Abstract: Novel compounds and pharmaceutical compositions thereof, and methods of using same in treating anxiety, depression, and other psychiatric and neurological disorders. The novel compounds provided by this invention are those of the following formulae: wherein R1, R13, X, Y, Z, G and Q are as defined herein.

Abstract: A process for preparing 7-benzylpurine derivatives is provided. An acetylpurine nucleoside is reacted with a benzyl halide to benzylate the 7-position of the purine base, and an acid is then added to the reaction mixture to hydrolyze the glycoside bond. The 7-benzylpurines may be used to prepare 9-substituted purine derivatives.

Abstract: The present invention provides a process for the synthesis of penciclovir and famciclovir by 9-substituting 2-amino-6-chloropurine (ACP) with an appropriate side chain precursor, followed by conversion of the 6-chloro moiety to a hydroxy moiety (i.e. to form a guanine) or hydrogen (to form a 2-aminopurine), respectively.

Abstract: Purine derivatives in which a desired substituent is introduced into the 9-position only are synthesized by first introducing an easily-removable substituent in the 7-position of a purine base of natural purine nucleosides obtained through fermentation or derivatives thereof, then hydrolyzing the ribose moiety to form purine derivatives having the substituent in the 7-position, subsequently introducing the desired substituent in the 9-position, and then removing the substituent in the 7-position.

Abstract: A process for the preparation of guanine, by reacting 2,4-diamino-5-formylamino-6-hydroxypyrimidine (DAFHP) with formic acid, in the absence of formalize. The process may be conducted with the addition of water and at reflux temperature.

Abstract: Processes for the preparation of 1,3-oxathiolane nucleosides are provided that include efficient methods for the preparation of the 1,3-oxathiolane ring and subsequent condensation of the 1,3-oxathiolane with a pyrimidine or purine base. Using the processes described herein, the compounds can be provided as isolated enantiomers.

Abstract: A process for preparing guanine, in which 2,4-diamino-5-formylamino-6-hydroxypyrimidine (DAFHP) in formic acid is reacted at superatmospheric pressure, optionally in the absence of formamide and/or in the presence of catalytic amounts of an additive which acts as a reducing agent.

Abstract: The novel process of this invention involves the stereoselective synthesis of certain 16-substituted 4-aza-5&agr;-androst-1-en-3-ones, and the useful intermediates obtained therein.

Abstract: Methods and novel intermediates of the formula: wherein R6 and R7 are lower alkyl or benzyl or R6 and R7 taken together are —CH2CH2—, —CH2CH2CH2— or —CH2CH2CH2CH2CH2—, R8 is C1-C21 alkyl or a C2-C21 monounsaturated alkenyl, which may optionally be substituted with substitution substituents independently selected from the group consisting of hydroxy, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkoxy C1-C6 alkyl, C1-C6 alkanoyl, amino, halo, cyano, azido, oxo, mercapto and nitro, and R9 is an alcohol protecting group. The intermediates are useful for the preparation of acyclic nucleoside derivatives of the formula: where one of R1 and R2 is an amino acid acyl group and the other of R1 and R2 is a —C(O)C3-C21 saturated or monounsaturated, optionally substituted alkyl and R3 is OH or H; or a pharmaceutically acceptable salt thereof.

Abstract: Disclosed are processes for preparing compounds of the formula (I) and pharmaceutically acceptable salts or esters thereof: wherein R2 is a purine or pyrimidine base or an analogue or derivative thereof; and Z is S, S═O or SO2. The invention also relates to intermediates of use in the preparation of these compounds.

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: A purine derivative having a cyclopropane ring represented by the formula (I): ##STR1## wherein A is --CH.sub.2 -- group or --CO-- group; X.sup.1 is hydrogen atom, a halogen atom, an alkoxy group having 1 to 10 carbon atoms, or hydroxyl group; each of X.sup.2, X.sup.3, and X.sup.4 is independently hydrogen atom or a halogen atom; R.sup.1 is hydrogen atom, a halogen atom, or a protected or unprotected amino group; and each of R.sup.2 and R.sup.3 is independently hydrogen atom, a substituted or unsubstituted alkyl group having 1 to 7 carbon atoms, a substituted or unsubstituted aralkyl group, having 7 to 11 carbon atoms, or a substituted or unsubstituted acyl group having 1 to 7 carbon atoms, with proviso that in a case where A is --CO-- group, neither R.sup.2 nor R.sup.3 is a substituted or unsubstituted acyl group having 1 to 7 carbon atoms, and each of X.sup.3 and X.sup.4 is independently a halogen atom, and a process for preparing the same.

Abstract: A monoester compound of formula I:Nu--O--Fawherein O is oxygen, Nu is a nucleoside analog, Fa is an acyl group of a mono-unsaturated C18 or C20 omega-9 fatty acid, which fatty acid is esterified with a hydroxyl group in the 5'-position of the sugar moiety of the nucleoside analog or with a terminal hydroxyl group on the non-cyclic group of the nucleoside analog, and wherein Nu is represented by the formula II:B--Swherein S is a mono-saccharide derivative and B is a heterocyclic ring system.

Abstract: Corticotropin releasing factor (CRF) antagonists of formula (I): ##STR1## and their use in treating psychiatric disorders and neurological diseases, anxiety-related disorders, post-traumatic stress disorder, supranuclear palsy and feeding disorders as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress in mammals.

Abstract: A method is disclosed for preparing novel purine PNA synthons having protecting groups which may be removed under mild conditions. The purine PNA synthons generally are prepared by coupling purine derivatives having carbamate protection to a protected N-(2-aminoethyl)-glycine backbone. By a method of this invention, purine PNA synthons may have orthogonal protection of the carbamate protected purine and the protected backbone. The purine PNA synthons are useful in the synthesis of peptide nucleic acids (PNAs) and other oligomers such as PNA-DNA chimeras, and may be used in automated synthesizers. In practicing methods of the invention, novel compositions of matter also are disclosed.

Abstract: Nucleotide analogues having the general formula (I) and pharmaceutically acceptable derivatives: ##STR1## wherein n is 0 or an integer; X is O or S, CH.sub.2, CH--halogen, CH--N.sub.3, or C.dbd.CH.sub.2 ;Q and U are independently selected from: O, S, and CH(R.sub.a) wherein R.sub.a is hydrogen, OH, halogen, N.sub.3, NH.sub.2, SH, carboxyl, C.sub.1-6 alkyl or R.sub.a is CH.sub.2 (R.sub.b) wherein R.sub.b is hydrogen, OH, SH, NH.sub.2, C.sub.1-6 alkyl or carboxyl; or both Q and U are CH when Q and U are linked by a double bond;Z is selected from: O, a C.sub.1-6 alkoxy, a C.sub.1-6 thioalkyl, a C.sub.1-6 aminoalkyl, (CH.sub.2).sub.m wherein m is 0 or an integer, and N(R.sub.c).sub.2 wherein both R.sub.c are independently hydrogen or a C.sub.1-6 alkyl; andR2 is a purine or pyrimidine base or an analogue or derivative thereof. Members of this series of analogues possess anti-viral activity.

Abstract: The present invention is directed compositions of the formula: ##STR1## wherein: D is a residue of a biologically active moiety;X is an electron withdrawing group;Y and Y' are independently O or S;(n) is zero (0) or a positive integer, preferably from 1 to about 12;R.sub.1 and R.sub.2 are independently selected from the group consisting of H, C.sub.1-6 alkyls, aryls, substituted aryls, aralkyls, heteroalkyls, substituted heteroalkyls and substituted C.sub.1-6 alkyls;R.sub.3 is a substantially non-antigenic polymer, C.sub.1-12 straight or branched alkyl or substituted alkyl, C.sub.5-8 cycloalkyl or substituted cycloalkyl, carboxyalkyl, carboalkoxy alkyl, dialkylaminoalkyl, phenylalkyl, phenylaryl or ##STR2## R.sub.4 and R.sub.5 are independently selected from the group consisting of H, C.sub.1-6 alkyls, aryls, substituted aryls, aralkyls, heteroalkyls, substituted heteroalkyls, and substituted C.sub.1-6 alkyls or jointly form a cyclic C.sub.5 -C.sub.7 ring.

Abstract: A pure (-)-9-[1'S, 2'R-bis(hydroxymethyl)cyclopropan-1'-yl]methylguanine is prepared by:suspending or dissolving a mixture comprising (-)-9-[1'S, 2'R-bis(hydroxymethyl)cyclopropan-1'-yl]methylguanine and (7-[1'S,2'R-bis(hydroxymethyl)cyclopropan-1'-yl]methylguanine in an alcohol or a hydrous alcohol, reacting the resulting suspension or solution with an alkali metal hydroxide or alkoxide, and selectively precipitating crystals of nucleic acid derivatives of formula (I) ##STR1## wherein M represents an alkali metal.

Abstract: The invention relates to an anhydrous crystalline form of (2-[2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy]ethyl L-valinate hydrochloride (otherwise known as valaciclovir hydrochloride) and a process for preparing it.

Abstract: Intermediates of Formula (III) ##STR1## wherein P.sup.1 is hydrogen or an amino-protecting group, R is lower alkyl, allyl or aralkyl, and Z is hydrogen, lower alkyl, aryl or aralkyl; and Formula (VI) ##STR2## wherein P.sup.1 is hydrogen or an amino-protecting group, P.sup.2 is an amino protecting group, and Z is hydrogen, lower alkyl, aryl or aralkyl, are useful in a novel process for preparing the mono-L-valine ester of 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol (ganciclovir). The mono-L-valine ester of ganciclovir and its pharmaceutically acceptable salts are of value as antiviral agents with improved absorption.

Abstract: A phosphodiesterase IV inhibiting cathecol derivatives of the general formula I: ##STR1## or a pharmaceutically acceptable salt thereof in which R1 is C.sub.1-7 alkyl; C.sub.3-7 cycloalkane; phenyl optionally substituted with lower alkyl lower alkoxy, nitro or halogen; pyrimidine optionally substituted with lower alkyl, lower alkoxy, nitro or halogen; or pyridine optionally substituted with lower alkyl, lower alkoxy, nitro or halogen; X, Y and Z are each independently oxygen, nitrogen or sulfur optionally substituted with C.sub.1-7 alkyl, C.sub.3-7 cycloalkane or phenyl; W is oxygen or sulfur is disclosed. In addition, a process for producing the compound of the general formula I and a pharmaceutical composition containing pharmaceutically effective amount of the compound of the general formula I are disclosed.

Abstract: The present invention relates to 9-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)purine derivatives having antiviral activity, represented by formula [I]: ##STR1## wherein B represents a base selected from the group consisting of purine, azapurine and deazapurine, which may be substituted with halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, amino, alkylamino, hydroxyl, hydroxyamino, aminoxy, alkoxy, mercapto, alkylmercapto, aryl, aryloxy or cyano; and R represents a hydrogen atom or a phosphoric acid residue, and to a process for the production and use thereof.

Abstract: A process for preparing 2-amino-6-chloropurine or a 2-acylated derivative thereof, comprising reacting guanine or 2,9-diacylguanine with a chlorinating agent, in the presence of methyltriethylammonium chloride as phase transfer catalyst, and thereafter when necessary, removing the 9-acyl group by hydrolysis.

Abstract: 9-Substituted purine derivatives of formula (4) ##STR1## are prepared by debenzylating a compound of formula (3): ##STR2##

Abstract: The L-monovaline ester derived from 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol and its pharmaceutically acceptable salts are of value as antiviral agents with improved absorption.

Abstract: There are described N-ethylglycine derivatives of the formula I ##STR1## in which PG is a urethane-type or trityl-type amino protective group which is labile to weak acids, X is NH, O or S, Y is CH.sub.2, NH or O, and B' are bases customary in nucleotide chemistry, the exocyclic amino or hydroxyl groups of which being protected by suitable, known protective groups, or are base substitute compounds, and their salts with tert-organic bases, as well as a process for their preparation. The N-ethylglycine derivatives of the formula I are used in the preparation of PNA and PNA/DNA hybrids.

Abstract: N-7 isomer of the formula ##STR1## is converted into a N-9 isomer of the formula ##STR2## by heating a suspension of the N-7 isomer in an alkylating agent of the formula ##STR3##

Abstract: 9-[(2-Hydroxyethoxy)methyl]guanine (acyclovir) dihydrate sodium salt and the process for the preparation thereof comprising the dissolution of acyclovir monosodium salt in an aqueous medium and the precipitation of the resultant dihydrate sodium salt in an organic solvent.

Abstract: Process and novel intermediates for preparing the L-mono-valine ester of 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol and its pharmaceutically acceptable salts. The present process and intermediates provide for reduced impurities in the mono-valine ester end-product and lower overall production costs. The process involves the condensation of a silylated guanine compound with a substituted glycerol derivative and esterification of this product with an L-valine derivative. These mono-valine products are of value as antiviral agents with improved absorption.

Abstract: Nucleoside derivatives represented by formula (I); ##STR1## wherein, R.sub.1 represents hydrogen, phosphate or phosphonate group, R.sub.2 represents substituted or unsubstituted pyrimidine or purine base, and Z represents S, SO, SO.sub.2, O or C; or pharmaceutically acceptable salts thereof. Compound (I) can be obtained by reacting a compound of the formula (II); ##STR2## wherein, R.sub.7 represents hydrogen or hydroxy-protecting group, L represents aromatic or nonaromatic acyl, halide or alkoxy, and Z represents S, SO, SO.sub.2, O or C, with a base.

Abstract: Disclosed are novel prodrugs represented by the following structural formula: ##STR1## Z is oxygen or sulfur; Y is, together with a hydroxy group, acyclovir or an analog of acyclovir; A is a substituted benzyl group with one or more protected hydroxy or protected amine groups in the ortho or para positions, relative to the phosphate ester, which can be converted in vivo to a hydroxy or amino group. Also disclosed is a method of treating a viral infection in an individual or animal. The method comprises administering to the individual or animal a therapeutically effective amount of a prodrug represented by structural formula shown above.

Abstract: Disclosed herein are methods directed generally to the control of neural activity and for selectively and controllably inducing the in vivo genetic expression of one or more naturally occurring genetically encoded molecules in mammals. More particularly, the present invention selectively activates or derepresses genes encoding for specific naturally occurring molecules such as neurotrophic factors through the administration of carbon monoxide dependent guanylyl cyclase modulating purine derivatives. The methods of the present invention may be used to affect a variety of cellular and neurological activities and to therapeutically or prophylactically treat a wide variety of neurodegenerative, neurological, and cellular disorders.

Abstract: This invention relates to novel purine derivatives of formula (I): ##STR1## where R.sup.2 and R.sup.9 are hydrocarbon groups, R.sup.6 is an amino group and R.sup.8 is a hydroxyl, or acyloxy group. These purine derivatives are effective at promoting secretion of interferon in patients, and can be used to treat diseases against which interferon is effective.

Abstract: There are disclosed compounds of formula (I) ##STR1## and pharmaceutically acceptable salts thereof which are useful as antagonists of GnRH and as such may be useful for the treatment of a variety of sex-hormone related and other conditions in both men and women.

Abstract: The present invention relates to the discovery that certain .beta.-L-dioxolane nucleoside analogs which contain a uracil base, and preferably, a 5-halosubstituted uracil base, exhibit unexpectedly high activity against Epstein-Barr virus (EBV), Varciella-Zoster virus (VZV) and Herpes Virus 8 (HV-8). In particular, the compounds according to the present invention show potent inhibition of the replication of the virus (viral growth) in combination with very low toxicity to the host cells (i.e., animal or human tissue). Compounds are useful for treating EBV, VZV and HV-8 infections in humans.

Abstract: The present invention relates to compounds of the formula IA--B--D--E--F--G (I)in which A, B, D, E, F and G have the meanings given in the patent claims, to their preparation and to their use as medicaments. The compounds of the invention are used as vitronectin receptor antagonists and as inhibitors of bone resorption.

Abstract: Method for prophylaxis and treatment of a viral infection characterized by the administration of a composition comprising a substantial molar excess of the D-stereoisomer of 2'CdG over the L-stereoisomer.

Abstract: Compounds of structural Formula (I) ##STR1## and pharmacologically acceptable salts and esters thereof possess 5.alpha.-reductase inhibitory activity. These compounds inhibit 5.alpha.-reductase type 1 and type 2. The compounds of structural Formula I are useful in the systemic, including oral, and parenteral, including topical, treatment and prevention of hyperandrogenic conditions including prostatic carcinoma, benign prostatic hyperplasia, acne vulgaris, seborrhea, androgenic alopecia (also called androgenetic alopecia) which includes male- and female-pattern baldness, female hirsutism, and prostatitis. A class of compounds of the present invention are also potent antiandrogens. The present invention also relates to novel compositions containing such compounds, methods of their use and methods of their manufacture.

Abstract: The present invention comprises a compound of formula I: ##STR1## R.sub.1 of Formula I is substituted amino represented by formula NR.sup.5 R.sup.6 wherein R.sup.5 and R.sup.6 are independently selected from the group consisting of hydrogen, C.sub.1-4 alkyl, and unsubstituted amino with the proviso that R.sup.5 and R.sup.6 are not both hydrogen, and further that R.sup.5 and R.sup.6 are not both amino. R.sub.2 and R.sub.3 of Formula I are independently selected from the group consisting of hydrogen; C.sub.1-4 alkyl; amino; substituted or unsubstituted thiol; and halogen. Moreover, R.sub.4 of Formula I is represented by the formula R.sup.12 -X.sup.12 wherein R.sup.12 is a saturated or unsaturated linear hydrocarbon chain of 5-20 carbons optionally containing one or more interruptions within the chain by a heteroatom, and optionally substituted with one or more .dbd.O, or .dbd.S. Finally, X.sup.12 is selected from the group consisting of hydroxy, an aminoalkyl group, and a known amino acid bound by its .alpha.

Abstract: Purine or triazolopurine compounds are disclosed represented by formula (I) or (II): ##STR1## wherein R.sup.1 and R.sup.4 represent each hydrogen, halogeno, hydroxy, mercapto, or amino; R.sup.2 represents alkyl or aryl; and R.sup.3 and R.sup.5 represent each hydrogen, alkyl, or aryl; and pharmaceutical compositions comprising these compounds as xanthine oxidase inhibitors, remedies for hyperuricemia, or remedies or preventive agents for gout.

Abstract: The present invention relates to compounds of the formula I,A--B--D--E--F--G (I)in which A, B, D, E, F and G have the meanings given in the patent claims, to their preparation and to their use as medicaments. The compounds of the invention are used as vitronectin receptor antagonists and as inhibitors of bone resorption.

Abstract: This invention relates to certain novel 2'-halomethylidene, 2'-ethenylidene and 2'-ethynyl cytidine, uridine and guanosine derivatives, and compositions thereof, which are useful in the treatment of patients afflicted with neoplastic or viral disease states.

Abstract: New purine retinoid compounds according to the formula: ##STR1## wherein R is a purine derivative, and pharmaceutical compositions thereof, are provided which exhibit cancer-inhibiting activity.

Abstract: Novel bicyclic condensed pyrimidine compounds having general formula (I) ##STR1## wherein X is --CH.sub.2 --, --NH--(CH.sub.2).sub.n --, --O--(CH.sub.2).sub.n -- or --S--(CH.sub.2).sub.n -- in which n is zero or 1; A is a 4,5-fused imidazole ring N-substituted by R.sub.3 which is hydrogen, C.sub.1 -C.sub.4 alkyl or benzyl, or A is a 2,3-fused pyridine ring C-substituted by R.sub.4 which is hydrogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halogen or NR.sub.5 R.sub.6 in which each of R.sub.5 and R.sub.6 independently is H or C.sub.1 -C.sub.4 alkyl; B is a bicyclic ring chosen from tetralin, indane and 2-oxindole; each of R.sub.1 and R.sub.2 independently is hydrogen, C.sub.1 -C.sub.4 alkyl, halogen, hydroxy, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkoxycarbonyl, nitro, cyano or CF.sub.3 ; and the pharmaceutically acceptable salts thereof.

Abstract: A therapeutic method is provided, employing an antiviral compound of the general formula: ##STR1## wherein Z is H, OR' or N(R).sub.2, wherein R' is H, (C.sub.1 -C.sub.4)alkyl, aryl, CHO, (C.sub.1 -C.sub.16)alkanoyl or O.dbd.P(OH).sub.2, Y is CH or N, and X is selected from the group consisting of H, N(R).sub.2, SR, OR' or halogen, wherein R is H, lower(C.sub.1 -C.sub.4)alkyl, aryl or mixtures thereof, and the pharmaceutically acceptable salts thereof.

Abstract: A method for treating a mammal having a damaged central nervous system, as the result of trauma or disease, for reestablishing previously destroyed neurological functions in a traumatized or diseased mammal, or for controlling spasticity and for providing protection from such injury to the central nervous system. The method comprises administering to the mammal at least one neurologically active compound comprising two groups, one group providing alpha-adrenergic agonist activity, specifically a guanidino group, and the second group providing agonist activity selected from the group consisting of beta-adrenergic agonist activity, serotinergic agonist activity, and GABA-ergic agonist activity (for example a methylated xanthine group, having beta-adrenergic agonist activity) as the primary therapeutic agent. The neurologically active compound is administered in a dosage amount and at a dosage rate sufficient to at least partially restore the lost neurological function or to control spasticity.

Abstract: The instant disclosure is directed to cyclopentyl analogues of .alpha.- and .beta.-L-2', 3'-dideoxypurine ribonucleosides wherein the 3- and 4-cyclopentyl substituents may be either --H or --CH.sub.2 --OH.

Abstract: A process for preparing 7-benzylpurine derivatives is provided. An acetylpurine nucleoside is reacted with a benzyl halide to benzylate the 7-position of the purine base, and an acid is then added to the reaction mixture to hydrolyze the glycoside bond. The 7-benzylpurines may be used to prepare 9-substituted purine derivatives.

Abstract: Disclosed is a compound of the formula (I): whereinR.sub.3, R.sub.6a and R.sub.8 are the same or different and represent a C.sub.2-8 alkyl which is unbranched or branched and unsubstituted or substituted; C.sub.3-8 cycloalkyl which is unsubstituted or substituted; C.sub.4-8 cycloalkylalkyl wherein the cycloalkyl portion is unsubstituted or substituted; aryl which is unsubstituted or substituted; aralkyl C.sub.1-4 ; heterocyclyl; and heterocyclylalkyl (C.sub.1 -C.sub.4)R.sub.6b represents H or R.sub.6a, or together R.sub.6b, N, and R.sub.6a make a C.sub.3 -C.sub.