GB2367816A — Urea- and thiourea-containing derivatives of beta-amino acids

USPTO Abstract

Compounds of general formula (I) wherein R<SP>1</SP> is a substituted 4- to 9-membered, saturated or unsaturated heterocyclic or carbocyclic ring, R<SP>6</SP> is a phenyl or 5- to 6-membered heterocyclic ring which is substituted by a urea or thiourea group and X is a direct bond or an optionally substituted methylene group. The phenyl or heterocyclic ring of R<SP>6</SP> may be halogen-substituted and the urea or thiourea may be substituted and may form part of a ring. R<SP>2</SP> and R<SP>5</SP> are independently H or optionally substituted C<SB>1</SB>-C<SB>10</SB> alkyl, C<SB>2</SB>-C<SB>10</SB> alkenyl, C<SB>2</SB>-C<SB>10</SB> alkynyl, C<SB>6</SB> or C<SB>10</SB> aryl or C<SB>3</SB>-C<SB>7</SB> cycloalkyl, R<SP>3</SP>, R<SP>4</SP>, R<SP>7</SP> and R<SP>8</SP> are independently H or optionally substituted C<SB>1</SB>-C<SB>10</SB> alkyl, C<SB>2</SB>-C<SB>10</SB> alkenyl, C<SB>2</SB>-C<SB>10</SB> alkynyl, C<SB>6</SB> or C<SB>10</SB> aryl, C<SB>3</SB>-C<SB>7</SB> cycloalkyl or an optionally substituted 4- to 9-membered saturated or unsaturated heterocyclic ring. Alternatively, R<SP>3</SP> and R<SP>4</SP> and the carbon to which they are attached and/or R<SP>7</SP> and R<SP>8</SP> and the carbon to which they are attached together form part of a 4- to 7-membered, saturated or unsaturated, optionally substituted heterocyclic ring. The compounds may be integrin antagonists and may be used to treat inflammatory, autoimmune and immune disorders including asthma, rheumatoid arthritis and transplant rejection. Compounds of formula (I) may be prepared via compounds of general formula (I') where R<SP>1</SP>, R<SP>2</SP>, R<SP>3</SP>, R<SP>4</SP>, R<SP>7</SP> and R<SP>8</SP> are as defined for (I) and PG<SB>1</SB> is a protecting group for the carboxyl group. <EMI ID=1.1 HE=71 WI=92 LX=566 LY=1463 TI=CF>