- Structure-Activity Relationships in Prazosin-Related Compounds. 2. Role of the Piperazine Ring on α-Blocking Activity
-
Several prazosin-related compounds have been synthesized and evaluated for their blocking activity toward α-adrenoreceptors.The structural modification performed on the prazosin structure included the replacement of the piperazine ring with 2,3-dialkylpiperazine or 1,2-cyclohexanediamine moieties to characterize a lipophilic binding pocket in the α1 adrenoreceptor surface.Cyclohexanediamine derivatives 3-6 were almost devoid of potency and selectivity, whereas dialkylpiperazine compounds 7-14 showed high affinity and selectivity toward α1-adrenoreceptors.The cis derivative 13 (cyclazosin) was the most potent and selective with an α1/α2 selectivity ratio value of 7800.The particular trend of antagonist activity within cis/trans stereoisomeric compounds not only supports the presence of a lipophilic binding area on α1-adrenoreceptor surface but also suggests that the lipophilic pocket is endowed with a well-defined size and spatial orientation.The most active compound of the series, 13, was tested also in vivo for antihypertensive activity on spontaneously hypertensive rats.It showed an interesting long-lasting hypotensive effect, very similar to that of doxazosin, which was statistically significant 12 h after oral administration.
- Giardina, Dario,Gulini, Ugo,Massi, Maurizio,Piloni, Maria G.,Pompei, Pierluigi,et al.
-
-
Read Online
- Optimization of piperazine-derived ureas privileged structures for effective –antiadenovirus agents
-
In recent years, human adenovirus (HAdV) infections have shown a high clinical impact in both immunosuppressed and immunocompetent patients. The research into specific antiviral drugs for the treatment of HAdV infections in immunocompromised patients cons
- Mazzotta, Sarah,Marrugal-Lorenzo, José Antonio,Vega-Holm, Margarita,Serna-Gallego, Ana,álvarez-Vidal, Jaime,Berastegui-Cabrera, Judith,Pérez del Palacio, José,Díaz, Caridad,Aiello, Francesca,Pachón, Jerónimo,Iglesias-Guerra, Fernando,Vega-Pérez, José Manuel,Sánchez-Céspedes, Javier
-
-
Read Online
- New 4-Acyl-1-phenylaminocarbonyl-2-phenylpiperazine Derivatives as Potential Inhibitors of Adenovirus Infection. Synthesis, Biological Evaluation, and Structure-activity Relationships
-
The search for human adenovirus (HAdV)-specific antiviral drugs for the treatment of HAdV infections in immunocompromised patients continues to be a challenging goal for medicinal chemistry. Here, we report the synthesis, biological evaluation, and struct
- Sánchez-Céspedes, Javier,Martínez-Aguado, Pablo,Vega-Holm, Margarita,Serna-Gallego, Ana,Candela, José Ignacio,Marrugal-Lorenzo, José Antonio,Pachón, Jerónimo,Iglesias-Guerra, Fernando,Vega-Pérez, José Manuel
-
-
Read Online
- PARP inhibitor containing phthalazine-1 -(2H)-ketone structure as well as preparation method and medical application of PARP inhibitor
-
The invention discloses a PARP inhibitor containing a phthalazine-1(2H)-ketone structure as well as a preparation method and medical application of the PARP inhibitor. A compound as shown in a generalformula (I) or a pharmaceutically acceptable salt there
- -
-
Paragraph 0032; 0034-0035
(2021/02/20)
-
- Optimization of 5-substituted thiazolyl ureas and 6-substituted imidazopyridines as potential HIV-1 latency reversing agents
-
A persistent latent reservoir of virus in CD4+ T cells is a major barrier to cure HIV. Activating viral transcription in latently infected cells using small molecules is one strategy being explored to eliminate latency. We previously described the use of a FlpIn.FM HEK293 cellular assay to identify and then optimize the 2-acylaminothiazole class to exhibit modest activation of HIV gene expression. Here, we implement two strategies to further improve the activation of viral gene expression and physicochemical properties of this class. Firstly, we explored rigidification of the central oxy-carbon linker with a variety of saturated heterocycles, and secondly, investigated bioisosteric replacement of the 2-acylaminothiazole moiety. The optimization process afforded lead compounds (74 and 91) from the 2-piperazinyl thiazolyl urea and the imidazopyridine class. The lead compounds from each class demonstrate potent activation of HIV gene expression in the FlpIn.FM HEK293 cellular assay (both with LTR EC50s of 80 nM) and in the Jurkat Latency 10.6 cell model (LTR EC50 220 and 320 nM respectively), but consequently activate gene expression non-specifically in the FlpIn.FM HEK293 cellular assay (CMV EC50 70 and 270 nM respectively) manifesting in cellular cytotoxicity. The lead compounds have potential for further development as novel latency reversing agents.
- Blackmore, Timothy R.,Jacobson, Jonathan,Jarman, Kate E.,Lewin, Sharon R.,Nguyen, William,Purcell, Damian F.,Sabroux, Helene Jousset,Sleebs, Brad E.
-
-
- PIPERAZINE DERIVATIVES AS ANTIVIRAL AGENTS WITH INCREASED THERAPEUTIC ACTIVITY
-
The present invention provides 2-phenylpiperazine derivatives having a benzofuran-2-yl group which contributes to increase the antiviral activity as well as, for some substituents, the CC50, giving more active and less cytotoxic compounds. Alth
- -
-
Page/Page column 21
(2017/09/15)
-
- INHIBITORS OF WDR5 PROTEIN-PROTEIN BINDING
-
The present application is directed to compounds of Formula I: compounds comprising these compounds and their uses, for example as medicaments for the treatment of diseases, disorders or conditions mediated or treatable by inhibition of binding between WDR5 protein and its binding partners.
- -
-
Paragraph 00481
(2017/09/15)
-
- HEPATITIS B VIRAL ASSEMBLY EFFECTORS
-
Novel assembly effector compounds having a therapeutic effect against hepatitis B viral (HBV) infection are disclosed. Assembly effector molecules described herein can lead to defective viral assembly and also may affect other viral activities associated with chronic HBV infection. Also disclosed is a process to synthesize disclosed compounds, method of treatment of HBV by administration of disclosed compounds, and use of these compounds in the manufacture of medicaments against HBV.
- -
-
Paragraph 00286
(2016/10/31)
-
- Design, synthesis and antibacterial evaluation of novel fluoroquinolone and its derivatives
-
Gatifloxacin isomers, [1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(2- methyl-1-piperazinyl)-4-oxo-3-quinoline carboxylic acid] and a series of its derivatives were designed and synthesized and evaluated for their in vitro antibacterial activities. Pre
- Wang, Kang-Min,Qin, Yuan-Cheng,Cheng, Guan-Jun,Zhu, Hua-Jun,Liang, Long,Cheng, Zhi-Peng,Luo, Mei-Ming
-
p. 209 - 215
(2014/03/21)
-
- Hetero-difunctional dimers as building blocks for the synthesis of poly(amidoamine)s with hetero-difunctional chain terminals and their derivatives
-
This article reports on a simple and straightforward preparation method of poly(amidoamine)s (PAAs) with hetero-difunctional chain ends as well as of several up to now hardly obtainable PAA derivatives of biotechnological interest, such as for instance PAAs of controlled molecular weight and narrow polydispersity mono-functionalized at one end with an acrylamide group, PAAs with star-like molecular architecture, graft-PAA-protein conjugates, "tadpole-like" PAA conjugates with hydrophobic moieties able to self assemble into nanoparticles in aqueous media. The key step was to design suitable building blocks consisting of hetero-difunctional dimers (HDDs). In particular, the HDDs considered were the mono-addition products of bis-sec-amines and bisacrylamides expected to give PAAs of proven biomedical potential and were obtained as hydrochlorides or trifluoroacetates. In this form, they could be indefinitely kept dormant at 0-5 °C in the dry state, whereas at room temperature and in aqueous media, they polymerized at pH > 7.5. The preparation of the above-cited PAA derivatives did not necessarily involve the preliminary synthesis of hetero-difunctional PAAs but was directly achieved by one-pot polymerization of HDDs in the presence of the substrates of interest.
- Ferruti, Paolo,Mauro, Nicolo,Manfredi, Amedea,Ranucci, Elisabetta
-
p. 4947 - 4957
(2013/01/15)
-
- METHODS OF USING DIHYDROPYRIDOPHTHALAZINONE INHIBITORS OF POLY (ADP-RIBOSE)POLYMERASE (PARP)
-
Provided herein are methods of treating cancer comprising administering a topoisomerase inhibitor, temozolomide, or a platin in combination with a Compound of Formula (I) or Formula (II), where the substituents Y, Z, A, B, R1, R2, R3, R4 and R5 are as defined herein.
- -
-
Page/Page column 180
(2011/11/01)
-
- DIHYDROPYRIDOPHTHALAZINONE INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE (PARP)
-
A compound having the structure set forth in Formula (I) and Formula (II): wherein the substituents Y, Z, A, B, R1, R2, R3, R4 and R5 are as defined herein. Provided herein are inhibitors of poly(ADP-ribose)polymerase activity. Also described herein are pharmaceutical compositions that include at least one compound described herein and the use of a compound or pharmaceutical composition described herein to treat diseases, disorders and conditions that are ameliorated by the inhibition of PARP activity.
- -
-
Page/Page column 92
(2010/03/02)
-
- INDOLYLALKYL DERIVATIVES OF PYRIMIDINYLPIPERAZINE AND METABOLITES THEREOF FOR TREATMENT OF ANXIETY, DEPRESSION, AND SEXUAL DYSFUNCTION
-
The present invention relates to a method for alleviation, prevention, and treatment of anxiety, depression, and sexual dysfunction by administering certain indolylalkyl derivatives of pyrimidinylpiperazine or metabolites thereof. A preferred embodiment is of the following formula:
- -
-
-
- FIVE-MEMBERED HETEROCYCLIC DERIVATIVE
-
The present invention relates to a compound represented by formula (I): a salt of the compound, or a solvate of the compound or the salt; a drug containing any of the compounds, the salts, and the solvates; a preventive and/or therapeutic agent for an ischemic disease containing any of the compounds, the salts, and the solvates; and a platelet coagulation inhibitor containing any of the compounds, the salts, and the solvates. The compound of the present invention is useful as a strong platelet coagulation inhibitor without inhibiting COX-1 or COX-2.
- -
-
Page/Page column 39-40
(2010/11/08)
-
- PROCESS FOR PRODUCING OXYCARBONYL-SUBSTITUTED PIPERAZINE DERIVATIVE
-
If an organic solvent with a water content of 15% or less is used when an oxycarbonyl-substituted piperazine derivative is produced from a piperazine derivative, the piperazine derivative can be oxycarbonylated.
- -
-
Page/Page column 19
(2008/06/13)
-
- BENZIMIDAZOLE QUINOLINONES AND USES THEREOF
-
Methods of inhibiting various enzymes and treating various conditions are provided that include administering to a subject a compound of Structure I or IB, a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer. Compounds having the Structure I and IB have the following structures and have the variables described herein. Such compounds may be used to prepare medicaments for use in inhibiting various enzymes and for use in treating conditions mediated by such enzymes.
- -
-
-
- Substituted dipeptides having nos inhibiting activity
-
The present invention a compound represented by the formula (I): where the structural variables R1-R6are defined herein.
- -
-
Page column 28
(2010/02/09)
-
- Cyanophenyl derivative
-
This application relates to a piperazino-substituted novel cyanophenyl derivative in which a substituted carbamoyl or substituted sulfamoyl group having an aryl, heterocyclic or the like group that may have a substituent group is bonded to one nitrogen atom on the piperazine ring. The compound of this application has an anti-androgen action and is useful in preventing or treating prostatic cancer, benign prostatic hyperplasia and the like diseases.
- -
-
Page column 12
(2010/11/30)
-
- PIPERAZINE AND HOMOPIPERAZINE COMPOUNDS
-
Compounds are provided having a piperazine or homopiperazine ring which are useful in the treatment of thrombosis.
- -
-
-
- CYANOPHENYL DERIVATIVES
-
This application relates to a piperazino-substituted novel cyanophenyl derivative in which a substituted carbamoyl or substituted sulfamoyl group having an aryl, heterocyclic or the like group that may have a substituent group is bonded to one nitrogen atom on the piperazine ring. The compound of this application has an anti-androgen action and is useful in preventing or treating prostatic cancer, benign prostatic hyperplasia and the like diseases.
- -
-
-
- Antimigraine 4-pyrimidinyl and pyridinyl derivatives of indol-3yl-alkylpiperazines
-
A series of novel alkoxypyridin-4-yl and alkoxypyrimidin-4-yl derivatives of indol-3-ylalkylpiperazines of Formula I are intended to be useful agents STR1 for alleviation of vascular headache on the basis of their potent affinity and agonist activity at 5-HT1D binding sites.
- -
-
-
- INDOLYLALKYL DERIVATIVES OF PYRIMIDINYLPIPERAZINE FOR TREATING VASCULAR HEADACHE
-
A series of novel indol-3-ylalkyl derivatives of alkoxypyrimidinylpiperazines are disclosed as Formula I. STR1 These compounds are intended to be useful agents for alleviation of vascular headache on the basis of their potent affinity and agonist activity at 5-HT1D binding sites.
- -
-
-
- N-aryl-piperazinealkanamides useful for improving sleep
-
A method of improving sleep in warm-blooded animals suffering from sleep disorders, which method comprises the administration of particular N-aryl-piperazinealkanamide derivatives and compositions containing the same. Novel N-aryl-piperazinealkanamide derivatives.
- -
-
-