- Discovery of novel “Dual-site” binding oseltamivir derivatives as potent influenza virus neuraminidase inhibitors
-
From our research group, it was noticed that oseltamivir derivatives targeting 150-cavity of neuraminidase enzyme (NA) could significantly increase antiviral activity. Thus, we further enriched the C5–NH2 position of oseltamivir structure to ob
- Ai, Wei,Cherukupalli, Srinivasulu,Ding, Xiao,Huang, Bing,Jia, Ruifang,Jiang, Xiangyi,Li, Zhong,Liu, Xinyong,Ma, Xiuli,Sun, Lin,Sun, Zhuosen,Wang, Defeng,Zalloum, Waleed A.,Zhan, Peng,Zhang, Jian
-
-
- BENZIMIDAZOLE COMPOUNDS AND USE THEREOF FOR TREATING ALZHEIMER'S DISEASE OR HUNTINGTON'S DISEASE
-
Benzimidazole compounds of formula (I), shown below, are disclosed. The compounds are potent human glutaminyl cyclase inhibitors. Also disclosed is a pharmaceutical composition containing one of these compounds and a pharmaceutical acceptable carrier, as well as a method of treating Alzheimer's disease or Huntington's disease by administering to a subject in need thereof an effective amount of such a compound.
- -
-
Page/Page column 13; 29
(2020/03/23)
-
- BENZIMIDAZOLE COMPOUNDS AND USE THEREOF FOR TREATING ALZHEIMER'S DISEASE OR HUNTINGTON'S DISEASE
-
Benzimidazole compounds of formula (I), shown below, are disclosed. The compounds are potent human glutaminyl cyclase inhibitors. Also disclosed is a pharmaceutical composition containing one of these compounds and a pharmaceutical acceptable carrier, as well as a method of treating Alzheimer's disease or Huntington's disease by administering to a subject in need thereof an effective amount of such a compound.
- -
-
Paragraph 0038-0039; 0058-0059
(2020/03/23)
-
- COMPOUND USED AS AUTOPHAGY REGULATOR, AND PREPARATION METHOD THEREFOR AND USES THEREOF
-
It is related to compounds used as autophagy modulators and a method for preparing and using the same, specifically providing a compound of general formula (I), or pharmaceutically acceptable salts thereof, which is a type of autophagy modulators, particularly mammalian ATG8 homologues modulators.
- -
-
Paragraph 0274-0275
(2020/07/07)
-
- Design and Synthesis of Poly(ADP-ribose) Polymerase Inhibitors: Impact of Adenosine Pocket-Binding Motif Appendage to the 3-Oxo-2,3-dihydrobenzofuran-7-carboxamide on Potency and Selectivity
-
Poly(adenosine 5′-diphosphate-ribose) polymerase (PARP) inhibitors are a class of anticancer drugs that block the catalytic activity of PARP proteins. Optimization of our lead compound 1 ((Z)-2-benzylidene-3-oxo-2,3-dihydrobenzofuran-7-carboxamide; PARP-1 IC50 = 434 nM) led to a tetrazolyl analogue (51, IC50 = 35 nM) with improved inhibition. Isosteric replacement of the tetrazole ring with a carboxyl group (60, IC50 = 68 nM) gave a promising new lead, which was subsequently optimized to obtain analogues with potent PARP-1 IC50 values (4-197 nM). PARP enzyme profiling revealed that the majority of compounds are selective toward PARP-2 with IC50 values comparable to clinical inhibitors. X-ray crystal structures of the key inhibitors bound to PARP-1 illustrated the mode of interaction with analogue appendages extending toward the PARP-1 adenosine-binding pocket. Compound 81, an isoform-selective PARP-1/-2 (IC50 = 30 nM/2 nM) inhibitor, demonstrated selective cytotoxic effect toward breast cancer gene 1 (BRCA1)-deficient cells compared to isogenic BRCA1-proficient cells.
- Velagapudi, Uday Kiran,Langelier, Marie-France,Delgado-Martin, Cristina,Diolaiti, Morgan E.,Bakker, Sietske,Ashworth, Alan,Patel, Bhargav A.,Shao, Xuwei,Pascal, John M.,Talele, Tanaji T.
-
p. 5330 - 5357
(2019/06/07)
-
- NOVEL S1P RECEPTOR MODULATING AGENT
-
An object of the present invention is to provide a compound having a modulating activity at an S1P receptor which is useful for preventing and treating autoimmune diseases, allergic diseases, and the like. According to the present invention, a compound re
- -
-
Paragraph 0240
(2013/08/28)
-
- Methods of treatment using an EP2 selective receptor agonist
-
The present invention relates to methods of treating pulmonary hypertension, facilitating joint fusion, facilitating tendon and ligament repair, reducing the occurrence of secondary fracture, treating avascular necrosis, facilitating cartilage repair, facilitating bone healing after limb transplantation, facilitating liver regeneration, facilitating wound healing, reducing the occurrence of gastric ulceration, treating hypertension, facilitating the growth of tooth enamel or finger or toe nails, treating glaucoma, treating ocular hypertension, and repairing damage caused by metastatic bone disease using an EP2 selective receptor agonist.
- -
-
Page/Page column 48
(2010/02/13)
-
- 6-O-acyl ketolide antibacterials
-
6-O-Acyl ketolide antibacterials of the formula: wherein R1, R2, R3, R4, W, X, X′, Y, and Y′ are as described herein and in which the substituents have the meaning indicated in the description. These compounds are useful as antibacterial agents.
- -
-
-
- Method for treating glaucoma
-
Methods of using prostaglandin agonists for the reduction of intraocular pressure, and accordingly glaucoma.
- -
-
-
- Prostaglandin agonists and their use to treat bone disorders
-
This invention relates to prostaglandin agonists, methods of using such prostaglandin agonists, pharmaceutical compositions containing such prostaglandin agonists and kits containing such prostaglandin agonists. The prostaglandin agonists are useful for the treatment of bone disorders including osteoporosis.
- -
-
-
- Prevention of loss and restoration of bone mass by certain prostaglandin agonists
-
Prostaglandin agonists of formula (I), in which, for example, A is a sulphonyl or acyl group, B is N or CH, M contains a ring and K and Q are linking groups, methods of using such prostaglandin agonists, pharmaceutical compositions containing such prostaglandin agonists and kits useful for the treatment of bone disorders including osteoporosis. STR1
- -
-
-
- Pyrimidine derivatives and processes for the preparation thereof
-
4-Amino-1H-pyrazolo[3,4-d]pyrimidine derivatives of formula I wherein the substituents are as defined in claim 1, are described.These compounds inhibit the tyrosine kinase activity of the receptor for epidermal growth factor (EGF) and c-erbB2 kinase and can be used as anti-tumor agents.
- -
-
-
- AROMATIC AMINE DERIVATIVES, PROCESS FOR THE PREPARATION THEREOF AND AGENTS CONTAINING THE SAME
-
Compounds of a formula: wherein Ring A represents an optionally-substituted aromatic ring; Ring B represents an optionally-substituted cyclic hydrocarbon group; Z represents an optionally-substituted cyclic group; R1 represents a hydrogen atom, an optionally-substituted hydrocarbon group, an optionally-substituted heterocyclic group, or an acyl group; R2 represents an optionally-substituted amino group; D represents a chemical bond or a divalent group; E represents -CO-, -CON(Ra)-, COO-, -N(Ra)CON(Rb)-, -N(Ra)COO-, -N(Ra)SO2-, -N(Ra)-, -O-, -S-,-SO- or -SO2- (in which Ra and Rb each independently represent a hydrogen atom or an optionally-substituted hydrocarbon group); G represents a chemical bond or a divalent group; L represents (1) a chemical bond or (2) a divalent hydrocarbon group optionally having from 1 to 5 substituents selected from;(i) a C1-6 alkyl group,(ii) a halogeno-C1-6 alkyl group,(iii) a phenyl group,(iv) a benzyl group,(v) an optionally-substituted amino group,(vi) an optionally-substituted hydroxy group, and(vii) a carbamoyl or thiocarbamoyl group optionally substituted by: a C1-6 alkyl group, an optionally-substituted phenyl group, or an optionally-substituted heterocyclic group, and optionally interrupted by -O- or -S-; X represents an oxygen atom, an optionally-oxidized sulfur atom, an optionally-substituted nitrogen atom, or an optionally-substituted divalent hydrocarbon group; Y represents two hydrogen atoms, an oxygen atom or a sulfur atom; .... means that R2 may be bonded to the atom on Ring B to form a ring, or their salts, and a method for producing them.
- -
-
-
- New aza-dipeptide analogues as potent and orally absorbed HIV-1 protease inhibitors: Candidates for clinical development
-
On the basis of previously described X-ray studies of an enzyme/aza- dipeptide complex, aza-dipeptide analogues carrying N-(bis-aryl-methyl) substituents on the (hydroxethyl)hydrazine moiety have been designed and synthesized as HIV-1 protease inhibitors. By using either equally (12) or orthogonally (13) protected dipeptide isosteres, symmetrically and asymmetrically acylated aza-dipeptides can be synthesized. This approach led to the discovery of very potent inhibitors with antiviral activities (ED50) in the subnanomolar range. Acylation of the (hydroxethyl)hydrazine dipeptide isostere with the L-tert-leucine derivative 29 increased the oral bioavailability significantly when compared to the corresponding L-valine or L-isoleucine derivatives. The bis (L-tert-leucine) derivatives CGP 75355, CGP 73547, CGP 75136, and CGP 75176 combine excellent antiviral activity with high blood concentration after oral administration. Furthermore, they show no cross-resistance with saquinavir-resistant strains and maintain activity against indinavir-resistant ones. Consequently they qualify for further profiling as potential clinical candidates.
- Bold, Guido,F?ssler, Alexander,Capraro, Hans-Georg,Cozens, Robert,Klimkait, Thomas,Lazdins, Janis,Mestan, Jürgen,Poncioni, Bernard,R?sel, Johannes,Stover, David,Tintelnot-Blomley, Marina,Acemoglu, Figan,Beck, Werner,Boss, Eugen,Eschbach, Martin,Hürlimann, Thomas,Masso, Elvira,Roussel, Serge,Ucci-Stoll, Katharina,Wyss, Dominique,Lang, Marc
-
p. 3387 - 3401
(2007/10/03)
-
- ANTIVIRALLY ACTIVE HETEROCYCLIC AZAHEXANE DERIVATIVES
-
There are described compounds of formula I*, STR1 wherein R. sub.1 is lower alkoxycarbonyl,R 2 is secondary or tertiary lower alkyl or lower alkylthio-lower alkyl, R. sub.3 is phenyl that is unsubstituted or substituted by one or more lower alkoxy radicals, or C 4-C 8 cycloalkyl,R. sub.4 is phenyl or cyclohexyl each substituted in the 4-position by unsaturated heterocyclyl that is bonded by way of a ring carbon atom, has from 5 to 8 ring atoms, contains from 1 to 4 hetero atoms selected from nitrogen, oxygen, sulfur, sulfinyl (--SO--) and sulfonyl (--SO 2--) and is unsubstituted or substituted by lower alkyl or by phenyl-lower alkyl,R 5, independently of R 2, has one of the meanings mentioned for R 2, andR 6, independently of R. sub.1, is lower alkoxycarbonyl,or salts thereof, provided that at least one salt-forming group is present. The compounds are inhibitors of retroviral aspartate protease and can be used, for example, in the treatment of AIDS. They exhibit outstanding pharmacodynamic properties.
- -
-
-