537results about How to "Good metabolic stability" patented technology

The purinone derivative 6-amino-9-[(3R)-1-(2-butynoyl)-3-pyrrolidinyl]-7-(4-phenoxyphenyl)-7,9-dihydro-8H-purin-8-one hydrochloride has Btk-selective inhibitory activity and, in addition to having excellent metabolic stability, it is a compound that exhibits a high level of solubility and absorption with respect to the free base and can be crystallized, hence it can serve as a therapeutic agent for diseases involving B cells and mast cells.

A xanthine phosphodiesterase V inhibitor having the formula (I), with the variables defined herein, which is especially useful for treating male (erectile) and female sexual dysfunction and other physiological disorders: For example, a representative compound of the invention is:

The present invention relates to methods for treating cancer comprising utilizing a combination of signal transduction inhibitors. More specifically, the present invention relates to combinations of so called cell cycle inhibitors with mitogen stimulated kinase signal transduction inhibitors, more specifically combinations of CDK inhibitors with mitogen stimulated kinase signal transduction inhibitors, more preferably MEK inhibitors. Other embodiments of the invention relate to additional combinations of the aforesaid combinations with standard anti-cancer agents such as cytotoxic agents, palliatives and antiangiogenics. Most specifically this invention relates to combinations of 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one including salt forms, which is a selective cyclin-dependent kinase 4 (CDK4) inhibitor, in combination with one or more MEK inhibitors, most preferably N-[(R)-2,3-dihydroxy-propoxy]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide. The aforementioned combinations are useful for treating inflammation and cell proliferative diseases such as cancer and restenosis.

A compound of the formula:or a pharmaceutically acceptable salt thereof, wherein R is unsubstituted, mono-, di- or tri-substituted (C3-C11)cycloalkyl or (C3-C11)cycloalkenyl or the like, A is unsubstituted (C1-C7)alkyl or (C2-C5 )alkenyl, or unsubstituted, mono-, di- or tri-substituted aryl, or aromatic-heterocyclic or the like, Y is hydrogen, halo, amino or mercapto, or unsubstituted, mono-, di- or tri- substituted (C1-C10)alkyl-M-, (C3-C7)cycloalkyl-M-, (C2-C6)alkenyl-M-, (C1-C4)alkyl-NH-((C1-C4)alkyl)-M-, di(C1-C4)alkyl-N-((C1-C4)alkyl)-M-, aryl-M-, aromatic or non-aromatic heterocyclic-M-, aryl-(C1-C5)alkyl-M- or aromatic non-aromatic heterocyclic-(C1-C5)alkyl-M-, wherein M is a covalent bond O, S, NH or the like, or the like; Z1, Z2, Z3 and Z4 are hydrogen or the like, has ORL1-receptor agonist activity, and are useful as analgesics or the like in mammalian subjects.

Alpha substituted carboxylic acids of formula (I):

wherein R¹ and R² are as defined in the specification and R³ is

wherein Y, Ar¹, Ar², Ar³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R^9a, R¹⁰, R¹¹, R¹², R¹⁷, ring A, and p are as defined in the specification; pharmaceutical compositions containing effective amounts of said compounds or their salts are useful for treating PPAR, specifically PPAR α/γ related disorders, such as diabetes, dyslipidemia, obesity and inflammatory disorders.

Alpha substituted carboxylic acids of formula (I):

wherein R¹ and R² are as defined in the specification and R³ is

wherein Y, Ar¹, Ar², Ar³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R^9a, R¹⁰, R¹¹, R¹², R¹⁷, ring A, and p are as defined in the specification; pharmaceutical compositions containing effective amounts of said compounds or their salts are useful for treating PPAR, specifically PPAR α/γ related disorders, such as diabetes, dyslipidemia, obesity and inflammatory disorders.

The present invention provides the S enantiomer of a compound of formula (I); wherein R¹ represents 2,4-difluorophenyl or cyclohexyl as well as pharmaceutically acceptable salts, solvates, crystalline forms and prodrugs thereof, to processes for preparing such compounds, to their the utility in treating clinical conditions including lipid disorders (dyslipidemias) whether or not associated with insulin resistance, to methods for their therapeutic use and to pharmaceutical compositions containing them.

The present invention provides substituted 2-aminopyridines of formula I, wherein R1, A1, W, X, and Y are as defined in the specification, useful in treating cell proliferative disorders. The novel compounds of the present invention are potent inhibitors of cyclin-dependent kinases 4 (Cdk4).

The present invention provides novel triazole derivatives as ghrelin analogue ligands of growth hormone secretagogue receptors according to formula (I) that are useful in the treatment or prophylaxis of physiological and/or pathophysiological conditions in mammals, preferably humans, that are mediated by GHS receptors. The present invention further provides GHS receptor antagonists and agonists that can be used for modulation of these receptors and are useful for treating above conditions, in particular growth retardation, cachexia, short-, medium- and/or long term regulation of energy balance; short-, medium- and/or long term regulation (stimulation and/or inhibition) of food intake; adipogenesis, adiposity and/or obesity; body weight gain and/or reduction; diabetes, diabetes type I, diabetes type II, tumor cell proliferation; inflammation, inflammatory effects, gastric postoperative ileus, postoperative ileus and/or gastrectomy (ghrelin replacement therapy).

The present invention is directed to the method of increasing the metabolic stability of adamantane containing compounds that are inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 (11-beta-HSD-1) enzyme. The stability is achieved by substitutions of the adamantane ring.

A formulation for drug delivery, providing enhanced modulation of solubility, stability, absorption, metabolism, and/or pharmacokinetic profile of a lipophilic therapeutic agent by formulation with sterols and/or sterol esters, resulting in higher bioavailability of a therapeutic agent administered to a subject in need of such therapeutic agent. The formulation contains a therapeutic agent and a sterol or sterol ester, and can, optionally, further contain a solubilizer and/or an enhancing agent. Also described are pharmaceutical compositions containing the formulations and methods of making and methods of using the formulations and pharmaceutical compositions. Formulations of the disclosure can be constituted to minimize the synthesis of dihydrotestosterone when the therapeutic agent includes testosterone or testosterone esters.

The present invention relates to a compound of formula (I):

or a pharmaceutically acceptable salt or solvate thereof, wherein:

• • Ring A is (4-12)-membered heterocyclyl;
  • Ring B is a fused benzene ring selected from the group consisting of:

A compound of the formula: or a pharmaceutically acceptable salt, ester or ether thereof, wherein R1 through R12 are independently hydrogen or the like; X1 and X2 are independently CH2 or the like; R13 is hydrogen or the like; or R12 and R13 taken together with three ring atoms of the quinoline ring separating said substituents form a heterocyclic ring; R14 and R15 are hydrogen or the like or these groups taken together form oxo; and the dotted line represents a single or double bond. These compounds are ligands for ORL-1 receptor and especially are antagonists for said receptor.

8-Substituted-2,6-methano-3-benzazocines of general structure

are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications. One embodiment is the subgenus of biphenylethyl compounds:

The present invention relates to the use of a compound of formula I wherein R2 is R-NH wherein R is a branched or unbranched alkyl radical, a piperidinyl group or pyrrolidinyl group, each of which may be optionally substituted by one or more -OH, halogen, amino or hydroxyalkyl groups; R6 is phenylamino, benzylamino or pyridyl-methylamino, indan-5-amino, where in each case the aryl group may be unsubstituted or substituted by one or more -OR'', halogen, NO2, amino or COOR' groups, wherein R' and R'' are each independently H or a branched or unbranched alkyl group; and R9 is a branched or unbranched alkyl group or a cycloalkyl group; in the treatment of an autoimmune disorder. The invention further relates to a method of treating an autoimmune disorder comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I.

The invention relates to compounds of the formula 1

or a pharmaceutically acceptable salt, prodrug or hydrates thereof, wherein Q, A, L, R¹, R² and R³ are as defined herein. The invention also relates to pharmaceutical compositions containing the compounds of formula 1 and to methods of treating hyperproliferative disorders in a mammal by administering the compounds of formula 1.