A phosphine-based compound and an organic electroluminescence device including the same, the phosphine-based compound being represented by the following Formula 1: ##STR00001##

Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NK.sub.1) receptor. The compounds have the general formula (I): ##STR00001##

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): ##STR00001##
and/or a salt thereof, wherein R.sub.1 is OH or OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

This invention is based on the discovery that many lung diseases associated with aging are mediated at least in part by cells bearing a senescent phenotype. Senescent cells accumulate with age, and express factors that contribute to the pathophysiology of age related conditions. The severity of age-related conditions typically correlates with the abundance of senescent cells: thus, clearing senescent cells can help abrogate the condition: providing symptomatic relief, and potentially inhibiting disease progression. In accordance with this invention, a family of Bcl protein inhibitors has been developed for the treatment of lung diseases. These senolytic agents have an appropriate dose and specificity profile to be effective in the clinical management of previously intractable pulmonary diseases.

The present invention relates to novel impurities of cyclophosphamide having structure V, VI or VII, stabilized form of these novel impurities, a process of preparing a stabilized form and isolating thereof. The invention also relates cyclophosphamide formulations which include cyclophosphamide, at least one pharmaceutically acceptable excipient, and a certain level of these impurities having structure V, VI or VII. The invention further relate to method of using such stable liquid formulations of cyclophosphamide for parenteral administration in treating various cancer disorders.

The present invention provides IP4-4,6 substituted derivatives, their methods of synthesis and their uses. In some aspects, the IP4-4,6 derivative is a compound of formula I wherein R.sub.1, R.sub.3, R.sub.7, and R.sub.11 are OPO.sub.3.sup.2?, and R.sub.5 and R.sub.9 are selected from the group consisting of O(Alkyl).sub.nX, O(Alkyl).sub.yCy(Alkyl.sub.2).sub.y-Z, O(Alkyl).sub.yA(Alkyl).sub.y-Z, and their thiophosphate analogs. Also provided are methods, pharmaceutical compositions and formulations, methods of use, articles of manufacture, and kits for the treatment of diseases and conditions such as pathological crystallization-related diseases and conditions.

This disclosure provides compounds with Bcl inhibitory activity based on a new chemical scaffold. Phosphonamidate compounds typically include a P-phenyl phosphonamidate moiety which is substituted with an N-aryl or N-heteroaryl group. The P-phenyl phosphonamidate moiety may be optionally substituted at phosphorus with thio (S) instead of oxo (O), and/or with a thioxy group or a second amino group instead of an oxy group. One of the heteroatoms attached to phosphorus may be cyclically linked to the N-substituted nitrogen atom that is attached to the phosphorus to provide a heterocyclic ring. By incorporating such a cyclic constraint between two phosphorus substituents of the core linking moiety, a favorable binding conformation may be promoted in the compounds. Selected compounds promote apoptosis in senescent cells, and can be developed for treating senescent-related conditions, such as osteoarthritis, ophthalmic disease, pulmonary disease, and atherosclerosis. Selected compounds promote apoptosis in cancer cells, and can be developed as chemotherapeutic agents.

Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NK.sub.1) receptor. The compounds have the general formula (I):

##STR00001##

A lipid compound or a derivative thereof and a pharmaceutical composition employing the same are provided. The lipid compound has a structure represented by Formula (I):

##STR00001## wherein Z.sup.1, Z.sup.2, Z.sup.3 and Z.sup.4 are as disclosed in the specification.

The invention relates to a Cu(1) complex of Formula (I), wherein L is a ligand of Formula (II), wherein n1, n2, n3 are independently to each other, an integer from 0 to 1, A1, A2 and A3 are independently from each other,a phenyl optionally substituted with (C.sub.1-C.sub.3)alkoxy, (C.sub.1-C.sub.3)alkyl, F, formyl, carboxyl, sulphonyl hydroxyl, hydroxyl, methoxy(C.sub.1-C.sub.3)alkoxy oran heterocyclic ring selected from piperazinyl, morpholynyl, thiomorpholynyl, optionally substituted with (C.sub.1-C.sub.3)alkyl, where the heterocyclic ring is linked with the nitrogen atom to CH.sub.2 residue, with the proviso that when A1, A2 or A3 is optionally substituted phenyl, then n1, n2 or n3, respectively, is 0, and when A1, A2 or A3 is optionally substituted heterocyclic ring, then n1, n2 or n3, respectively, is 1, for use in the treatment of tumours.