MXPA96006111A - Macroli antibiotics - Google Patents

Abstract

Derived antibiotics 3-deoxy macrolides with rings of 16 members, obtained from rosaramycin, repromycin, 5-micaminosiltilonólido, desmicosina, lactenocina, O-desmetil-lactenocina, cirramycin A1 and 23-desoximicamonosiltilonólido, which are useful against bacterial pathogens and microplasms in animal

Description

ANTIBIOTICS MQCROLIOOS BACKGROUND PE THE INVENTION This invention is related to new antibiotics. In particular, this invention relates to compounds that are derivatives of the 3-deoxyrnacrylide antibiotics that have been obtained from rosaramycin, repromycin, 5-tricarcinosilyltonolide, desmicosin, lactenocin, 0-denenetyl-lac encinin, cirramycin fia. and 23-deoxyrnicaminosyltilonolide; to the pharmaceutically acceptable acid addition salts of said derivatives; to methods of using such derivatives in the treatment of diseases of animals provacated by bacterial and mycoplasmic pathogens; and pharmaceutical compositions useful for this. The term "animals" includes mammals, fish and birds. There are numerous agents known to fight bacterial infectious diseases in animals, but in many specific diseases, the current choice of agents leaves much to be desired. In some cases, agents may not persist long enough in the recipient organism and, therefore, require frequent dosing to maintain therapeutically effective levels in the blood and / or tissues. For meat-producing animals (eg, cattle, poultry, sheep and pigs) this will require considerably tedious animal handling, which is expensive for the product. In other cases, the agent can be poorly tolerated or even toxic to the recipient organism in therapeutically effective doses. Agents with higher potency, a higher dose, a higher therapeutic index and a broader spectrum of antibacterial activity, as well as agents with increased oral absorption, would improve the range of animal diseases that could be treated more effectively. Thus, the need for new antibacterial and antimicrobial agents with better properties persists. The diseases of interest are: bovine respiratory disease, whose main bacterial pathogens are Pasten, relia haemolv ica. _ £, muítoei da y HaemoDhilijs aomnua -. pasteurellosis in pigs, goats, sheep and poultry farmyard (P. multocida)? Porcine pleuroneuronuria (flctinobacillus pleuronnumumonia): porcine infections caused by streptococci (Streotococcus suis)? and for all the recipient organisms mentioned above, infections by Mvcoolasma snn- Tylosin derivatives and their related acrylics have been shown to be effective against infections in poultry, cattle and swine, caused by certain gram-positive and gram-negative bacteria: Kirst et al., U.S. Patent 4,920,103; Tao et al U.S. Patent 4,921,947; Kirst et al., UK Patent Application GB 21356700.

Other macrolide antibiotics have been described in the patent applications of the United States, being processed together with the present Application No. 08 / 362,496, filed on January 11, 1995 (published in document UO 94/02496) and Application No . 08 / 311,285, filed on September 22, 1994, and in the PCT applications, being processed together with this, Request BNBo. PCT / US94 / 00095, filed on January 6, 1994 and published in document UO 94/21657 and Application No. PCT / IB94 / 00199, filed on July 4, 1994 and published in document UO 95/02594, of which all have been assigned to the owner of this.

SUMMARY? E INVENTION This invention is related to new antibiotics which are 3-deoxynacrolide antibiotics derivatives which have been obtained from repromycin, rosararnicin, 5-micaminosiltilonolide, desicose, lactenocin, O-demethyl-lactenocin, cirra icine fl__ and 23-desoximicaminosiltilonólido and with the salts of acid addition of such derivatives. These new antibiotics have a higher potency against bacterial pathogens with respect to the parental compounds and are active against rnicoplasmic pathogens. The compounds of the present invention are of the formula (I) or (II) > 2 (I) < II) or the pharmaceutically acceptable salts thereof, wherein m is 1 or 2; Z1 is H, OH or micarosiloxy; represents a single or double bond, where the double bond results in geometry or cis or trans; 0 is selected from the group consisting of H, OH, fluorine, chlorine, bromine, iodine, OX-1-, $ £ ¡7 0CH: 'OH 0CH3 OH ° "0CH- OCH, azetidin-1-yl; pyrrolidin-1-yl, piperidin-1-yl, 3,3-dimethyl-1-ylperidin-1-yl, hexahydroazepin-1-yl, octahydroazocin-1-yl, octahydroi-dol-1-yl, l, 3,3a , 4,7,7a-hexahydroisoindol-2-yl, d-cahohydroquinol-1-yl, decahydroisoquinol-2-yl, 1,2,3,4-tet ahydroisoquinol-2-yl, 1, 2,3,6-tetrahydropyridin- l-yl, 4-alkylpiperazin-1-yl having 1 to 4 carbons in the alkyl part, morpholino, 2,6-dimethylmorpholin-4-yl, thiomofolino and -NXaX3; X is selected from the group consisting of optionally substituted alkyl having 1 to 4 carbons, optionally substituted cycloalkyl having 4 to 8 carbon atoms and an optionally substituted aryl, aralkyl or heteroaryl group, selected from the group consisting of phenyl , benzyl, pyridinyl, quinolinyl, isoquinolinyl, quinazolinyl, pyrimidinyl, imidazolyl, oxazolyl, thiazolyl, bßnci idazolyl, indolyl, benzoxazolyl and bßnzothiazolyl; wherein the optionally substituted aryl, aralkyl and heteroaryl groups are optionally substituted with 1 or 2 substituents independently selected from the group consisting of alkyl having 1 to 4 carbons, fluoro, chloro, bromo, acetyl, amino, nitro, cyano, trifluoromethyl , N-alkylamino having the 4 carbons, N, N-dialkylarnino having a total dS 21 to 6 carbons, carboxyl, carboalkoxy having 1 to 4 carbons, carboxarnido, sulfonarnido, hydroxyalkyl having 1 to 4 carbons, M-alkylaminoalkyl having 1 to 4 carbons in each of the alkyl and N, N-dialkylaminoalkyl moieties having a total of 2 to 6 carbons in the dialkylamino part and 1 to 4 carbons in the alkyl part; Xa and Xβ are each independently selected from the group consisting of hydrogen, alkyl having 4 carbons, hydroxyalkyl having 2 to 4 carbons, cycloalkyl having 3 to 8 carbons, alkenyl having 3 or 4 carbons, alkoxyalkyl which has 1 to 4 carbons in the alkoxy part and 2 a 4 carbons in the alkyl and alkoxyalkoxyalkyl part having 1 to 4 carbons in each of the alkoxy moieties and 2 to 4 carbons in the alkyl moiety; T is -C (= 0) (Za), -CH __- N (B) (CH __), - C (= 0) (Z3), -CHa-N (Za) (C = 0) - (CHa). -Za, -CH __- N (B) (CHa) ß-N (B) (CH __) .- C (= 0) (Za), -CH = CH- (CHa) "- N (Z *) (Za ), -CH (Zß) N (Z *) (77), -CHa-NZ3-3) (SOaZ3-3), -CH-2-N (Z a) (C (= 0) - (Z * -Zxa), -CHa-N (Z a) (CHa) ß- N (Zxs) (C (= 0) -Z * -Z a) O -CHa-N (Z a) (CHa) ß- N (Z ß) (S0a-Z 3) where n is a whole number of 1 to 4; B, in each case, is independently selected from the group consisting of hydrogen, alkyl (C -C_,), an aminoacyl group and a dipeptidyl group, Za is hydrogen or alkyl (C_v); N (R: _ Ra), -NH-CH (Ra) - (CHa) -e-C00R * or -NH-CHI R3) - (CHa) «- C (= 0) -NH- (CHa) f -COOR._ .; R and Ra are each, independently, selected from the group consisting of hydrogen, methyl, optionally substituted alkyl having 2 to 6 carbons, optionally substituted cycloalkyl having 3 to 8 carbons, aminoalkyl having 2 to 6 carbons, hydroxyalkyl having 2 to 6 carbons, N-alkylamino-alkyl having 1 to 4 carbons in the alkyl part, optionally substituted benzyl, optionally substituted phenyl, alkoxyalkyl having 2 to 4 carbons in the alkyl part and 1 to 4 carbons in the alkoxy part, N, N-dialkylaminoalkyl having a total of 2 to 6 carbons in the dialkylamino part and 2 to 4 carbons in the alkyl part, - (CHa) a-rnorfolino, - (CH-2) a-piperidino, - (CHa) β-pyrrolidino, - (CH α) β-azetidin-1-yl and - (CH α) β-hexahydroazepin-1-yl; or RZ and R a become together with the nitrogen to which they are united and form z or °; R3 corresponds to the side chain portion of amino acids and in each case is independently selected from the side chain of the group of amino acids consisting of the D or L form, where applicable, of alanine, arginine, asparagine, glutaric acid, glutamine, glycine, histidine, hydroxyproline, hydroxyproline, isoleucine, leucine, Usin, rnethionine, phenylalanine, proline, serine, threonine, tryptopine, tyrosine, valine, beta -alanine, β-lysine, α, α-dimethylglycine, α-aminobutyric acid, 4-hydroxyphenylglycine, phenylglycine, acid, t-diarninobutyric acid, ornithine and homoserine; e is 0 or 1, with the condition d that when e is 1, then R3 corresponds to the side chain of β-lysine or β-alanine, - f is o or 1, with the proviso that when f is 1, then Ra corresponds to the side chain of β-lysine or β-alanine; R * is H, alkyl having 1 to 4 carbons or benzyl; Z * is selected from the group consisting of hydrogen, an amino acid group, a dipeptidyl group, alkenyl having 3 to 5 carbons with the proviso that the double bond is not adjacent to the nitrogen to which Z '* is attached, alkynyl having 3 to 5 carbons with the proviso that the triple bond is not adjacent to the nitrogen to which Z ** is attached, hydroxyalkyl having 2 to 4 carbons in the alkyl, 0 0, 0, 0, and alkoxyalkyl part having 2 to 4 carbons in the alkyl part and 1 to 4 carbons in the alkoxy part; Za is selected from the group consisting of hydrogen, alkenino having 3 to 5 carbons with the proviso that the double bond is not adjacent to the nitrogen to which Z3 is attached, alkynyl having 3 5 carbons with the proviso that the triple bond is not adjacent to the nitrogen to which Z3 is attached, hydroxyalkyl having 2 to 4 carbons in the alkyl part, 0 to 0, 0, Q3, alkoxyalkyl having 2 to 4 carbons in the alkyl part and 1 to 4 carbons in the part alkoxy and -Rβ-N (RtRβ); Qxo in each case is, independently, where u is an integer from 1 to 5 and Qxβ, in each case, is independently selected from the group consisting of alkyl (C __-C_, alkoxy (Ca. ~ C *), .fluoro, chloro, bromo, iodo, nitro. , amino, cyano, hydroxy, trifluoromethyl and carboalkoxy having 1 to 4 carbons; Qao, in house case is independently an alkyl (C -C_ optionally substituted, optionally substituted with a substituent and selected from the group consisting of hydroxy, cyano, N-alkylamino having 1 to 5 carbons and N, N-dialkylamino having a total of 2 to 6 carbons; Q3 °, in house case, is independently where d is an integer dβ 1 to 5 and O33 is selected from the group consisting of dβ hydroxy, cyano, N-alkylamino having l 5 carbons and N, N-dialkylamino having a total of 2 to 6 carbons; R * is alkylene (Ca-C); R "7" ST selects from the group consisting of hydrogen, alkyl having 1 to 4 carbons, cycloalkyl having 3 to 8 carbons and alkoxyalkyl having 2 to 4 carbons in the alkyne part and 1 to 4 carbons in the alkoxy moiety; R "is selected from the group consisting of alkyl having 1 to 4 carbons, optionally substituted hydroxyalkyanoyl having 1 to 6 carbons, an aminoacyl group and a dipeptidyl group, wherein the optionally substituted hydroxyalkanoyl group is optionally substituted with a phenyl group optionally substituted, or R and Rβ are taken together with the nitrogen to which they are attached and form a cyclic amine having 3 to 6 carbon atoms, or Z- * and Z3 are taken together with the nitrogen to which they are bound and form Z or, Zß is an animoacyl group, a dipeptidyl group or is independently selected from the same group as defined for Rx; 27 is independently selected from the same group as defined for R or from the group consisting of - [(CHa) ß-R st] a- (CHa) ß-N (Zx *) a and -R »-N (RxoR); where q is 1, 2 or 3; R * is alkylene (Ca-C_ *.) Optionally substituted by alkyl (C-CA) or hydroxy, with the proviso that the hydroxy can only be attached to C2 of the alkylene group, when the alkylene has a length of three d atoms. carbon, or C3 of the alkylene group when the alkylene has a length of four carbon atoms; R o is selected from the group consisting of hydrogen, methyl and ethyl; R x is selected from the group consisting of optionally substituted hydroxyalkanoyl having 1 to 6 carbons, an amino acyl group and a dipeptidyl group, the hydroxyalkanoyl group optionally substituted with optionally substituted phenyl; or R o and Rxx are taken together with the nitrogen to which they are bound and form Zxaa; R a is S u 0; Z, s, in each case, is independently selected from the aminoacyl group,? N dipeptidyl group and the same group of substituents as defined below for Z a, Z 3 and ZX 3; or Z * and 77 are taken together with the nitrogen to which they are bound and form Z ao; Z3 is H or CN; 77 is an alkyl (C_L-C__),? N aminoacyl group,? N dipeptidyl group, hydroxyalkanoyl having 1 to 6 carbons, aminoalkyl having 2 to 6 carbons, hydroxyalkyl having 2 to 4 carbons, N-alkylaminoalkyl having 1 to 4 carbons in the alkylamino part and 2 to 4 carbons in the alkyl part, alkoxyalkyl having 2 to 4 carbons in the alkyl part and 1 to 4 carbons in the alkoxy part, N, N-dialquialarninoalkyl having a total of 2 to 6 carbons in the dialkylamino part and 2 to 4 carbons in the alkyl part, -C0-Z * -Z ao -S0a-Z a; Z a, Z a and Z 13, in house case, are independently selected from the same group as defined for R x, with the condition d β that Z a is hydrogen only when Z * is NH; Z *, in each case, is independently 0 or NH; a, at home case, is independently 1 or 2; in each case of the amino acyl group and the dipeptidyl group, the amino acyl group and the amino acyl groups of the dipeptidyl group are independently selected from the group consisting of the form D or L, when applicable, of alanyl, arginyl, asparagile, aspartyl, cylteinyl, cystyl, glutayl, glutamyl, glycyl, histidyl, hydroxylysyl, hydroxyprolyl, isoleucyl, lissucyl, lysyl, ethionyl, phenylalanyl, prolyl, seryl, threonyl, triptophoyl, tyrosyl, valyl, ß- alanyl, β-lysyl, N, N-di ethylglycyl, α, α-di ethylglycyl, α-aminobutyryl acid, 4-hydroxyphenylglycyl, phenylglycyl, α, α-t-diaminobutyryl acid, ornithyl, homoseryl, bicyl, N, N-diethyl- β-alanyl, N, N-diethyl-t-aminobutyryl and sarcosyl, with the proviso that N, N-dimethyl-t-aminobutyryl can only be the terminal aminoacyl when they are in a dipeptidyl group; in each case of an optionally substituted alkyl, optionally substituted alkyl or optionally substituted cycloalkyl, optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of hydroxy, cyano, fluoro, tri-loomomethyl, optionally substituted amino, N- optionally substituted alkylamino having 1 to 4 carbons, N, N-dialkylamino having n total of 2 to 6 carbons, N- (hydroxyalkyl) amino having 2 to 4 carbons, N, N-bis (hydroxyalkyl) in which each alkyl part has 2 to 4 carbons, alkoxy having 1 to 4 carbons, alkoxycarbonyl having 1 to 4 carbons in the alkoxy part, N, N-dialkylaminoalkoxy having a total of 2 to 6 carbons in the dual part? and 2 to 4 carbons in the alkoxy part, alkoxyalkoxy having 1 to 4 carbons in each of the alkoxy, alkoxyalkoxyalkoxy moieties having 1 to 4 carbons in each of the spirocycloalkyl alkoxy moieties having 4 to 6 carbons, wherein the optionally substituted amino and the optionally substituted N-alkylamino are each, independently, optionally mono-substituted with an aminoacyl group or a dipeptidyl group; R 3 and R x * are each independently selected from the group consisting of hydrogen and alkyl having 1 to 4 carbons; or R a and Rx ** are taken together with the nitrogen to which they are bound and form Z or °; R s, R x β and R - * - 7"are each independently selected from the group consisting of hydrogen, alkyl (C __ - C_v), an aminoacyl group and a dipeptidyl group; R ß is NH, S-alkyl (C -C_,), N- (amino acyl group) or N- (dipeptidyl group); R * - * is selected from the group consisting of C, CH, CHa, N and NH; Rao is alkyl having 1 to 4 carbons or -COORax; Ra, in each case, is independently H or alkyl having 1 to 4 carbons; Raa is selected from the group consisting of H, alkyl having 1 to 4 carbons, hydroxy, alkoxy having 1 to 3 carbons, arnino, N-alkylamino having 1 to 4 carbons and N, N-dialkylamino having a total of 2 ad carbons, or Ra and Raa are taken together and form an oxo group, Z or °, in each case, is selected independently between the group composed of where Raa is selected from the group consisting of C, CH, CHa, N NH, Níarnino acyl) or N (dipepetidyl group); Ra * is alkyl having 1 to 4 carbons, -C0-alkyl (Cx-C-4) or -C00-alkyl (Cx-C_; Raa is 0 or S; Ra * is selected from the group consisting of alkyl having 1 to 4 carbons, an optionally substituted hydroxyalkanoyl having 1 to 6 carbons, an amino acyl group and? N dipeptide group, wherein the optionally substituted hydroxyalkanoyl group is optionally substituted with an optionally substituted phenyl group; RS? Is alkyl HO having 1 to 4 carbons; Raß is H, alkyl having 1 to 4 carbons, hydroxy, alkoxy having 1 to 3 carbons, amino, N-alkylamino having 1 to 4 carbons or N, N-dialkylamino having a total of 2 to 6 carbons; or Ra-r and Ra? they occur together and form an oxo group; g, in each case, is independently 2,3, or 4; b, in each case, is independently 0.1 or 2; and in each case of the optionally substituted phenyl or optionally substituted dibenzyl, the optionally substituted phenyl or the benzyl optionally substituted with 1 or 2 substituents independently selected from the group consisting of alkyl having 1 to 4 carbons, fluoro, chloro, bromo, acetyl , amino, nitro, cyano, tri-louromethyl, N-alkylamino having 1 to 4 carbons, N, N-dialkylamino having total of 2 to 6 carbons, -NH-CO-CH3, carboxyl, carboalkoxy having 1 to 4 carbons, carboxamido, sulfonamido, hydroxyalkyl having 1 to 4 carbons, aminoalkyl having 1 to 4 carbons, N-alkylaminoalkyl having 1 to 4 carbons in each of the alkyl parts and N, N-dialkylaminoalkyl having total from 2 to 6 carbons in the dialkylamino part and 1 to 4 carbons in the alkyl part; with the following conditions: (1) that when T is -C (= 0) (Z3), -CH __- N (B) (CHa) «- C (= 0) (Za), -CHa-N (Za) (C = 0) - (CHa) _, - Za O -CHaN (B) (CHa) ß-N (B) (CHa) «- C (= 0) (Za). where Z3 is -N (R Ra) where R or Ra is a substituted alkyl or a substituted cycloalkyl, then the substitutent at the position d1 1 of the substituted alkyl or of the substituted cycloalkyl can not be fluoro ,. chlorine or a substitute attached to a heteroatom; and (2) when any of the substituents defined above which may be a substituted cycloalkyl is a substituted cycloalkyl, then the substituent at the 1-position of the substituted cycloalkyl can not be fluoro, chloro or a substituent attached to a heteroatom. The term "lower alkyl" means an alkyl having 1 to 4 carbons. It is understood that the term "alkyl" embraces straight and branched chain alkyl. Those skilled in the art will recognize that some of the compounds of the present invention possess stereochemical centers. In cases where stereochemical centers are presentIt is understood that all stereoisomers are within the scope of this invention. In addition, in cases where the link between C2 and C3 of the crosslinker is a double bond, both the cis and trans forms are within the scope of this application. Amino acyl groups are derivatives of the corresponding amino acids and are well known in the art. When appropriate, to obtain the arnino acyl groups of this invention, the following amino acids D or L are used: alanine, arginine, asparagine, aspartic acid, cystine, cystine ,. glutamic acid, glutamine, glycine, hietidine, hydroxylysine, hydroxyproline, isoleucine, lysine, lysine, nephionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, ß.alanine, ß-lysine, N, N-dimethylglycine, a , α-dimethylglycine, α-aminobutyric acid, 4-hydroxyphenylglycine, phenylglycine, a, α-diaminobutyric acid, ornithine, hornoserine, bicine, N, N-diethyl-β-alanine, N, N-dimethyl-Lt-aminobutyric acid and sarcosine The dipeptidyl groups comprise derivatives of any possible combination of two of the amino acids presented hereinabove which can be coupled by conventional peptide synthesis methods well known to those skilled in the art. A group of preferred compounds are compounds having formula (I) or pharmaceutically acceptable salts thereof, wherein rn is 1 and Z is H or OH. A group of more preferred compounds are the compounds having the formula (I) or the pharmaceutically acceptable salts thereof, wherein m is 1; Zx is H or OH; T is -CH-2-N (b) ((CH) a) «- C (= 0) (Z3), -CHa-N (Za) (C = 0) - (CHa) ß-Z3, -CHa -N (B) (CHa) ß-N (B) (CHa) ß-C (= 0) (Z3), - CH = CH- (CHa) nN (Z *) (Z3), CH (Zß) N (Z "*) (Z?), -CHa-N (Zxa) (SOaZX3), -CHa-N (Z a) (C (= 0) -Z * -Zxa), -CHa-N (Z a) (CHa) ß-N (Z 3) (C (= 0) (Z * -ZX3) or -CHa-N (Z a) (CHa) aN (Zxa) (S0aZxa) where a, g, n, Q, Za, Z3, Z *, Z3, Z *, Z ^, Z ", 2 *, Zxa, ZX3, Z ^ and Zxs are as defined above A group of a still more preferred group of compounds are the compounds having the formula (I) or a salt pharmaceutically acceptable thereof, wherein rn is 1; Z is H or OH, T is -CH = CH- (CHa) nN (Z *) (Z3), -CH (Zß) N (Zß) i2r), -CHa-N (Zxa) (? OaZ a), -CHa-N (Z a) (C (= 0) -ZX4-Z a), -CHa-N (Zxa) (CH-2) aN (Z 3) ) (C (= 0) (Z * -Z a) or -CHa-N (Zxa) (CH-) aN (Z a) (S0aZX3) where a, g, n, 0, Z *, Z3, Z * , Z?, Z ", Z9, Z a, Z 3, Z * yza are as defined above and Zß is H. A group of even more preferred compounds are the compounds having the formula (I) or a pharmaceutically acceptable salt thereof of the formula (I), wherein ee 1; Zx is H U OH; T is -CH = CH- (CHa) n ~ N (Z *) (Z3), -CHa (Z *) (Z?) Or where n is 1; Z * and Z3 are each independently selected from the group consisting of hydrogen, alkenyl having 3 to 5 carbon atoms, with the proviso that the double bond is not adjacent to the nitrogen to which the alkenyl, alkynyl is attached having 3 to 5 carbons with the proviso that the triple bond is not adjacent to the nitrogen to which the alkynyl is attached, hydroxyalkyl having 2 to 4 carbons in the alkyl, Qxo, Qao, Qao and alkoxyalkyl part having 2 to 4 carbons. carbons in the alkoxy part, or Z * and Za are together with the nitrogen to which they are bound and form Zxo °; and a, 0, Z *, 77, Z9, Qxo, Qao, 0ao and Z are as previously defined for formulas (I) and (II). A group of especially preferred compounds are compounds having the formula (I) or a pharmaceutically acceptable salt thereof, wherein it is 1; Z is H or OH; T is -CHa- (Zß) i Z? ) or where Z * is independently selected from the same group of substitutes as R; Z ^ is independently selected from the same group of substituents as R or is -R ** - N (R or R x); or Z * and Z "7 turn next to the nitrogen to which they are bound and form Zxas, and Z * is an amino acyl group, aminoalkyl having 2 to 6 carbons, hydroxyalkyl having 2 to 4 carbons, N-alkylaminoalkyl; ilo having 1 to 4 carbons in the alkylamino part and 2 to 4 carbons in the alkyl part, alkoxyalkyl having 2 to 4 carbons in the alkyl part and 1 to 4 carbons in the akoxy part, N, N-dialkyl ilarninoalkyl has a total of 2 to 5 carbons in the dialkylamide part and 2 to 4 carbons in the alkyl part or -C0-Z3 - * - Z-3; a, 0, R, R "*, R a, R x, Zxa , Z * and zxao are as defined above for formulas (I) and (II). A first group of more preferred compounds are those compounds having the formula (I) or a pharmaceutically acceptable salt thereof, wherein m is 1; 0 is OH; Z is H; T is -CHa-IZ *) i.27) where Z * is hydrogen, methyl or optionally substituted alkyl having 12 to 6 carbon atoms; Z? is N-alkylaminoalkyl having 1 to 4 carbons in the alkylamino part and 2 to 4 carbons in the alkyl, optionally substituted alkyl portion having 2 to 6 carbon atoms or optionally substituted cycloalkyl having 3 to 8 carbons; or Z * and Z "7 are taken together with the nitrogen to which they are bound and form pyrrolidino, piperidino, 3,4-deehydropiperidino or azabicyclononan-3-yl. Especially preferred, within the first group of preferred compounds, are the compounds or an acceptable pharmaceutical salt thereof in which said optionally substituted alkyl of Z * is propyl, 3- (dirnethylamino) -propyl or 2-spirocyclopentyl-3-hydroxypropyl, and said optionally substituted cycloalkyl dβ T7 is cyclohexyl. A second group of more preferred compounds are the compounds having the formula (I) or a pharmaceutically acceptable salt thereof, wherein m is 1; 0 is OH; Zx is H; and T is -CHa-N (Zß ) (Z ^) where Z * is hydrogen or methyl; Z? is methyl, 2-fluoroethyl, 2,2-dimethyl-3-hydroxyethyl, 2-hydroxyethyl, propyl, 3-hydroxypropyl, 2,5- (hydroxy) cyclohexyl or 3-aminopropyltrio; or Z * and Z7 are together with the nitrogen to which they are attached and form 4-methylpiperazino, azetidino, 4-hydroxypiperidino, morpholino or 3-hydroxypiperi i o. A third group of more preferred compounds are the compounds having the formula (I) or a pharmaceutically acceptable salt thereof, wherein m is 1; 0 is OH; Zx is OH; T is -CHa-N (Z *) (Z7) where Z * is hydrogen; T7 is 2,2-dimethyl-3-hydroxypropyl; or Zßy Z? they are taken together with the nitrogen to which they are bound and form hexahydroazepin-1-yl. A fourth group of compounds more preferred are compounds having the formula (I) or a pharmaceutically acceptable salt thereof, wherein m is 1; the bond between C2-C3 of the rnacrolide is a double bond, 0 is OH; Zx is OH; and T is -CHa-N (Zß) iZ7) where Z * is hydrogen, methyl or propyl; Z07 is 2,2, -dimethyl-3-hydroxypropyl, methyl, propyl or 3- (dimethylamino) propyl; or Z * and Z7 are taken together with the nitrogen 1 which are attached and form hexahydroazepin-1-yl or 3-azabicyclononan-3-yl. Thus, in a further aspect, the invention provides pharmaceutical compositions comprising a compound of the formula (I). or (II), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent. This invention also provides methods for treating a bacterial infection or an infection 00 Mycoplasma in an animal in need thereof, methods comprising administering to said animal an amount of bacterial or icoplasmic treatment of a compound of the formula (I) or (II), or a pharmaceutically acceptable salt thereof. This invention further provides a method for using the compounds of claim 1 or pharmaceutically acceptable salts thereof, prophylactically in the treatment of animals susceptible to a bacterial or mycoplasmal infection.

DESCRIPTION PETRLLflPR PE Lfl INVENTION The compounds of the present invention, having the formula (I) or (II), as defined above, are prepared easily and generally by reductive amination reactions of the appropriate 3-deoxynacrolide derivatives of rosararnici a, rßporomycin, -micaminosiltilonólido, desrnicosina, lactenocina, O-deemßtillactenocina, cirranicina flx or 23-deoxirnicaminosiltilonólido, with an amine, optionally followed by conversation in the salts of addition of acids as it is shown in the procedures of the Examples later, in analogous procedures to them and by procedures described below. Rispromycin was prepared according to the following fermentation procedure.

ESCfllñ E FERGIENTRPPR.

To prepare frozen flock for use as a conventional inoculum, Micromonoepora rosaría, RTCC 55709, was inoculated on September 5, 1995, in JDYTT medium (10 g / 1 dß cussella, 5 g / 1 corn starch, 2.5 g / 1 macerated corn solids, 5 g / 1 NZ Omine YTT, 0.002 g / 1 CoCl-2.6HaO, 1 ml / 1 P-2000 (polyglycol, available from George Mann and Co., Inc., 175 Terminal Road, Providence, Rl) and 3 g / 1 of CaCO ») and stirred (250 rpm, 30 ° C, vertical displacement of 5.08 cm) for approximately three days. The ZJDYTT medium, bound to pH about 7.0 ee sterilized at about 121 ° C for about 30 minutes before use. Glycerol (20% final concentration) is added as cryoprotectant, and the culture is stored at about -80 ° C. To prepare the inoculum, 5 rnl of the frozen culture lot is transferred to 1 liter of JDYTT medium in a 2.8 liter fernbach flask. The culture is grown for about 3 days at about 30 ° C with shaking (250 rpm, vertical displacement of 5.08 cm). The complete fernbach content is transferred to 8 1 of RSM-6 production medium in a 14 1 fermenting vessel (New Brunswick Scientific, New Brunswick, NJ) with two 12.065 cm stirring blades. The composition of RSp-6 is 50 g / 1 of corn starch, 10 g / 1 dß cßrelosa, 5 g / 1 of ardamine PH (available from Cha Plain Industries Inc., 79 State Street, Harbor BEach, NY), 8 -10 g / 1 Pharnarnedia (available from THe Buckeye Cellulose Corporation, P: 0, Box 8407, Memphis, TN), 10 g / 1 MgHP0_, 3Ha0, 2.5 g / 1 casein hydrolyzate (available from Sheffield Chemical, Norwich, NY), 0.5 g / 1 asparagine, 0.028 g / 1 FeSO _, 7HaO, 0.5 g / 1 NgS0 _, 7Ha0, 0.75 g / 1 Kxs_HP0._., , 0.003 g / 1 of CuSO * .5Ha0, 0.003 g / 1 of MnCla4HaO, 0.003 g / 1 dß ZnS0 Ha0, 0.003 g / 1 of CoCla.6Ha0 and 1 rnl / 1 of P2000. The RDM-6 is adjusted to approximately pH 7.0 and treated in an autoclave for approximately 121 ° C before use. The fermentation is carried out at approximately 30 ° C, 450 rpm, 0.34 v / v / m air, controlled the pH between 6.7 and 7.3 with Na0H / HaSo_v? by adding 6 g / 1 of MOPS to the production medium. Reproductive concentrations typically have peaks between 69 and 116 hours. The samples are extracted in a mixture of solvents (3.5: 6.5 rnetanol: buffer KHaP0_v 0, 1,? N, pH 3.5).

Scale 'Je naraz.

An inoculum is prepared as described above or by the addition of 2 ml of frozen culture batch in 30 ml of medium Dβ inoculum JDYTT in a Erlenmeyßr flask of 300 ml. The culture is grown for about 3 days at about 30 ° C with shaking (250 rpm, vertical displacement of 5.08 cm). Two rnl of inoculum are transferred to approximately 30 ml of modified RSM-5 medium (320 g / 1 of corn starch), 10 g / 1 of pharmamedia, 10 g / 1 of cerelosa, 5 g / 1 of FeSO_v.7Ha =, 0,5 g / 1 of rigS0_v.7H._0, 0,75 g71 of KaHPO, 0,002 g / 1 of CuS0_v.5Ha0, 0.003 g / 1 of tnCla.4Ha0, 0.003 g / 1 dß ZnS0A.7H20, 6 g / 1 of MOPS 2.5 g / 1 of casein hydrolyzate, 10 g / 1 of HgHP0_v .3HaO and 1 ml / 1 of P-2000, pH 7.0 and treated in an autoclave at approximately 121 ° C for approximately 20 minutes) in a 300 ml Erlen eyer flask. The flasks are stirred for 3-4 days at approximately 30 ° C. The fermentation broth is extracted as described above. The transformation of the parent macrolide at the C-23 position is carried out according to a procedure analogous to the procedure well known to those of ordinary skill in the art and as described in J: flntibiotics, 40 (6), p. 823-842, 1987, the content of which is incorporated herein by reference. 5-? Pt was obtained according to the procedure indicated in r: B: Morin Gorman, Tßt. Let., 2339 (1964). The starting macrolide rosaramycin eß is produced and processed according to the procedure described by? Agman et al. in Journal iof flntibiotics, Vol. XXV, No. 11, p. 641-646, Nov. 1972. Desmisinin, lactnnocin, O.desmethyl-lactenocin, and 23-deoxymethylaminoethyltilonolide are produced and added according to the procedure described in Journal of flntibiotic., 35 (12) p. 1675-1582, 1982. Cirramycin fl is produced and isolated according to the procedure described in Journal of flntibiotics, 22 pp. 61.1969. A content of the above references is incorporated herein by reference. All other starting materials and reagents necessary for the synthesis of the compounds of the present invention are readily available in the market or can be prepared according to procedures known in the art. The compounds of the present invention of formula (1) or (II) wherein m is 2, can be prepared by applying Uitting chemistry using the ylide prepared from d (exomethyl) triphenyl phosphonium chloride, Typically, the The phosphonium salt is suspended in an aprotic solvent such as THF, diethyl ether or dioxane. This mixture is added with a base such as potassium t-butoxide, n-butyl lithium or sodium hydride, usually at a temperature of about -20 ° to 30 ° C, and the solution is then stirred for about 10 to 120 minutes. . a solution of 3-deeoxi macrolide is then added and the resulting solution is stirred for 1 to 24 hours at room temperature. After a conventional extractive treatment, the crude product is dissolved in such a solvent with THF or dioxane and aqueous acid, for example, HCl, is added. Stirring for 2 to 12 hours and the extractive treatment produces a macrolide aldehyde which can be used for other reactions described herein. This invention relates to compounds that are 3-deoxy acrylic acid antibiotic derivatives. A number of methods are known to those skilled in the art to convert 3-hydroxy, acrylics to the 3-desoxy analogues. Normally the C3 alcohol of a suitably protected macrolide is converted into a sulfonate or an acetate, preferably a? -sylate. This is typically done with methanesulfonyl chloride in pyridine. The activated group is then removed, usually by treatment with base such as potassium carbonate or an amine. The preferred procedure is to use ammonium hydroxide in methanol. In certain cases, the re-bonding double bond is reduced, usually by hydrogenation with a metal catalyst such as Raney nickel. Some of the compounds described in this invention require the formation of ureae and eulphonamides from an amine d? departure. Ureas are formed using conventional conditions, such as the reaction of the amine in an inert solvent (eg, toluene or CHacla) with an isocyanate. An external base such as triethylamine can be used. Some isocyanates are commercially available and can be prepared by the reaction of a primary amine with phosgene or an equivalent (e.g., triefoegeno). Other processes for the formation of isocyanate * such as the transitions of Hofmann, Curtius, Lossßn or Schmidt from d-carboxylic acid derivatives are also suitable. The sulfonamides are more easily formed by the reaction of an amine with a sulfonyl chloride, usually in an inert solvent such as DMF with a base such as sodium carbonate. The following procedure is used for a Uittig reaction when T ee -CH = CH- (CHa) n-N (Z *) (Z3). To a solution of foephonium bromide in excess (usually a three times excess of the macrolide), prepared as described below, in an inert reaction solvent such as toluene, an equimolar amount of a base such as potassium bie (trimethylsilyl) amide, 0.5 M in toluene, The reaction mixture is stirred for. about 5 to 90 minutes, usually for about 15 minutes, at a temperature of about 5 to 35 ° C, usually at room temperature, the yellow-orange mixture is added with solid 3-deoxydehydroxydehyde followed by stirring at a temperature ambient. After stirring for about 20 minutes to 24 hours, preferably about one hour, it is isolated from the desired olefin product by technique, such as silica gel chromatography or recrystallization. The phosphonium bromide reagents used for the above Uittig reactions can be prepared by numerous methods. Generally, (2-α-inosethyl) tri-phenyl-osphonic bromides are synthesized by reacting a secondary amine with d-vinyltriflynil phosphonium bromide, usually without additional dielectrums, and stirring the mixture at a temperature of about 25 to 150 ° CA normally at about 80. ° C, for 0.5 to 3 days, usually for a day. (Modified procedure J. J. Org Chem. 29, pp. 1746-1751, 1964). At this time, the reaction mixture is mixed with an aprotic dieolvent, preferably diethyl ether, and the solids solvent. After drying, these products are used directly in the following olefination procedures. Another route for obtaining ammonium-containing phosphonium bromides is by treatment of an appropriate amino alcohol with triphenyl phosphine hydrobromide (Helv. Chim. Acta, 61 pp. 1708-1720, 1978). Some of the phosphonium bromides are available in the market. They can also prepare urea-d-phosphonium using diamines, usually with one of the protected amines, with t-BOC as one of the preferred protecting groups. After Uittig olefination, the t-BOC group can by conventional procedures and the recently exposed amine can be further functionalized with an aminoacyl, dipeptidyl or hydroxyalkanoyl group according to the following procedure. A solution in dichloromethane of an N-protissid amino acid, or N-protidized dipeptide dieside (t-BOC is one of the preferred protectant groups), or of a 0-protected hydroxyalkanoic acid (the acetate is one of the preferred protecting groups), or of a 0-protected hydroxyalkanoic acid (acetate is one of the preferred protecting groups), dicyclohexylcarbodiirnide and, frequently, a coupling agent such as hydroxybenzotriazole, (of which, all are prespressed in equimolar amounts). In the cold solution, a macrolide derivative is added where T is -CH = CH- (CHa) nN (Z *) (Z3), where Z * is as defined above, Za is -R * -n (RtRβ ), where R * and Rβ are as defined above and R? It is hydrogen. The solution is allowed to warm to room temperature and stirring is continued for about 6 to 72 hours, followed by conventional treatment procedures well known to those skilled in the art. The crude product is isolated by conventional procedures such as chromatographies. The N-protected aminoacyl derivative, N-protected dipstptidyl or 0-protysed hydroxyalkanoyl then is deprotected by procyestimethoenides. In all the following syntheses, the link between the Ca-C3 po- sitions of the macrolide is a double bond, then preferentially carried out to inactivity and reductive to the conditions of formic acid described below. The reaction conditions and reagents particularly used to synthesize a compound of formula I or II in which T is -CH (Z ") N (Z" *) I Z7) or they are dictated by the type of amine used in the reaction.

When a secondary amine of the formula HN (Z- *) (Z7) is used in which Z * and Z "7 are not hydrogen, and are as defined above for formula I or II in reactive amination, ee Use the following procedure: A solution of a 3-deoxy derivative of the appropriate macrolide aldehyde is mixed with a xxceeo, usually about 1.5 equivalent, of a secondary amine, in a reaction-inert solvent such as ethyl acetate. The reaction mixture is heated to a temperature at about 60 ° C to B ° C, preferably about 70 ° C, with stirring, a slight excess of formic acid, usually about 1 μl, is added dropwise to the reaction mixture. molar equivalents, and the temperature of the d-reaction mixture decreases by about 5 ° C. The reaction is stirred for four to seven hours but usually for about five hours.The reaction is stopped by cooling to room temperature. The environment and the desired amino derivative of the 3-deoxy-macrolide is alleviated by conventional techniques well known for loßßßßßßßßßlßalistat in the art, such as column chromatography or crietalization. The compounds of formula (I) or (II), wherein / Y is -CH (Z3) -n (Z *) i Z7), where Z3 is hydrogen and -N (Zß) (Z7) are derivatives of a primary amine, employ the following procedure, Mix a solution in methanol of the 3-deoxy-macrolide aldehyde with the appropriate amine and stir at room temperature for about 30 minutes. Then, the reaction mixture is cooled to about 0 ° C, and an equirnolar amount of glacial acetic acid is added to the mixture and the reaction is allowed to stir. After about ten minutes of stirring, a solution in methanol of sodium cyanoborohydride is added to the reaction mixture, and the resulting solution is stirred for about one hour at about 0 ° C. The reaction is stopped by heating to room temperature and concentrating the reaction mixture, and the desired 3-deoxynrnacrolide derivative is isolated. A preferred method for performing the same type of reaction is as follows. A stirred solution of the 3-deoxy-macrolide aldehyde in methanol is added to the appropriate amine and the reaction is stirred for about 30 minutes. Then, the solution is cooled to about 0 ° C and sodium biorohydride is added. After stirring for about 2 hours, the solution is concentrated almost to dryness and the desired compound is isolated by conventional procedures well known in the art. A primary amino derivative of 3-deoxy macrolide, formed by the above process, can be further transformed by N-methylation of the secondary amino group just added. This synthesis is carried out by suspending the secondary amino derivative of 3-deoxy-macrolide in water and then adding dournic acid. The resulting solution is added to a 38% solution of aqueous formaldehyde and the reaction mixture is heated to reflux temperature. The reaction mixture is stirred at reflux for about four to six hours, preferably about five hours. The mixture is then cooled to room temperature and the desired compound is added. When T is -CH (Z3) -N (Z *) (7 ^) where -N (Z?) I77, comes from a secondary amine, the macrolide can be further functionalized with an amino acyl group according to the following process. A solution in dichloromethane of an N-protected amino acid, an N-protensized dipeptide (the t-BOC TS one of the preferred protecting groups) or of a 0-protected hydroxyalkanoic acid (to the acetate is one d) is cooled to 0 ° C. preferred protecting groups), dicyclohexylcarbodiimide and, frequently, with coupling agent, such as hydroxybenzotriazole ,. (of which all are present in ¼ molar quantities). The cold solution is added a secondary amino compound of formula I or II; wherein Z * ee hydrogen and Z7 ee as defined above. The solution is allowed to warm to room temperature and stirring is continued for about 48 to 72 hours. The crude product is isolated by conventional procedures such as chromatography. The N-protected amino acyl derivative, N-protected dipep-tidyl or 0-protected hydroxyalkanoyl derivative is protected by conventional procedures to produce the desired product. A compound of formula II, in which T is -CH (Z3) -N (Z *) (Z "7) where -NÍZ *) (Z ^) is an aminoalkylamino, can be transformed into the terminal amine by a group amino acyl according to the following procedure: a stirring solution of a compound of formula I or II having an indoalkylamine group in the position T in dimethylphoramide, is added a N-protected amino acid ester d-hydroxy-euccinimide (the BOC is a preferred protecting group) (, an N-protected dipeptide (t-BOC is one of the preferred protecting groups) or a 0-protected hydroxyalkanoic acid (acetate is one of the preferred protecting groups), and the mixture is stirring for about 6 hours The crude product is isolated by conventional procedures such as chromatography on silica gel.The N-protected aminoacyl derivative, protected N-dipeptidyl or 0-protected hydroxyalkanoyl is protected by conventional processes to produce the desired products. The compounds of this invention in which T is -C (= 0) (Za) are synthesized according to the following procedure. The 3-deoxy-macrolide aldehyde is oxidized to the carboxylic acid. The intermediate carboxylic acid derivative of 3-dsoxyko macrolide dßsp ?e is coupled with a diversity of amines to then form amide derivatives. For example, 3-bissoxy macrolide is conveniently protected, protected as 2'-acetate, with about 1.3 equivalents of sodium phosphate monobasic and an excess of 2-methyl-2-butene, about 7.0 equivalents. This oxidation step is usually carried out at room temperature (20-25 ° C) using a mixture of 3: 1 dß acetone / butanol as solvent (molar concentration of 0.3 to 0.5). To form the amide derivatives, the carboxylic acid is coupled with primary or secondary amines in the presence of about 1.1 equivalents of triethylamine at about 0 ° C, using anhydrous DMF as solvent (0.1 molar concentration). The reaction is treated by pouring into saturated aqueous NaHC03 and extraction with EtOAc. The isolated product is purified by ultrafast chromarography to produce the amide derivative. The 2'-acetate group can be removed by dissolving the above product in methanol (MeOH). Thereafter, the reelant solution is stirred at room temperature (20-25 ° C) for approximately 18-24 hours. The reaction mixture ST concentrates under reduced pressure to produce the de-protected d-amide derivative of the 3-deoxy macrolide. Alternatively, the compound of this invention in which T is -C (= 0) (Z3) are synthesized from the 2'-acetate carboxylic acid of the 3-deoxy-macrolides according to the following procedure, , 1 M of the carboxylic acid in a polar aprotic solvent such as CHaCla / which has been cooled to about 0 ° C, is added about 5 equivalents of a primary or secondary amine. Propylphosonic anhydride (1.4 equivalents) is added as a 50% solution in CHaCla V and the reaction is allowed to warm to room temperature. After stirring for approximately 1-5 hours, the reaction mixture is concentrated under vacuum and then redissolved in MβOH to cleave the 2'-acetate. The reaction mixture is concentrated after stirring overnight and extracted from a basic aqueous solution to provide the 3-deeoxi macrolide measurement. The compounds of this invention in which T is -CHa-N (Za) (C = 0) - (CHa) «-Za are easily prepared by the following procedure. The desired 3-deoxy macrolide is subjected to reductive ination with an amine in the presence of sodium triacetoxyborohydride., or formic acid if the bond between C2 and C3 of the 3-deoxy macrolide is? n double bond, as described above. The resulting aminated macrolide is then coupled with the desired carboxylic acid according to one of the coupling methods described above. The amino amide compounds of this invention in which T is -CHa-N (B) (CHa) »- (C = 0) (Z3) O -CHa-N (B) (CH __) aN (B) (CHaβ (C = 0) (Za) can be synthesized by the following two general procedures: Certain amino amide fragments are commercially available or can be prepared from an amino acid such as glycine, sarcosine or β-alanine and a variety of amines, by the same procedures described above for the carboxylic acid derivatives of the 3-deoxy acrylics described in this invention.The amine radical of the part of the amino acid depuped may be coupled with the 3-deoxy-macrolide aldehyde by known reductive amining methods. Those skilled in the art can be used in the following process: The desired 3-deoxy-macrolide aldehyde, an amine, usually about 1.5 equivalents, and acetic acid are stirred in a reaction-inert solvent such as β-ethyl chloride during Approx 30 to 60 minutes. After cooling to about 0 ° C, powdered sodium sulfate (approximately 10 equivalents) and sodium triacetoxyborohydride, or formic acid are added if the bond between C2 and C3 of the 3-deoxy macrolide is a double bond, approximately 1.1 equivalents , and the reaction solution is stirred at room temperature for about 1 to 12 hours. The desired 3-deoxy-macrolide amino derivative is then isolated by conventional techniques well known to those of ordinary skill in the art, such as column chromatography and crystallization. Alternatively, reductive amination may be carried out first with the 3-deoxy-macrolide aldehyde and a protected amino acid. After deprotection, the acid can be coupled to a variety of amines by the procedures described above. In addition, reductive inactivation is preferably carried out with formic acid when the C2-C3 bond of the macrolide is a double bond, as described above. The pharmaceutically acceptable acid addition salts of the 3-bishoxy macrolide derivatives can be obtained by the following general procedure. For example, the HCl salts can be dissolved by dissolving the 3-deeoxi macrolide derivative in a methanolic HCl solution and evaporating the volatile component to produce the desired eal. The methanolic HC solution can be prepared by mixing acetyl chloride with methanol. In addition to the d-HCl salts, other preferred pharmaceutically acceptable acid addition salts include the citrate, phosphate, sulfate salts. methanoeulphonate, benzenesulfonate, palrnitate, succinate, lactate, malate, tartrate, fumarate and etherate, All salts are prepared in a procedure analogous to the procedure used to form HCl salt. The antibacterial activity of the co-testoe of the present invention against bacterial pathogens is demonstrated by the ability of the co-beds to inhibit the growth of Pasteurella mul ori and / or P * fi eure1.1a ha rnQj, t .., Car Loe following procedures are typical essays. In trial I it is used to eneay the activity against Paste? Rella m? Ltocida and the eneayo II ee uses to eneayar the activity against Pasteurella haernnl ut i r.x ASSAY I (P. MULTOCIDfl) This test is based on the liquid dilution procedure in the grinding format. A single colony of P. ulicia (strain 59A067) is inoculated in 5 ml of infusion liquid cbrbrocaediaca (BHI). Loe co pueetos d? The preparation is prepared by soldering 1 ng of the compound in 125 μl of dirnetileulfoxide (DMSO). Dilutions of the eneay compound are prepared by uninnoculated BHI broth. The concentrations of the eneay compound used vary between 200 μg / ml to 0.098 μg / rnl per consecutive dilutions. The BHI inoculated with P. ultocida dilutes a non-inoculated BHI broth to obtain a suspension of 10 * cells per 200 μl. The cell suspensions in BHO are mixed with respective dilutions of the test compound and incubated at 37 ° C for 18 hours. The minimum inhibitory concentration (MIC) ee is equal to the concentration of the product that pre-supposes a 100% inhibition of the growth of P multocida as determined by comparison with a non-inoculated control.

TEST ? .p. HRE? QLYTICR? This assay is based on the agar dilution procedure using a Steers Replicator. Two to five colonies isolated from an agar plate are inoculated in BHI broth and incubated overnight at 37 ° C with shaking (200 rpm). On the following morning, 300 tl of the completely dewarped P. haßrnolvtica preculture are inoculated in 3 ml of fresh BHI broth and incubated at 37 ° C with shaking (200 rpm). The appropriate amounts of the test compounds are dissolved in ethanol and a series of consecutive half dilutions are prepared. Doe my of the respective consecutive dilution is mixed with 18 rnl of molten BHI agar and solidified. When the inoculated P. falciparum culture reaches a standard density of 0.5 McFarland, approximately 5 μl of the P. haernol-vica culture is inoculated onto BHI agar plates containing the various concentrations of the test compound using a Steers Replicator and incubate for 18 hours at 37 ° C. The initial concentrations of the eneayo composition vary between 100-200 tg / l. The MIC is equal to the concentration of the test compound which exhibits a 100% inhibition of P. haemoïctica growth as determined by comparison with a non-inoculated control. The in vivo activity of the compounds of formula (I) or (II) can be determined by conventional animal protection studies well known per se, especially in the art, usually performed with mice. Mice are dieted in cages (10 per cage) after arrival and allowed to acclimate for a minimum of 48 hours before use, and animals are inoculated with 0.5 ml of a bacterial suspension of 3 x 10a CFU / ml (P multocida strain 59A006) intraperitoneally. Each experiment has at least 3 non-medicated control groups that include one infected with a 0.1X injection dose and two infected with a dose of IX injection; A group of 10X injection data can also be used. Generally, all mice in a given study may inject for a period of 30-90 minutes, especially if a repeating syringe (such as a Cornwallu syringe) is used to administer the injection. Thirty minutes after the injection has begun, the first treatment compound is administered. It may be necessary for a second person to start dosing the compound if all the animals have not been injected at the end of 30 minutes. The route of administration is subcutaneous or per os. Subcutaneous doses are administered to the skin in the neck, while oral doses are provided by means of a feeding needle. In both cases, a volume of 0.2 ml per mouse is used. The compounds are administered 30 minutes, 4 hours and 24 hours after the injection. A control compound of known efficacy administered by the same route is included in each assay. The animals are observed daily and the number of survivors of each group is recorded. The control of the P. muítoe.ida model continues for 96 hours (four days) after the injection. Is the DPao dose calculated that the compound tested protects 50% d? a group of mice of mortality due to bacterial infection that could be lethal in the absence of drug treatment. To perform the methods of this invention, a dose of a compound of formula (I) or (II) or a pharmaceutically acceptable salt thereof is administered to an orally or topically detectable or infected parenteral (i.v., o. or s.c.) animal. The effective dose will affect the severity of the disease and the age, weight and condition of the animal. However, the daily dose will usually vary from about 0.25 to about 150 mg / kg, preferably from about 0.25 to about 25 rng / kg. A suitable vehicle for administering the dose parenterally is a solution of the compound in sterile water or a solution of the compound in a solvent comprising at least 50% water and a cosolvent or pharmaceutically acceptable cosolvents such as methanol, β-ethanol, isopropyl alcohol , propylene glycol, glycerol, carbonate esters such as diethyl carbonate, dimethyl sulfoxide, N, N-dirnethyl ormamide, N, N-dimethylacetamide and l-methyl-2-pyrrolidinone. The suspension may be, for example, aqueous carboxyhypolarnose, inert oils such as peanut oil, very refined mineral oils and aqueous polyvinylpyrrolidone. Suitable physiologically acceptable adjuvants may be necessary to maintain the compound in suspension. Adjuvant strains can be selected from among the tailing agents such as carboxypyrronelosa, polyvinylpyrrolidone, gelatin and the suspeneion agents. These surfactants include: aliphenol adduct and polyethylene oxide, n phthalenesulonates, alkoxybenzenesulonates and polyoxyethylene sorbitan esters. They can also help in the manufacture of useful suspensions agents that affect the surface tension. Talee agents include antifoam before silicone sorbitol and sugars. For intravenous use, the total concentration of solutes should be controlled to make the preparation isotonic. The present invention is illustrated by the following examples, but is not limited to the details thereof. The retention times of the High Performance Liquid Chromatography (HPLC) of the products of this invention are determined on a Zorbaxf ,, 1 C8 column of 5 micrometers (4.6 mrn: D x 15 cm in length) of Dupont (available from Mac-Mod Analytical Inc., 127 Co mons Court, Chadds Ford, PA 19317 1-800-441-7508). As the solvent, a 45:55 (col: col) mixture of acetonitrile and 50 millimolar aqueous ammonium acetate is used. The temperature of the column is maintained at 40 ° C and the flow rate is 1.0 ml per minute. The samples were eluted in the eluent (2 mg / ml) and AXIS? PLQ I 3. '-PÍ ^ esQ? I-20-4esQXQ-20- (? AhIDQa¿epin-l-il? -5-Q-micaminosiltilonólido Procedure R (using HCO ^ H? A mixture of 3,4'-dideoxy- was dissolved 0MT (150 rng; 0.265 mmol) and hexamethylenimine (40 g, 0.40 mol) in ethyl acetate (4 ml) and heated to a gentle reflux for about 1.0 hour. The mixture was cooled slightly and formic acid (18 mg, 0.39 mmol) was added. The reaction mixture was heated again to gentle reflux for about 0.5 hour, at which time it was considered by HPLC that the reaction was complete. The mixture was cooled to room temperature and evaporated to a residue (180 mg). The desired product was purified from this residue by preparative HPLC: Column: Kromasil C * (50 x 250 mm) (Available from Bodman Industries, Aston PA 19014, 1-800-241-8774). Mobile phase: linear gradient; ta / ACN of 84/16, to 77/23 in 140 buffer rnin = KHaP0_. 50 rnM at pH = 3.0 Flow: 80 ml / rnin Detection: UV at 290 n Volume of fraction: 125 rnl Fractions containing the title compound were combined and evaporated to give a white solid (109 mg, 63%). ); FAB-MS: rn / e = 649; HPLC retention time: 5.20 min. Method H (using NaBH (Oflc),) to a solution of 3,4'-dideoxy-5-0-rniconyminoethylolide (400 mg, 0.71 mmol) and hexarnetlylenimine (0.096 ml, 0.85 mmol) in 3.6 ml of CHaCla at room temperature, anhydrous NaaSO * powder (1.0 g, 7.1 mmol) was added. After stirring at room temperature for about one hour, the mixture was heated to reflux for about one hour. After cooling to room temperature, acetic acid (0.2 ml, 3.6 mmol) was added and stirring was continued for about one hour at room temperature. The reaction was then cooled to approximately 0 ° C and eß added NaBH (OAc) »(180 rng, 0.85 nmol) in one portion. The reaction was allowed to warm slowly to room temperature and stirred overnight. The mixture was filtered and the filtrate was concentrated. The residue was dissolved in CHCla and washed with saturated aqueous NaHCOa and saturated sodium chloride. The organic layer was dried over anhydrous sodium sulfate, filtered and after evaporation under reduced pressure to give 400 mh of the product (87% yield, 91.5% purity by HPLC).

EXAMPLES 2-23 • 15 The compounds of Examples 2-23 have the general formula shown below and were synthesized according to a procedure analogous to the indicated procedure. Í Example NZV Mo. 15 25 N.T. Not touched, E3FMPI OS 74-7 * The compositions of Examples 24-25 have the general formula shown below and were synthesized according to a procedure analogous to the procedure indicated. ) e E ^ MPLQS 26-31 The compounds of Examples 26-31 have the general formula shown below and were synthesized according to a procedure analogous to the indicated procedure. ) 2 * The solvent used for the reaction is indicated in the parentheses.

PRFPflRflTION 1 3-P-8SQXi -, - 0-mi? Ap? IlnQsiltilQnól_l Q fl a solution of bie-ethylene ketal of 5-0-micarninoeiltilonólido (ONT) (2,120 g, 3,091 mmol) (prepared as described in Bull. Soc. ZJpn., 1992, 65, p. 3405) in 10 ml of DMF, d-dimethylhexylsilyl chloride (829 rng, 4.636 mmol) and imidazole (421 mg, 6.182 mmol) were added. The reaction mixture was stirred at room temperature under nitrogen overnight. The solvent was removed in vacuo and the residue was taken up in 60 ml of CHCla and washed with 60 ml of water. The organic layer was dried over NaaS0_v, filtered, evaporated and subjected to flash chromatography on silica gel (MeOH at 8 / CHCl_2 with NH_, 0.2% 0H). The appropriate fractions were pooled and < 3e evaporated to dryness to yield 2,600 g (55, X) of the dimethylhexylsilyl-diketal intermediate. After a solution of the dimethylhexysilyildicetal intermediate (2.148g, 2.59 mmol) in 20 ml of acetonitrile, acetic anhydride (0.635 g, 6.22 mmol) was added. The reaction mixture was stirred at room temperature under nitrogen overnight. The solvent was removed in vacuo and the residue was taken up in 100 ml of toluene and washed with a saturated NaHCOa solution. The organic layer was dried over MgSO-4, filtered and evaporated to dryness to yield 1.978 g (83.7%) of the bos-acetylated intermediate. EM LSIMS: 912. fl a bie-acetylated intermediate dl solution (1.412 g, 1.48 mmol) in 2 ml of anhydrous pyridine, methanesulfonyl chloride (0.433 g, 3,870 rnols) was added. The turbine reaction mixture was stirred at room temperature under nitrogen for about 3 hours. The solution was added to 50 mL of the NaHCO 3 acid solution. The mixture was extracted several times with toluene. The combined organic layers were dried over MgSO0, filtered and evaporated to dryness to yield 1.461 g (95.3%) of the intermediate rhnosylate. After a solution of the intermediate esylate (1.420 g, 1.434 mmol) in 30 ml of methanol, 10 ml of concentrated NR_, 0H were added. The reaction mixture was stirred at room temperature for about 2.5 hours and then heated at 50 ° C overnight. The solvent was removed under reduced pressure and the residue partitioned between chloroform and saturated NaCl solution. The organic layer was dried over Na__S0_v? it was filtered and evaporated to dryness to yield 1.101 g (94.8%) of the intermediate 2,3-trane-olefin. After a solution of intermediate 2, .3-trans olefin (0.935 g, 1.154 mmol) in 33 ml of methanol was added KaC0a (0? 475 g, 3.437 mmol) and Raney Nickel (one euspension of about 0.5 ml. Water). The mixture was hydrogenated on a Parr shaker at 103.42 Pa for about 10 minutes. The catalyst was filtered rapidly and the filtrate was evaporated under reduced pressure. The residue was taken up in methylene chloride and washed with saturated NaHCO »solution. The organic layer was dried over NaaSO_v, filtered and evaporated to dryness to give 0.914 g (98%) of the desired protected intermediate. The protected intermediate was shrunk in 20 ml of 0.25 N HCl and 5 ml of acetonitrile and stirred at room temperature for about 2 hours. The mixture was poured into 200 mg of saturated NaHCO3 solution. The cloudy mixture was extracted several times with chloroform. The combined organic layers were dried over NaOH, filtered, evaporated, dried to dryness and subjected to flash chromatography on silica gel (5% MeOH / CH.sub.Cls with 0.5% NH0H). . The appropriate fractions were combined and the dryness evaporated to give 0.699 g (quantitative) of the title compound as a white solid foam. MS (El) 581.4.

PRFPQROTION 2 3-DeS0XÍ-7.3-didehydro-R-0-miraminosiltilonólido fl a solution of OMT (5.00 g, 8.36 mmol) in 56 rnl of EtOH at room temperature, molecular sieves of 4fl powder and p-toluene phonic acid (2.38 g, 12.54 nrnol) were added.

Stirring was continued at room temperature for about 5 hours, at which time the reaction with EtaN (1.6 ml, 11.7 mmol) was stopped. The reaction mixture was filtered and concentrated to dryness. The residue was dissolved in CHaCl-2 and washed with saturated aqueous NaHCO 3 and brine. The organic layer was dried over NaaSI._ > , filtered and concentrated to provide 3.4 g of the diethyl acetal intermediate (61% yield). With a solution of the intermediate diethyl acetal (7.99 g, 11.9 mmol) in 39.6 ml of DMF, imidazole (1.62 g, 23.8 mmol) was added, followed by dimethylsilyl chloride (3.5 g). g, 17.85 mmol). After stirring overnight at room temperature under nitrogen, more imidazole (810 g, 11.9 mmol) and dimethylhexylsilyl chloride (1.75 ml, 8.9 mmol) were added. The reaction was stirred for about 5 hours, at which point the Thin Layer Chromatography (TLC) analysis (89: 10: 1 CH13: MeOH: NH_, 0H) indicated that the starting material had been consumed. The solvent was removed in vacuo. The reflux was dissolved in CHßCls_ and washed with water and brine. The organic layer was dried over NaaSO_¡ > , a yellow oil was filtered and concentrated, which was chromatographed on silica gel ((2% MeOH / CHCla with 0.1% NH.sub.1 OH) to yield 6.2 g of the intermediate 23-dimethylhexysilyl-20- clean diethyl acetal (yield 64%) EM (particle beam) 815. To the intermediate 23-dimethylhexysilyl-20-diethyl acetal / 7, 6 mmol) in 38 mL of acetonitrile, acetic anhydride (1.58 mL, 16.7 mmol) was added. The reaction was stirred overnight at room temperature under nitrogen. The solvent was removed in vacuo and the residue was dissolved in CHaCl__ and washed with saturated aqueous NaHCOa and brine. The organic layer was dried over NaSO 4, filtered and evaporated to dryness to yield 6.5 g of diacetate intermediate (96% yield). MS (particle beam) 899.f a solution of the intermediate diacetate (7.2 mmol) in pyridine (72 ml), netanosulfonyl chloride (1.39 mmol, 18 mmol) was added. The cloudy reaction mixture was stirred at room temperature under nitrogen for about 5 hours. Analysis of TLC (cyclohexane: acetone 3: 1) indicated that the starting material had been completely consumed. The solvent was removed in vacuo and dissolved in toluene. The toluene solution was washed with saturated aqueous NaHCIa and brine. The organic layer was dried over Na2SO_v, filtered and concentrated to 7.0 g of the 3-0-rnesyl intermediate (99% yield). MS (particle beam) 977, 811. fl a solution of the 3-0-rnesyl intermediate in 180 ml of methanol, concentrated NH 1 H (90 rnl) was added dropwise with vigorous stirring. The sticky precipitate that formed gradually faded. The reaction was stirred at room temperature for about 3 hours. The solvent was removed in vacuo. The residue was re-dissolved in methanol (90 nmol) and the reaction was heated at 50 ° C overnight. The solvent was removed in vacuo. The residue was dissolved in CHCla and washed with water and the outside. The organic layer was dried over Na2SO_v, filtered and concentrated to 5.0 g of off-white 2,3-trans olefin (88% yield). To the intermediate 2,3-trans olef.ina in acetonitrile (80 ml), 0.25 N aqueous HCl (320 ml) was added dropwise. The reaction was stirred at room temperature for about 4.5 hours, at which time the reaction mixture was adjusted to pCH g with saturated aqueous NaHVOa. This mixture was stirred for about 30 minutes at room temperature and then extracted with CHCla. The organic layer was washed with brine, filtered and concentrated. The residue (3.5 g) was chromatographed on silica gel (2% MeOH / CHCla with 25% aqueous (NH.H.H.) The appropriate fractions were combined and concentrated to yield 1.4 g of the title compound. title in the form of a white foam (38% yield) High Recycling MS 579.3047.

PREPARATION 3 3. 4 ^ -Didesoxy-R-p-micaminosiltilonolide This material was prepared as described in Bull.

Chern. Soc. CJpn., 1992, 65, p. 3405. Having defined the invention as above, the contents of the following are declared as property

Claims (15)

1. NOVELTY DF I Q INVFNCTON RFIVINDtCQCTQNFS 1. A compound d? Formula I or II and pharmaceutically acceptable lae ealee thereof, wherein rn ee 1 or 2; Z1 is H, OH or micaroeryloxy; represents a single or double bond, the double bond results in geometry or cis or trans; 0? .e is selected from the group consisting of H, OH, fluoro, chlorine, bromine, iodine, OX3-, azetidin-1-yl; pyrrolidin-1-yl, piperidin-1-yl, 3,3-dirnethyl-1-eridin-1-yl, hexahydroazepin-1-yl, octahydroazocin-1-yl, octahydroindol-1-yl, 1, 3.3a, 4,7,7a-hexahydroisoindol-2-yl, decahydroquinol-1-yl, decahydroisoquinol-2-yl, 1,2,3,4-tetrahydroieoquinol-2-yl, 1,2,3,6-tetrahydropyridin-1 -yl, 4-alkylpiperazin-1-yl having 1 to 4 carbons in the alkyl part, orfolin, 2,6-dimethylmorpholin-4-yl ,. thiomorpholino and -NXssX3X: l- is selected from the group consisting of alkyl, optionally substituted having 1 to 4 carbons, optionally substituted cycloalkyl having 4 to 8 carbon atoms and an aryl, aralkyl or heteroaryl group optionally substituted, selected from the group consisting of compound group consisting of phenyl, benzyl pyridinyl, quinolinyl * isoquinolinyl, quinazolinyl, pyrimidinyl, isoquinolinyl, quinazolinyl, pyrirnidinyl, imidazolyl, oxazolyl, thiazolyl, benzimidazolyl, indolyl, benzoxazolyl and benzothiazolyl; wherein the optionally substituted aryl, aralkyl and heteroaryl groups are optionally substituted with 1 or 2 suetituyentas independently selected from the group consisting of alkyl having 1 to 4 carbon. gold, chlorine, bromine, acetyl, amino, nitro cyano, tri-luoromethyl, N-alkylamino having 1 to 4 carbons, N, N, -dialkylamino having a total of 2 to 6 carbons, carboxyl, carboalkoxy having 1 to 4 carbon, carboxamide, eulfonamido, hydroxyalkyl having 1 to 4 carbons, to inoalkyl having 1 to 4 carbons, N-alkylaminoalkyl having 1 to 4 carbons in each of the alkyl and N, N- parts dialkylaminoalkyl having a total of 2 to 6 carbon in the dialkylamide part and 1 to 4 carbons in the alkyl part; Xa and X3 are each independently selected from the group consisting of hydrogen, alkyl having 1 to 4 carbons, hydroxyalkyl having 2 to 4 carbons, cycloalkyl having 3 to 8 carbons, alkenyl having 3 or 4 carbons, alkoxyalkyl having 1 to 4 carbon in the alkoxy part and 2 to 4 carbons in the alkyl part, and alkoxyalkoxyalkyl having 1 to 4 carbons in each of the alkoxy portions and 2 to 4 carbons in the alkyl part; T is -C (= 0 = (Z3) "-CH __- N (B) (CH ..) _.- C (= 0) (Za), -CH __- N (Za) (C = 0) ~ ( CH2) «- Z3? -CHa-N (B) (CHa) ß-N (B) (CH __) _.- C (= 0) (Z3), -CH = CH- (CHa) NN (Z *) (Za), -CH (ZT) (Z *) (Z7), -CH ^ -NÍZ3-2) (SO ^ Z3-3), -CHa-NÍZ ^) (C (= 0) - (Z1 * - Za-ß), -CH ^ -NÍZ3-2) (CHa) ^ - ÍZ3- ») where n is an integer from 1 to 4; B, in each case, is independently selected from the group consisting of hydrogen, alkyl (C -C ".), An aminoacyl group and an aminoacyl group and a dipeptidyl group; Z2 is hydrogen or alkyl (Ct-c *); Z3 ES - ÍR ^ R2, -NH-CH (R) - (CH __)? - C00R * or -NH-CH (R3) - (CH2) «.- C (= O) -NH- (CH2) f- C0OR ?; R3- H R2 are each independently selected from the group consisting of hydrogen, methyl, optionally substituted alkyl having 2 to 6 carbons, optionally substituted cycloalkyl having 3 to 8 carbons, aminoalkyl having 2 to 6 carbons, hydroxyalkyl which has 2 to 6 carbons, N-alkylaminoalkyl having 1 to 4 carbons in the alkylamino part and 2 to 4 carbons in the alkyl part, benzyl optionally substituted, phenyl optionally substituted, alkoxyalkyl having 2 to 4 carbon in the alkyl part and 1 to 4 carbons in the alkoxy part, N, N-dialkylaminoalkyl has a total of 2 to 6 carbons in the dialkylamino part and 2 to 4 carbons in the part - (CH2) β-pyrrolidino, - (CHβ) β-pyrrolidino , - (CHs_) ß-azetidin-l-yl and - (CHa) a-hexahydroazepin-1-yl; or R3- and R52 are coupled together with the nitrogen to which they are bound and form Z; R3 corresponds to the part of the side chain of amino acids and in each case is selected independently from the side chain of the group of amino acids that binds the D or L form, when applicable, of alanine, arginine, asparagine, aspartic acid, cysteine, cystine, glutamic acid, glutamine, glycine, hietidine? hydroxylysine, hydroxyproline, ieoleucine, leucine, lieine, ethionine, phenylalanine, proline, eterine, threonine, tryptophan tyrosine, valine, 3-alanine, beta-lieine, a, a-dirnethylglycine, oc-arninobutyric acid, 4-hydroxyphenylglycine, phenylglycine , acid < x, t-diaminobutyric, ornithine and hooserin; ee 0 or 1, with the proviso that when e ee 1, then R3 corre- sponds to the side chain of β-lieine or β-alanine; f ee or 1, with the proviso that when f ee 1, then R3 corresponds to the side chain of β-lysine or β-alanine; R is H, alkyl having 1 to 4 carbons or benzyl; Z * is selected from the group consisting of hydrogen, an aminoacyl group, a dipeptidyl group, alkenyl having 3 to 5 carbone, with the proviso that the double bond is not adjacent to the nitrogen to which Z *, alkynyl, is attached. it has 3 to 5 carbons with the proviso that the triple bond is not adjacent to the nitrogen to which Z * is bonded, hydroxyalkyl having 2 to 4 carbons in the alkyl part 0 O, Qao, 0ao and alkoxyalkyl having 2 to 4 carbon in the alkyl part and 1 to 4 carbon in the alkoxy part; Za is selected from the group consisting of hydrogen, alkenyl having 3 to 5 carbon, with the proviso that the double bond is not adjacent to the nitrogen to which Za, alkynyl having 3 to 5 carbone is attached with the proviso The triple bond is not adjacent to the nitrogen to which Za "hydroxyalkyl having 2 to 4 carbons in the alkyl part, 03-0, Qao, Q3 °, alkoxyalkyl having 2 to 4 carbons in the alkyl part and to 4 carbons in the alkoxy part and -Rß- ÍR ^ R3); 03-0, in each case is, independently, independently selected from the group consisting of alkyl (C a_, (C __-C) alkoxy, fluoro, chloro, bromo, iodo, nitro, amino, cyano, hydroxy, trifluoromethyl, and carboalkoxy having 1 to 4 carbon; is independently an optionally substituted alkyl (dC.), optionally substituted with an eustite selected from the group consisting of hydroxy, cyano, N-alkylamino having 1 to 5 carbons and N, N-dialkylamino having has a total of 2 to 6 carbons; O30, in each case, is independently where d is an integer from 1 to 5 and Q3a is selected from the group consisting of hydroxy, cyano, N-alkylamino having 1 to 5 carbon and N, N-dialkylamino having a total of 2 to 6 carbon; R * is alkylene Cs_-C__); R7 is selected from the group consisting of hydrogen, alkyl having 1 to 4 carbons, cycloalkyl having 3 to 8 carbons and alkoxyalkyl having 2 to 4 carbons in the alkyl part and 1 to 4 carbon in the alkoxy part; Rβ is selected from the group consisting of alkyl having 1 to 4 carbons, an optionally substituted hydroxyalkanoyl having 1 to 6 carbons, an aminoacyl group and a dipeptidyl group, wherein the optionally substituted hydroxyalkanoyl group is optionally substituted with a phenyl group optionally replaced; or f 7 and β ee taken together with the nitrogen to which they are attached and form a cyclic amine having 3 to 6 carbon atoms; or Z * and Za are taken together with the nitrogen to which they are bound and form Z3-00; Z is an aminoacyl group, a dipeptidyl group or ee independently selected from the ie or group that has been defined for R3-; Z7 ee selects independently between the same group that has been defined for R3- or between the group compitted by -C (CHa) w-R3-sa_l _, - (CH _.) ß-N (Z3 - *) a and -R'- R R3-3-); where q ee 1, 2 or 3; R * is alkylene (Ca-C_.) Optionally substituted with alkyl (C __-C_.) Or hydroxy, with the proviso that the hydroxy can only be attached to the C2 of the alkylene group when the alkylene has a length of three carbon atornoe or to C3 of the alkylene group when the alkylene has a length of four carbon atornoe or to the C3 of the alkylene group when the alkylene has a length of four carbon atoms; R3-0 is selected from the group consisting of hydrogen, methyl and ethyl; R3-3- is selected from the group consisting of an optionally substituted hydroxyalkanoyl having 1 to 6 carbons, an amino acyl group and a dipeptidyl group, the optionally substituted hydroxyalkanoyl group is optionally substituted; or R3-0 and R3-3- are taken together with the nitrogen to which they are bound and form Zxo °; R3-2 is? u 0; Z3- *, in each case, is independently selected from the group consisting of an aminoacyl group, a dipeptidyl group and the same substituent group as defined below for Z a, Z3-3 and Z a; or Z *, and Z7 are taken together with the nitrogen to which they are bound and form Z100; Zß is H or CN; 77 is (C -Cß) alkyl, an arninoacyl group, a dipeptidyl group, hydroxyalkanoyl having 1 to 6 carbons, aminoalkyl having 2 to 6 carbons, hydroxyalkyl having 2 to 4 carbons, N-alkylaminoalkyl having 1 to 4 carbons. carbons in the alkylamino part and 2 to 4 carbons in the alkyl part, alkoxyalkyl having 2 to 4 carbons in the alkyl part and 1 to 4 carbons in the alkoxy part, N, N, -dialkylaminoalkyl having a total of 2 to 6. carbons in the dialkylamino part and 2 to 4 carbons in the alkyl part, -C0-Z * -Zxa or -S0 __-xa; Z a, Zxa and Z a, in each case, are independently selected from the same group as defined for R, with the condition dß that Z3-3 is hydrogen only when Z * is NH; Z3-, in each case, is independently 0 or NH; a, in each case, ee independently, independently is 1 or 2; in each case of the amino acyl group and the dipeptidyl group, the amino acyl group and the amino acyl groups of the dipeptidyl group are independently selected from the group consisting of the D or LA form when applicable, of alanyl, arginyl, aeparagil, aspartyl, cysteinyl? cystyl, glutamyl, glutamyl, glycyl, hietidyl, hydroxylysyl, hydroxyprolyl, isoleucyl, leucyl, lysyl, methionyl, phenylalanyl, prolyl, seryl, threonyl, triptophoyl, tyrosyl, valyl, β-alanyl, β-lieyl, N, N-dimethylglycyl , a, a, -dimethylglycyl, a-aminobutyryl, 4-hydroxyphenylglycyl, phenylglycyl, a, t-diarninobyryl, ornithyl, benzyl, bicyclo, N, N-diethyl-β-alanyl, N, N -diethyl-t-aminobutyryl and sarcosyl, with the proviso that N, NV-diethyl-t-aminobutyryl can only be the terminal aminoacyl when they are in a dipeptidyl group; in each case of an optionally euetitized alkyl or an optionally euetitiated cycloalkyl, optionally substituted alkyl or optionally substituted cycloalkyl are independently selected from an optionally substituted alkyl or an optionally substituted cycloalkyl, optionally substituted with 1A 2 or 3 substituents. ??? independently selected from the group consisting of hydroxy, cyano, fluoro, trifluoromethyl, amino optionally substituted, N-alkylamino optionally substituted having 1 to 4 carbons, N, N-dialkylamino having a total of 2 to 6 carbons, N- (hydroxyalkyl) amino in which each alkyl part has 2 to 4 carbons, alkoxy having 1 to 4 carbons, alkoxycarbonyl having the 4 carbon in the alkoxy part, N, N-dialkylaminoalkoxy having a total of 2 to 6 carbone in the dialkylamino part and 2 to 4 carbons in the alkoxy part, alkoxyalkoxy having 1 to 4 carbons n each of the alkoxy, alkoxyalkoxyalkox moieties which has 1 to 4 carbons in each of the alkoxy, spirocycloalkyl groups having 4 to 6 carbons, R "N- (CH, -C- > M.ioR1H4 í ... í) 's • N-. wherein the optionally substituted amine and the optionally substituted N-alkylamino are each, independently, openable mono-usutent with one or more amino acids or one dipeptide group; R13 and R1 * are each, independently, selected from the group consisting of hydrogen and alkyl having 1 to 4 carbons; or R 3 and R 1 become together with the nitrogen to which they are bound and form Zioo; Ris t RIS R? ee are each independently selected from the group consisting of hydrogen, alkyl (C? ~ C?), an aminoacyl group and uri dipeptidyl group; Rl8 is NH, N, (C1-C4) alkyl, N- (arnino ac lo group) or N- (gr * or di peptide); R19 is selected from the group consisting of -CH, OH2, N and NH; R20 is alkyl having 1 4 carbons or -C00R21; R21 / in each case, is independently H or alkyl having 1 to 4 carbons; Raa is selected from the group consisting of H, alkyl having 1 to 4 carbons, hydroxy, alkoxy having 1 to 3 carbons, amino, N-.alkylamino having 1 to 4 carbons and N, N-dialkylamino having a total from 2 to 6 carbons; or Ra and Raa are taken together and form an oxo group; Z or °, in each case, is independently selected from the group composed by -, T ~ 3 .- ""? -r ~~ V5. -G ~ VR26 _ 'N /' N 1 'N f (R24) b where Raa is selected from the group consisting of C, CH, CH2, N, NH, Niamino acyl) or N (dipeptidyl group); Ra * is alkyl having 1 to 4 carbons, -C0-alkyl (C3_-C) or -C00-alkyl (C -C_v); Ras is 0 or S; Ra < * is selected from the group consisting of alkyl having 1 to 4 carbons, a hydroxyalkanoyl optionally substituted having 1 to 6 carbons? an amino acyl group and a dipeptidyl group, wherein the optionally substituted hydroxyalkanoyl group optionally is substituted with an optionally substituted phenyl group; R2"7, ee H or alkyl having 1 to 4 carbons; Raß ee H, alkyl having 1 to 4 carbon, hydroxy, alkoxy having 1 to 3 carbon, amino, N-alkylamino having 1 to 4 carbon or N, N-dialkylamino having a total of 2 to 6 carbons; or R7"7 and R028 turn together and form an oxo group; g, in each case, is independently 2, 3 or 4; b? in each case, it is independently 0, 1 or 2; and each case of the optionally substituted phenyl or optionally substituted benzyl, optionally substituted phenyl or optionally substituted benzyl is optionally substituted with 1 or 2 independently selected constituents from the group > or. compound by alkyl having 1 to 4 carbon, fluoro, chloro, bromo, acetyl, amino, nitro, cyano, trifluoromethyl, N-alkylamino having 4 carbon, N, N-dialkylamino having a total of 2 to 6 carbons, -NH-C0_CH3, carboxyl, carboalkoxy having 1 to 4 carbons, carboxy gone, sulfone gone, hydroxyalkyl having 1 to 4 carbons, aminoalkyl having 1 to 4 carbons, N-alkylaminoalkyl having 1 to 4 carbons in each of the alkyl and N, N-dialkylaminoalkyl moieties having a total of 2 to 6 carbons in the dialkylamino part and 1 to 4 carbons in the alkyl moiety; with the following conditions: (1) that when T ee -C (= 0) (Z3), -CHa-N (B) (CHa) ß-C (= 0) (Z3), -CHa-N (Za) ) C = 0) - (CHa) ß-Z3 O -CHa-N (B) (CHa) ß-N (B) (CHa-aC (= 0) (Z3), where Z3 ee -N (R Ra) Where Rx or Ra is a substituted alkyl or a substituted cycloalkyl, then the solid at position 1 of the substituted alkyl or the substituted cycloalkyl can not be fluoro, chloro or a substituent attached to a heteroatom, and (2) when any of the above defined constituents which can be a substituted cycloalkyl and a substituted cycloalkyl, then the euent in the 1-position of the substituted cycloalkyl can not be fluoro, chloro or a substituent attached to a heteroatom attached to a heteroatom. The pharmaceutically acceptable salt thereof of formula (I) according to claim 1, wherein is 1 and Z is H or OH 3. A compound or a pharmaceutically acceptable salt of the same of formula (I) according to the claim on 2, where T ee -CHa-N (B) (CHa) ß-C (= 0) (Z3), -CHa-N (Za) -C (= 0) - (CHa) .- Za, -CHa-N (B) (CHa) ß-N (B) (CHa)? -C (= 0) (Z3), -CH = CH- (CHa) "- N (Z *) (Za), CH (Zß) N (Z *) iZ7)), -CH __- N (Z a (SOaZ3-3), -CHa-N (Z a) - (C (= 0) _Z -Z 3), -CH2-N (Z a) (CHa) ß_N (Z a) (C (= 0) (Z * -ZX3) or -CHa-N (Zxa) (CHa) ß-N (Zx *) (S0aZX3) 4. A compound or an eal pharmaceutically acceptable thereof of formula (I) according to claim 3, wherein T ee -CH = CH- (CHa), -N (Z) (Za), -CH (Zß) N (Zß) (Z) ?)) t -CHa-N (Z a) (SOaZx3), -CHaN (Zxa) (C (= 0) -Z * -Z0 a), -CH __- N (Zxa) (CHa) ß-N (za) (C ( = 0) (Z "-Z 3) or -CHaN (Zxa) (CHaß-N (Zxa) (SOaZ3-3), where Za ee H. 5. A compound or a pharmaceutically acceptable salt thereof of formula (I) according to claim 4, wherein T is -CH = CH- (CHa) NN (Z *) (Za), -CHa (Z *) i Z7) or where n is 1; Z * and Zs are each, independently, selected from the group consisting of hydrogen, alkenyl having 3 to 5 carbon atoms with the proviso that the double bond is not adjacent to the nitrogen to which it is attached to the alkenyl, alkynyl having 3 to 5 carbons, with the proviso that the triple bond is not adjacent to the nitrogen to which the alkynyl hydroxyalkyl having 2 to 4 carbons is attached in the alkyl, QxO, 0a, 030 and alkoxyalkyl moiety having 2 to 4 carbons in the alkyl part and 1 to 4 carbons in the alkoxy part, or Z * and Za become together with the nitrogen to which they are bound and form ZXDD. 6. A compound or a pharmaceutically acceptable salt thereof of formula (I) according to claim 5, wherein T is -CHa (Zß) iZ7) or where Z * is independently selected from the same group of substituents as R; Z7 is independently selected from the same group of substituents as Rx or is -R * -N (RxoR x); or Z * and Z7 become together with the nitrogen group to which they are bound and form Zxo °; and T * is an amino acyl group, aminoalkyl having 2 to 6 carbons, hydroxyalkyl having 2 to 4 carbons, N-alkylaminoalkyl having 1 to 4 carbons in the alkylamino part and 2 to 4 carbons in the alkyl part , alkoxyalkyl having 2 to 4 carbons in the alkyl part and 1 to 4 carbons in the alkoxy, N, N-dialkylaminoalkyl part having a total of 2 to 6 carbons in the dialkylamino part and 2 to 4 carbons in the alkyl part, or -C0-Zx "- Zx3. 7. A pharmaceutically acceptable salt or compound of the formula (I) according to claim 6, wherein 0 is OH; Z is H T is -CHa (Z *) i Z7), where Zß is hydrogen, methyl or optionally substituted alkyl having 2 6 carbon atoms; 27 is N-alkylaminoalkyl having from 1 to 4 carbons in the alkylamino part and 2 to 4 carbons in the alkyl part, optionally substituted alkyl having 2 to 6 carbon atoms or optionally substituted cycloalkyl having 3 to 8 carbons; or Z * and Z7 are taken together with the nitrogen to which they are added and form pyrrolidino, piperidino, 3,4-deehydropiperidino or azabicyclononan-3-yl. 8. A compound or a pharmaceutically acceptable salt of the mie or of formula (i) according to claim 7, wherein said optionally euetitized alkyl of Z * is propyl; said alkyl optionally substituted Z07 is propyl, 3- (dimethylamino) -propyl or 2-spirocyclopentyl-3-hydroxypropyl; and said optionally substituted cycloalkyl of Z7 is cyclohexyl. 9. A compound or a pharmaceutically acceptable salt thereof of formula (I) according to claim 6, wherein 0 is OH; Z is H; T is -CHa (Z *) (Z7), where Z * is hydrogen or methyl; Z7 is methyl, 2-fluoroethyl, 2, 2-dirnethyl-3-hydroxypropyl, 2-hydroxyethyl, propyl, 3-hydroxyethyl, 2,5- (dihydroxy) cyclohexyl or 3-arninopropyl; or Z * and Z7 are taken together with the nitrogen to which they are attached and form 4-rnethylpiperazino, azetidino, 4-hydroxypiperidino, morpholino or 3-hydroxypiperidino. 10. A compound or a pharmaceutically acceptable salt thereof of the formula (I) according to claim 6, wherein 0 is OH; Zx is OH; T is -CHa (Z *) i Z7), where Z * is hydrogen; Z7 is 2,2, -dimethyl-3-hydroxypropyl; or Z * and Z7 are together with the nitrogen to which they are bound and form hexahydroazepin-1-yl. 11. A compound or a pharmaceutically acceptable salt thereof of formula (I) according to claim 6, wherein the bond between C2-C3 of the macrolide is a double bond, 0 is OH; Z is OH; T is -CHa (Z *) (Z ""), where Z * is hydrogen, methyl or propyl or 3- (dimethylamino) propyl; or Z * and Z7 are taken together with the nitrogen to which they are attached and form hexahydroazepin-1-yl or 3-azabicyclononan-3-yl. 12. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent. 13. A method of treating a bacterial infection in an animal in need thereof, comprising administering to said animal a bacterial treatment amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof. 14. A method for treating a rnicoplasmic infection in an animal in need thereof, comprising administering to said animal a mycoplasic treatment amount of a compound of claim 1, or a pharmaceutically acceptable moiety of the animal. 15. A method for prophylactically treating an animal susceptible to a bacterial or mycoplasma infection, which comprises administering to said animal a prolificactic amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof. RESI1HFN PF L fl INVENTION Derivatives of antibiotics 3-deoxy macrolides with rings of 16 members, obtained from roearaicin, repromycin, 5-micaminosiltilonólido, desmicosina, lactenocina, O-desmetil-lactenocina, cirramycin Aa. and 23-desoximica onosiltilonólido, that are? tilee against bacterial pathogens and icroplásmicoe in animalee. P96 / 774 PF / rnvs