Patent EA-002631-B1 (EA)
Title: 4-cyano-4-deformylsordarin derivatives
Inventor: NIELSEN-KAHN JENIFER
IPC: A61P31/10
Filed: 1998-08-18
Abstract: 1. A compound having the formula I:   and wherein Z is a tetrahydropyrano group selected from   and salts and solvates (e.g. hydrates) or metabolically labile derivatives thereof, wherein R<a> is C(O)CH3 or CH3; R<1> is hydrogen, halogen, hydroxyl, C1-4alkoxy or acyloxy; R<2> and R<3> are each independently hydrogen, C1-6alkyl or C1-4alkoxy C1-4alkyl, or R<2> and R<3> together with the carbon atom to which they are attached represent C=O, C=S or C3-8cycloalkyl; R<4> is hydrogen or CH2R<7> (where R<7> is hydrogen, hydroxyl, C1-4alkoxy or a group OCOR<8> in which R<8> is C1-4alkyl or aryl); R<5> and R<6> are each independently hydrogen, C1-6alkyl or C1-4alkoxy C1-4alkyl, or R<5> and R<6> together with the carbon atom to which they are attached represent C=O, C=S or C3-8cycloalkyl, n is zero or 1; X and Y are each independently oxygen, sulfur or CR<9>R<10> (where R<9> and R<10> are each independently hydrogen, C1-6alkyl, C1-4alkoxy or C1-4alkoxy C1-4alkyl; or R<9> and R<10> together with the carbon atom to which they are attached represent C=O, C=S, C3-8cycloalkyl or C=CHR<11> wherein R<11> represents hydrogen or C1-4alkyl); or when X or Y is oxygen and n is zero then -Y-CR<2>R<3> or -X-CR<2>R<3>- respectively may also represent -N=CR<3>- or NR<12>-CR<2>R<3>- (where CR<2> and CR<3> are C=O and R<12> is C1-4alkyl or an acyl group COR<13> where R<13> is C1-6alkyl) or when Y is oxygen and n is zero, X may be represent the group CR<11> (wherein R<11> has the meanings defined above) which is attached to the pyran ring by a double bond; R<15> is hydrogen, halogen, azido, C1-6alkyl, hydroxy, C1-6alkoxy (optionally substituted by 1 or 2 hydroxy groups or ketals thereof or 1 or 2 C1-3alkoxy groups), aryl C1-4alkoxy, C3-6alkenyloxy, a group OCOR<18> (where R<18> is aryl C1-4alkoxy or a C1-10alkyl group optionally containing one or two double bonds) or C1-6alkoxycarbonyl C1-4alkoxy, and R<16> represents hydrogen or R<15> and R<16> may together with the carbon atom to which they are attached represent C=O or C=CH2; R<17> is CH2R<19> where R<19> is hydrogen, hydroxyl, C1-14alkoxy or a group OCOR<20> in which R<20> is C1-4alkyl; and W is oxygen, sulfur, or CH2; and the dotted line in group (a) indicates the optional presence of an additional bond; R<1a> is hydrogen, halogen, hydroxyl or C1-4alkoxy; R<2a> is hydrogen, halogen, hydroxyl, C1-10alkoxy, C1-10alkylthio, C1-6alkoxyC1-4alkoxy, arylC1-6alkyloxy, arylC3-6alkenyloxy, azido, NR<5a>COR<5a> (where each R<5a> is independently hydrogen or C1-6alkyl), OR<6a> (where R<6a> is a cyclic ether containing 4 to 8 atoms linked to the oxygen atom via a ring carbon atom adjacent to the ring oxygen atom) or a group Y<a>C(=O)-X<a>-R<7a>, where Y<a> is oxygen, sulfur or NH, X<a> is either a bond, an oxygen atom or a moiety NR<8a> in which R<8a> is hydrogen or C1-6alkyl, and R<7>a is C1-10alkyl optionally containing one or two double bonds, aryl, arylC1-4alkyl, arylC2-4alkenyl, haloC1-6alkyl, or C1-6alkoxyC1-4alkyl), and R<3a> represents hydrogen, or R<2a> and R<3a> together with the  carbon atom to which they are attached represent C=O or C=NOR<9a> (where R<9a> is C1-6alkyl); and R<4a> is hydroxyl, C1-6alkoxy or OC(=O)R<7a> (where R<7a> is as defined above). 2. A compound of Claim 1 with the following structural formula:   3. A compound of Claim 1 with the following structural formula:   4. A compound of Claim 1 with the following structural formula:   5. A compound of Claim 1 with the following structural formula:   6. A compound of Claim 1 with the following structural formula:   7. A compound of Claim 1 with the following structural formula:   8. A compound of Claim 1 with the following structural formula:   9. A pharmaceutical composition, which comprises a compound of Claim 1 and a pharmaceutically acceptable carrier. 10. An agrochemical composition, which comprises a compound of Claim 1 and an agriculturally acceptable carrier. 11. A method for the treatment or prevention of fungal infection in an animal, which comprises administering to said animal an antifungal effective amount of a compound of Claim 1. 12. A method for controlling phytopathogenic fungi which comprises administering to a plant in need of such control an antifungal effective amount of a compound of Claim 1. 13. A method for the preparation of 4-cyano-4-deformyl-4'-demethylsordarin which comprises: contacting 4-cyano-4-deformylsordarin with a culture of a strain of Streptomyces avermitilis in a fermentation medium containing assimilable sources of carbon and nitrogen; and isolating 4-cyano-4-deformyl-4'-demethylsordarin from said fermentation medium.