2, ═S, —SR e , ═NR e , ═NOR e , ═NNR e R e1 , ═NN(R g2 )C(O)NR e R e1 , —NR e R e1 , —ONR e R e1 , —N(R g2 )NR e R e1 , halogen, —CF 3 , —CN, —NC, —OCN, —SCN, —NO, —NO 2 , ═N 2 , —N 3 , —S(O)R e , —S(O)OR e , —S(O) 2 R e , —S(O) 2 OR e , —S(O)NR e R e1 , —S(O) 2 NR e R e1 , —OS(O)R e , —OS(O) 2 R e , —OS(O) 2 OR e , —OS(O)NR e R e1 , —OS(O) 2 NR e R e1 , —C(O)R e , —C(O)OR e , —C(O)SR e , —C(O)NR e R e1 , —C(O)N(R g2 )NR e R e1 , —C(O)N(R g2 )OR e , —C(NR g2 )NR e R e1 , —C(NOH)R e , —C(NOH)NR e R e1 , —OC(O)R e , —OC(O)OR e , —OC(O)SR e , —OC(O)NR e R e1 , —OC(NR g2 )NR e R e1 , —SC(O)R e , —SC(O)OR e , —SC(O)NR e R e1 , —SC(NR g2 )NR e R e1 , —N(R g2 )C(O)R e , —N[C(O)R e ][C(O)R e1 ], —N(OR g2 )C(O)R e , —N(R g2 )C(NR g3 )R e , —N(R g2 )N(R g3 )C(O)R e , —N[C(O)R e2 ]NR e R e1 , —N(R g2 )C(S)R e , —N(R g2 )S(O)R e , —N(R g2 )S(O)OR e —N(R g2 )S(O) 2 R e , —N[S(O) 2 R e ][S(O) 2 R e1 ], —N(R g2 )S(O) 2 OR e , —N(R g2 )S(O) 2 NR e R e1 , —N(R g2 )[S(O) 2 ] 2 R e , —N(R g2 )C(O)OR e , —N(R g2 )C(O)SR e , —N(R g2 )C(O)NR e R e1 , —N(R g2 )C(O)NR g3 NR e R e1 , —N(R g2 )N(R g3 )C(O)NR e R e1 , —N(R g2 )C(S)NR e R e1 , —[N(R g2 )C(O)][N(R g3 )C(O)]R e , —N(R g2 )[C(O)] 2 R e , —N{[C(O)] 2 R e }{[C(O)] 2 R e1 ], —N(R g2 )[C(O)] 2 OR e , —N(R g2 )[C(O)] 2 NR e R e1 , —N{[C(O)] 2 OR e }{[C(O)] 2 OR e }, —N{[C(O)] 2 NR e R e1 }{[C(O)] 2 NR e2 R e3 }, —[N(R g3 )C(O)][N(R g3 )C(O)]OR e , —N(R g2 )C(NR g3 )OR e , —N(R g2 )C(NOH)R e , —N(R g2 )C(NR g3 )SR e , —N(R g2 )C(NR g3 )NR e R e1 , —N(R g2 )C(═N—CN)NR e R e1 and —N═C(R g2 )NR e R e1
each R e , R e1 , R e2 , R e3 and R e4 independently of one another denotes hydrogen or a group selected from among C 1-6 alkyl, 2-6 membered heteroalkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, C 4-16 cycloalkylalkyl, C 6-10 aryl, C 7-16 arylalkyl, 5-12 membered hetero-aryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl, where R e together with R g2 and/or R e1 and/or R e2 and/or R e3 or R e2 together with R e3 may form a 3-8 membered heterocyclalkyl residue via a shared C-, N-, O- or S-atom, and where R e , R e1 , R e2 , R e3 and R e4 independently optionally being substituted by one or more identical or different R f and/or R g6 , and
each R f denotes a suitable group and in each case is selected independently of one another from among ═O, —OR g , C 1-3 haloalkyloxy, —OCF 3 , —OCHF 2 , ═S, —SR g , ═NR g4 , ═NOR g4 , ═NNR g4 R g5 , ═NN(R h )C(O)NR g4 R g5 , —NR g4 R g5 , —ONR g4 R g5 , —N(R h )NR g4 R g5 , halogen, —CF 3 , —CN, —NC, —OCN, —SCN, —NO, —NO 2 , ═N 2 , —N 3 , —S(O)R g4 , —S(O)OR g4 , —S(O) 2 R g4 , —S(O) 2 OR g4 , —S(O)NR g4 R g5 , —S(O) 2 NR g4 R g5 , —OS(O)R g4 , —OS(O) 2 R g4 , —OS(O) 2 OR g4 , —OS(O)NR g4 R g5 , —OS(O) 2 NR g4 R g5 , —C(O)R g4 , —C(O)OR g4 , —C(O)SR g4 , —C(O)NR g4 R g5 , —C(O)N(R h )NR g4 R g5 , —C(O)N(R h )OR g4 , —C(NR h )NR g4 R g5 , —C(NOH)R g4 , —C(NOH)NR g4 R g5 , —OC(O)R g4 , —OC(O)OR g4 , —OC(O)SR g4 , —OC(O)NR 4g R g5 , —OC(NR h )NR g4 R g5 , —SC(O)R g4 , —SC(O)OR g4 , —SC(O)NR g4 R g5 , —SC(NR h )NR g4 R g5 , —N(R h )C(O)R g4 , —N[C(O)R g4 ] 2 , —N(OR h )C(O)R g4 , —N(R h )C(NR h1 )R g4 , —N(R h )N(R h1 )C(O)R g4 , —N[C(O)R g6 ]NR g4 R g5 , —N(R h )C(S)R g4 , —N(R h )S(O)R g4 , —N(R h )S(O)OR g4 , —N(R h )S(O) 2 R g4 , —N[S(O) 2 R g4 ][S(O) 2 R g5 ], —N(R h )S(O) 2 OR g4 , —N(R h )S(O) 2 NR g4 R g5 , —N(R h )[S(O) 2 ] 2 R g4 , —N(R h )C(O)OR g4 , —N(R h )C(O)SR g4 , —N(R h )C(O)NR g4 R g5 , —N(R h )C(O)NR h1 NR g4 R g5 , —N(R h )N(R h1 )C(O)NR g4 R g5 , —N(R h )C(S)NR g4 R g5 , —[N(R h )C(O)][N(R h1 )C(O)]R g4 , —N(R h )[C(O)] 2 R g4 , —N{[C(O)] 2 R g4 }{[C(O)] 2 R g5 }, —N(R h )[C(O)] 2 OR g4 , —N(R h )[C(O)] 2 NR g4 R g5 , —N{[C(O)] 2 OR g4 }{[C(O)] 2 OR g4 }, —N{[C(O)] 2 NR g4 R g5 }{[C(O)] 2 NR g4 R g5 }, —[N(R h )C(O)][N(R h1 )C(O)]OR g4 , —N(R h )C(NR h1 )OR g4 , —N(R h )C(NOH)R g4 , —N(R h )C(NR h1 )SR g4 , —N(R h )C(NR h1 )NR

Assignees

• Schneider Siegfried
• Kessler Dirk
• Van Der Veen Lars
• Wunberg Tobias
• Boehringer Ingelheim Int

Inventors

• Schneider Siegfried
• Kessler Dirk
• Van Der Veen Lars
• Wunberg Tobias

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title