Back to results
US 9,308,194 B2Granted
Indanyloxyphenylcyclopropanecarboxylic acids
AssigneeBoehringer Ingelheim International GmbH
InventorsIain Lingard, Dieter Hamprecht
Life of this patent
Estimating the term…
Abstract
A compound of formula I, wherein the groups R1, R2, R3, X, m, and n are defined as in claim 1, which have valuable pharmacological properties, in particular bind to the GPR40 receptor and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2. Furthermore, the invention relates to novel intermediates, useful for the synthesis of compounds of formula I.
Claims13
A compound of formula (I)
- wherein:
- R1 is selected from the group consisting of a phenyl ring, a tetrazolyl ring,
- a 5-membered heteroaromatic ring containing 1 —NH—, —O—, or —S— group,
- a 5-membered heteroaromatic ring containing 1 —NH—, —O—, or —S— group and additionally 1 or 2 ═N— atoms,
- a 6-membered heteroaromatic ring containing 1, 2 or 3 ═N— atoms,
- wherein optionally a second ring is annulated to the phenyl ring or to the 5- or 6-membered heteroaromatic rings and the second ring is 5- or 6-membered, unsaturated or aromatic and optionally contains 1, 2, or 3 heteroatoms independently selected from ═N—, —NH—, —O—, and —S— with the proviso that only up to two of the heteroatoms are O and S and no O—O, S—S, and S—O bond is formed, and wherein in the second ring independently of the presence of heteroatoms 1 or 2 CH2 groups are optionally replaced by —C(O)—, —S(O)—, or —S(O)2—,
- wherein the phenyl ring, tetrazolyl ring, 5- or 6-membered heteroaromatic ring, annulated phenyl ring, and annulated 5- or 6-membered heteroaromatic ring are optionally substituted at a carbon atom with one group R1a, and
- wherein the phenyl ring, tetrazolyl ring, 5- or 6-membered heteroaromatic ring, annulated phenyl ring, and annulated 5- or 6-membered heteroaromatic ring are optionally additionally substituted at carbon atoms with 1 to 3 groups independently selected from R1b, and
- wherein the H-atom in one or more NH groups present in the tetrazolyl ring, 5- or 6-membered heteroaromatic ring, annulated phenyl ring, or annulated 5- or 6-membered heteroaromatic ring optionally is replaced by RM;
- R2 is F, Cl, Br, I, C1-4-alkyl, C3-6-cycloalkyl, NC—, H2N—C(O)—, C1-4-alkyl-NRM—C(O)—, C1-4-alkyloxy, or C1-4-alkyl-S(O)2—, wherein any alkyl and cycloalkyl group or sub-group thereof is optionally substituted with one or more F atoms, and wherein multiple R2 are identical or different, if m is 2 or 3;
- R3 is F, Cl, Br, NC—, C1-6-alkyl, C3-6-cycloalkyl-, C1-6-alkyl-O—, or C3-6-cycloalkyl-O—, wherein each alkyl and cycloalkyl group and each alkyl and cycloalkyl sub-group thereof is optionally substituted with one or more F atoms;
- X is —O—, >S═O, >S(═O)2, —CH2—, or —S—;
- m is 0, 1, 2, or 3;
- n is 0, 1, or 2;
- R1a is selected from the group consisting of C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-6-cycloalkyl-, C3-6-cycloalkyl-C1-6-alkyl, C1-4-alkyl-NH—, (C1-4-alkyl)2N—, —NHRN, HNRM—C(O)—, C1-4-alkyl-NRM—C(O)—, C1-6-alkyl-O—, C3-6-cycloalkyl-O—, C3-6-cycloalkyl-C1-6-alkyl-O—, C1-4-alkyl-S—, C1-4-alkyl-S(O)—, C1-4-alkyl-S(O)2, and aryl-C1-3-alkyl-O—,
- wherein a —CH2— member within a C4-6-cycloalkyl- group or sub-group within the groups thereof is optionally replaced by —NRN—, —O—, —S—, —S(O)—, or —S(O2)—, or
- wherein a >CH—CH2— member or a —CH2—CH2— member within a C5-6-cycloalkyl-group or sub-group within the groups thereof is optionally replaced by >N—C(O)—, >N—S(O)—, >N—S(O)2—, —N(RM)—C(O)—, —N(RM)—S(O)—, or —N(RM)—S(O)2—, and
- wherein each alkyl and cycloalkyl group and each alkyl and cycloalkyl sub-group within the groups thereof is optionally substituted with HO—, HO—C1-4-alkyl-, C1-4-alkyl-oxy, C1-4-alkyl-oxy-C1-4-alkyl-, C1-4-alkyl-sulfanyl, C1-4-alkyl-sulfinyl, C1-4-alkyl-sulfonyl, H2N—C(O)—, C1-4-alkyl-NH—C(O)—, (C1-4-alkyl)2N—C(O)—, or C3-6-cycloalkyl-NRM—C(O)—, and/or optionally substituted with one or more F atoms,
- a phenyl ring, a tetrazolyl ring,
- a 5-membered heteroaromatic ring containing 1 —NH—, —O—, or —S— group,
- a 5-membered heteroaromatic ring containing 1 —NH—, —O—, or —S— group and additionally 1 or 2 ═N— atoms,
- a 6-membered heteroaromatic ring containing 1, 2, or 3 ═N— atoms,
- wherein the rings are optionally substituted with one or more groups selected from R1b, and
- wherein the H-atom in one or more NH groups present in the tetrazolyl ring or 5-membered heteroaromatic ring is replaced by RM;
- R1b is F, Cl, CN, —OH, C1-4-alkyl, C3-6-cycloalkyl-, HO—C1-4-alkyl, C1-4-alkyl-O—C1-4-alkyl, C1-4-alkyl-O—, C3-6-cycloalkyl-O—, C1-4-alkyl-O—C1-4-alkyl-O—, C1-4-alkyl-S—, C1-4-alkyl-S(O)—, or C1-4-alkyl-S(O)2—, wherein any alkyl and cycloalkyl group or sub-group within the groups thereof is optionally substituted with one or more F atoms;
- RN is independently H, C1-4-alkyl, HO—C2-4-alkyl (with the proviso that at least 2 carbon atoms are between the HO-group and an NH), C1-4-alkyl-O—C2-4-alkyl-(with the proviso that at least 2 carbon atoms are between an O-group and an NH), C1-4-alkyl-C(O)—, C1-4-alkyl-O—C(O)—, or C1-4-alkyl-S(O)2—, wherein any alkyl group or sub-group within the groups thereof is optionally substituted with one or more F atoms;
- and
- RM is independently H, C1-4-alkyl, HO—C2-4-alkyl (with the proviso that at least 2 carbon atoms are between the HO-group and an NH), or C1-4-alkyl-O—C2-4-alkyl-(with the proviso that at least 2 carbon atoms are between an O-group and an NH), wherein any alkyl group or sub-group within the groups thereof is optionally substituted with one or more F atoms, or
- a salt thereof.
26 more elements
Dependencies are inferred from the claim text.