- Preparation method of sildenafil citrate
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The invention discloses a preparation method of sildenafil. The method comprises the following steps: activating an intermediate compound B in an aprotic solvent by using thionyl chloride, reducing with 1-methyl-4-nitro-3-propyl-1H-pyrazole-5-formamide in a zinc powder-ammonium chloride system in the presence of an acid-binding agent to obtain an intermediate compound E, and condensing to obtain an intermediate compound C; and cyclizing the intermediate compound C in an alcohol solvent under an alkaline condition to prepare sildenafil. The preparation method disclosed by the invention is short in reaction time, greatly shortens the production period so as to reduce the production cost, and is simple in operation and suitable for large-scale production.
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Paragraph 0023-0031; 0038-0043
(2021/04/07)
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- Sildenafil intermediate 4 - amino -1 - methyl -3 - n-propyl pyrazole -5 - carboxamide green new synthetic process
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The invention discloses a new green process of a medicament for treating male erectile dysfunction, namely a sildenafil citrate key intermediate compound 4-amino-1-methyl-3-n-propyl pyrazole-5-formamide. According to the method provided by the process, the safety is high, the reaction is easy to control, less pollution is caused to the environment, and solvent can be recovered and repeatedly used, thereby lowering the cost, reducing the emission, and ensuring that the process is greener and more environment-friendly.
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Paragraph 0025; 0031-0032; 0034-0035
(2018/12/02)
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- Preparation method of sildenafil citrate
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The invention belongs to the field of chemical drugs, and in particular relates to a preparation method of sildenafil citrate. The invention provides the preparation method of sildenafil citrate. Thepreparation method comprises the following steps: a) adding a compound of a structure as shown in a formula (I) and thionyl chloride into chlorosulfonic acid, and carrying out a sulfonation reaction to generate a compound of a structure as shown in a formula (II); b) dissolving the compound of the structure as shown in the formula (II) in dichloromethane and adding N-methyl piperazine to carry outa substitution reaction at 20-30 DEG C to obtain sildenafil; and c) adding citric acid into a sildenafil aqueous solution to adjust the pH value for a salt forming reaction so as to obtain the sildenafil citrate. Experimental results verify that the sildenafil citrate prepared by the preparation method is high in yield and high in purity.
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Paragraph 0031; 0032; 0049
(2018/06/16)
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- Preparing sildenafil intermediate 4 - amino - 1 - methyl - 3 - n-propyl pyrazole - 5 - carboxamide new method
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The invention discloses a novel method for preparing Sildenafil intermediate 4-amino-1-methyl-3-n-propyl-pyrazole-5-formamide. According to the method, the 4-amino-1-methyl-3-n-propyl-pyrazole-5-formamide is prepared from 1-methyl-3-n-propyl-pyrazole-5-ethyl formate through bromation and ammoniation. The novel method disclosed by the invention is safe, efficient and environment-friendly and is suitable for industrial production.
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Paragraph 0024-0025; 0027
(2017/10/07)
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- NOVEL COMPOUNDS FOR USE IN COGNITION IMPROVEMENT
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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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- Novel pyrazole-5-carboxamide and pyrazole-pyrimidine derivatives: Synthesis and anticancer activity
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A series of novel pyrazole-5-carboxamide and pyrazole-pyrimidine derivatives were designed and synthesized. All compounds have been screened for their antiproliferative activity against MGC-803, SGC-7901 and Bcap-37 cell lines in vitro. The results revealed that compounds 8a, 8c and 8e exhibited strong inhibitory activity against MGC-803 cell line. The flow cytometric analysis result showed that compound 8e could inhibit MGC-803 proliferation. Some title compounds were tested against telomerase, and compound 8e showed the most potent inhibitory activity with IC50 value at 1.02 ± 0.08 μM. The docking simulation of compound 8e was performed to get the probable binding model, among them, LYS 189, LYS 372, LYS 249 and ASP 254 may be the key residues for the telomerase activity.
- Shi, Jing Bo,Tang, Wen Jian,Qi, Xing Bao,Li, Rong,Liu, Xin Hua
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p. 889 - 896
(2015/06/02)
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- PYRAZOLOPYRIMIDINONES FOR THE TREATMENT OF IMPOTENCE AND PROCESS FOR THE PREPARATION THEREOF
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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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- NOVEL COMPOUNDS AS DUAL INHIBITORS OF PHOSPHODIESTERASES AND HISTONE DEACETYLASES
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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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- HIGHLY SELECTIVE and LONG-ACTING PDE5 MODULATORS
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Disclosed herein are substituted phosphodiesterase type 5 enzyme modulators of Formula I, processes of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.
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Page/Page column 57
(2008/12/07)
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- Comparison of different heterocyclic scaffolds as substrate analog PDE5 inhibitors
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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
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p. 3900 - 3907
(2007/10/03)
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- 5,7-DIAMINOPYRAZOLO`4,3-D!PYRIMIDINES USEFUL IN THE TREATMENT OF HYPERTENSION
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This invention relates to compounds of formula (I).
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- Fused 7-oxo-pyrimidinyl compounds, preparation, composition and use thereof
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The present invention relates to novel antiobesity and hypocholesterolemic compounds, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates and pharmaceutically acceptable compositions containing them. More particularly, the present invention relates to novel β-aryl-α-oxysubstituted alkylcarboxylic acids of the general formula (I), their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates and pharmaceutically acceptable compositions containing them. The present invention also relates to a process for the preparation of the above said novel compounds, their analogs, their derivatives, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, pharmaceutically acceptable solvates and pharmaceutical compositions containing them. The present invention also relates to novel intermediates, processes for their preparation and their use in the preparation of compounds of formula (I).
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- Method of treating a patient having precancerous lesions with phenyl purinone derivatives
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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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- Process for preparation of pyrazolo[4,3-d]pyrimidin-7-ones and intermediates thereof
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A process is provided for the preparation of a compound of formulae (IA) (sidenafil) and (IB) comprising reacting a compound of formula (IIA) and (IIB) respectively in the presence of—OR, wherein R in the case of formation of compound (IA) is CH2CH3and R in the case of formation of compound (IB) is CH2CH2CH3, where X is a leaving group:
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- Polymer-supported reagents for multi-step organic synthesis: Application to the synthesis of sildenafil
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Sildenafil 1 (Viagra(TM)), a well known and commercially important pharmaceutical drug, has been prepared using polymer-supported reagents in a multi-step, convergent process resulting in a clean and efficient preparation without the need for conventional purification methods. (C) 2000 Elsevier Science Ltd.
- Baxendale, Ian R.,Ley, Steven V.
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p. 1983 - 1986
(2007/10/03)
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- The chemical development of the commercial route to sildenafil: A case history
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This paper is a case history of the chemical development of sildenafil which covers various aspects of work in chemical development namely: route selection, scale-up issues, the development of an efficient synthesis with high throughput, process safety, and environmental issues. Interesting chemical points include improved methods of preparing pyrazolo[4,3-d]-pyrimidines and the unusual isolation of an intermediate as its double salt (10). The potential dangers of nitrating pyrazole-5-carboxylic acids which are activated to a decarboxylation reaction are discussed.
- Dale, David J.,Dunn, Peter J.,Golightly, Clare,Hughes, Michael L.,Levett, Philip C.,Pearce, Andrew K.,Searle, Patricia M.,Ward, Gordon,Wood, Albert S.
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- Process for preparing sildenafil
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A process for the preparation of a compound of formula (I): STR1 which comprises cyclization of a compound of formula (II): STR2
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- Sildenafil (Viagra(TM)), a potent and selective inhibitor of type 5 CGMP phosphodiesterase with utility for the treatment of male erectile dysfunction
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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
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p. 1819 - 1824
(2007/10/03)
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- PYRAZOLOPYRIMIDINONE ANTIANGINAL AGENTS
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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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- Pyrazolopyrimidinone antianginal agents
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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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