Abstract: The present invention comprises compounds having the general formula I: 1

Abstract: Disclosed are compounds of the formula: wherein R3, R6a, R6b and R8 are substituted as disclosed herein. The compounds are effective in effecting PDE IV inhibition in patients in need thereof.

Abstract: A compound of the formula: wherein R2 is O or S; R3, R6a and R8 are the same or different and each represent a C1-8 alkyl which is unbranched or branched and unsubstituted or substituted with OH, alkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; C3-8 cycloalkyl which is unsubstituted or substituted with OH, alkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; C4-8 cycloalkylalkyl wherein the cycloalkyl portion is unsubstituted or substituted with OH, alkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; aryl which is unsubstituted or substituted with Cl, NH2, alkylamino, dialkylamino, amido, C1-C8 alkylamido, C1-C3 dialkylamido, OH, alkoxy, HC═NOH, HC═NOCONH2, C1-C3 alkyl, phenyl or benzyl; aralkyl (C1-4); heterocyclyl; heterocyclylalkyl (C1-C4); and heteroaryl; R6b represents a H or R6a, or together R6b, N, and R6a make a 3 to 8 member ring containing at least one carbon, from one to three nitrogen atoms, from zero to two oxygen atoms, from zero to two sulfur atoms, said ring op

Abstract: A compound of the formula: wherein R3 represent a C1-8 alkyl which is unbranched or branched and unsubstituted or substituted with OH, alkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; C3-8 cycloalkyl which is unsubstituted or substituted with OH, alkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; C4-8 cycloalkylalkyl wherein the cycloalkyl portion is unsubstituted or substituted with OH, alkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; aryl which is unsubstituted or substituted with Cl, NH2, alkylamino, dialkylamino, amido, C1-C8 alkylamido, C1-C3 dialkylamido, OH, alkoxy, HC═NOH, HC═NOCONH2, C1-C3 alkyl, phenyl or benzyl; aralkyl (C1-4); heterocyclyl; heterocyclylalkyl (C1-C4); and heteroaryl; R8 represents H or a C1-8 alkyl which is unbranched or branched and unsubstituted or substituted with OH, alkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; C3-8 cycloalkyl which is unsubstituted or substituted with OH, alkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; C4-8 cyclo

Abstract: With the above and other objects in view, the present invention comprises compounds having the general formula (I): wherein: R1 is a C2-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkenyl or cycloalkynyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl or cycloalkynyl is optionally substituted with hydroxy, C1-5 alkoxy, C3-5 cycloalkoxy, halogen, oxo, carbamido, hydroxycarbamido, oximido, C1-5 alkyloximido, C3-5 cycloalkyloximido, C1-5 acyloximido or C3-5 cycloacyloximido; Q is methylene or ethylene; R3 is aryl or heteroaryl wherein said aryl or heteroaryl has one to three substituents selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, cycloalkynyl, C3-5 alkylene, C3-5 cycloalkylene, haloC1-6 alkyl, haloC1-6 cycloalkyl, hydroxy, C1-5 alkoxy, C3-5 cycloalkoxy, C1-2 alkylenedioxy, C1-6 acyl, C3-6 cycloacyl, C1-6 acyloxy, C3-6 cycloacyloxy, halogen, nitro or cyano; R8 is C1-5 alkyl or C3-5 cycl

Abstract: Disclosed are compounds of the formula (I): wherein R3 is selected from the group consisting of C1-10 alkyl, C1-10 alkenyl, C3-10 cycloalkyl, C4-10 cycloalkylalkyl or C3-10 cycloalkenyl, wherein said alkyl, alkenyl, cycloalkyl, cycloalkylalkyl or cycloalkenyl is optionally substituted in one position with hydroxy; or benzyl, wherein said benzyl is optionally substituted in one or two positions with halogen, alkoxy, cycloalkoxy or polycycloalkyl, and wherein said alkyl moiety of said alkoxy or cycloalkoxy substituent is optionally substituted in one position with hydroxy; R8 is selected from the group consisting of hydrogen, C1-10 alkyl, C1-10 alkenyl, C3-10 cycloalkyl, C4-10 cycloalkylalkyl or C3-10 cycloalkenyl, wherein said alkyl, alkenyl, cycloalkyl, cycloalkylalkyl or cycloalkenyl is optionally substituted in one position with hydroxy; or benzyl, wherein said benzyl is optionally substituted in one or two positions with halogen, alkoxy, cycloalkoxy or polycycloalkyl, and wherein said a

Abstract: The present invention comprises compounds having the general formula I: wherein: Y, is N or CH Z is selected from the group consisting of alkyl groups such as alkylene groups such as CH2, CH2CH2, CH(CH3); alkenyl groups such as CH═CH; alkynyl groups such as C≡C; and NH, N(C1-C3 alkyl), O, S, C(O)CH2 and OCH2; R1 and R2 are selected from the group consisting of hydrogen and a C1-C8 straight or branched alkyl or a C3-C8 cycloalkyl; R3 is a C3-C12 straight or branched alkyl; R4 is a C3-C10 cycloalkyl optionally substituted with OH or C3-C10 cycloalkenyl optionally substituted with OH; and R8 is a C1-C8 straight or branched alkyl or a C3-C8 cycloalkyl, optionally substituted with OH; and methods of synthesis.

Abstract: Novel compounds which are effective PDE IV inhibitors are disclosed. The present invention is directed to compounds having the general formula I ##STR1## wherein: X is a halogen;Q is --CH.sub.2 --CH.sub.2 --, --CH.sub.2 --, a single or a double bond, or --NR.sub.1 --;R.sub.1 is a C.sub.

Abstract: Novel compounds which are effective PDE IV inhibitors are disclosed. The compounds possess improved PDE IV inhibition as compared to theophylline or rolipram as well as with improved selectivity with regard to PDE III inhibition. In certain aspects of the invention, the compounds also demonstrate PDE V inhibition. Pharmaceutical compositions containing the same and methods of treatment are also disclosed.

Abstract: The present invention comprises methods of synthesizing compounds having the formula I: ##STR1## wherein: Y.sub.1, Z, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.8 are as described herein, which comprises the steps of(a) reacting a compound of the formula III ##STR2## with a base to cause cyclization to compound IV ##STR3## (b) transforming said hydroxy group of said compound IV to an amine by successive halogenation by a halogenating agent and displacement of the resultant halogen with an amide to form compound V ##STR4## (c) reacting said compound V with an effective amount of compound VI ##STR5## to form the compound of formula 1.

Abstract: The present invention comprises a method of synthesizing compounds having the formula (I): ##STR1## wherein: Z, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.8 are defined herein, which comprises the steps of(a) reacting a compound of the formula (II) ##STR2## wherein Q is a halogen, with an effective amount of a compound selected from the group consisting of an acid anhydride or an acid halide; to form a compound of the formula (III) ##STR3## b) transforming the 6-halo group of said compound (III) to an amine by displacement with ammonia to form compound (IV) ##STR4## (c) reacting said compound (IV) with a base to cause cyclization to a 6-halo intermediate, said 6-halo group is then transformed to an amine by displacement with an amine to form compound (V) ##STR5## (d) reacting said compound (V) with an effective amount of compound (VI) ##STR6## wherein X is a halogen; to form the compound of formula (I).

Abstract: The present invention comprises a method of synthesizing compounds of formula (I): wherein Z, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.8 are as described herein; comprising the steps of.

Abstract: Rolipram-based PDE IV inhibitors containing phenyl- or benzyl-substituted moieties of the formula: ##STR1## wherein X.sub.1 and X.sub.2 may be the same or different and each is O or S;R.sub.1 is selected from the group consisting of hydrogen, saturated or unsaturated straight-chain or branched C.sub.2-12 alkyl groups, cycloalkyl and cycloalkyl-alkyl groups containing from 3 to 10 carbon atoms in the cycloalkyl moiety;R.sub.2 =R.sub.1 or --CH.sub.3 ;R.sub.3 is hydrogen, halogen, or a saturated or unsaturated straight-chain or branched C.sub.1-12 alkyl group, a cycloalkyl or cycloalkyl-alkyl groups containing from 3 to 7 carbon atoms in the cycloalkyl moiety;Z is a linkage selected from --CH.sub.2 CONH-- or --CH.sub.2 NHCO--, andR.sub.

Abstract: The invention provides amide derivatives of the general formula (I) ##STR1## wherein R.sup.1 is a hydrogen atom or a C.sub.1-6 alkyl group; Y represents a group --(CH.sub.2).sub.m --, where m represents 2, 3 or 4 or a group --X(CH.sub.2).sub.p, where p represents 2 or 3, X represents an oxygen or a sulphur atom or a group NR.sup.5, where R.sup.5 is a C.sub.1-6 alkyl group, and X is attached to the benzene ring moiety of the molecule; and Im represents an imidazolyl group of the formula: ##STR2## wherein one of the groups represented by R.sup.2, R.sup.3 and R.sup.4 is a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-6 alkenyl, phenyl or phenylC.sub.1-3 alkyl group, and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C.sub.1-6 alkyl group; and physiologically acceptable salts and solvates thereof.The compounds of formula (I) are potent and selective antagonists of 5-hydroxytryptamine at 5-HT.sub.

Abstract: The present invention provides ketones of the general formula (I): ##STR1## and physiologically acceptable salts and solvates thereof, wherein R.sup.1 and R.sup.2, which may be the same or different, each represents a hydrogen atom or a C.sub.1-6 alkyl group; Im represents an imidazolyl group of formula: ##STR2## wherein one of the groups represented by R.sup.3, R.sup.4 and R.sup.5 is a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-6 alkenyl, phenyl or phenylC.sub.1-3 alkyl group, and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C.sub.1-6 alkyl group; andA is a group of the formula (a), (b), (c), (d), (e), (f) or (g) as set forth hereinafter,and when A is the group (g), the group --COCR.sup.1 R.sup.2 CH.sub.2 Im is attached at the 2- or 4- position of the indole moiety.The compounds are potent and selective antagonists of the effect of 5-HT at 5-HT.sub.

Abstract: The invention relates to compounds of the general formula (I): ##STR1## wherein R.sup.1 and R.sup.2 together form a C.sub.3-5 alkylene chain and R.sup.3 is a hydrogen atom; orR.sup.1 and R.sup.3 together form a C.sub.2-4 alkylene chain and R.sup.2 is a hydrogen atom;A-B represents the group R.sup.4 R.sup.5 C--CH.sub.2 or R.sup.4 C.dbd.CH;R.sup.4 and R.sup.5, which may be the same or different, each represent a hydrogen atom or a C.sub.1-6 alkyl group; andIm represents an imidazolyl group of formula: ##STR2## wherein one of the groups represented by R.sup.6, R.sup.7 and R.sup.8 is a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-6 alkenyl, phenyl or phenylC.sub.1-3 alkyl group and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C.sub.1-6 alkyl group; and physiologically acceptable salts and solvates thereof.The compounds are potent and selective antagonists of the effect of 5-HT at 5-HT.sub.

Abstract: The invention relates to indole derivatives of the general formula (I) ##STR1## wherein Im represents an imidazolyl group of the formula: ##STR2## and R.sup.1 represents a hydrogen atom or a group selected from C.sub.1-6 alkyl, C.sub.3-6 alkenyl, C.sub.3-10 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkylC.sub.1-4 alkyl, phenyl or phenylC.sub.1-3 alkyl;R.sup.2 represents a hydrogen atom or a group selected from C.sub.1-6 alkyl, C.sub.3-6 alkenyl, C.sub.3-7 cycloalkyl, phenyl or phenylC.sub.1-3 alkyl;X represents an oxygen atom or the group NR.sup.3 (where R.sup.3 represents a hydrogen atom or a C.sub.1-6 alkyl group);one of the groups represented by R.sup.4, R.sup.5 and R.sup.6 is a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-6 alkenyl, phenyl or phenylC.sub.1-3 alkyl group, and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C.sub.1-6 alkyl group;Q represents a hydrogen or a halogen atom, or a hydroxy, C.sub.1-4 alkoxy, phenylC.sub.

Abstract: The invention provides imidazole derivatives of the general formula (I) ##STR1## wherein Im representes an imidazolyl group of the formula: ##STR2## and one of the groups represented by R.sup.3, R.sup.4 and R.sup.5 is a hydrogen atom, or a C.sub.1-6 alkyl, C.sub.3-7 cycoalkyl, C.sub.3-6 alkenyl, phenyl or phenylC.sub.1-3 alkyl group, and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C.sub.1-6 alkyl group;R.sup.1 and R.sup.2 each represent a hydrogen atom, or together with the carbon atoms to which they are attached form a phenyl ring;X represents an oxygen or a sulphur atom, or a group NR.sup.6, wherein R.sup.6 represents a C.sub.1-6 alkyl group;Z--Y represents the group CH--CH.sub.2 or C.dbd.CH;and physiologically acceptable salts and solvates thereof.The compounds of formula (I) are potent and selective antagonists of 5-hydroxytryptamine at 5-HT.sub.

Abstract: The invention relates to compounds of the general formula (I): ##STR1## wherein R.sup.1 and R.sup.2 together form a C.sub.3-5 alkylene chain and R.sup.3 is a hydrogen atom; orR.sup.1 and R.sup.3 together form a C.sub.2-4 alkylene chain and R.sup.2 is a hydrogen atom;A-B represents the group R.sup.4 R.sup.5 C--CH.sub.2 or R.sup.4 C.dbd.CH;R.sup.4 and R.sup.5, which may be the same or different, each represent a hydrogen atom or a C.sub.1-6 alkyl group; andIm represents an imidazolyl group of formula: ##STR2## wherein one of the groups represented by R.sup.6, R.sup.7 and R.sup.8 is a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-6 alkenyl, phenyl or phenylC.sub.1-3 alkyl group and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C.sub.1-6 alkyl group;and physiologically acceptable salts and solvates thereof.The compounds are potent and selective antagonists of the effect of 5-HT at 5-HT.sub.

Abstract: The invention relates to ketones of the general formula (I): ##STR1## wherein R.sup.1 represents a hydrogen atom or a group selected from C.sub.1-6 alkyl, C.sub.3-6 alkenyl, C.sub.3-10 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkylC.sub.1-4 alkyl, phenyl, phenylC.sub.1-3 alkyl, --CO.sub.2 R.sup.8, --COR.sup.8, --CONR.sup.8 R.sup.9 or --SO.sub.2 R.sup.8 (wherein R.sup.8 and R.sup.9, which may be the same or different, each represents a hydrogen atom, a C.sub.1-6 alkyl or C.sub.3-7 cycloalkyl group, or a phenyl or phenylC.sub.1-4 alkyl group, in which the phenyl group is optionally substituted by one or more C.sub.1-4 -alkyl, C.sub.1-4 alkoxy or hydroxy groups or halogen atoms, with the proviso that R.sup.8 does not represent a hydrogen atom when R.sup.1 represents a group --CO.sub.2 R.sup.8 or --SO.sub.2 R.sup.8);R.sup.2 represents a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-6 alkenyl, C.sub.3-7 cycloalkyl, phenyl or phenylC.sub.1-3 alkyl group;R.sup.3 and R.sup.