cas 139756-21-1, 5-(2-ETHOXYPHENYL)-1-METHYL-3-N-PROPYL-1,6-DIHYDRO-7H-PYRAZOLO[4,3-D]-7-PYRIMIDINONE

Articles about 139756-21-1Total 31 be found

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Design, synthesis and biological evaluation of pyrazolopyrimidinone based potent and selective PDE5 inhibitors for treatment of erectile dysfunction
Our previous discovery of series of pyrazolopyrimidinone based PDE5 inhibitors led to find potent leads but with low aqueous solubility and poor bioavailability, and low selectivity. Now, a new series of same pyrazolopyrimidinone scaffold is designed, synthesized and evaluated for its PDE5 inhibitory potential. In this study, some of the molecules are found more potent and selective PDE5 inhibitors in vitro than sildenafil. The studies revealed that compound 5 is 20 fold selective to PDE5 against PDE6. As PDE6 enzyme is involved in the phototransduction pathway in the retina and creates distortion problem, the selectivity for PDE5 specifically against PDE6 enzyme is preferred for any development candidate and in present study, compound 5 has been found to be devoid of this liability of selectivity issue. Moreover, compound 5 has shown excellent in vivo efficacy in conscious rabbit model, it's almost comparable to sildenafil. The preclinical pharmacology including pharmacokinetic and physicochemical parameter studies were also performed for compound 5, it was found to have good PK properties and other physicochemical parameters. The development of these selective PDE5 inhibitors can further lead to draw strategies for the novel preclinical and/or clinical candidates based on pyrazolopyrimidinone scaffold.
Reddy, G. Lakshma,Dar, Mohd. Ishaq,Hudwekar, Abhinandan D.,Mahajan, Priya,Nargotra, Amit,Baba, Adil Manzoor,Nandi, Utpal,Wazir, Priya,Singh, Gurdarshan,Vishwakarma, Ram A.,Syed, Sajad Hussain,Sawant, Sanghapal D.
(2019)
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An efficient one-pot synthesis of pyrazolopyrimidines, intermediates for potential phosphodiesterase inhibitors
A simple high-yielding procedure is presented for the synthesis of pyrazolopyrimidinones overcoming limitations found in earlier work and of considerable utility for the production of intermediates for potential phosphodiesterase inhibitors. Springer-Verlag 2005.
Abdel-Jalil, Raid J.,Khanfar, Monther,Abu-Safieh, Kayed,Al-Gharabli, Samer,El-Abadelah, Mustafa,Voelter, Wolfgang
p. 619 - 624
(2005)
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Sulphonated graphene oxide catalyzed continuous flow synthesis of pyrazolo pyrimidinones, sildenafil and other PDE-5 inhibitors
Sulphonated graphene oxide was used for cascade condensation and cyclization reactions towards accessing substituted pyrazolo pyrimidinones. Further, sulphonation and amination reactions were integrated through continuous flow chemistry to access PDE-5 inhibitors. Herein, we report a simple continuous synthetic platform that reduce tedious manual operations and accelerate the synthesis of several potent inhibitors of phosphodiesterase type-5. The developed platform enabled us to perform one-flow multi-step, multi-operational process to synthesize the PDE-5 inhibitors such as sildenafil and its analogues in 32.3 min of the reaction time, with minimal human intervention and single solvent.
Karra, Purushotham Reddy,Mahajan, Bhushan,Pabbaraja, Srihari,Singh, Ajay K.,Sthalam, Vinay Kumar
p. 326 - 330
(2022/01/19)

Diversity in Heterocycle Synthesis Using α-Iminocarboxylic Acids: Decarboxylation Dichotomy
Despite the structural similarity with imines, α-iminocarboxylic acids have seldom been used in heterocycles synthesis. The reactions of ortho-substituted anilines and arylglyoxylic acids in DMSO at 40 °C gave various benzo-fused five- to six-membered N-heterocycles in good to excellent yields. The reaction proceeds via intramolecular Michael addition of α-iminocarboxylic acids, generated in situ, with an ortho-substituted nucleophile, yielding an isolable unprecedented tetrahedral carboxylic acids, which upon decarboxylation without any aid of additional reagents forms the N-heterocycles. DMSO is crucial in this reaction, perhaps because of improved solubility and the ease of decarboxylation of these tetrahedral carboxylic acids. However, a copper-catalyzed reaction of ortho-substituted anilines and 2-bromoarylglyoxylic acids gave a dibenzo-fused seven-membered N-heterocycle under a basic reaction condition. Unlike intramolecular cyclization with α-iminocarboxylic acids in the first case, α-iminocarboxylic acid undergoes a competitive decarboxylation under the copper-catalyzed conditions, which upon subsequent heteroarylation form the heterocycles. Taken together, the study described herein represents two different modes of decarboxylation observed with α-iminocarboxylic acids, leading to the synthesis of divergent heterocycles and pharmaceuticals, which remained unexplored previously.
Hunjan, Mandeep Kaur,Laha, Joydev K.
(2022/02/07)

α-Keto Acids as Triggers and Partners for the Synthesis of Quinazolinones, Quinoxalinones, Benzooxazinones, and Benzothiazoles in Water
A general and efficient method for the synthesis of quinazolinones, quinoxalinones, benzooxazinones, and benzothiazoles from the reactions of α-keto acids with 2-aminobenzamides, benzene-1,2-diamines, 2-aminophenols, and 2-aminobenzenethiols, respectively, is described. The reactions were conducted under catalyst-free conditions, using water as the sole solvent with no additive required, and successfully applied to the synthesis of sildenafil. More importantly, these reactions can be conducted on a mass scale, and the products can be easily purified through filtration and washing with ethanol (or crystallized).
Huang, Jian,Chen, Wei,Liang, Jiazhi,Yang, Qin,Fan, Yan,Chen, Mu-Wang,Peng, Yiyuan
p. 14866 - 14882
(2021/10/25)

Improved, gram-scale synthesis of sildenafil in water using arylacetic acid as the acyl source in the pyrazolo[4,3-d]pyrimidin-7-one ring formation
An improved, gram-scale synthesis of the blockbuster drug sildenafil, used for the treatment of male erectile dysfunction, has been developed. Unlike the previous literature, the current method demonstrates the use of arylacetic acid as an acyl source, a cheap oxidant K2S2O8, and water as the reaction medium in the key step of pyrrazolo[4,3-d]pyrimidin-7-one ring formation. As well as being a green and benign approach, the current method reduces the cost by half compared to our previous strategy. In addition, the general relevance of the method has been demonstrated in the synthesis of a variety of quinazolinone and benzothiazole derivatives with excellent functional group tolerance.
Laha, Joydev K.,Gulati, Upma,Saima,Gupta, Anjali,Indurthi, Harish Kumar
p. 2643 - 2648
(2021/02/16)

Improved synthesis process of sildenafil
The invention discloses an improved synthesis process of sildenafil, belonging to the technical field of preparation of drug intermediates. In the process, high-concentration chlorosulfonic acid is prevented from being used as a reaction solvent and reagent, and 3-5 equivalent chlorosulfonic acid is used as a reaction reagent. Compared with the prior art, the process has the characteristics of economical performance, environmental protection, safety and the like, for example, equipment cannot be corroded, the post-treatment of reaction becomes simpler, the solvent is single and can be reused, product purity is high, and the like.
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(2021/06/21)

Ortho -Naphthoquinone-catalyzed aerobic oxidation of amines to fused pyrimidin-4(3 H)-ones: A convergent synthetic route to bouchardatine and sildenafil
A facile access to fused pyrimidin-4(3H)-one derivatives has been established by using the metal-free ortho-naphthoquinone-catalyzed aerobic cross-coupling reactions of amines. The utilization of two readily available amines allowed a direct coupling strategy to quinazolinone natural product, bouchardatine, as well as sildenafil (Viagra) in a highly convergent manner. This journal is
Kim, Hun Young,Kim, Kyeongha,Oh, Kyungsoo
p. 31101 - 31105
(2020/09/23)

Method for preparing sildenafil citrate
The invention discloses a method for preparing sildenafil citrate. The preparation method comprises the following steps: (a) adding a compound II into chlorosulfonic acid for a reaction to generate anintermediate III; (b) reacting the intermediate III with N-methyl piperazine to generate a crude sildenafil product; (c) recrystallizing the crude sildenafil product to obtain a pure sildenafil product; and (d) carrying out a salifying reaction on the pure sildenafil product to obtain sildenafil citrate. The method is beneficial for industrial production.
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(2020/05/30)

Method for synthesizing 2-heterocyclic benzene (2,3-d) pyrimidine-4(3H)-ketone compounds
The invention discloses a method for synthesizing 2-heterocyclic benzene (2,3-d) pyrimidine-4(3H)-ketone compounds. Carbon bond rupture of styrene compound carbon is utilized to generate benzaldehydecompounds, the generated benzaldehyde compounds and heterocyclic o-amino-formamide compounds are subjected to intermolecular condensation coupling reaction to obtain the 2-heterocyclic benzene (2,3-d)pyrimidine-4(3H)-ketone compounds, wherein the styrene compounds refer to styrene or 2-ethoxystyrene, and the heterocyclic o-amino-formamide compounds refer to 3-aminothiophene-2-formamide or 4-amino-1-methyl-3-n-propyl-1H-pyrazol-5-formamide. The method has the advantages that raw materials are easy to obtain, and more economy is achieved; efficient reaction and high yield are achieved; high temperature and high pressure are not needed, and reaction conditions are moderate; the synthesis process is easy to operate, and the obtained product is easy for post-processing and suitable for large scale production.
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Paragraph 0060; 0061; 0062

(2018/11/03)

Preparation method of 5-(2-ethyoxyl phenyl)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidine-7-ketone
The invention relates to a preparation method of 5-(2-ethyoxyl phenyl)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidine-7-ketone. According to the invention, in an organic solvent, under oxygen condition, 2-ethoxystyrene and 4-amino-1-methyl-3-propylpyrazole-5-methanamide is used as a reaction raw material, under co-promotion effect of a transition metal palladium catalyst and a nitrogen-containingligand, 2-ethyoxyl benzaldehyde is obtained through oxidative cleavage of olefin carbon-carbon double bonds, and the 5-(2-ethyoxyl phenyl)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidine-7-ketone is obtained through closed-loop condensation of 4-amino-1-methyl-3-propylpyrazole-5-methanamide and 2-ethyoxyl benzaldehyde. The method has the advantages of simple reaction condition, and high product yield and purity, develops a novel synthesis route and a method for developing the 5-(2-ethyoxyl phenyl)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidine-7-ketone, and has good application potential and research value.
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Paragraph 0014; 0036-0039; 0045-0059

(2018/11/27)

Sildenafil intermediate synthesis method
Sildenafil has a good effect of treating male erectile dysfunction (ED) in clinic. Many preparation methods of sildenafil have been already reported and mostly belong to two-step synthesis. The two-step post-treatment operation is relatively tedious, and yield is low. The invention provides a synthesis method of a sildenafil intermediate, comprising the following steps: dissolving a compound II inan organic aprotic solvent, and adding a compound I to carry out a condensation reaction; adding alkali to carry out a cyclization reaction after it is monitored that the compound II is completely reacted so as to obtain a compound IV. By ''one-pot'' synthesis, generation of ''three wastes (waste gas, waste water and industrial residue)'' is reduced, reaction time is greatly shortened, reaction yield is raised, and stability is good.
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Paragraph 0033-0046

(2018/10/19)

5 - aryl - 1 H - pyrazolo [4, 3 - d] pyrimidin - 7 (6 H) - ketone synthesis process
The invention discloses a synthesis technology of 5-aryl-1H-pyrazolopyridine[4,3-d]pyrimidine-7(6H)-ketone. The synthesis technology comprises the following steps: mixing substituted aryl aldehyde with 1-methyl-3-propyl-4-amino pyrazole-5-formylamine, and contracting the mixture so as to obtain bisiminophosphorane benzyl benzoate; placing the bisiminophosphorane benzyl benzoate in a solvent, and under the common action of a ring forming agent and a pro-oxygenic agent, performing cyclization oxidization so as to obtain the 5-aryl-1H-pyrazolopyridine[4,3-d]pyrimidine-7(6H)-ketone. The synthesis technology disclosed by the invention is mild in reacting conditions, greatly higher in the conversion rate of a cyclization oxidation reaction, short in the reaction time, and less in the side reactions. The reaction can be carried out in different reactors in two steps, and can also be carried out in the same reactor. A stepwise synthesis method is favorable for the quality control of the bisiminophosphorane benzyl benzoate and the purification of products, the adoption of a one-step synthesis method simplifies the synthetizing working procedures and shortens the reaction time, and all the methods can effectively synthetize the 5-aryl-1H-pyrazolopyridine[4,3-d]pyrimidine-7(6H)-ketone. The used reagent is basically non-toxic or low-toxic, and besides, the synthesis technology is low in cost and is low in synthesis cost.
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Paragraph 0067; 0068; 0069; 0070

(2017/08/31)

Formation of amides, their intramolecular reactions for the synthesis of N-heterocycles, and preparation of a marketed drug, sildenafil: A comprehensive coverage
A unified approach to the tandem preparation of diverse nitrogen heterocycles via decarboxylative acylation of ortho-substituted amines with α-oxocarboxylic acids and subsequent intramolecular cyclizations has been developed. The key features of this work include: the first example of transition-metal-free decarboxylative amidation of α-oxocarboxylic acids with ortho-substituted amines, realization of intramolecular cyclization of amides employing nucleophiles that have previously been unexplored, mechanistic investigation of an unprecedented K2S2O8 promoted amide formation and its subsequent intramolecular cyclizations, and application to the synthesis of a best-selling marketed drug.
Laha, Joydev K.,Patel, Ketul V.,Satyanarayana Tummalapalli,Dayal, Neetu
supporting information
p. 10245 - 10248
(2016/08/23)

NOVEL COMPOUNDS FOR USE IN COGNITION IMPROVEMENT
Novel compounds for use in cognition improvement It relates to certain compounds having a polycyclic structure and a -(C=O)NRaRb moiety, wherein the polycyclic structure comprises at least three ring systems, wherein one ring system is a polycyclic ring system comprising from 2 to 4 rings; at least one ring is an aromatic ring; and wherein the structure comprises at least 3 nitrogen atoms and 1 oxygen atom. It also relates to pharmaceutical compositions containing them, and to their use in medicine, in particular in the treatment and/or prevention of neurological disorders coursing with a cognition deficit or impairment, or neurodegenerative diseases.
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Page/Page column 51

(2016/04/19)

Sedinafine derivatives of the microwave-assisted method for preparing
The invention discloses a microwave-assisted synthesis method of sildenafil derivatives, which mainly comprises the following steps: by using 2-alkoxybenzoic acid and 4-amino-1-methyl-3-n-propyl-1H-pyrazolyl-5-formamide as initial raw materials, carrying out amidation, cyclization, mononitration, nitro reduction, guanidylation and the like to obtain the sildenafil derivatives. The method greatly shortens the reaction time, enhances the reaction efficiency, has the advantages of high yield and high purity, is simple to operate and easy to control, and is beneficial to industrial production of sildenafil analogs.
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(2016/12/07)

PYRAZOLOPYRIMIDINONES FOR THE TREATMENT OF IMPOTENCE AND PROCESS FOR THE PREPARATION THEREOF
The present invention relates to Pyrazolopyrimidinone compounds as PDE5 inhibitors with better IC50 value, good in vivo efficacy and PK profile and a process for the preparation thereof. The present invention covers the pyrazolo pyrimidinone based compounds that have been designed, synthesized and screened for PDE5 inhibitory activity and its PDE5 inhibitory potential is provided in this invention. These designer compounds have shown nanomolar potency when screened for PDE5 inhibitory activity and also shown better in vivo efficacy. These compounds can be used in the treatment of male erectile dysfunction or in the treatment of impotence.
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Page/Page column 48

(2015/09/23)

Synthesis of 5-substituted-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one analogs and their biological evaluation as anticancer agents: mTOR inhibitors
A microwave assisted strategy for synthesis of series of 1H-pyrazolo[4,3-d]pyrimidin-7(6H)-ones has been developed and their biological evaluation as anticancer agents is described. The synthetic protocol involves simple procedure by oxidative coupling of 4-amino-1-methyl-3-propyl-1H-pyrazole- 5-carboxamide with different aldehydes in presence of K2S 2O8 offering 5-substituted-1H-pyrazolo[4,3-d]pyrimidin- 7(6H)-one compounds in excellent yields. The in vitro anticancer activity screening against human cancer cell lines HeLa, CAKI-I, PC-3, MiaPaca-2, A549 gave good results. The in detailed mechanistic correlation studies of compound 3m revealed that the compound shows anticancer activity through apoptosis mechanism and also inhibits mTOR with nonomolar potency. The design was based on docking with mTOR protein. The concentration dependent cell cycle analysis, western blotting experiment and nuclear cell morphology studies have been described.
Reddy, G. Lakshma,Guru, Santosh Kumar,Srinivas,Pathania, Anup Singh,Mahajan, Priya,Nargotra, Amit,Bhushan, Shashi,Vishwakarma, Ram A.,Sawant, Sanghapal D.
p. 201 - 208
(2014/05/20)

NOVEL COMPOUNDS AS DUAL INHIBITORS OF PHOSPHODIESTERASES AND HISTONE DEACETYLASES
It relates to certain compounds having a polycyclic structure and a hydroxamic acid moiety, wherein the polycyclic structure comprises at least three ring systems, wherein one ring system is a polycyclic ring system comprising from 2 to 4 rings; at least one ring is an aromatic ring; and wherein the structure comprises at least 3 nitrogen atoms and 1 oxygen atom. It also relates to a process for their preparation, as well as to pharmaceutical compositions containing them, and to their use in medicine, in particular in the treatment and/or prevention of neurological disorders coursing with a cognition deficit or impairment, or neurodegenerative diseases. wherein B1 is a radical selected from the group consisting of formula (A"), formula (B"), formula (C"), and formula (D"):
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Page/Page column 81; 82

(2014/09/16)

Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 1. Sildenafil analogs
Parasitic diseases, such as African sleeping sickness, have a significant impact on the health and well-being in the poorest regions of the world. Pragmatic drug discovery efforts are needed to find new therapeutic agents. In this Letter we describe target repurposing efforts focused on trypanosomal phosphodiesterases. We outline the synthesis and biological evaluation of analogs of sildenafil (1), a human PDE5 inhibitor, for activities against trypanosomal PDEB1 (TbrPDEB1). We find that, while low potency analogs can be prepared, this chemical class is a sub-optimal starting point for further development of TbrPDE inhibitors.
Wang, Cuihua,Ashton, Trent D.,Gustafson, Alden,Bland, Nicholas D.,Ochiana, Stefan O.,Campbell, Robert K.,Pollastri, Michael P.
p. 2579 - 2581
(2012/05/05)

Liquid-chromatography determination of impurities in sildenafil citrate
A simple, economic and time-efficient stability-indicating, reversed phase liquid chromatographic (RP-LC) method has been developed for the analysis of sildenafil citrate in the presence of both process related impurities and degradation products generated by decomposition. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. Considerable degradation was found to occur in alkali and oxidative stress conditions. The drug was found to be stable to other stress conditions attempted. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 99.6 %. The method was validated with respect to specificity, linearity, accuracy, precision, robustness, limit of detection and quantification. The method is simple, rapid, selective, accurate and stability indicating, useful in the quality control of bulk manufacturing of sildenafil.
Kumar, A.Phani,Ganesh,Prasad, K. Hari,Hariharakrishnan,Dubey,Rao, B. Venugopala
experimental part
p. 1219 - 1222
(2012/01/05)

Synthesis and pharmacological evaluations of sildenafil analogues for treatment of erectile dysfunction
The 5-[2-ethoxy-5-(4-methylpiperazin-1-ylsulfonyl)phenyl]-1-methyl-3- propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one, sildenafil, is a cGMP-specific phosphodiesterase-5 (PDE5) inhibitor used for penile erectile dysfunction. In the search for more potent and selective PDE5 inhibitors, new sildenafil analogues (6a-v), characterized by the presence on the sulfonyl group in the 5′ position of novel N-4-substituted piperazines or ethylenediamine moiety, were prepared by traditional and microwave-assisted synthesis and tested in rabbit isolated aorta and corpus cavernosum. Similarly to sildenafil, several analogues showed IC50 values in the nanomolar range. In the in vitro studies, all the tested compounds caused concentration-dependent relaxations in both rabbit isolated aorta and corpus cavernosum. All sildenafil analogues potentiated the nitric oxide-dependent vasodilation in endothelium-intact rabbit aorta. Compound 6f exhibited great pEC50 value in corpus cavernosum, and compounds 6r and 6u in isolated aorta were found as potent as sildenafil for inhibiting PDE5. Because several analogues were significantly more lipophilic than sildenafil, these compounds may offer a new lead for development of new sildenafil analogues.
Flores Toque, Haroldo A.,Priviero, Fernanda B. M.,Teixeira, Cleber E.,Perissutti, Elisa,Fiorino, Ferdinando,Severino, Beatrice,Frecentese, Francesco,Lorenzetti, Raquel,Baracat, Juliana S.,Santagada, Vincenzo,Caliendo, Giuseppe,Antunes, Edson,De Nucci, Gilberto
p. 2807 - 2815
(2008/12/22)

PYRAZOLOPYRIMIDINETHIONE DERIVATIVES, SALTS AND SOLVATES THEREOF, PREPARATION METHODS AND USE THEREOF
The present invention disclosed the pyrazolopyrimidinethione derivatives, salts and solvates thereof, preparation methods and use thereof. The pyrazolopyrimidinethione derivatives according to the present invention possess the structure of general formula I , wherein, R1, R2, R3, and R4 represent alkyl, alkenyl, or aryl; R5 represents hydrogen, alkyl, alkenyl, alkoxy, cycloalkyloxy, aryl, or alkylacyl; and R6 represents hydrogen, alkyl, alkenyl, cycloalkyloxy, or alkylacyl. The pharmaceuticals containing the compound of the present invention and used for the treatment of impotence and sexlessness have the advantages of high selectivity over PDEV, long action time, and less side reactions, and the pharmaceuticals will arouse no side reactions of blood pressure decreasing and heart rate increasing, and it has broad market propect.
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Example 2

(2008/06/13)

High throughput synthesis of pyrazolopyrimidines via copper- catalysed cyclization and X-ray study
A rapid and easy high-yielding synthesis of pyrazolopyrimidinones in the presensce of copper chloride is described. To fully confirm the structure of a Viagra intermediate, the X-Ray structure of 5-(2-ethoxyphenyl)-1-methyl-3- propyl-1,6-dihydropyrazolo[4,3-d]pyrimidin-7-one (2a) was determined.
Abdel-Jalil, Raid J.,Khanfar, Monther,Al-Gharabli, Samer,El-Abadelah, Mustafa M.,Eichele, Klaus,Anwar, Muhammad Usman,Voelter, Wolfgang
p. 1821 - 1827
(2007/10/03)

Comparison of different heterocyclic scaffolds as substrate analog PDE5 inhibitors
Several different heterocyclic systems were compared as PDE5 inhibitor scaffolds. In addition to the known 3H-imidazo[5,1-f][1,2,4]triazin-4-ones and pyrazolopyrimidinones, isomeric imidazo[1,5-a][1,3,5]triazin-4(3H)-ones were also shown to be potent and selective PDE inhibitor scaffolds with in vivo activity. SAR trends were elucidated for sulfonamide derivatives with generality across different scaffolds.
Haning, Helmut,Niewoehner, Ulrich,Schenke, Thomas,Lampe, Thomas,Hillisch, Alexander,Bischoff, Erwin
p. 3900 - 3907
(2007/10/03)

A modified, economical and efficient synthesis of variably substituted pyrazolo[4,3-d]pyrimidin-7-ones
1-Methyl-3-propyl-1H-pyrazole-5-carboxylic acid (3) was exclusively brominated at the 4-position by bromine in the dark. Brominated product 8 was then converted into 1-methyl-3-propyl-1H-pyrazole-5-carboxamide 9 by successive treatment with thionyl chloride and ammonium hydroxide. Carboxamide 9 was treated with various aroyl amides under microwave (MW) irradiation to afford 4-aroylamino-1-methyl-3-propyl-1H-pyrazole-5-carboxamides 10-22 and 5-aryl-1-methyl-3-propyl-1,6-dihydro-1H-pyrazolo[4,3-d]pyrimidin-7-ones 23-35. The 1H-pyrazole-5-carboxamides 10-22 were also converted to pyrimidinones 23-35 either by conventional heating or by MW irradiation. However, MW irradiation method gives excellent yields in very short time.
Khan, Khalid Mohammed,Maharvi, Ghulam Murtaza,Choudhary, Muhammad Iqbal,Atta-Ur-Rahman,Perveen, Shahnaz
p. 1085 - 1093
(2007/10/03)

Method of treating a patient having precancerous lesions with phenyl purinone derivatives
Derivatives of Phenyl Purinone are useful for the treatment of patients having precancerous lesions. These compounds are also useful to inhibit growth of neoplastic cells.
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(2008/06/13)

An improved process for preparing a therapeutically active pyrazolopyrimidinone derivative
An improved process which allows to obtain 5-[2-ethoxy-5-(4-methylpiperazin-1-ylsulphonyl)phenyl]-1-methyl-3-n.propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one, also known with the generic name sildenafil, in pure form and very good yield and further demontrated to be economically advantageous when compared to the known processes.
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(2008/06/13)

Sildenafil (Viagra(TM)), a potent and selective inhibitor of type 5 CGMP phosphodiesterase with utility for the treatment of male erectile dysfunction
5-(2'-Alkoxyphenyl)pyrazolo[4,3-d]pyrimidin-7-ones, and in particular our preferred compound, sildenafil (VIAGRA(TM)), discovered through a rational drug design programme, are potent and selective inhibitors of the type 5 cGMP phosphodiesterase from both rabbit platelets and human corpus cavernosum. Sildenafil is currently in the clinic for the oral treatment of male erectile dysfunction.
Terrett, Nicholas K.,Bell, Andrew S.,Brown, David,Ellis, Peter
p. 1819 - 1824
(2007/10/03)

PYRAZOLOPYRIMIDINONE ANTIANGINAL AGENTS
Compounds of the formula:wherein R1 is H, C1-C3 alkyl, C3-C5 cycloalkyl or C1-C3 perfluoroalkyl; R2 is H, C1-C6 alkyl optionally substituted by OH, C1-C3 alkoxy or C3-C6 cycloalkyl, or C1-C3 perfluoroalkyl; R3 is C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C3-C7 cycloalkyl, C1-C6 perfluoroalkyl or (C3 -C6 cycloalkyl)C1-C6 alkyl; R4 taken together with the nitrogen atom to which it is attached completes a pyrrolidinyl, piperidino, morpholino, or 4-N-(R6)-piperazinyl group; R5 is H, C1-C4 alkyl, C1-C3 alkoxy, NR7 R8, or CONR7 R8 ; R6 is H, C1-C6 alkyl, (C1-C3 alkoxy) C2-C6 alkyl, hydroxy C2-C6 alkyl, (R7 R8 N)C2 -C6 alkyl, (R7 R8 NCO)C1-C6 alkyl, CONR7 R8, CSNR7 R8 or C(NH)NR7 R8 ; R7 and R8 are each independently H, C1-C4 alkyl, (C1-C3 alkoxy)C2-C4 alkyl or hydroxy C2-C4 alkyl; and pharmaceutically acceptable salts thereof, are selective cGMP PDE inhibitors useful in the treatment of cardiovascular disorders such as angina, hypertension, heart failure and atherosclerosis
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(2008/06/13)

Pyrazolopyrimidinone antianginal agents
Compounds of the formula STR1 and pharmaceutically acceptable salts thereof are selective cGMP PDE inhibitors which are useful in the treatment of such diseases and adverse conditions as angina, hypertension, congestive heart failure, reduced blood vessel patency, peripheral vascular disease, stroke, bronchitis, chronic asthma, allergic asthma, allergic rhinitis, glaucoma, and diseases characterized by disorders of gut motility.
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(2008/06/13)