Monoacyl-substituted guanidines, a process for their preparation, their use as a medicament or diagnostic aid, and pharmaceutical compositions containing them

A compound of formula III or a salt or acid thereof:

• in which X(2) is
• R(101)
• is F, Cl, CH3 or CF3;
• R(102)
• is hydrogen, F, Cl, Br, —CN, R(110b)R(110c)N—CO—, or R(111a)—CO—;
• R(110b) and R(111a)
• are, independently, (C1-C4)-alkyl, (C3-C4)-alkenyl, —CnH2n-R(115a) or CF3;
• n is zero or 1;
• R(115a) is (C3-C6)-cycloalkyl or phenyl,
• in which R(115a) is unsubstituted or is substituted by 1 to 2 substituents chosen from F, Cl, CF3, methyl, methoxy and NR(116a)R(117a);
• wherein R(116a) and R(117a) are hydrogen or methyl;
• or
• R(110b) and R(111a)
• are hydrogen;
• R(110c)
• is hydrogen or methyl;
• R(103)
• is —Y-para-C6H4-(C═O)h-(CHOH)i-(CH2)j-(CHOH)k-R(123),
• -Y-m-C6H4-(C═O)ad-(CHOH)ae-(CH2)af-(CHOH)ag-R(124) or
• -Y-ortho-C6H4-(C═O)ah-(CHOH)ao-(CH2)ap-(CHOH)ak-R(125);
• Y is oxygen, S or —NR(83);
• R(123), R(124), R(125) and R(83)
• are, independently, hydrogen or methyl;
• h, ad and ah
• are, independently, zero or 1;
• i, k, ae, ag, ao and ak
• are, independently, zero, 1, 2 or 3;
• j, af and ap
• are, independently, zero or 1;
• with the proviso that, h, i and k are not simultaneously zero,
• ad, ae and ag are not simultaneously zero and
• ah, ao and ak are not simultaneously zero;
• or
• R(103)
• is F, Br, CN, CF3 or —CgH2gR(118a);
• g is zero, 1 or 2;
• R(118a) is phenyl,
• in which R(118a) is unsubstituted or is substituted by 1 to 2 substituents chosen from F, Cl, CF3, methyl, methoxy and NR(119a)R(119b);
• wherein R(119a) and R(119b)
• are H or CH3;
• or
• R(103)
• is pyrrolyl;
• or
• R(103)
• is —SR(129) or —CR(133)R(134)R(135);
• R(129) and R(133)
• are -CaH2a-(C1-C9)-heteroaryl,
• which is unsubstituted or is substituted by 1 to 3 substituents chosen from F, Cl, CF3, CH3, methoxy, hydroxyl, amino, methylamino and dimethylamino;
• a is zero or 1;
• R(134) and R(135)
• are, independently of each other, hydrogen or CH3;
• or
• R(103)
• is R(110a)-SO2- or R(112a)R(113a)N—SO2-;
• R(110a) is (C1-C4)-alkyl, CF3, (C3-C4)-alkenyl or -CsH2s-R(115a);
• s is zero or 1;
• R(115a) is (C3-C6)-cycloalkyl or phenyl,
• in which R(115a) is unsubstituted or is substituted by 1 to 2 substituents chosen from F, Cl, CF3, methyl, methoxy and NR(116a)R(117a);
• wherein R(116a) and R(117a)
• are hydrogen or CH3;
• R(112a)
• is (C1-C4)-alkyl, CF3, (C3-C4)-alkenyl or −CwHw2w-R(115a);
• w is zero or 1;
• R(115a) is (C3-C6)-cycloalkyl or phenyl, in which R(115a) is unsubstituted or is substituted by 1 to 2 substituents chosen from F, Cl, CF3, methyl, methoxy and NR(116a)R(117a);
• wherein R(116a) and R(117a) are hydrogen or CH3;
• R(113a) is hydrogen or CH3;
• or
• R(112a) and R(113a)
• are together 4 or 5 methylene groups of which one CH2 group is optionally replaced by oxygen, S, NH, N—CH3 or N-benzyl;
• or
• R(103)
• is R(176)—NH—SO2—;
• R(176) is R(177)R(178)N—(C═Y′)—;
• Y′ is oxygen, S or N—R(179);
• R(177) and R(178) are identical or different and are (C1-C4)-alkyl, (C3-C4)-alkenyl or —CfH2f-R(180);
• f is zero or 1;
• R(180) is (C5-C7)-cycloalkyl or phenyl,
• in which R(180) is unsubstituted or is substituted by 1 to 2 substituents chosen from F, Cl, CF3, methoxy and methyl;
• or
• R(177) and R(178)
• together form 4 or 5 methylene groups of which one CH2 group is optionally replaced by oxygen, S, NH, N—CH3 or N-benzyl;
• R(179) is defined as R(177);
• R(104)
• is R(110a)-SO2—;
• R(110a) is (C1-C4)-alkyl or CF3;
• and
• R(105) is hydrogen.

A method for diagnosing hypertension and proliferative diseases, comprising providing within a host an effective amount of a compound of formula III or a salt or acid thereof:

• in which X(2) is
• R(101)
• is F, Cl, CH3 or CF3;
• R(102)
• is hydrogen, F, Cl, Br, —CN, R(110b)R(110c)N—CO—, or R(111a)—CO—;
• R(110b) and R(111a)
• are, independently, (C1-C4)-alkyl, (C3-C4)-alkenyl, —CnH2n-R(115a) or CF3;
• n is zero or 1;
• R(115a) is (C3-C6)-cycloalkyl or phenyl,
• in which R(115a) is unsubstituted or is substituted by 1 to 2 substituents chosen from F, Cl, CF3, methyl, methoxy and NR(116a)R(117a);
• wherein R(116a) and R(117a) are hydrogen or methyl;
• or
• R(110b) and R(111a)
• optionally are hydrogen;
• R(110c)
• is hydrogen or methyl;
• R(103)
• is —Y-para-C6H4-(C═O)h-(CHOH)i-(CH2)j-(CHOH)k-R(123),
• -Y-meta-C6H4-(C═O)ad-(CHOH)ae-(CH2)af-(CHOH)ag-R(124) or
• -Y-ortho-C6H4-(C═O)ah-(CHOH)ao-(CH2)ap-(CHOH)ak-R(125);
• Y is oxygen, S or —NR(83);
• R(123), R(124), R(125) and R(83)
• are, independently, hydrogen or methyl;
• h, ad and ah
• are, independently, zero or 1;
• i, k, ae, ag, ao and ak
• are, independently, zero, 1, 2 or 3;
• j, af and ap
• are, independently, zero or 1;
• with the proviso that, h, i and k are not simultaneously zero,
• ad, ae and ag are not simultaneously zero and
• ah, ao and ak are not simultaneously zero;
• or
• R(103)
• is F, Br, CN, CF3 or —CgH2gR(118a);
• g is zero, 1 or 2;
• R(118a) is phenyl,
• in which R(118a) is unsubstituted or is substituted by 1 to 2 substituents chosen from F, Cl, CF3, methyl, methoxy and NR(119a)R(119b);
• wherein R(119a) and R(119b) are H or CH3;
• or
• R(103)
• is pyrrolyl;
• or
• R(103)
• is —SR(129) or —CR(133)R(134)R(135);
• R(129) and R(133)
• are -CaH2a-(C1-C9)-heteroaryl,
• which is unsubstituted or is substituted by 1 to 2 substituents chosen from F, Cl, CF3, CH3, methoxy, hydroxyl, amino, methylamino and dimethylamino;
• a is zero or 1;
• R(134) and R(135)
• are, independently of each other, hydrogen or CH3;
• or
• R(103)
• is R(110a)—SO2— or R(112a)R(113a)N—SO2—;
• R(110a) is (C1-C4)-alkyl, CF3, (C3-C4)-alkenyl or -CsH2s-R(115a);
• s is zero or 1;
• R(115a) is (C3-C6)-cycloalkyl or phenyl,
• in which R(115a) is unsubstituted or is substituted by 1 to 2 substituents chosen from F, Cl, CF3, methyl, methoxy and NR(116a)R(117a);
• wherein R(116a) and R(117a)
• are hydrogen or CH3;
• R(112a)
• is (C1-C4)-alkyl, CF3, (C3-C4)-alkenyl or −CwHw2w-R(115a);
• w is zero or 1;
• R(115a) is (C3-C6)-cycloalkyl or phenyl,
• in which R(115a) is unsubstituted or is substituted by 1 to 2 substituents chosen from F, Cl, CF3, methyl, methoxy and NR(116a)R(117a);
• wherein R(116a) and R(117a) are hydrogen or CH3;
• R(113a) is hydrogen or CH3;
• or
• R(112a) and R(113a)
• are together 4 or 5 methylene groups of which one CH2 group is optionally replaced by oxygen, S, NH, N—CH3 or N-benzyl;
• or
• R(103)
• is R(176)—NH—SO2—;
• R(176) is R(177)R(178)N—(C═Y′)—;
• Y′ is oxygen, S or N—R(179);
• R(177) and R(178)
• are identical or different and are (C1-C4)-alkyl, (C3-C4)-alkenyl or —CfH2f-R(180);
• f is zero or 1;
• R(180) is (C5-C7)-cycloalkyl or phenyl,
• in which R(180) is unsubstituted or is substituted by 1 to 2 substituents chosen from F, Cl, CF3, methoxy and methyl;
• or
• R(177) and R(178)
• together form 4 or 5 methylene groups of which one CH2 group is optionally replaced by oxygen, S, NH, N—CH3 or N-benzyl;
• R(179) is defined as R(177);
• R(104)
• is R(110a)—SO2—;
• R(110a) is (C1-C4)-alkyl or CF3;
• and
• R(105) is hydrogen.

The method of claim 13, wherein

• R(101) is F, Cl, CH3 or CF3;
• R(102) is hydrogen, F, Cl, Br, —CN, R(110b)R(110c)N—CO—, R(111a)—CO—;
• R(110b) and R(111a)
• are independently, (C1-C8)-alkyl, (C3-C4)-alkenyl, -CnH2n-R(115a) or CF3;
• n is zero or 1;
• R(115a) is (C3-C6)-cycloalkyl or phenyl,
• in which R(115a) is unsubstituted or is substituted by 1 to 2 substituents chosen from F, Cl, CF3, methyl, methoxy and NR(116a)R(117a);
• wherein R(116a) and R(117a) are hydrogen or methyl;
• or
• R(110b) and R(111a)
• optionally are hydrogen;
• R(110c)
• is hydrogen or methyl;
• R(103) is F, Br, CN, CF3, or -CgH2gR(118a);
• g is zero, 1 or 2;
• R(118a) is phenyl, in which R(118a) is unsubstituted or is substituted by 1 to 2 substituents chosen from F, Cl, CF3, methyl, methoxy and NR(119a) and R(119b);
• wherein R(119a) and R(119b) are H or CH3;
• or
• R(103) is —SR(129) or —CR(133)R(134)R(135);
• or
• R(103)
• is R(110a)—SO2—or R(112a)R(113a)N—SO2—;
• or
• R(103)
• is pyrrolyl;
• R(104)
• is R(110a)—SO2—;
• R(110a) is (C1-C4)-alkyl or CF3;
• and
• R(105) is hydrogen.