Omega-carboxyaryl substituted diphenyl ureas are disclosed which are useful as raf kinase inhibitors. This disclosure also relates to the use of a group of these aryl ureas in treating raf mediated diseases, and pharmaceutical compositions for use in such therapy.

Omega-Carboxyaryl Substituted Diphenyl Ureas As Raf Kinase Inhibitors

This invention relates to the use of a group of aryl ureas in treating cytokine mediated diseases and proteolytic enzyme mediated diseases, and pharmaceutical compositions for use in such therapy.

Inhibition of p38 kinase using symmetrical and unsymmetrical diphenyl ureas

This invention relates to the use of a group of aryl ureas in treating p38 mediated diseases, and pharmaceutical compositions for use in such therapy.

OMEGA-CARBOXY ARYL SUBSTITUTED DIPHENYL UREAS AS p38 KINASE INHIBITORS

This invention relates to the use of a group of aryl ureas in treating cytokine mediated diseases other than cancer and proteolytic enzyme mediated diseases other than cancer, and pharmaceutical compositions for use in such therapy.

Inhibition of p38 kinase activity by aryl ureas.

Inhibition of p38 kinase activity using aryl and heteroaryl substituted heterocyclic ureas

Short synthesis of 4-chloro-4′-(chlorodifluoromethoxy)benzophenone

The novel substituted 3-thienylthioureas, -isothioureas and -carbodiimides of formula I ##STR1## in which R1 is C1 -C12 alkyl, C1 -C4 alkyl substituted by a C3 -C6 cycloalkyl radical, C3 -C8 cycloalkyl, or C3 -C6 cycloalkyl substituted by a C1 -C4 alkyl radical; R2, R3 and R4 are each, independently of the others, hydrogen, C1 -C6 alkyl, phenyl, or phenyl substituted by from 1 to 3 radicals from the group halogen, C1 -C6 alkyl, C1 -C4 alkoxy and C1 -C6 haloalkyl having from 1 to 9 halogen atoms; Z is a group --NH--CS--NH--, --N ═C(SR5)--NH-- or --N═C═N--; and R5 is C1 -C6 alkyl or C3 -C5 alkenyl; with the proviso that at least one of the radicals R2, R3 and R4 is other than hydrogen; and the salts of compounds of formula I in which Z is the group --N═C(SR5 )--NH--, have valuable pesticidal properties. Compositions containing those compounds, processes for the preparation thereof and their use as pesticides, especially as insecticides and acaricides in agriculture, are described.

Thienylthioureas, -isothioureas and -carbodiimides

A broad range of benzophenone hydrazone derivatives was prepared and tested against selected chewing insect pests, allowing the analysis of structure-activity relationships. Good activity was found only when the aromatic rings were substituted at the 4-positions with an halogen atom and a triflate or perhaloalkoxy group. In contrast, a number of substituents on the hydrazone part led to active compounds, the best results being achieved with acyl-type substituents. The excellent laboratory and greenhouse activity of the best representatives was confirmed in semi-field trials against Spodoptera littoralis.

Synthesis and structure–activity relationships of benzophenone hydrazone derivatives with insecticidal activity

Substitued N-(isoxazol-4-yl)thioureas 1 undergo a transformation in the presence of hexacarbonylmolybdenum and acid to yield functionalized thiazoles 3 in a one-pot reaction. In a few cases, 1,4,5-trisubstituted dihydroimidazolethiones 4 are also isolated as side products. Mechanistic considerations are outlined and scope and limitations of this new methodology discussed.

Transformations in the Isoxazole Series: Synthesis of Substituted 2-Aminothiazoles†

In the course of optimization studies around diafenthiuron, the central aromatic nucleus linked directly to the thiourea unit was replaced by a pyridine moiety. A series of N-(pyrid-3-yl)thioureas, -isothioureas and -carbodiimides was synthesised and evaluated for acaricidal activity. The synthetic methodology used and the screening results against some spider mites (Tetranychus spp. and Panonychus ssp.) are discussed.

Alfons Pascual

Papers

Short synthesis of 4-chloro-4′-(chlorodifluoromethoxy)benzophenone

Thienylthioureas, -isothioureas and -carbodiimides

Synthesis and structure–activity relationships of benzophenone hydrazone derivatives with insecticidal activity

Transformations in the Isoxazole Series: Synthesis of Substituted 2-Aminothiazoles†

N‐(pyrid‐3‐yl)thioureas and derivatives as acaricides. I. Synthesis and biological properties