US 6,982,353 B2
C2-disubstituted indan-1-ol compounds, their derivatives, processes for their preparation, and their use as pharmaceuticals
Gerhard Jaehne, Frankfurt (Germany); Volker Krone, Hofheim (Germany); Martin Bickel, Bad Homburg (Germany); and Matthias G ssel, Hofheim (Germany)
Assigned to Aventis Pharma Deutschland GmbH, Frankfurt (Germany)
Filed on Aug. 29, 2002, as Appl. No. 10/231,418.
Claims priority of application No. 101 42 663 (DE), filed on Aug. 31, 2001.
Prior Publication US 2003/0181491 A1, Sep. 25, 2003
Int. Cl. C07C 319/00 (2006.01); C07C 321/00 (2006.01); C07C 323/00 (2006.01); C07C 381/00 (2006.01); C07C 319/14 (2006.01)
U.S. Cl. 568—38 6 Claims
 
1. A compound of formula I,
OG Complex Work Unit Drawing
in which
R1, R2, R3, R4 are each independently selected from the group consisting of H, F, Cl, Br, I, —CN; N3, —NO2, —OH, —O(C1-C8)-alkyl, —O(C3-C8)-cycloalkyl, —O—CH2-phenyl, —O—phenyl, —O—CO—(C1-C8)-alkyl, —O—CO—(C3-C8)-cycloalkyl, —S(O)0-2(C1-C8)-alkyl, —S(O)0-2(C3-C8)-cycloalkyl, —NH2, —NH—(C1C8)-alkyl, —NH—(C3-C8)-cycloalkyl, —N[(C1-C8)-alkyl]2, —N[(C3-C8)-cycloalkyl]2, —NH—CO—(C1-C8)-alkyl, —NH—CO—(C3-C8)-cycloalkyl, —SO3H, —SO2—NH2, —SO2—NH—(C1-C8)-alkyl, —SO2—NH—(C3-C8)-cycloalkyl, —NH—SO2—NH2, —NH—SO2—(C1-C8)-alkyl, —NH—SO2—(C3-C8)-cycloalkyl, —O—CH2—COOH, —O—CH2—CO—O(C1-C8)-alkyl, —COOH, —CO—O(C1-C8)-alkyl, —CO—O—(C3-C8)-cycloalkyl, —CO—NH2, —CO—NH(C1-C8)-alkyl, —CO—N[(C1-C8)-alkyl]2, —(C1-C8)-alkyl, —(C3-C8)cycloalkyl, —(C2-C8)-alkenyl, and —(C2-C8)-alkynyl wherein,
the alkyl, alkenyl and alkynyl groups in each case one to seven hydrogen atoms which are optionally replaced by fluorine or one hydrogen is optionally replaced by —OH, —OC(O)CH3, —O—CH2-Ph, —NH2, —NH—CO—CH3, or —N(COOCH2Ph)2,
an aryl group wherein,
the aryl group is phenyl, or 1- or 2-naphthyl, or a heterocycle wherein,
the heterocycle is 5-tetrazolyl,
1-[(C1-C6)-alkyl]-5-tetrazolyl,
2-[(C1-C6)-alkyl]-5-tetrazolyl,
1-imidazolyl,
1- or 4-[1,2,4]-triazolyl,
2- or 3-thienyl,
2- or 3-furyl,
2-, 3- or 4-pyridyl,
2-, 4- or 5-oxazolyl,
3-, 4- or 5-isoxazolyl,
2-, 4- or 5-thiazolyl, or
3-, 4- or 5-isothiazolyl;
wherein the aryl group or heterocycle is optionally substituted up to two times by F, Cl, Br, —CN, —OH, (C1-C4)-alkyl, —CF3, —O—(C1-C4)-alkyl, —S(O)0-2(C1-C6)-alkyl, —NH2, —NH—SO2—(C1-C4)-alkyl, —COOH, —CO—O—(C1-C4)-alkyl, or —CO—NH2, and wherein,
the alkyl groups one to seven hydrogen atoms which is optionally replaced by fluorine;
X is S, —SO, or —SO2;
Y is —(CH2)p, wherein p is 0-3;
R5 is —CF3, —(C1-C18)-alkyl, —(C3-C4)-cycloalkyl, or (C6-C8)-cycloalkyl, wherein the alkyl groups one to seven hydrogen atoms which is optionally replaced by fluorine;
—(CH2)r—COR16, wherein, r is 1-6 and R16 is —OH, —O—(C1-C6)-alkyl or —NH2, —CH2—CH(NHR13)—COR8, wherein, R13 is H or —C(O)—(C1-C4)-alkyl and R8 is —OH, —O—(C1-C6)-alkyl or —NH2, phenyl, 1- or 2-naphthyl, biphenyl or a heterocyclic radical, wherein the rings or ring systems of the phenyl, 1- or 2-naphthyl or heterocyclic radical are optionally substituted up to two times by F, Cl, Br, I, —CN, —OH, —O(C1-C8)-alkyl, —O(C3-C8)-cycloalkyl, —O—CO—(C1-C8)-alkyl, —O—CO—(C3-C8)-cycloalkyl, —S(O)0-2(C1-C8)-alkyl, —S(O)0-2(C3-C8)-cycloalkyl, —NH2, —NH—(C1-C8)-alkyl, —NH—(C3-C8)-cycloalkyl, —NH—CO—(C3-C8)-cycloalkyl, —SO3H, —SO2—NH2, —SO2—NH—(C1-C8)-alkyl, —SO2—NH—(C3-C8)-cycloalkyl, —NH—SO2—NH2, —NH—SO2—(C1-C8)-alkyl, —NH—SO2—(C3-C8)-cycloalkyl, —O—CH2—COOH, —O—CH2—CO—O(C1-C8)-alkyl, —COOH, —CO—O(C1-C8)-alkyl, —CO—O—(C3-C8)-cycloalkyl, —CO—NH2, —CO—NH(C1-C8)-alkyl, —CO—N[(C1-C8)-alkyl]2, —(C1-C8)-alkyl, or —(C3-C8)-cycloalkyl, wherein, the alkyl groups in each case one to seven hydrogen atoms is optionally replaced by fluorine;
R6 is F, Cl, Br, —CN, —CF3, —(C1-C18)-alkyl, or —(C3-C8)-cycloalkyl wherein, the alkyl groups one to seven hydrogen atoms is optionally replaced by fluorine,
—(CH2)s—CH(NHR9)—COR10 wherein s is 1-6 and R9 is H or —C(O)—(C1-C6)-alkyl, and wherein R10 is —OH, —O—(C1-C6)-alkyl or —C(O)—(C1-C6)-alkyl, and wherein R10 is —OH, —O—(C1-C6)-alkyl or
—NH2, —(CH2)u-aryl or —(CH2)u-heteroaryl wherein, u is 0-6 and aryl is phenyl, 1- or 2-naphthyl or biphenyl and the aryl or heteroaryl ring is unsubstituted or substituted by at least one and up to two substituents chosen from F, Cl, Br, I, —CN, —OH, —O(C1-C8)-alkyl, and —O—CO—(C1-C8)-alkyl wherein,
the alkyl radicals one to seven hydrogen atoms is optionally replaced by fluorine, —S(O)0-2(C1-C8)-alkyl, —NH2, —NH—(C1-C8)-alkyl, —NH—CO—(C1-C8)-alkyl, —SO3H, —SO2—NH2, —SO2—NH—(C1-C8)-alkyl, —NH—SO2—(C1-C8)-alkyl, —O—CH2—COOH, —O—CH2—CO—O(C1-C8)-alkyl, —COOH, —CO—O(C1-C8)-alkyl, —CO—NH2, or (C1-C8)-alkyl, wherein,
the alkyl groups one to seven hydrogen atoms is optionally replaced by fluorine; and
R7 is H;
provided that R1, R2, R3 and R4 are not concurrently H; and
further provided that when R1 and R4 are H, and only one of R2 or R3 is —O-phenyl or —NH—SO2—(C1-C8)-alkyl, then the other of R2 or R3 is other than —O-phenyl or —NH—SO2—(C1-C8)-alkyl;
or a pharmaceutically acceptable salt or physiologically functional derivative thereof.