- Improved synthesis of the bifunctional chelator p-SCN-Bn-HOPO
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The bifunctional ligand p-SCN-Bn-HOPO, which has four 1,2-hydroxypyridinone groups on a spermine backbone with an isothiocyanate linker, has been shown to be an efficient and stable chelator for Zr(iv) and, more importantly, the radioisotope 89Zr for use in radiolabeling antibodies for positron emission tomography (PET) imaging. Previous studies of 89Zr-HOPO-trastuzumab in mice showed low background, good tumor to organ contrast, and very low bone uptake which show p-SCN-Bn-HOPO to be an important next-generation bifunctional chelator for radioimmunoPET imaging with 89Zr. However, the reported synthesis of p-SCN-Bn-HOPO involves nine steps and multiple HPLC purifications with an overall yield of about 1.4%. Herein we report an improved and efficient synthesis of p-SCN-Bn-HOPO in four steps with 14.3% overall yield which will improve its availability for further biological studies and wider application in PET imaging. The new synthetic route also allows variation in linker length and chemistries which may be helpful in modifying in vivo clearance behaviors of future agents.
- Bhupathiraju, N.V.S. Dinesh K.,Younes, Ali,Cao, Minhua,Ali, Jafar,Cicek, Huseyin T.,Tully, Kathryn M.,Ponnala, Shashikanth,Babich, John W.,Deri, Melissa A.,Lewis, Jason S.,Francesconi, Lynn C.,Drain, Charles Michael
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Read Online
- Dissipative Catalysis with a Molecular Machine
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We report on catalysis by a fuel-induced transient state of a synthetic molecular machine. A [2]rotaxane molecular shuttle containing secondary ammonium/amine and thiourea stations is converted between catalytically inactive and active states by pulses of a chemical fuel (trichloroacetic acid), which is itself decomposed by the machine and/or the presence of additional base. The ON-state of the rotaxane catalyzes the reduction of a nitrostyrene by transfer hydrogenation. By varying the amount of fuel added, the lifetime of the rotaxane ON-state can be regulated and temporal control of catalysis achieved. The system can be pulsed with chemical fuel several times in succession, with each pulse activating catalysis for a time period determined by the amount of fuel added. Dissipative catalysis by synthetic molecular machines has implications for the future design of networks that feature communication and signaling between the components.
- Biagini, Chiara,Fielden, Stephen D. P.,Leigh, David A.,Schaufelberger, Fredrik,Di Stefano, Stefano,Thomas, Dean
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Read Online
- 1-tert-butoxy-2-tert-butoxycarbonyl-1,2-dihydroisoquinoline: A novel and chemoselective tert-butoxycarbonylation reagent
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(formula presented) The use of 1-tert-butoxy-2-tert-butoxycarbonyl-1,2-dihydroisoquinoline (BBDI) as tert-butoxycarbonylation reagent for aromatic and aliphatic amine hydrochlorides and phenols in the absence of a base has been demonstrated. The reactions proceed chemoselectively in high yield under mild conditions.
- Ouchi, Hidekazu,Saito, Yukako,Yamamoto, Yutaka,Takahata, Hiroki
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Read Online
- D2 Dopamine Receptor G Protein-Biased Partial Agonists Based on Cariprazine
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Functionally selective G protein-coupled receptor ligands are valuable tools for deciphering the roles of downstream signaling pathways that potentially contribute to therapeutic effects versus side effects. Recently, we discovered both Gi/o-bi
- Shen, Yudao,McCorvy, John D.,Martini, Michael L.,Rodriguiz, Ramona M.,Pogorelov, Vladimir M.,Ward, Karen M.,Wetsel, William C.,Liu, Jing,Roth, Bryan L.,Jin, Jian
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p. 4755 - 4771
(2019/05/08)
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- Design of a True Bivalent Ligand with Picomolar Binding Affinity for a G Protein-Coupled Receptor Homodimer
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Bivalent ligands have emerged as chemical tools to study G protein-coupled receptor dimers. Using a combination of computational, chemical, and biochemical tools, here we describe the design of bivalent ligand 13 with high affinity (KDB1 = 21 pM) for the dopamine D2 receptor (D2R) homodimer. Bivalent ligand 13 enhances the binding affinity relative to monovalent compound 15 by 37-fold, indicating simultaneous binding at both protomers. Using synthetic peptides with amino acid sequences of transmembrane (TM) domains of D2R, we provide evidence that TM6 forms the interface of the homodimer. Notably, the disturber peptide TAT-TM6 decreased the binding of bivalent ligand 13 by 52-fold and had no effect on monovalent compound 15, confirming the D2R homodimer through TM6 ex vivo. In conclusion, by using a versatile multivalent chemical platform, we have developed a precise strategy to generate a true bivalent ligand that simultaneously targets both orthosteric sites of the D2R homodimer.
- Pulido, Daniel,Casadó-Anguera, Verònica,Pérez-Benito, Laura,Moreno, Estefanía,Cordomí, Arnau,López, Laura,Cortés, Antoni,Ferré, Sergi,Pardo, Leonardo,Casadó, Vicent,Royo, Miriam
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supporting information
p. 9335 - 9346
(2018/10/24)
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- In situ deprotection and dynamic covalent assembly using a dual role catalyst
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Utilization of constituent molecular precursors bearing covalently coreactive functional groups for self-assembly risks premature reaction, impeding synthetic and purification efforts. To prevent premature amine-aldehyde condensation for oligomers bearing both groups, we employ a dual-role Lewis acid catalyst for both in situ acetal deprotection and subsequent imine exchange, effecting oligomer assembly.
- Wei,Furgal,Scott
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supporting information
p. 3874 - 3877
(2017/04/06)
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- CONJUGATE OF MONOMETHYL AURISTATIN F AND TRASTUZUMAB AND ITS USE FOR THE TREATMENT OF CANCER
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The present invention relates to an antibody-drug-conjugate or pharmaceutical composition comprising the same. From one aspect, the invention relates to an antibody-drug-conjugate (ADC) comprising an antibody consisting of the Trastuzumab or a biosimilar thereof, said antibody being conjugated to at least one drug consisting of a monomethyl auristatin F derivative. The invention also comprises method of treatment of cancer comprising administering to the subject an effective amount of said antibody-drug-conjugate or composition comprising the same.
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Paragraph 0364; 0365
(2017/05/15)
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- COMPOSITION FOR THE TREATMENT OF IGF-1R EXPRESSING CANCER
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The present invention relates to a method for the treatment of IGF-IR expressing cancers as well as to a compositions and a kit for said traitment. From one aspect, the invention reates to the combined use of a first antibody for the determination of the IGF-IR status of a cancer and a second antibody used as an ADC for the treatment of said cancer.
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Page/Page column 132
(2017/05/17)
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- A method of preparing P ethylamine
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The invention discloses a preparation method of p-aminophenylethylamine, belonging to the technical field of organic synthesis. The technical scheme is as follows: the preparation method comprises the following steps: by using p-nitrophenylethanol as a raw material, carrying out catalytic hydrogenation to reduce the para-position nitro groups of the p-nitrophenylethanol into amino groups, carrying out Boc acid anhydride protection on the para-position nitro groups, carrying out substitution reaction on hydroxy groups with sulfonyl chloride compounds to obtain sulfonic acid compounds, aminating, and finally, removing Boc groups to obtain the p-aminophenylethylamine. The preparation process is simple and easy to implement, and has the advantages of cheap and accessible raw materials, higher reaction efficiency and favorable repetitiveness.
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Paragraph 0026; 0027; 0028; 0029; 0030; 0031; 0032-0034
(2017/04/14)
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- CONJUGATE OF MONOMETHYL AURISTATIN F AND TRASTUZUMAB AND ITS USE FOR THE TREATMENT OF CANCER
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The present invention relates to an antibody-drug-conjugate. From one aspect, the invention relates to an antibody-drug-conjugate comprising an antibody consisting of the Trastuzumab, said antibody being conjugated to at least one drug consisting of a monomethyl auristatin F derivative. The invention also comprises method of treatment and the use of said antibody-drug-conjugate for the treatment of cancer.
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Page/Page column 61
(2016/11/17)
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- Total Synthesis of Millingtonine
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Millingtonine is a glycosidic alkaloid that exists as a pair of pseudo-enantiomeric diastereomers. Consideration of the likely biosynthetic origins of this unusual natural product has resulted in the development of a seven-step total synthesis. Results fr
- Brown, Patrick D.,Lawrence, Andrew L.
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supporting information
p. 8421 - 8425
(2016/07/19)
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- INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
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Compounds of Formula I, including pharmaceutically acceptable salts thereof, and compositions and methods for treating human immunodeficiency virus (HIV) infection are set forth: (I)
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Page/Page column 129
(2016/11/14)
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- Development of subnanomolar radiofluorinated (2-pyrrolidin-1-yl)imidazo[1,2-b]pyridazine pan-Trk inhibitors as candidate PET imaging probes
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Dysregulation of tropomyosin receptor kinases (TrkA/B/C) expression and signalling is recognized as a hallmark of numerous neurodegenerative diseases including Parkinson's, Huntington's and Alzheimer's disease. TrkA/B/C is known to drive tumorogensis and
- Bernard-Gauthier, Vadim,Bailey, Justin J.,Aliaga, Arturo,Kostikov, Alexey,Rosa-Neto, Pedro,Wuest, Melinda,Brodeur, Garrett M.,Bedell, Barry J.,Wuest, Frank,Schirrmacher, Ralf
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supporting information
p. 2184 - 2193
(2015/12/11)
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- IGF-1R ANTIBODY-DRUG-CONJUGATE AND ITS USE FOR THE TREATMENT OF CANCER
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The present invention relates to an antibody-drug-conjugate capable of binding IGF-1R. From one aspect, the invention relates to an antibody-drug-conjugate comprising an antibody capable of binding to IGF-1R, said antibody being conjugated to at least one drug selected from derivatives of dolastatin 10 and auristatins. The invention also comprises method of treatment and the use of said antibody-drug- conjugate for the treatment of cancer.
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Page/Page column 130; 131
(2015/11/16)
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- ANTIBODY-DRUG-CONJUGATE AND ITS USE FOR THE TREATMENT OF CANCER
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The present invention relates to an antibody-drug-conjugate. From one aspect, the invention relates to an antibody-drug-conjugate comprising an antibody capable of binding to a Target, said antibody being conjugated to at least one drug selected from derivatives of dolastatin 10 and auristatins. The invention also comprises method of treatment and the use of said antibody-drug-conjugate for the treatment of cancer.
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Page/Page column 154; 155
(2015/11/10)
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- Guanidine-based polymer brushes grafted onto silica nanoparticles as efficient artificial phosphodiesterases
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Polymer brushes grafted to the surface of silica nanoparticles were fabricated by atom-transfer radical polymerization (ATRP) and investigated as catalysts in the cleavage of phosphodiesters. The surfaces of silica nanoparticles were functionalized with an ATRP initiator. Surface-initiated ATRP reactions, in varying proportions, of a methacrylate moiety functionalized with a phenylguanidine moiety and an inert hydrophilic methacrylate species afforded hybrid nanoparticles that were characterized with potentiometric titrations, thermogravimetric analysis, and SEM. The activity of the hybrid nanoparticles was tested in the transesterification of the RNA model compound 2-hydroxypropyl para-nitrophenylphosphate (HPNP) and diribonucleoside monophosphates. A high catalytic efficiency and a remarkable effective molarity, thus overcoming the effective molarities previously observed for comparable systems, indicate the existence of an effective cooperation of the guanidine/guanidinium units and a high level of preorganization in the nanostructure. The investigated system also exhibits a marked and unprecedented selectivity for the diribonucleoside sequence CpA. The results presented open up the way for a novel and straightforward strategy for the preparation of supramolecular catalysts.
- Savelli, Claudia,Salvio, Riccardo
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p. 5856 - 5863
(2015/03/31)
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- Pyrimidinone Derivatives as Antimalarial Agents
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The invention relates to novel pyrimidinone-based heterocyclic compounds which are parasite growth inhibitors, having the general formula (I) in which Y is a morpholine chosen from three bridged morpholines, L is a bond or a linker, n=0 or 1 and R2 is a methyl group when n=0 and a hydrogen atom when n=1. Process for the preparation thereof and therapeutic use thereof.
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Paragraph 0688
(2015/07/15)
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- DERIVATIVES OF DOLASTATIN 10 AND AURISTATINS
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The present invention concerns a compound of following formula (I): where: - R1 is H or OH, - R2 is a (C1-C6)alkyl, COOH, COO-((C1-C6)alkyl) or thiazolyl group, - R3 is H or a (C1-C6)alkyl group, and - R4 is: ■ a straight-chain or branched, saturated or unsaturated hydrocarbon group having 1 to 8 carbon atoms substituted by one or more groups chosen from among OH and NR5R6, ■ -(CH2CH2X1)(CH2CH2X2)a2(CH2CH2X3)a3(CH2CH2X4)a4(CH2CH2X5)a5R7, ■ an aryl-(C1-C8)alkyl group substituted by one or more groups chosen from among OH and NR9R10 groups, or ■ a heterocycle-(C1-C8)alkyl group optionally substituted by one or more groups chosen from among (C1-C6)alkyl, OH and NR12R13 groups, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and its uses in particular for the treatment of cancer, pharmaceutical compositions containing the same and the preparation methods thereof.
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Page/Page column 58
(2014/11/13)
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- DERIVATIVES OF DOLASTATIN 10 AND AURISTATINS
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The present invention concerns a compound of following formula (I) where: - R1 is H or OH, - R2 is a (C1-C6)alkyl, COOH, COO-((C1-C6)alkyl) or thiazolyl group, - R3 is H or a (C1-C6)alkyl group, and - R4 is an aryl-(C1-C8)alkyl group substituted by one or more groups chosen from among OH and NR9R10 groups, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and its uses in particular for the treatment of cancer, pharmaceutical compositions containing the same and the preparation methods thereof.
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Page/Page column 47
(2014/11/13)
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- DERIVATIVES OF DOLASTATIN 10 AND AURISTATINS
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The present invention concerns a compound of following formula (I) where: - R1 is H or OH, - R2 is a (C1-C6)alkyl, COOH, COO-((C1-C6)alkyl) or thiazolyl group, - R3 is H or a (C1-C6)alkyl group, and - R4 is: - an aryl-(C1-C8)alkyl group substituted by one or more groups chosen from among OH and NR9R10 groups, or - a heterocycle-(C1-C8)alkyl group optionally substituted by one or more groups chosen from among (C1-C6)alkyl, OH and NR12R13 groups, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and its uses in particular for the treatment of cancer, pharmaceutical compositions containing the same and the preparation methods thereof.
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Page/Page column 54
(2014/11/13)
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- PYRIMIDINONE DERIVATIVES AS ANTIMALARIAL AGENTS
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The invention relates to novel pyrimidinone-based heterocyclic compounds which are parasite growth inhibitors, having the general formula (I) in which Y is a morpholine chosen from three bridged morpholines, L is a bond or a linker, n = 0 or 1 and R2 is a methyl group when n = 0 and a hydrogen atom when n = 1. Process for the preparation thereof and therapeutic use thereof.
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Page/Page column 72; 73
(2014/01/09)
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- Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from plasmodium falciparum
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The malaria parasite Plasmodium falciparum employs two metallo- aminopeptidases, PfA-M1 and PfA-M17, which are essential for parasite survival. Compounds that inhibit the activity of either enzyme represent leads for the development of new antimalarial drugs. Here we report the synthesis and structure-activity relationships of a small library of phosphonic acid arginine mimetics that probe the S1 pocket of both enzymes and map the necessary interactions that would be important for a dual inhibitor.
- Kannan Sivaraman, Komagal,Paiardini, Alessandro,Sieńczyk, Marcin,Ruggeri, Chiara,Oellig, Christine A.,Dalton, John P.,Scammells, Peter J.,Drag, Marcin,McGowan, Sheena
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p. 5213 - 5217
(2013/07/26)
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- C-LINKED HYDROXAMIC ACID DERIVATIVES USEFUL AS ANTIBACTERIAL AGENTS
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The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors, and more specifically their use to treat bacterial infections.
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Page/Page column 76
(2011/05/05)
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- NOVEL TRICYCLIC DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, PROCESS FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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The present invention relates to novel tricyclic derivatives having an excellent inhibitory activity on poly (ADP-ribose) polymerase, or pharmaceutically acceptable salts thereof, a process for the preparation thereof, and a pharmaceutical composition comprising the same. The tricyclic derivatives of the present invention inhibit the activity of poly (ADP-ribose) polymerase, thereby being used for the prevention or treatment of diseases that are caused by excessive activation of PARP, in particular, neuropathic pain, neurodegenerative diseases, cardiovascular diseases, diabetic neuropathic pain, inflammatory diseases, osteoporosis, and cancer.
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Page/Page column 50
(2009/06/27)
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- Novel Urokinase Inhibitors
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The present invention relates to novel compounds with inhibitory activity towards urokinase plasminogen activator (uPA); to methods for preparation of said uPA inhibitor compounds; to pharmaceutical compositions comprising said uPA inhibitor compounds; to
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Page/Page column 28-29; 36
(2009/01/24)
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- NOVEL UROKINASE INHIBITORS
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The present invention relates to novel compounds with inhibitory activity towards urokinase plasminogen activator (uPA); to methods for preparation of said uPA inhibitor compounds; to pharmaceutical compositions comprising said uPA inhibitor compounds; to
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Page/Page column 67-68; 70-71; 81-83
(2010/11/27)
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- A p-[18F]fluoroethoxyphenyl bicyclic nucleoside analogue as a potential positron emission tomography imaging agent for varicella-zoster virus thymidine kinase gene expression
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We recently reported a new positron emission tomography (PET) reporter gene, namely, varicella-zoster virus thymidine kinase (VZV-tk) in combination, with carbon-11 or fluorine-18 labeled m-alkoxyphenyl bicyclic nucleoside analogues (BCNAs) as PET reporte
- Chitneni, Satish K.,Deroose, Christophe M.,Balzarini, Jan,Gijsbers, Rik,Celen, Sofie,Debyser, Zeger,Mortelmans, Luc,Verbruggen, Alfons M.,Bormans, Guy M.
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p. 6627 - 6637
(2008/09/17)
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- PURINE DERIVATIVES AND THEIR USE FOR TREATMENT OF AUTOIMMUNE DISEASES
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Compounds useful in the treatment of autoimmune disease are described by the following general formula (I): n = 0-2 m = 0-2 m is not necessarily equal to n; where R1, R3 = NH2, F, Cl, C1-C4 alkoxy or
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Page/Page column 21-23
(2008/06/13)
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- Diphenyl phosphonate inhibitors for the urokinase-type plasminogen activator: Optimization of the P4 position
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This paper describes the structure-activity relationship in a series of tripeptidyl diphenyl phosphonate irreversible urokinase plasminogen activator (uPA) inhibitors, originally derived from an arginyltripeptide. uPA is considered an interesting target i
- Joossens, Jurgen,Van Der Veken, Pieter,Surpateanu, Georgiana,Lambeir, Anne-Marie,El-Sayed, Ibrahim,Ali, Omar M.,Augustyns, Koen,Haemers, Achiel
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p. 5785 - 5793
(2007/10/03)
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- A novel tert-butoxycarbonylation reagent: 1-tert-butoxy-2-tert-butoxycarbonyl-1,2-dihydroisoquinoline (BBDI)
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The use of 1-tert-butoxy-2-tert-butoxycarbonyl-1,2-dihydroisoquinoline (BBDI) as a tert-butoxycarbonylation reagent for acidic proton-containing substrates such as phenols, aromatic and aliphatic amines hydrochlorides, and aromatic carboxylic acids in the absence of a base is described. The reactions proceed chemoselectively in high yield under mild conditions.
- Saito, Yukako,Ouchi, Hidekazu,Takahata, Hiroki
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p. 11599 - 11607
(2007/10/03)
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- 9-KETOSPINOSYN DERIVATIVES
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The invention relates to derivatives of 9-ketospinosyn derivatives, which are substituted in the C-9 position by a radical =N-(O, NH or NRx)-Ry, to a method for the production thereof, and to their use for controlling animal pests.
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Page/Page column 148-149
(2010/02/07)
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- Development of Irreversible Diphenyl Phosphonate Inhibitors for Urokinase Plasminogen Activator
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In this letter we report the synthesis and biochemical evaluation of selective, irreversible diphenyl phosphonate inhibitors for urokinase plasminogen activator (uPA). A diphenyl phosphonate group was introduced on the substratelike peptide Z-D-Ser-Ala-Arg, and modification of the guanidine side chain was investigated. A guanylated benzyl group appeared the most promising side chain modification. A kapp value in the 103 M -1 s-1 range for uPA was obtained, together with a selectivity index higher than 240 toward other trypsin-like proteases such as tPA, thrombin, plasmin, and FXa.
- Joossens,Van Der Veken,Lambeir,Augustyns,Haemers
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p. 2411 - 2413
(2007/10/03)
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- Synthesis of N-substituted 9-azabicyclo[3.3.1]nonan-3α-yl phenylcarbamate analogs as sigma-2 receptor ligands
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Aseries of N-substituted-9-azabicyclo[3.3.1]nonan-3α-yl)carbamate analogs was prepared and their affinities for sigma (σ1 and σ2) receptors was measured in vitro. The results of this structure-activity relationship study identified a
- Mach, Robert H.,Vangveravong, Suwanna,Huang, Yunsheng,Yang, Biao,Blair, Joseph B.,Wu, Li
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p. 380 - 398
(2007/10/03)
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- Phenalkyloxy-phenyl derivatives
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The present invention relates to certain phenalkyloxy-phenyl derivatives of formula (I) and analogs, to a process for preparing such compounds, having the utility in clinical conditions associated with insulin resistance, to methods for their therapeutic use and to pharmaceutical compositions containing them.
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- Serotonin reuptake inhibitor
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A serotonin reuptake inhibitor containing a cyclic amine represented by the following formula, a prodrug thereof, or a pharmaceutically acceptable salt of said cyclic amine or prodrug as an active ingredient: wherein R0 is a hydrogen atom, a halogen atom, an alkyl group, a substituted alkyl group, a hydroxyl group, an alkoxy group or the like, R3 is a hydrogen atom or the like, Y is an alkylene group or the like, Z is a hydrogen atom, a cycloalkyl group, an aryl group or the like, n is 1, 2 or 3, and m is 2, 3, 4, 5 or 6.
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- Amine derivative compounds
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An amine compound of the formula (I): wherein R1 represents an optionally substituted carbamoyl group, etc., R2 represents a hydrogen atom, etc., R3 represents a C1-C10 alkyl group etc., W1, W2 and W3 are the same or different and each represent a single bond or a C1-C8 alkylene group, X, Y and Q represent a sulfur atom, etc., Z represents a =CH- group, etc., Ar represents a benzene ring, etc. and L represents a hydrogen atom, etc., or a pharmacologically acceptable salt thereof. These compounds are useful in the treatment and/or prophylaxis of diseases such as diabetes, hyperlipemia, arteriosclerosis, cancer, etc.
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- Derivatives of 2-(iminomethyl)amino-phenyl, their preparation, their use as medicaments and the pharmaceutical compositions containing them
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A compound selected from the group consisting of a compound of the formula wherein A is selected from the group consisting of and the other substituents are defined in the specification having an inhibitory activity of NO-synthase enzymes producing nitrogen mono-oxide and/or an activity which traps the reactive oxygen species.
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Page column 87
(2008/06/13)
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- 3-aryl-2-hydroxypropionic acid derivative III
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A novel 3-aryl-2-hydroxypropionic acid derivative, a process and intermediate for its manufacture, pharmaceutical prepartions containing it and the use of the compound in clinical conditions associated with insulin resistance.
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- New oxybenzamide derivatives useful for inhibiting factor Xa or VIIa
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The present invention relates to compounds comprising the following formula: R0—Q—X—Q′—W—U—V—G—M??(I) These compounds are useful as pharmacologically active compounds. They exhibit an antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardiovascular disorders such as thromboembolic diseases or restenoses. These compounds are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and/or factor VIIa (FVIIa), and can generally be used to treat, prevent, or cure conditions in which an undesired activity of factor Xa and/or factor VIIa is present, or where inhibition of factor Xa and/or factor VIIa is intended. The invention further relates to processes for the preparation of these compounds, methods of their use (e.g., as active ingredients in pharmaceuticals), and pharmaceutical preparations comprising them.
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- AMINE DERIVATIVES
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An amine derivative compound of the formula (I):wherein R1 represents an optionally substituted carbamoyl group, etc., R2 represents a hydrogen atom, etc., R3 represents a C1-C10 alkyl group etc., W1, W2 and W3 are the same or different and each represent a single bond or a C1-C8 alkylene group, X, Y and Q represent a sulfur atom, etc., Z represents a =CH- group, etc., Ar represents a benzene ring, etc. and L represents a hydrogen atom, etc. or a pharmacologically acceptable salt thereof is useful as a therapeutic and/or preventing agent for diabetes, hyperlipemia, arteriosclerosis, cancer, etc.
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- Subtype-selective NMDA receptor ligands and the use thereof
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The invention relates to subtype-selective NMDA receptor ligands and the use thereof for treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, as well as treating neuro-degenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Down's syndrome, treating or preventing the adverse consequences of the overstimulation of the excitatory amino acids, treating anxiety, psychosis, convulsions, aminoglycoside antibiotics-induced hearing loss, migraine headache, chronic pain, Parkinson's disease, glaucoma, CMV retinitis, urinary incontinence, opioid tolerance or withdrawal, and inducing anesthesia, as well as for enhancing cognition.
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- Thiazolidinedione, oxazolidinedione and oxadiazolidinedione derivatives
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Novel thiazolidinedione, oxazolidinedione and oxadiazolidinedione derivatives, process for their manufacture, pharmaceutical preparations containing them and the use of the compounds in conditions associated with insulin resistance.
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- Antihypertensive dihydropyridine compositions, optical isomers and intermediates
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Compositions containing dihydropyridine derivatives which are useful for treating congestive heart failure, hypertension, or angina have the formula: STR1 or a pharmaceutically acceptable acid addition salt thereof, wherein n is an integer from 0 to 8; Y is --O--, --NH--, --NR2 --, --S--, --S(O)--, --S(O)2 --, or a bond; R1 and R2 are each independently A1, A2, A3 or A4 where A1 is --(CH2)m (CHOH)p CH2 OH; A2 is --(CH2)q CH(3-r) [(CH2)s OH]r ; A3 is --(CH2)q CH(3-r) [(CH2)p COOR3 ]r ; and A4 is --(CH2)m COOR3 ; where m is an integer from 1 to 8; p is an integer from 0 to 4; q is an integer from 0 to 8; r is 2 or 3; s is an integer from 1 to 4; and R3 is H or alkyl of 1 to 18 carbon atoms; R4 is --NO2, --CF3, or halo; and R5 is lower alkyl or --CH2 CH2 OCH3. Also disclosed are optical isomers of the above compounds, as well as intermediates in the preparation of these final products.
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