Abstract:
The present invention comprises small molecular weight, non-peptidic inhibitors of formula (I) and (II) of Protein Tyrosine Phosphatase 1 (PTP1) which are useful for the treatment and/or prevention of Non-Insulin Dependent Diabetes Mellitus (NIDDM).
Abstract:
A compound having formula (I) or a pharmaceutically acceptable salt thereof wherein one of R , R and R is a cyclic or heterocyclic acidic functional group having a pKa value below 8 or a group which is convertible in vivo to such a group; R , R and the two other substitutents R , R and R are each independently selected from hydrogen; alkyl; alkoxy; hydroxy; halogen; trifluoromethyl; cyano; nitro; amino; alkylamino; -COOR ; -NHSO2-alkyl; -SO2N(R )2; -SO2OR ; -CO-R ; aryl, biphenyl, phenylamino, phenoxy or heteroaryl, wherein the aryl, biphenyl, phenylamino, phenoxy or heteroaryl group may be substituted one or more times with substituents selected from alkyl, hydroxy, alkoxy, halogen, trifluoromethyl, cyano, nitro, amino and alkylamino; aryl and heteroaryl, or R and R or R and R together form a cyclic structure and the other substituents R , R , R , R and R is as defined above; and R is hydrogen, alkyl, amino or phenyl; Y is -CO-, -CS-, -SO2-, or -C(=N-R )-, wherein R is hydrogen, alkyl, or cyano; X is -NH-, -CH2-NH-, or -SO2-NH-; Z is NR , O, -CH=CH-, -N=CH-, or -CH=N-; R is hydrogen, or alkyl; R , R , R , R and R are each independently selected from hydrogen; alkyl; alkoxy; hydroxy; halogen; trifluoromethyl; cyano; nitro; amino; alkylamino; -COOR ; -NHSO2-alkyl; -SO2N(R )2; -SO2OR ; -CO-R ; aryl, biphenyl, phenylamino, phenoxy or heteroaryl, wherein the aryl, biphenyl, phenylamino, phenoxy or heteroaryl group may be substituted one or more times with substituents selected from alkyl, hydroxy, alkoxy, halogen, trifluoromethyl, cyano, nitro, amino and alkylamino; aryl and heteroaryl, or one of R and R , R and R , R and R and R and R together form a cyclic structure and the other substituents R , R , R , R and R is as defined above and R is as defined above; these compounds are particularly useful in the treatment of sickle-cell anaemia.
Abstract:
Therapeutic sulfonamide compounds with the formula R-Q-Ar-SO 2 NH 2 are disclosed, wherein R is an aryl, hetaryl, alkyl or cycloalkyl group, Q is the group -L(CH 2 ) n -, wherein n = 0,1 or 2 and L is the group - NHCXNH-, -NHC(S)SNH-, -NHCONHCSNH- or -SO 2 NH-, X is O or S and Ar is a C 6 -C 10 aromatic or a heteroaromatic group that contains at least one heteroatom of oxygen, nitrogen or sulphur, which compounds selectively inhibit CAIX and CAXII, and which are effective in inhibiting hypoxic tumor growth, suppress metastases, and impair and deplete cancer stem cells in mammals.
Abstract:
The invention provides a pharmacophore for identifying or designing an agonist that binds to a beta-3 adrenergic receptor, wherein the pharmacophore requires the following features: (a) a hydrogen accepting group adjacent to an aromatic moiety; (b) an aromatic moiety containing either an hydroxyl group in the para position or a nitrogen atom in the aromatic ring; (c) a chain having a stereogenic centre bearing a hydroxyl group; (d) a hydrophobic chain having a length of 6 carbon atoms or more; and (e) a hydrophobic chain wherein the direction of the hydrophobic chain is conferred by, or is the same as would be conferred by, the presence of an amide moiety at the start of the chain.
Abstract:
N-aryl arylsulfonamide derivatives are bradykinin B1 antagonists or inverse agonists useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway.
Abstract:
The present invention relates to novel CD40:CD154 binding interruptor compounds of the formula (I), and use of these compounds and pharmaceutical compositions comprising them, to treat conditions associated with inappropriate CD154 activation in a subject. Specifically, this invention provides compounds which are identified by screening a library of small molecules for those that are capable of specifically binding CD154 and interrupting CD40:CD154 interaction.
Abstract:
Novel benzene derivatives represented by the general formula (||), which exhibit vanilloid receptor agonism and are useful as preventive and therapeutic drugs for pollakisuria and urinary incontinence, analgesic, or the like: (||) wherein R , R and R are each independently hydrogen, halogeno, or hydrocarbyl; R is hydrocarbyl or a heterocyclic group; R is hydrocarbyl, NR R , or OR (wherein R is hydrogen or hydrocarbyl and R is a non-aromatic group, or alternatively R and R together with the nitrogen atom adjacent thereto may form a ring; and R is hydrocarbyl or a heterocyclic group); R is hydrocarbyl or a heterocyclic group (except quinolyl) and R is hydrogen or hydrocarbyl, or R and R together with the nitrogen atom adjacent thereto may form a ring; and R is hydrogen or hydrocarbyl.
Abstract translation:由通式(||)表示的新型苯衍生物,其表现出香草素受体激动作用,并且可用作预防和治疗药物用于预防和尿失禁,止痛剂等:(||)其中R 1, 4>和R 6各自独立地为氢,卤素或烃基; R 2是烃基或杂环基; R 3是烃基,NR 7 R 7或OR 8(其中R 7'是氢或烃基,R 7是非芳族基团,或者R 7 和R 7与其相邻的氮原子一起形成环; R 8是烃基或杂环基)。 R 5为烃基或杂环基(喹啉基除外),R 5为氢或烃基,或R 5和R 5与其相邻的氮原子一起形成环; 和R 5“是氢或烃基。
Abstract:
The present invention comprises the use of insulin receptor activating compounds, optionally in conjunction with insulin, for the treatment of HIV protease inhibitor-induced metabolic disorders. Any insulin receptor activating compounds is suitable for the practice of the invention. In addition, preferred compounds are disclosed. Methods of treating a person suffering from HIV protease inhibitor-induced metabolic disorders such as lipodystrophy, hypertriglyceridemia, insulin resistance, hyperglycemia, diabetes and ketoacidosis are also provided.
Abstract:
This invention relates to novel compounds of Formula (I) to (VII), and compositions thereof, useful in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).