Sankyo Company, Limited

Rokuro Endo

Isao Kawamoto

Masao Miyauchi

Satoshi Ohya

Eiji Nakayama

Yukio Utsui

Masayuki Iwata

Hiroshi Yasuda

Teruo Tanaka

Katsuya Ishikawa

Katsuhiko Watanabe

Takeshi Oshima

Shigeru Ushiyama

Keiichi Matsuda

Compound of formula (I): ##STR1## wherein R.sup.1 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl or --C(.dbd.NH)R.sup.0 where R.sup.0 is hydrogen or C.sub.1 -C.sub.6 alkyl;

Carbapenem derivatives, their preparation and their use as antibiotics

Compounds of formula (I): ##STR1## wherein R.sup.1x is hydrogen or methyl, R.sup.2x is hydrogen optionally substituted aliphatic hydrocarbon or acylimidoyl, R.sup.3x is hydrogen or an ester group, and Q.sup.x is cyclic or acyclic nitrogen-containing group. The compounds are potent antibiotics which are resistant to dehydropeptidase I, and are thus useful for the treatment of many microbial infections.

Carbapenem compounds of formula (I): ##STR1## [in which: A is a fully saturated heterocyclic group, of which at least one ring atom is nitrogen; R.sup.1 is hydrogen or methyl; R.sup.2 is hydrogen or alkyl; R.sup.3 is hydrogen or a negative ion; Q is: (i) --B--N.sup.+ R.sup.8 R.sup.9 R.sup.10, where R.sup.8, R.sup.9 and R.sup.10 are alkenyl, alkynyl or optionally substituted alkyl, and B is alkylene or alkylidene; (ii) a heterocyclic group of which one ring atom is a &gt;N.sup.+ R.sup.11 R.sup.12, where R.sup.11 and R.sup.12 are alkenyl, alkynyl or optionally substituted alkyl; (iii) alkyl substituted by a heterocyclic group as defined in (ii) above; or (iv) alkyl substituted by an aromatic heterocyclic group, of which one ring atom is ##STR2## or R.sup.2 and Q, and the nitrogen to which they are attached, form a group of formula (II): ##STR3## where m and n are 1, 2 or 3; R.sup.6 is optionally substituted alkyl; and R.sup.7 is alkenyl, alkynyl or optionally substituted alkyl] and pharmaceutically acceptable salts and esters thereof have valuable antibacterial activity with enhanced resistance to dehydropeptidase I and .beta.-lactamase. Methods of preparing and using the compounds are also provided.

Carbapenem derivatives having antibiotic activity, their preparation and

Carbapenem compounds of formula (I): ##STR1## in which: A is a fully saturated heterocyclic group, of which at least one ring atom is nitrogen; R.sup.1 is hydrogen or methyl; R.sup.2 is hydrogen or alkyl; R.sup.3 is hydrogen or a negative ion; Q is: (i) --B--N.sup.+ R.sup.8 R.sup.9 R.sup.10, where R.sup.8, R.sup.9 and R.sup.10 are alkenyl, alkynyl or optionally substituted alkyl, and B is alkylene or alkylidene.

Compounds of formula (I): ##STR1## in which R.sup.a is a group of formula (II): ##STR2## where one of R' is a bond to the remainder of the compound, one more of R' is R.sup.2 and the others of R' are all hydrogen, R.sup.1 is hydrogen or methyl, R.sup.2 is hydrogen, optionally substituted alkyl, halogen, hydroxy, alkoxy, amino, alkanoylamino, alkanoyloxy, alkanoyl, carboxy, alkoxycarbonyl, cyano, --S(O).sub.j R.sup.9 where j is 0, 1 or 2 and R.sup.9 is alkyl, or --CONR.sup.6 R.sup.7 which is optionally substituted carbamoyl or heterocyclyl-carbonyl, --NR.sup.3 R.sup.4 is optionally substituted amino or heterocyclic, and --COOR.sup.5 is carboxy, --COO.sup.-, --COOM.sub.x, where M is a cation and x is the reciprocal of the valence of the cation M or protected carboxy and, where --COOR.sup.5 is carboxy, --COOM.sub.x or protected carboxy, the compound of formula (I) also contains an anion; l, m and n are independently 0, 1, 2 or 3, provided that (m+n) is an integer from 2 to 6; p is 0, 1 or 2; Y is a single bond, oxygen, sulfur or ##STR3## wherein R.sup.8 is hydrogen, alkyl or alkanoyl, and pharmaceutically acceptable salts and esters thereof. Such compounds are useful as antibiotics.

2-(heterocyclylthio) carbapenem derivatives, their preparation and their

Compounds of formula (I): ##STR1## in which R.sup.a is a group of formula (II): ##STR2## or a group of formula (III): ##STR3## (where one of R' is a bond to the remainder of the compound, one more of R' is R.sup.2 and the others of R' are all hydrogen), R.sup.1 is hydrogen or methyl, R.sup.2 is hydrogen, optionally substiuted alkyl, halogen, hydroxy, alkoxy, amino, alkanoylamino, alkanoyloxy, alkanoyl, carboxy, alkoxycarbonyl, cyano, --S(O).sub.j R.sup.9 (where j is 0, 1 or 2 and R.sup.9 is alkyl), or --CONR.sup.6 R.sup.7 (which is optionally substituted carbamoyl or heterocyclyl-carbonyl), R.sup.2a is hydrogen, alkyl or alkanoyl, --NR.sup.3 R.sup.4 is optionally substituted amino or heterocyclic, and --COOR.sup.5 is carboxy, --COO.sup.-, --COOM.sub.x (where M is a cation and x is the reciprocal of the valence of the cation M) or protected carboxy and, where --COOR.sup.5 is carboxy, --COOM.sub.x or protected carboxy, the compound of formula (I) also contains an anion; l, m and n are independently 0, 1, 2 or 3, provided that (m+n) is an integer from 2 to 6; p is 0, 1 or 2; Y is a single bond, oxygen, sulfur or R.sup.8 N&lt;(wherein R.sup.8 is hydrogen, alkyl or alkanoyl) and pharmaceutically acceptable salts and esters thereof are potentially valuable antibiotics.

2-(heterocyclylthio)carbapenem derivatives, their preparation and their

Compounds of formula (I): ##STR1## (wherein n is 0, 1 or 2 and R.sup.1, R.sup.2, R.sup.4, R.sup.5, R.sup.6, X, Y and Z are a variety of groups and atoms) have the ability to inhibit the synthesis of thromboxane A.sub.2 and hence are useful in the treatment or prophylaxis of thrombotic conditions.

Imidazole derivatives as inhibitors of TXA.sub.2 synthesis

Carbapenem derivatives useful as antibacterial agents have the formula ##STR1## wherein: X represents a hydrogen atom or a methyl group; and

Growing community of inventors

Tokyo, Japan

Rokuro Endo