# US 4,396,613 A · 23-Ester derivatives of DMT and method of using same > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 4,396,613 A - Document ID: US4396613A - Status: Granted - Kind: A - Application number: 06/330,294 - Filed: 1981-12-14 - Granted: 1983-08-02 - Earliest claimed: 1981-12-14 - Assignees: Eli Lilly and Company - Inventors: Herbert A. Kirst - Web page: https://patentgrep.com/patent/US4396613A ## CPC - C07H 17/08: Hetero rings containing eight or more ring members, e.g. erythromycins - C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13) ## Abstract 23-Ester derivatives of demycinosyltylosin (DMT) of the formula: ##STR1## wherein R is selected from hydrogen, optionally substituted C.sub.1 -C.sub.5 -alkanoyl or optionally substituted benzoyl, phenylacetyl, or phenylpropionyl; and R.sup.1 is an acyl group selected from: ##STR2## p is 0 or 1; m and n are integers from 0 to 4; R.sup.2 is hydrogen, halo, C.sub.1 -C.sub.4 -alkyl, C.sub.3 -C.sub.8 -cycloalkyl, phenyl, C.sub.5 -C.sub.8 -cycloalkenyl, naphthyl, indenyl, tetralinyl, decalinyl, adamantyl, cinnoxacinyl, a monocyclic heterocyclic ring system comprising 3 to 8 atoms or a bicyclic heterocyclic ring system comprising 6 to 11 atoms, provided that at least 1 atom of the ring system is carbon and at least 1 atom of the ring system is a heteroatom selected from O, N, and S; and wherein R.sup.2 and the connecting alkyl groups --(CH.sub.2).sub.m -- and --(CH.sub.2).sub.n -- are optionally substituted by one or two halo, methyl, ethyl, methoxy, amino, N-protected-amino, methylamino, dimethylamino, nitro, acetoxy, acetamido, azido, carbomethoxy, carboxamido, cyano, or hydroxyl groups, provided that, if the substituent is other than halo or alkyl, there can be no more than one substituent on any connecting --CH.sub.2 -- group; X is O, S, --NH--, --N(CH.sub.3)--, --C.tbd.C--, --CH.dbd.CH--, --C(CH.sub.3).dbd.CH--, --CH.dbd.C(CH.sub.3)-- or --C(CH.sub.3).dbd.C(CH.sub.3)--; R.sup.3 and R.sup.4 are C.sub.1 -C.sub.5 -alkyl or optionally substituted phenyl or benzyl; and salts thereof are useful antibiotics or intermediates to antibiotics. ## Claims ### Claim 1 A compound of the formula ##STR7## wherein R is selected from hydrogen, C.sub.1 -C.sub.5 -alkanoyl, C.sub.1 -C.sub.5 -alkanoyl having from one to three halo substituents, benzoyl, phenylacetyl or phenylpropionyl or benzoyl, phenylacetyl, or phenylpropionyl having on the phenyl ring from one to five halo or methyl or from one to two methoxyl, nitro or hydroxyl groups; and R.sup.1 is an acyl group selected from: ##STR8## p is 0 or 1; m and n are integers from 0 to 4; R.sup.2 is hydrogen, halo, C.sub.1 -C.sub.4 -alkyl, C.sub.3 -C.sub.8 -cycloalkyl, phenyl, C.sub.5 -C.sub.8 -cycloalkenyl, naphthyl, indenyl, tetralinyl, decalinyl, adamantyl, cinnoxacinyl, a monocyclic heterocyclic ring system comprising 3 to 8 atoms or a bicyclic heterocyclic ring system comprising 6 to 11 atoms, provided that at least 1 atom of the ring system is carbon and at least 1 atom of the ring system is a heteroatom selected from O, N, and S; and wherein R.sup.2 and the connecting alkyl groups --(CH.sub.2).sub.m -- and --(CH.sub.2).sub.n -- are optionally substituted by one or two halo, methyl, ethyl, methoxy, amino, methylamino, dimethylamino, nitro, acetoxy, acetamido, azido, carbomethoxy, carboxamido, cyano, or hydroxyl groups, provided that, when the substituent is other than halo or alkyl, there can be no more than one substituent on any connecting --CH.sub.2 -- group; X is O, S, --NH--, --N(CH.sub.3)--, --C.tbd.C--, --CH.dbd.CH--, --C(CH.sub.3).dbd.CH--, --CH.dbd.C(CH.sub.3)-- or --C(CH.sub.3).dbd.C(CH.sub.3)--; R.sup.3 and R.sup.4 are C.sub.1 -C.sub.5 -alkyl, phenyl or benzyl or phenyl or benzyl having on the phenyl ring from one to five halo or methyl or from one to two methoxy, nitro or hydroxyl groups; and the acid addition salts thereof. ### Claim 2 (depends on 1) A compound of claim 1 wherein the acyl group is ##STR9## and the acid addition salts thereof. ### Claim 3 (depends on 2) A compound of claim 2 wherein R.sup.2 is hydrogen or C.sub.1 -C.sub.4 -alkyl and the acid addition salts thereof. ### Claim 4 (depends on 2) A compound of claim 2 wherein p is 0 and the acid addition salts thereof. ### Claim 5 (depends on 2, 3) A compound of claim 2, 3, or 4 wherein R is hydrogen and the acid addition salts thereof. ### Claim 6 (depends on 2, 3) A compound of claim 2, 3, or 4 wherein R is C.sub.1 -C.sub.5 -alkanoyl and the acid addition salts thereof. ### Claim 7 (depends on 2, 3) A compound of claim 2, 3, or 4 wherein R is benzoyl, phenylacetyl or phenylpropionyl and the acid addition salts thereof. ### Claim 8 (depends on 3) The compound of claim 3 wherein R and R.sup.1 are acetyl and its acid addition salts. ### Claim 9 (depends on 3) The compound of claim 3 wherein R is hydrogen and R.sup.1 is acetyl and its acid addition salts. ### Claim 10 (depends on 3) The compound of claim 3 wherein R and R.sup.1 are propionyl and its acid addition salts. ### Claim 11 (depends on 3) The compound of claim 3 wherein R is hydrogen and R.sup.1 is propionyl and its acid addition salts. ### Claim 12 (depends on 3) The compound of claim 3 wherein R is acetyl and R.sup.1 is propionyl and its acid addition salts. ### Claim 13 (depends on 3) The compound of claim 3 wherein R is propionyl and R.sup.1 is acetyl and its acid addition salts. ### Claim 14 (depends on 3) The compound of claim 3 wherein R is acetyl and R.sup.1 is n-octanoyl and its acid addition salts. ### Claim 15 (depends on 3) The compound of claim 3 wherein R is acetyl and R.sup.1 is pivaloyl and its acid addition salts. ### Claim 16 (depends on 3) The compound of claim 3 wherein R is acetyl and R.sup.1 is methoxycarbonyl and its acid addition salts. ### Claim 17 (depends on 3) The compound of claim 3 wherein R is hydrogen and R.sup.1 is methoxycarbonyl and its acid addition salts. ### Claim 18 (depends on 3) The compound of claim 3 wherein R is hydrogen and R.sup.1 is [(8-amino-n-octyl)amino]carbonyl and its acid addition salts. ### Claim 19 (depends on 3) The compound of claim 3 wherein R is hydrogen and R.sup.1 is [(3-hydroxy-n-propyl)amino]carbonyl and its acid addition salts. ### Claim 20 (depends on 2) A compound of claim 2 wherein R.sup.2 is halo and the acid addition salts thereof. ### Claim 21 (depends on 20) The compound of claim 20 wherein R is acetyl and R.sup.1 is trichloroacetyl and its acid addition salts. ### Claim 22 (depends on 2) A compound of claim 2 wherein R.sup.2 is phenyl and the acid addition salts thereof. ### Claim 23 (depends on 22) The compound of claim 22 wherein R is acetyl and R.sup.1 is phenylacetyl and its acid addition salts. ### Claim 24 (depends on 22) The compound of claim 22 wherein R is hydrogen and R.sup.1 is phenylacetyl and its acid addition salts. ### Claim 25 (depends on 22) The compound of claim 22 wherein R is acetyl and R.sup.1 is cinnamoyl and its acid addition salts. ### Claim 26 (depends on 22) The compound of claim 22 wherein R is acetyl and R.sup.1 is phenoxyacetyl and its acid addition salts. ### Claim 27 (depends on 22) The compound of claim 22 wherein R is acetyl and R.sup.1 is phenylpropionyl and its acid addition salts. ### Claim 28 (depends on 22) The compound of claim 22 wherein R is acetyl and R.sup.1 is p-chlorophenylacetyl and its acid addition salts. ### Claim 29 (depends on 22) The compound of claim 22 wherein R is acetyl and R.sup.1 is p-nitrophenylacetyl and its acid addition salts. ### Claim 30 (depends on 22) The compound of claim 22 wherein R is phenylacetyl and R.sup.1 is phenylacetyl and its acid addition salts. ### Claim 31 (depends on 22) The compound of claim 22 wherein R is acetyl and R.sup.1 is phenyl-n-valeryl and its acid addition salts. ### Claim 32 (depends on 22) The compound of claim 22 wherein R is acetyl and R.sup.1 is 2,5-dimethoxyphenylacetyl and its acid addition salts. ### Claim 33 (depends on 22) The compound of claim 22 wherein R is acetyl and R.sup.1 is benzylaminocarbonyl and its acid addition salts. ### Claim 34 (depends on 2) A compound of claim 2 wherein R.sup.2 is adamantyl and the acid addition salts thereof. ### Claim 35 (depends on 34) The compound of claim 34 wherein R is acetyl and R.sup.1 is adamantonoyl and its acid addition salts. ### Claim 36 (depends on 2) A compound of claim 2 wherein R.sup.2 is a monocyclic heterocyclic ring system comprising 3 to 8 atoms and the acid addition salts thereof. ### Claim 37 (depends on 36) The compound of claim 36 wherein R is hydrogen and R.sup.1 is (4-hydroxy-1-piperidinyl)carbonyl and its acid addition salts. ### Claim 38 (depends on 36) The compound of claim 36 wherein R is acetyl and R.sup.1 is [[2-(4-morpholinyl)ethyl]amino]carbonyl and its acid addition salts. ### Claim 39 (depends on 36) The compound of claim 36 wherein R is acetyl and R.sup.1 is 1H-imidazol-1-ylcarbonyl and its acid addition salts. ### Claim 40 (depends on 36) The compound of claim 36 wherein R is hydrogen and R.sup.1 is 1H-imidazol-1-ylcarbonyl and its acid addition salts. ### Claim 41 (depends on 1, 2, 3, 20) A method for controlling susceptible gram-positive infections which comprises administering to an infected or susceptible warm-blooded animal an effective amount of a composition comprising a compound of claim 1, 2, 3, 20, or 36 or a pharmaceutically acceptable acid addition salt thereof and a suitable pharmaceutical vehicle. ### Claim 42 (depends on 1, 2, 3, 20) A composition for the control of susceptible gram-positive infections comprising an amount of a compound of claim 1, 2, 3, 20, or 36 or a pharmaceutically acceptable acid addition salt thereof which is effective against such infections and a suitable pharmaceutical vehicle.