23059 results about "Medicinal chemistry" patented technology

New thiol and disulfide-containing maytansinoids bearing a mono or di-alkyl substitution on the α-carbon atom bearing the sulfur atom are disclosed. Also disclosed are methods for the synthesis of these new maytansinoids and methods for the linkage of these new maytansinoids to cell-binding agents. The maytansinoid-cell-binding agent conjugates are useful as therapeutic agents, which are delivered specifically to target cells and are cytotoxic. These conjugates display vastly improved therapeutic efficacy in animal tumor models compared to the previously described agents.

The invention relates to compounds of formula

wherein

• R¹, R², and R³ are as defined herein and to a pharmaceutically suitable acid addition salts thereof for the treatment of CNS disorders.

Disclosed herein is a composition comprising: (A) a lubricant or a hydrocarbon fuel; (B) at least one hydroxy carboxylic acid ester or hydroxy polycarboxylic acid ester having the generic formula defined herein; and (C) at least one phosphorus-containing additive.

Charged or pro-charged cross-linking moieties and conjugates of cell binding agents and drugs comprising the charged or pro-charged cross-linking moieties and method of making the same.

A γ,δ-unsaturated carboxylic acid silyl ester is prepared by reacting an α,β-unsaturated carboxylic acid ester with a hydrosilane or hydrosiloxane in the presence of tris(pentafluorophenyl)borane. γ,δ-Unsaturated carboxylic acid derivatives are readily prepared through fewer steps and in high yields.

FBPase inhibitors of the formula I and Xare useful in the treatment of diabetes and other conditions associated with elevated blood glucose or excess glycogen storage.

Oligonucleotides with a novel sugar-phosphate backbone containing at least one 2′-arabino-fluoronucleoside and an internucleoside 3′-NH—P(—O)(OR)—O-5′ linkage, where R is a positively charged counter ion or hydrogen, and methods of synthesizing and using the inventive oligonucleotides are provided. The inventive phosphoramidate 2′-arabino-fluorooligonucleotides have a high RNA binding affinity to complementary nucleic acids and are base and acid stable.

A pharmaceutical preparation for the treatment of schizophrenia and/or tardive dyskinesia using an oil comprising eicosapentaenoic acid (EPA) and/or stearidonic acid (SA) in amounts of more than 20%, preferably more than 40% and very preferably more than 70% by weight of the total (preferably of the total unsaturated) fatty acids present.

Novel indole and azaindole compounds of the following structure and their use as fructose-1,6-bisphosphatase inhibitors is described: and pharmaceutically acceptable prodrugs and salts thereof.

A composition and method of preparation, to provide silane compounds that are free of chlorine. The compounds are hexakis(monohydrocarbylamino)disilanes with general formula (I)

((R)HN)₃—Si—Si—(NH(R))₃  (I)

wherein each R independently represents a C₁ to C₄ hydrocarbyl. These disilanes may be synthesized by reacting hexachlorodisilane in organic solvent with at least 6-fold moles of the monohydrocarbylamine RNH₂ (wherein R is a C₁ to C₄ hydrocarbyl). Such compounds have excellent film-forming characteristics at low temperatures. These films, particularly in the case of silicon nitride and silicon oxynitride, also have excellent handling characteristics.

Novel purine compounds of the following structure and their use as fructose-1,6-bisphosphatase inhibitors is described.whereinA is selected from the group consisting of -NR82, -NHSO2R3, -OR5, -SR5, halo, lower alkyl, -CON(R4)2, guanidino, amidino, -H, and perhaloalkyl;E is selected from the group consisting of -H, halo, lower alkylthio, lower perhaloalkyl, lower alkyl, lower alkenyl, lower alkynyl, lower alkoxy, -CN, and -NR72;X is selected from the group consisting of -alk-NR-, alkylene, alkenylene, alkynylene, arylene, heteroarylene, -alk-NR-alk-, -alk-O-alk-, -alk-S-alk-, -alk-S-, alicyclicene, heteroalicyclicene, 1,1-dihaloalkylene, -C(O)-alk-, -NR-C(O)-NR'-, -alk-NR-C(O)-, -alk-C(O)-NR-, -Ar-alk-, and -alk-Ar-, all optionally substituted, wherein each R and R' is independently selected from -H and lower alkyl, and wherein each "alk" and "Ar" is an independently selected alkylene or arylene, respectively;Y is selected from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclic, heteroalicyclic, aralkyl, aryloxyalkyl, alkoxyalkyl, -C(O)R3, -S(O)2R3, -C(O)-OR3, -CONHR3, -NR22, and -OR3, all except H are optionally substituted; andpharmaceutically acceptable prodrugs and salts thereof.

Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (I):

including stereoisomers and pharmaceutically acceptable salts thereof, wherein R¹, X, W, Y¹, Y², Z¹, and Z⁴ are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

The invention provides the compounds of formula (I) or pharmaceutically acceptable salts thereof. The invention also provides pharmaceutical compositions comprising one or more compounds of formula I or intermediates thereof and one more of pharmaceutically acceptable carriers, vehicles or diluents. The invention further provides methods of preparation and methods of use of prodrugs including NO-releasing prodrugs, double prodrugs and mutual prodrugs comprising the compounds of formula I.

This application relates to monomers of the general formula (I) for the preparation of PNA (peptide nucleic acid) oligomers and provides method for the synthesis of both predefined sequence PNA oligomers and random sequence PNA oligomers:

wherein

• R1, R2, R3, R4, R5 is independently H, halogen, C₁–C₄ alkyl, nitro, nitrile, C₁–C₄ alkoxy, halogenated C₁–C₄ alkyl, or halogenated C₁–C₄ alkoxy, wherein at least one of R1, R3, and R5 is nitro;
• R6 is H or protected or unprotected side chain of natural or unnatural α-amino acid; and
• B is a natural or unnatural nucleobase, wherein when said nucleobase has an exocyclic amino function, said function is protected by protecting group which is labile to acids but stable to weak to medium bases.

A dry powder composition comprising one or more potent pharmaceutically active substances and a carrier substance, all of which are in finely divided form, wherein the formulation has a poured bulk density of from 0.28 to 0.38 g/ml is useful in the treatment of respiratory disorders.

The present invention relates to a compound represented by Formula (I):

(wherein Ar₁ represents an imidazolyl group which may be substituted with 1 to 3 substituents; Ar₂ represents a pyridinyl group, a pyrimidinyl group, or a phenyl group which may be substituted with 1 to 3 substituents; X₁ represents (1) —C≡C— or (2) a double bond etc. which may be substituted; R¹ and R² represent, for example, a C1-6 alkyl group or C3-8 cycloalkyl group which may be substituted)

or a pharmacologically acceptable salt thereof and to the use thereof as pharmaceutical agents. The object of the present invention is to find a therapeutic or preventive agent for diseases caused by Aβ. According to the present invention, a therapeutic or preventive agents for diseases caused by Aβ can be provided.

The invention provides novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies where the compounds have the general formula I:

wherein X, Y, A, R₁, R₂, R₃, R₄, R₄′, R₅, R₅′, R₆ and R₆′ are as described herein.

An 8-oxoadenine compound useful as an immuno-modulator having specific activity against Th1/Th2, specifically a prophylactic and therapeutic agent for a topical application for allergic diseases, viral diseases and cancers, which is represented by the following formula (1):

wherein A is a group of a formula represented by the formula (2):

• • wherein R² is a substituted or unsubstituted alkyl group and so on, R³ is hydrogen atom or an alkyl group, R is a halogen atom and so on, n is 0˜2,
• X¹ is oxygen atom, Z is straight or branched chain alkylene, and R¹ is an alkyl group which is optionally substituted by hydroxy group, an alkoxy group, alkoxycarbonyl group and so on, or its pharmaceutically acceptable salt.

Provided are thiadiazolidine compounds of formula I

wherein R₁ is an organic group having at least 8 atoms selected from C or O, which is not linked directly to the N through a —C(O)— and comprising at least an aromatic ring, and their pharmaceutical compositions. These compounds are selective GSK-3 inhibitors and have improved bioavailability. They are useful for the treatment of GSK-3 mediated diseases, among others Alzheimer's disease, type II diabetes, depression and brain injury.

The present invention provides for compounds of formula (I)-(XIII), as well as pharmaceutically acceptable salts thereof, metabolites thereof, pro-drugs thereof, and pharmaceutical kits that include such compounds. The present invention also provides for the compounds of formula (I)-(XIII) for use in medical therapy or diagnosis. The present invention also provides for the use of the compounds of formula (I)-(XIII) in treating cancer in mammals (e.g., humans), as well inhibiting tumor cell growth in such mammals. The present invention also provides for methods of inhibiting FAS. The methods include contacting FAS with an effective amount of a compound of formula (I)-(XIII). The present invention also provides for methods of inhibiting the TE domain of the FAS. The methods include contacting the thioesterase TE domain of the FAS with an effective amount of a compound of formula (I)-(XIII). The present invention also provides for methods of treating cancer in mammals, as well as methods of inhibiting tumor cell growth in such mammals. The methods include administering a compound of formula (I)-(XIII) to a mammal in need of such treatment.

The invention is directed to methods of making substituted 3-cyanoquinolines, including compounds according to the following formula:

The methods are amenable to large scale manufacture, avoid the use of chromatographic separations, and provide stable, high purity product more efficiently than in the prior art.

The present invention is directed to nanoparticulate compositions comprising sildenafil free base. The sildenafil free base particles of the composition have an effective average particle size of less than about 2000 nm.

A stable solid pharmaceutical composition consisting essentially of an effective amount of a salt of formula (II)

together with an alkaline-reacting component maintaining the pH preferably above 8, or a salt with a divalent metal cation; and at least one pharmaceutical excipient; said salt of formula (II) being essentially stable during storage at room temperature for a period of at least 3 years. A process for stabilizing the salt of formula (II). A crystalline salt of formula (II) and a process for preparing said salt.

An efficient synthetic route to antiviral 2′,3′-dideoxy-2′,3′-didehydro-nucleosides, such as 2′,3′-dideoxy and 2′- or 3′-deoxyribo-nucleoside analogs, from available precursors is disclosed, with the option of introducing functionality as needed. In one embodiment, a method for the preparation of β-D and β-L-2′,3′-dideoxy-2′,3′-didehydro-nucleosides is described that includes: activating a compound of structure (1)

wherein B is a pyrimidine or purine base and Y is O, S or CH₂ with an acyl halide of the formula X—C(═O)R¹, X—C(═O)C(R¹)₂OC(═O)R¹ or X—C(═O)OR¹ (wherein X is a halogen, and each R¹ is independently hydrogen, lower alkyl, alkyl, aryl or phenyl); reducing the resulting compound with a reducing agent to form a 2′,3′-dideoxy-2′,3′-didehydro-nucleoside; and optionally deprotecting the nucleoside. The haloacylation of the first step can form the 2′-acyl-3′-halonucleoside, the 3′-acyl-2′-halonucleoside, or a mixture thereof.

The present invention generally relates to aqueous, acidic compositions thickened with an amidoamine oxide gelling agent and/or viscoelastic surfactant of the general formula I:

wherein R₁ is a saturated or unsaturated, straight or branched chain aliphatic group of from about 7 to about 30 carbon atoms, R₂ is a divalent alkylene group of 2–6 carbon atoms which may be linear or branched, substituted or unsubstituted, and R₃ and R₄ are independently C₁–C₄ alkyl or hydroxyalkyl groups or together they form a heterocyclic ring of up to six members, and R₅ is hydrogen or a C₁–C₄ alkyl or hydroxyalkyl group. The aforementioned gelling agents advantageously provide gels that do not undergo phase separation over extended periods of time and exhibit high heat stability. The thickened acid gels of the invention have applications in household and industrial cleaners and degreasers, oilfield stimulation applications and the like.

(A1) Translate this text The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure (I) wherein R1 and R2 are each independently for each occurrence optionally substituted C10-C30 alkyl, optionally substituted C10-C30 alkenyl, optionally substituted C10-C30 alkynyl, optionally substituted C10-C30 acyl, or -linker-ligand; R3 is H, optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ?-aminoalkyls, ?-(substituted)aminoalkyls, ?-phosphoalkyls, ?-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; E is O, S, N(Q), C(O), N(Q)C(O), C(0)N(Q), (Q)N(CO)O, O(CO)N(Q), S(O), NS(O)2N(Q), S(O)2, N(Q)S(O)2, SS, O═N, aryl, heteroaryl, cyclic or heterocycle; and, Q is H, alkyl, ?-aminoalkyl, ?-(substituted)aminoalky, ?-phosphoalkyl or ?-thiophosphoalkyl.

The present invention provides C-glycoside derivatives and salts thereof, wherein B ring is bonded to A ring via —X— and A ring is directly bonded to the glucose residue, and it is usable as a Na⁺-glucose cotransporter inhibitor, especially for a therapeutic and/or preventive agent for diabetes such as insulin-dependent diabetes (type 1 diabetes) and insulin-independent diabetes (type 2 diabetes), as well as diabetes related diseases such as an insulin-resistant diseases and obesity.

The invention provides substituted diaryl compounds as shown in general formula (I) or their pharmaceutically acceptable salts, and also provides a preparation method; a class of novel broad-spectrum antiviral compounds and pharmaceutical salts targeting cytokines are screened and obtained through studies on structure-activity relationship and action mechanism of active compounds; the compounds not only have significant broad-spectrum antiviral activity, but also have the advantages of low toxicity and good pharmaceutical properties.

This invention relates to novel antimicrobial compounds of formula;wherein X, R1, R3, R5, R6, and R8 are defined in the claims, and to their optical isomers, diastereomers or enantiomers, as well as pharmaceutically-acceptable salts, hydrates, and biohydrolyzable esters, amides and imides thereof, and to compositions and uses of such compounds. The invention also relates to compounds derived from these compounds having antimicrobial uses.

Disclosed are compounds, compositions and methods for systemic and local delivery of biologically active molecules.