KR920019800A - New cephalosporin antibiotics and preparation method thereof - Google Patents

Abstract

No content

Description

New cephalosporin antibiotics and preparation method thereof

Since this is an open matter, no full text was included.

Claims (24)

The cephalosporin compound represented by the following general formula (I), a pharmaceutically acceptable nontoxic salt thereof, physiologically hydrolysable esters thereof, hydrates, solvates and isomers thereof. In the above formula, R ¹ represents a C _1-4 alkyl group, C _3-4 alkenyl group, C _3-4 alkynyl group, or —C (R ^a ) (R ^b ) COOH. Wherein R ^a , R ^b may be the same or different and each represent hydrogen or a C _1-4 alkyl group, or R ^a and R ^b together with a carbon atom to which they are attached a C _3-7 cycloalkyl group, R ² represents a C _1-4 alkyl group, C _3-4 alkenyl group, C _3-7 cycloalkyl group or amino group. Q is CH or N. The compound according to claim 1, wherein (6R, 7R) -7 [(Z) -2- (5-amino-1, 2, 4-thiadiazol-3-yl) -2- (ethoxyamino) acetamido ] -3- (2, 6-diamino-1-methylpyrimidin-4-yl) thiomethyl-3-cepem-4-carboxylate, pharmaceutically acceptable non-toxic salt thereof, physiologically hydrolysable A compound of formula (I) which is an ester, hydrate or solvate thereof. The compound according to claim 1, wherein (6R, 7R) -7 [(Z) -2- (5-amino-1, 2, 4-thiadiazol-3-yl) -2- (ethoxyamino) acetamido ] -3- (2,6-diamino-1-ethylpyrimidin-4-yl) thiomethyl-3-cepem-4-carboxylate, pharmaceutically acceptable non-toxic salt thereof, physiologically hydrolysable A compound of formula (I) which is an ester, hydrate or solvate thereof. The composition of claim 1, wherein (6R, 7R) -7 ((Z) -2- (2-aminothiazol-4-yl) -2- (carboxyprop-2-oxyamino) acetamido] -3 -(2, 6-diamino-1-methylpyrimidin-4-yl) thiomethyl-3-cepem-4-carboxylate, pharmaceutically acceptable non-toxic salt thereof, novelly hydrolysable ester thereof, A compound of formula (I) which is a hydrate or solvate. The composition of claim 1, wherein (6R, 7R) -7 ((Z) -2- (2-aminothiazol-4-yl) -2- (carboxyprop-2-oxyamino) acetamido] -3 -(2, 6-diamino-1-ethylpyrimidin-4-yl) thiomethyl-3-cepem-4-carboxylate, pharmaceutically acceptable nontoxic salt thereof, physiologically hydrolysable ester thereof, A compound of formula (I) which is a hydrate or solvate. (6R, 7R) -7 ((Z) -2- (2-aminothiazol-4-yl) -2- (2-propyn-1-oxyamino) acetamido] according to claim 1- 3- (2, 6-diamino-1-methylpyrimidin-4-yl) thiomethyl-3-cepem-4-carboxylate, pharmaceutically acceptable nontoxic salt thereof, physiologically hydrolysable ester thereof , Hydrate or solvate. The compound of claim 1, wherein (6R, 7R) -7 [(Z) -2- (2-aminothiazol-4-yl) -2- (2-propyn-1-oxyamino) acetami] -3 -(2, 6-diamino-1-ethylpyrimidin-4-yl) thiomethyl-3-cepem-4-carboxylate, pharmaceutically acceptable nontoxic salt thereof, physiologically hydrolysable ester thereof, A compound of formula (I) which is a hydrate or solvate. (6R, 7R) -7 ((Z) -2- (2-aminothiazol-4-yl) -2- (2-propene-1-oxyamino) acetamido] according to claim 1- 3- (2, 6-diamino-1-methylpyrimidin-4-yl) thiomethyl-3-cepem-4-carboxylate, pharmaceutically acceptable nontoxic salt thereof, physiologically hydrolysable ester thereof , Hydrate or solvate. A compound according to claim 1, wherein (6R, 7R) -7 [(Z) -2- (2-aminothiazol-4-yl) -2- (carboxymethoxyamino) acetamido] -3- (2, 6-diamino-1-methylpyrimidin-4-yl) thiomethyl-3-cepem-4-carboxylate, pharmaceutically acceptable nontoxic salt thereof, physiologically hydrolysable ester, hydrate or solvate thereof Phosphorus compound of general formula (I). A compound according to claim 1, wherein (6R, 7R) -7 [(Z) -2- (2-aminothiazol-4-yl) -2- (carboxymethoxyamino) acetamido] -3- (2, 6-diamino-1-ethylpyrimidin-4-yl) thiomethyl-3-cepem-4-carboxylate, pharmaceutically acceptable nontoxic salt thereof, physiologically hydrolysable ester, hydrate or solvate thereof Phosphorus compound of general formula (I). The compound according to claim 1, wherein (6R, 7R) -7 [(Z) -2- (2-aminothiazol-4-yl) -2- (R, S-carboxyl-1-oxyimino) acetamido ] -3- (2,6-diamino-1-methylpyrimidin-4-yl) thiomethyl-3-cepem-4-carboxylate, pharmaceutically acceptable non-toxic salt thereof, physiologically hydrolysable A compound of formula (I) which is an ester, hydrate or solvate thereof. The compound according to claim 1, wherein (6R, 7R) -7 [(Z) -2- (2-aminothiazol-4-yl) -2- (R, S-carboxyl-1-oxyimino) acetamido ] -3- (2, 6-diamino-1-ethylpyrimidin-4-yl) thiomethyl-3-cepem-4-carboxylate, pharmaceutically acceptable non-toxic salt thereof, physiologically hydrolysable A compound of formula (I) which is an ester, hydrate or solvate thereof. A compound according to claim 1, wherein (6R, 7R) -7 [(Z) -2- (2-aminothiazol-4-yl) -2- (methoxyamino) acetamido] -3- (2, 6 -Diamino-1-methylpyrimidin-4-yl) thiomethyl-3-cepem-4-carboxylate, a pharmaceutically acceptable nontoxic salt thereof, a physiologically hydrolysable ester, hydrate or solvate thereof Compound of general formula (I). A compound according to claim 1, wherein (6R, 7R) -7 [(Z) -2- (2-aminothiazol-4-yl) -2- (methoxyamino) acetamido] -3- (2, 6 -Diamino-1-ethylpyrimidin-4-yl) thiomethyl-3-cepem-4-carboxylate, a pharmaceutically acceptable non-toxic salt thereof, its ester, hydrate or solvate hydrolyzable to physiology Compound of general formula (I). The composition of claim 1, wherein (6R, 7R) -7 ((Z) -2- (2-aminothiazol-4-yl) -2- (carboxyprop-2-oxyamino) acetamido] -3 -(2, 6-diamino-1-aminopyrimidin-4-yl) thiomethyl-3-cepem-4-carboxylate, a pharmaceutically acceptable non-toxic salt thereof, its ester hydrolyzable by physiology, A compound of formula (I) which is a hydrate or solvate. A compound of formula (I), a pharmaceutically acceptable non-toxic salt thereof, physiologically hydrolysable, characterized by reacting a compound of formula (II) with a compound of formula (III) in the presence of a solvent Process for preparing esters, hydrates or solvates thereof. In the formula, R ¹ represents a C _1-4 alkyl group, C _3-4 alkynyl group, C _3-4 alkynyl group, or —C (R ^a ) (R ^b ) COOH. Wherein R ^a , R ^b can be the same or different and each represents hydrogen or a C _1-4 alkyl group, or R ^a and R ^b represent a C _3-7 cycloalkyl group together with the carbon atom to which they are attached. n is 0 or 1; R ² represents a C _1-4 alkyl group, C _3-4 alkenyl group, C _3-7 cycloalkyl group or amino group, and R ³ is hydrogen or an aminoprotecting group; R ⁴ is hydrogen or a carboxyl protecting group, R ⁵ is a C _1-4 alkyl group, C _3-4 alkenyl group, C _3-4 alkynyl group or -C (R ^a ) (R ^b ) -COO (R ^c ) group to be. R ^a , R ^b may be the same or different and each represent hydrogen or a C _1-4 alkyl group, or R ^a and R ^b together with a carbon atom to which they are attached represent a C _3-7 cycloalkyl group, R ^c is hydrogen or a carboxyl protecting group, Q is CH or N and L is a leaving group. The method of claim 16 wherein the solvent used is water or a mixed aqueous solution of water and a water miscible solvent. 18. The method of claim 17, wherein the water miscible solvent is acetonitrile, acetone. 17. The method of claim 16, wherein the amount of the compound of formula (III) is 1 to 2 equivalents based on the compound of formula (II). The method of claim 16, wherein the pH of the reaction solvent is 5-8. The method of claim 16 wherein the reaction is carried out in the presence of a stabilizer. 22. The method of claim 21, wherein the stabilizing agent is one or more selected from sodium iodide, potassium iodide, bromosodium, bromopotassium or potassium thiocyanate. The method according to claim 16, wherein the amino protecting group or acid protecting group is removed or the S-oxide is reduced before or after reacting the compound of formula (II) with the compound of formula (III). A therapeutically effective amount and pharmaceutically acceptable amount of at least one of the compound as defined in claim 1, pharmaceutically acceptable nontoxic salt thereof, physiologically hydrolysable ester, hydrate or solvate thereof as an active ingredient. Pharmaceutical composition, characterized in that consisting of a carrier, excipient or other additives that can be. ※ Note: The disclosure is based on the initial application.