Novel compounds

Patent metadata

Field	Value
Publication number	US-2016263122-A1
Application number	US-201414778568-A
Country	US
Kind code	A1
Filing date	Mar 17, 2014
Priority date	Mar 20, 2013
Publication date	Sep 15, 2016
Grant date	—

Abstract

The present invention relates to substituted N-(phenyl-heteroaryl)-3-acetylamino-benzamides and N-[3-(acetylamino)phenyl]-phenyl-heteroaryl-carboxamides of general formula (I) as described and defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease such as cancer, wherein i.a.: L A represents an optionally substituted methylene or ethylene group; L B represents —N(H)—C(═0)- or —C(═0)—N(H)—; R 1 represents an optionally substituted 5- to 8-membered heterocycloalkyl, 4- to 10-membered heterocycloalkenyl, aryl, heteroaryl or —N(R7)(Ci-C6-alkyl) group; R 2 represents an optionally substituted 5- or 6-membered heteroaryl group; R 3 represents an optionally substituted phenyl group.

First claim

1 . A compound of formula (I):

in which:
L A represents a methylene or ethylene group, said methylene or ethylene group being optionally substituted, one or more times, identically or differently, with a substituent selected from:
hydroxy-, cyano-, C 1 -C 3 -alkoxy-, hydroxy-C 1 -C 3 -alkyl-,
halo-C 1 -C 3 -alkoxy-, C 3 -C 7 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-;
or, when two substituents are present at the same carbon atom, the two substituents, together with the carbon atom they are attached to, may form a C 3 -C 6 -cycloalkyl- or 3- to 6-membered heterocycloalkyl- ring; wherein said ring is optionally substituted one or more times, identically or differently, with a substituent selected from:
halo-, hydroxy-, cyano-, C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-;

L B represents —N(H)—C(═O)— or —C(═O)—N(H)—;
R 1 represents a group selected from:
5- to 8-membered heterocycloalkyl-, 4- to 10-membered heterocycloalkenyl-, aryl-, heteroaryl-, and —N(R 7 )—(C 1 -C 6 -alkyl); wherein said 5- to 8-membered heterocycloalkyl-, 4- to 10-membered heterocycloalkenyl-, aryl-, heteroaryl-, and —N(R 7 )—(C 1 -C 6 -alkyl) group is optionally substituted, one or more times, identically or differently, with a substituent selected from: halo-, hydroxy-, cyano-, C 1 -C 3 -alkoxy-, hydroxy-C 1 -C 3 -alkyl-, halo-C 1 -C 3 -alkoxy-, C 3 -C 7 -cycloalkyl-;

R 2 represents a group selected from:

wherein “*” indicates the point of attachment to R 3 , and “**” indicates the point of attachment to L B ; wherein said group is optionally substituted, one or more times, identically or differently, with a C 1 -C 3 -alkyl- group;

R 3 represents a phenyl-group,
said phenyl-group being optionally substituted, one or more times, identically or differently, with a substituent selected from:
halo-, hydroxy-, —N(R 9 )(R 10 ), —N(H)C(═O)R 9 , cyano-, nitro-, C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-,
halo-C 1 -C 3 -alkyl-, hydroxy-C 1 -C 3 -alkyl-, amino-C 1 -C 3 -alkyl-, halo-C 1 -C 3 -alkoxy-;

R 4 represents a hydrogen atom or a C 1 -C 3 -alkyl- group;
R 5 represents a hydrogen atom or a halogen atom or a group selected from:
cyano-, C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-;

R 6 represents a group selected from:
C 1 -C 6 -alkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl-,
C 1 -C 6 -alkoxy-, C 3 -C 6 -cycloalkoxy-, halo-, hydroxy-, cyano-, aryl-,
heteroaryl-, —N(R 9 )(R 10 ), —C(═O)—O—C 1 -C 4 -alkyl, —C(═O)—N(R 9 )(R 10 , R 9 —S—, R 9 —S(═O)—, R 9 —S(═O) 2 —;
said C 1 -C 6 -alkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl-, aryl-, heteroaryl-, and C 1 -C 6 -alkoxy- group being optionally substituted, one or more times, identically or differently, with a substituent selected from: halo-, cyano-, nitro-, hydroxy-, C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-, halo-C 1 -C 3 -alkoxy-, hydroxy-C 1 -C 3 -alkoxy-, C 1 -C 3 -alkoxy-C 2 -C 3 -alkoxy-,
C 3 -C 7 -cycloalkyl-, C 4 -C 7 -cycloalkenyl-,
3- to 10-membered heterocycloalkyl-, 4- to 10-membered heterocycloalkenyl-,
aryl-, heteroaryl-, —C(═O)R 9 , —C(═O)O—(C 1 -C 4 -alkyl), —OC(═O)—R 9 , —N(H)C(═O)R 9 , —N(R 10 )C(═O)R 9 ,
—N(H)C(═O)NR 10 R 9 , —N(R 11 )C(═O)NR 10 R 9 , —N(H)R 9 , —NR 10 R 9 ,
—C(═O)N(H)R 9 , —C(═O)NR 10 R 9 , R 9 —S—, R 9 —S(═O)—, R 9 —S(═O) 2 —,
—N(H)S(═O)R 9 , —N(R 10 S(═O)R 9 , —S(═O)N(H)R 9 , —S(═O)NR 10 R 9 ,
—N(H)S(═O) 2 R 9 , —N(R 9 )S(═O) 2 R 10 , —S(═O) 2 N(H)R 9 , —S(═O) 2 NR 10 R 9 ,
—S(═O)(═NR 10 R 9 , —N═S(═O)(R 10 R 9 ;

R 7 represents a hydrogen atom or a C 1 -C 3 -alkyl- or C 1 -C 3 -alkoxy-C 1 -C 3 -alkyl- group;
R 9 , R 10 , R 11
represent, independently from each other, a hydrogen atom or a C 1 -C 3 -alkyl- or C 1 -C 3 -alkoxy-C 1 -C 3 -alkyl- group;

or
R 9 R 10 together with the atom or the group of atoms they are attached to, form a 3- to 10-membered heterocycloalkyl- or 4- to 10-membered heterocycloalkenyl- group;
m represents 0, 1, or 2;
or a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.

2 . A compound according to claim 1 , wherein:
L A represents —CH 2 —, —CH(CH 3 )— or

3 . A compound according to claim 1 , wherein:
R 1 represents a group selected from:

—N(CH 3 ) 2 , —N(H)—(CH 2 —CH 2 —O—CH 3 ), —N(CH 3 )—(CH 2 —CH 2 —O—CH 3 ); wherein * indicates the point of attachment to L A ; and wherein R 12 represents a methyl-, ethyl- or cyclopropyl- group.

4 . A compound according to claim 1 , wherein:
R 2 represents a group selected from:

preferably R 2 represents

wherein “*” indicates the point of attachment to R 3 , and “**” indicates the point of attachment to L B .

5 . A compound according to claim 1 , wherein:
R 3 represents:

wherein “*” represents the point of attachment to R 2 ;
R 31 , R 32 , R 34 and R 35 represent, independently from each other, a hydrogen atom or a group selected from: halo-, hydroxy-, —NH 2 , cyano-, nitro-, C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-, hydroxy-C 1 -C 3 -alkyl-, halo-C 1 -C 3 -alkoxy-; and R 33 represents a hydrogen atom or a substituent selected from: hydroxy-, —CHF 2 , —NH 2 , —NR 10 R 9 , —CH 2 NH 2 , —N(H)C(═O)CH 3 .

6 . A compound according to claim 1 , wherein:
R 4 represents a hydrogen atom; and R 5 represents hydrogen.

7 . A compound according to claim 1 , wherein:
R 6 represents a group selected from: C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-, C 3 -C 6 -cycloalkoxy-, halo-, hydroxy-, cyano-, —C(═O)—O—C 1 -C 4 -alkyl, —C(═O)—N(R 9 )(R 10 ), R 9 —S—, R 9 —S(═O)—, R 9 —S(═O) 2 —; said C 1 -C 6 -alkyl-, and C 1 -C 6 -alkoxy- group being optionally substituted, one or more times, identically or differently, with a substituent selected from: halo-, C 1 -C 3 -alkoxy-, C 1 -C 3 -alkoxy-C 2 -C 3 -alkoxy-, C 3 -C 7 -cycloalkyl-.

8 . A compound according to claim 1 , which is selected from the group consisting of:
N-[6-(2-fluorophenyl)pyridin-3-yl]-4-methoxy-3-[(morpholin-4-ylacetyl)amino]benzamide, N-[6-(2-fluorophenyl)pyridin-3-yl]-4-methoxy-3-[(8-oxa-3-azabicyclo[3.2.1]oct-3-ylacetyl)amino]benzamide, N-[6-(2-fluorophenyl)pyridin-3-yl]-4-methoxy-3-{[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-ylacetyl]amino}benzamide, 4-methoxy-3-[(morpholin-4-ylacetyl)amino]-N-(6-phenylpyridin-3-yl)benzamide, N-[6-(2-fluorophenyl)pyridin-3-yl]-3-[(morpholin-4-ylacetyl)amino]-4-(trifluoromethoxy)benzamide, N-[6-(2-fluorophenyl)pyridin-3-yl]-3-[(8-oxa-3-aza bicyclo[3.2.1]oct-3-ylacetyl)amino]-4-(trifluoromethoxy)benzamide, N-[6-(2-fluorophenyl)pyridin-3-yl]-3-{[2-(morpholin-4-yl)propanoyl]amino}-4-(trifluoromethoxy)benzamide, N-[6-(2-fluorophenyl)pyridin-3-yl]-3-{[(2S)-2-(morpholin-4-yl)propanoyl]amino}-4-(trifluoromethoxy)benzamide, N-[6-(2-fluorophenyl)pyridin-3-yl]-3-{[(2R)-2-(morpholin-4-yl)propanoyl]amino}-4-(trifluoromethoxy)benzamide, 3-{[2-(morpholin-4-yl)propanoyl]amino}-N-(6-phenylpyridin-3-yl)-4-(trifluoromethoxy)benzamide, N-[6-(2-fluorophenyl)pyridin-3-yl]-3-{[2-

Assignees

• Bayer Pharma AG

Inventors

• Thede Kai
• Scott William
• Bender Eckhard
• Golz Stefan
• Hägebarth Andrea
• Lienau Philip
• Puehler Florian
• Basting Daniel
• Schneider Dirk
• Mowes Manfred
• Richter Anja
• Zorn Ludwig
• Liu Ningshu
• Monning Ursula
• Siegel Franziska

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P7/12

  Antidiuretics, e.g. drugs for diabetes insipidus (ADH A61P5/10) · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P37/02

  Immunomodulators · CPC title