Compounds

Patent metadata

Field	Value
Publication number	US-10130633-B2
Application number	US-201414778568-A
Country	US
Kind code	B2
Filing date	Mar 17, 2014
Priority date	Mar 20, 2013
Publication date	Nov 20, 2018
Grant date	Nov 20, 2018

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(═O)— or —C(═O)—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

The invention claimed is:

1. A compound of formula (I):

wherein:
L A is
—CH 2 —, —CH(CH 3 )— or

L B is —N(H)—C(═O)— or —C(═O)—N(H)—;
R 1 is a
5- to 8-membered heterocycloalkyl-, optionally substituted, one or more times, identically or differently, with a substituent selected from the group consisting of:
halo-, hydroxy-, cyano-, C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-, halo-C 1 -C 3 -alkyl-, hydroxy-C 1 -C 3 -alkyl-, halo-C 1 -C 3 -alkoxy-, and C 3 -C 7 -cycloalkyl-;

R 2 is a group selected from the group consisting of:

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

R 3 is a phenyl- group,
wherein said phenyl- group is optionally substituted, one or more times, identically or differently, with a substituent selected from the group consisting of:
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-, and halo-C 1 -C 3 -alkoxy-;

R 4 is a hydrogen atom or a C 1 -C 3 -alkyl- group;
R 5 is a hydrogen atom, a halogen atom, or a group selected from the group consisting of:
cyano-, C 1 -C 3 -alkyl-, and C 1 -C 3 -alkoxy-;

R 6 is a group selected from the group consisting of:
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)—, and R 9 —S(═O) 2 —,
wherein 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 is optionally substituted, one or more times, identically or differently, with a substituent selected from the group consisting of:
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 , and —N═S(═O)(R 10 )R 9 ; and

R 9 , R 10 , and R 11
are independently a hydrogen atom, a C 1 -C 3 -alkyl- group, or a C 1 -C 3 -alkoxy-C 1 -C 3 -alkyl- group;

or
R 9 and R 10 are taken together with the atom or the group of atoms to which they are attached to form a 3- to 10-membered heterocycloalkyl- or 4- to 10-membered heterocycloalkenyl- group,
or a tautomer, an N-oxide, or a salt thereof, or a mixture of any of the foregoing.

2. The compound according to claim 1 , wherein:
R 1 is a group selected from the group consisting of:

wherein * indicates the point of attachment to L A , and wherein R 12 is a methyl-, ethyl- or cyclopropyl- group,
or a tautomer, an N-oxide, or a salt thereof, or a mixture of any of the foregoing.

3. The compound according to claim 1 , wherein:
R 2 is a group selected from the group consisting of:

wherein “*” indicates the point of attachment to R 3 , and “**” indicates the point of attachment to L B ,
or a tautomer, an N-oxide, or a salt thereof, or a mixture of any of the foregoing.

4. The compound according to claim 1 , wherein:
R 3 is

wherein “*” indicates the point of attachment to R 2 ;
R 31 , R 32 , R 34 and R 35 are independently a hydrogen atom or a group selected from the group consisting of:
halo-, hydroxy-, —NH 2 , cyano-, nitro-, C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-, halo-C 1 -C 3 -alkyl-, hydroxy-C 1 -C 3 -alkyl-, and halo-C 1 -C 3 -alkoxy-; and

R 33 is a hydrogen atom or a substituent selected from the group consisting of:
hydroxy-, —CHF 2 , —NH 2 , —NR 10 R 9 , —CH 2 NH 2 , and —N(H)C(═O)CH 3 ,

or a tautomer, an N-oxide, or a salt thereof, or a mixture of any of the foregoing.

5. The compound according to claim 1 , wherein:
R 4 is a hydrogen atom; and
R 5 is a hydrogen atom,
or a tautomer, an N-oxide, or a salt thereof, or a mixture of any of the foregoing.

6. The compound according to claim 1 , wherein:
R 6 is a group selected from the group consisting of:
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 1 ), R 9 —S—, R 9 —S(═O)—, and R 9 —S(═O) 2 —,
wherein said C 1 -C 6 -alkyl- and C 1 -C 6 -alkoxy- groups are optionally substituted, one or more times, identically or differently, with a substituent selected from the group consisting of:
halo-, C 1 -C 3 -alkoxy-, C 1 -C 3 -alkoxy-C 2 -C 3 -alkoxy-, and C 3 -C 7 -cycloalkyl-,
or a tautomer, an N-oxide, or a salt thereof, or a mixture of any of the foregoing.

7. The 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-azabicyclo[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;
3-[(morpholin-4-ylacetyl)amino]-N-(5-phenyl-1,3-thiazol-2-yl)-4-(trifluoromethyl)benzamide;
3-[(morpholin-4-ylacetyl)amino]-N-(6-phenylpyridin-3-yl)-4-(trifluoromethyl)benzamide;
3-[(morpholin-4-ylacetyl)amino]-N-(5-phenyl-1,3-thiazol-2-yl)-4-(trifluoromethoxy)benzamide;
3-[(morpholin-4-ylacetyl)amino]-N-(6-phenylpyridin-3-yl)-4-(trifluoromethoxy)benzamide;
N-{3-[(morpholin-4-ylacetyl)amino]-4-(trifluoromethoxy)phenyl}-5-phenyl-1,3-thiazole-2-carboxamide;
N-{3-[(morpholin-4-ylacetyl)amino]-4-(trifluoromethoxy)phenyl}-5-phenylthiophene-2-carboxamide;
N-{4-tert-butyl-3-[(morpholin-4-ylacetyl)amino]phenyl}-6-phenylnicotinamide;
N-{4-tert-butyl-3-[(morpholin-4-ylacetyl)amino]phenyl}-5-phenyl

Assignees

• Bayer Pharma AG

Inventors

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

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P7/06

  Antianaemics · CPC title