摘要:
Prostane derivatives of the formula ##STR1## wherein R.sub.1 is OR.sub.2 or NHR.sub.3 ;R.sub.2 is hydrogen, C.sub.1-10 alkyl, C.sub.4-10 cycloalkyl, C.sub.6-10 aryl, or a 5 or 6 membered heterocyclic ring having 1-3 hetero atoms selected from O, N and S;R.sub.3 is the residue of a hydrocarbon carboxylic or sulfonic acid of 1-15 carbon atoms;W is (a) an OH-substituted methylene group, (b) a ##STR2## wherein the OH-groups in (a) or (b) can be in the .alpha.- or .beta.-position, or (c) such a group wherein the H atom of the OH group is replaced by the residue of a hydrocarbon carboxylic or sulfonic acid of 1-15 carbon atoms or by a conventional etherifying OH-blocking group;R.sub.4 is OH or hydroxy whose H atom is replaced as defined for W; andR.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 each independently is hydrogen or alkyl of 1-5 carbon atoms; or R.sub.9 and R.sub.10 together represent a direct bond; and, when R.sub.11 is alkyl, R.sub.10 can also be chlorine;and, for a derivative wherein R.sub.2 is hydrogen, the salts thereof with physiologically compatible bases,have improved prostaglandin activity.
摘要:
Stabilized prostacyclins having a wide range of pharmacological activity and long duration of such activity, have the formula ##STR1## wherein R.sub.1 is (a) OR.sub.3, wherein R.sub.3 is hydrogen, alkyl, cycloalkyl, aryl or a heterocyclic residue; or (b) NHR.sub.4 wherein R.sub.4 is an acid residue;B is straight-chain or branched alkylene of 2-10 carbon atoms;A is --CH.sub.2 --CH.sub.2 --, cis--CH.dbd.CH--, trans--CH.dbd.CH-- or --C.tbd.C--,W is free or functionally modified hydroxymethylene or free or functionally modified ##STR2## wherein the OH-group can be in the .alpha.- or .beta.-position; D and E together are a direct bond; orD is straight-chain or branched alkylene of 1-5 carbon atoms; andE is oxygen or sulfur or a direct bond,R.sub.2 is alkyl, cycloalkyl, optionally substituted aryl or a heterocyclic group; andR.sub.5 is free or functionally modified hydroxy; and when R.sub.3 is hydrogen, the salts thereof with physiologically compatible bases.
摘要:
Carbacyclin derivatives of Formula I ##STR1## wherein R.sub.1 is OR.sub.2, wherein R.sub.2 is hydrogen, alkyl, cycloalkyl, aryl, a heterocyclic residue, or NHR.sub.3, wherein R.sub.3 is an acid residue or hydrogen;X is oxygen;A is --CH.sub.2 --CH.sub.2 --, trans--CH.dbd.CH--, or --C.tbd.C--;W is free or functionally modified hydroxymethylene or free or functionally modified ##STR2## wherein the OH-group can be in the .alpha.- or .beta.-position; D is a straight-chain or branched, saturated or unsaturated aliphatic group of 1-10 carbon atoms, which can optionally be substituted by fluorine atoms, 1,2-methylene, 1,1-trimethylene;E is --C.tbd.C-- or --CR.sub.6 .dbd.CR.sub.7 -- wherein R.sub.6 and R.sub.7 are hydrogen or alkyl of 1-5 carbon atoms;R.sub.4 is an aliphatic group, cycloalkyl, optionally substituted aryl, or a heterocyclic group;R.sub.5 is free or functionally modified hydroxy and,when R.sub.2 is hydrogen, the physiologically compatible salts thereof with bases, have valuable pharmacological properties.
摘要:
Carbacyclin derivatives of Formula I ##STR1## wherein R.sub.1 is OR.sub.2, wherein R.sub.2 is hydrogen, alkyl, cycloalkyl, aryl, a heterocyclic residue, or NHR.sub.3, wherein R.sub.3 is an acid residue or hydrogen;X is oxygen;A is --CH.sub.2 --CH.sub.2 --, trans--CH.dbd.CH--, or --C.tbd.C--;W is free or functionally modified hydroxymethylene or free or functionally modified ##STR2## wherein the OH-group can be in the .alpha.- or .beta.-position; D is a straight-chain or branched, saturated or unsaturated aliphatic group of 1-10 carbon atoms, which can optionally be substituted by fluorine atoms, 1,2-methylene, 1,1-trimethylene;E is --C.tbd.C-- or --CR.sub.6 .dbd.CH.sub.7 -- wherein R.sub.6 and R.sub.7 are hydrogen or alkyl of 1-5 carbon atoms;R.sub.4 is an aliphatic group, cycloalkyl, optionally substituted aryl, or a heterocyclic group;R.sub.5 is free or functionally modified hydroxy and,when R.sub.2 is hydrogen, the physiologically compatible salts thereof with bases, have valuable pharmacological properties.
摘要:
5-cyano-prostacyclins of the formula ##STR1## wherein R.sub.1 is OR.sub.2 or NHR.sub.3 ; R.sub.2 and R.sub.3 each independently is (a) H, (b) C.sub.1-10 -alkyl, (c) C.sub.1-10 -alkyl substituted by halo, C.sub.1-4 -alkoxy or phenyl, 1-naphthyl or 2-naphthyl, each optionally substituted as defined below, (d) C.sub.4-10 -cycloalkyl, (e) C.sub.4-10 -cycloalkyl substituted by C.sub.1-4 -alkyl, (f) phenyl, 1-naphthyl or 2-naphthyl, (g) phenyl, 1-naphthyl or 2-naphthyl substituted by 1-3 halogen atoms, phenyl, 1-3 alkyl groups of 1-4 C atoms each, or a chloromethyl-, fluoromethyl-, trifluoromethyl-, carboxyl-, hydroxy- or alkoxy-group of 1-4 C atoms, or (h) an aromatic, 5- or 6-membered heterocyclic ring containing one hetero atom which is O, N or S, the remaining atoms being carbon; R.sub.3 also possibly being an acyl group of a C.sub.1-15 -hydrocarbon carboxylic or sulfonic acid;B is straight chain or branched alkylene of 2-10 C atoms;W is hydroxymethylene or ##STR2## wherein the OH group may be in the alpha or beta position, and is optionally modified by replacement of the H atom of the OH with an ether or acyl group which is conventional for such replacements in prostaglandins and which is readily cleavable at physiological pH's;R.sub.4 is hydroxy, optionally modified as described for W above;R.sub.5, R.sub.6, R.sub.7 and R.sub.8 each independently is hydrogen, alkyl of 1-5 C atoms or methoxy; andR.sub.9 is alkyl of 1-5 C atoms orfor compounds wherein R.sub.2 is H, the salts thereof with physiologically compatible bases have valuable pharmacalogical properties, e.g., hypertonic and bronchodilatory activities.
摘要:
The invention relates to carbacyclins of general Formula I ##STR1## wherein R.sub.1 is the residue CH.sub.2 OH or ##STR2## with R.sub.2 meaning a hydrogen atom, an alkyl, cycloalkyl, aryl residue, a ##STR3## or heterocyclic residue, or R.sub.1 is the residue ##STR4## with R.sub.3 meaning an alkanoyl or alkanesulfonyl residue of respectively 1-10 carbon atoms or the residue R.sub.2, orR.sub.1 is the residue ##STR5## wherein m is the number 1 or 2, X is an oxygen atom or a CH.sub.2 -group,A is a trans--CH.dbd.CH- or --.tbd.C--group,W is a free or functionally modified hydroxymethylene group wherein the OH-group can be in the .alpha.- or .beta.- position,n is the number 1, 2, or 3,D is a straight-chain alkylene group of 1-5 carbon atoms,E is a --C.tbd.C---bond or a --CR.sub.6 =CR.sub.7 --group wherein R.sub.6 and R.sub.7 are different from each other and mean a hydrogen atom or an alkyl group of 1-5 carbon atoms or a hydrogen atom or a halogen atom, preferably chlorine,R.sub.4 is an alkyl, cycloalkyl, or optionally substituted arly group, or a heterocyclic group,R.sub.5 is a free or functionally modified hydroxy group, andif R.sub.2 means a hydrogen atom, the salts thereof with physiologically compatible bases;to processes for the preparation thereof, and to the use thereof as blood-pressure-lowering agents.
摘要:
Compounds of the formula ##STR1## wherein R.sub.1 is (a) hydrogen, (b) C.sub.1-10 alkyl, (c) C.sub.1-10 alkyl substituted by halogen; C.sub.1-4 alkoxy; C.sub.6-10 aryl; C.sub.6-10 aryl substituted by 1-3 halogen atoms, a phenyl group, 1-3 C.sub.1-4 alkyl groups or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C.sub.1-4 alkoxy group; di-C.sub.1-4 -alkylamino; or tri-C.sub.1-4 -alkylammonium, (d) C.sub.4-10 cycloalkyl, (e) C.sub.4-10 cycloalkyl substituted by C.sub.1-4 alkyl, (f) C.sub.6-10 aryl, (g) C.sub.6-10 aryl substituted by 1-3 halogen atoms, a phenyl group 1-3 C.sub.1-4 alkyl groups or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C.sub.1-4 alkoxy group, or (h) an aromatic heterocycle of 5 or 6 ring atoms one of which is O, N or S;A is --CH.sub.2 --CH.sub.2 --, trans--CH.dbd.CH-- or --C.tbd.C--;W is hydroxymethylene, RO-methylene, CH.sub.3 or CH.sub.3, ##STR2## wherein OH or OR is in the .alpha.- or .beta.-position and R is an in vivo hydrolyzable and physiologically acceptable ether or acyl group which is conventional for modifying OH groups in prostaglandins;D and E together are a direct bond, orD is C.sub.1-10 alkylene, C.sub.1-10 alkenylene or C.sub.1-10 alkynylene or one of these groups substituted by fluorine, andE is oxygen, --C.tbd.C-- or a direct bond;R.sub.2 is (a) a C.sub.1-10 hydrocarbon aliphatic radical, (b) a C.sub.6-10 hydrocarbon aliphatic radical substituted by C.sub.6-10 aryl or by C.sub.6-10 aryl substituted by 1-3 halogen atoms, a phenyl group, 1-3 C.sub.1-4 alkyl groups or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C.sub.1-4 alkoxy group; (c) C.sub.4-10 cycloalkyl, (d) C.sub.4-10 cycloalkyl substituted by C.sub.1-4 alkyl, (e) C.sub.6-10 aryl, (f) C.sub.6-10 aryl substituted by 1-3 halogen atoms, a phenyl group, 1-3 C.sub.1-4 alkyl groups or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C.sub.1-4 alkoxy group; or (h) an aromatic heterocycle of 5 or 6 ring atoms one of which is O, N or S; andR.sub.3 is OH or OR; and, when R.sub.1 is hydrogen, the salts thereof with physiologically compatible bases, are effective as antihypertensive, bronchiodilators, thrombocyte aggregation inhibitors, inter alia.
摘要:
Prostane derivatives of the formula ##STR1## wherein R.sub.1 is the residue OR.sub.2 and R.sub.2 is hydrogen, alkyl, cycloalkyl, aryl, or a heterocyclic residue; or is NHR.sub.3 wherein R.sub.3 is an acyl group derived from a hydrocarbon carboxylic or sulfonic acid of up to 15 carbon atoms;A is --CH.sub.2 --CH.sub.2 -- or cis--CH.dbd.CH--Z is carbonyl or ##STR2## wherein the OR.sub.4 group can be in the .alpha.- or .beta.-position and R.sub.4 is H or a hydroxy-protective groupX Y is ##STR3## wherein R.sub.4 is as defined above, --CH.sub.2 -- CH.sub.2 -- or --CH.sub.2 --CH-- wherein R.sub.5 is alkyl or 1-5 carbon atoms, if Z is R.sub.5 carbonyl or ##STR4## X Y represents --CH.dbd.CH-- if Z is carbonyl: R.sub.6, R.sub.7, R.sub.8, R.sub.9 and R.sub.10 each independently is hydrogen or an alkyl group of 1-5 carbon atoms; andR.sub.11 is alkyl of 1-5 carbon atoms;and if R.sub.2 is hydrogen, the salts thereof with physiologically compatible bases are prostaglandins having prolonged duration of activity and increased selectivity of effectiveness.
摘要:
Prostanoic acid esters of the formulaPG-- CH.sub.2 -- X-- Ywherein PG is the prostanoyloxy radical of a prostaglandin, X is a carbon-carbon single bond, carbonyl or carbonyloxy, and Y is substituted phenyl are easily crystallized compounds at least as active as the unesterified prostanoic acid and useful for the purification of the parent prostaglandin are prepared by reacting, in the presence of an agent which splits off hydrogen halide, the unesterified prostaglandin with a halide of the formula Hal--CH.sub.2 --X--Y, wherein Hal is a halogen atom and X and Y have the values given above.
摘要:
Prostaglandins of the formula ##SPC1##Wherein R.sub.1 is HOCH.sub.2, --COOH, a salt thereof or an ester thereof; R.sub.2 is OH; and R.sub.3 is H or R.sub.2 and R.sub.3 collectively are = O. A is --CH.sub. 2 --CH.sub.2 -- or --(trans)--CH=CH--, B is --CH.sub. 2 CH.sub.2 --or --(cis)--CH=CH-- and R.sub.4 --O--O--R.sub.5 is a ketal group, are superior in physiological activity to the corresponding 15-.alpha.-hydroxy-prostaglandins.