- A kind of avanafil impurity D and synthesis method and application thereof
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The present invention provides a new aphranarfil impurity and synthesis method thereof, by synthesizing and characterizing the impurity, the structure of the impurity is determined, the drug impurity profile of avanafil is perfected, the resulting product is of high purity, can be used as a control for drug quality control research.
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- Preparation method of avanafil
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The invention provides a preparation method of avanafil, and specifically relates to the technical field of pharmaceutical chemistry. The preparation method of avanafil comprises the following steps:sequentially carrying out cyclization and chlorination reactions on methyl thiourea sulfuric acid and diethyl ethoxymethylene malonate which serve as initial raw materials to obtain 4-chloro-2-methylthiopyrimidine-5-carboxylic acid ethyl ester; then substituting and hydrolyzing with 3-chloro-4-methoxybenzylamine; condensing with 2-pyrimidinemethanamine to obtain a key intermediate, namely, 4-[(3-chloro-methoxybenzyl)amino]-2-methylthio-N-(2-pyrimidine methyl)-5-pyrimidine formamide; oxidizing the intermediate and reacting with L-prolinol to generate the avanafil. The preparation method has theadvantages of easy availability of raw materials, easiness and convenience in operation, mild reaction conditions and higher product yield.
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- Atorvastatin that non-synthetic method
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The invention provides a synthesis method of avanafil. The synthesis method of avanafil comprises the following steps: carrying out nucleophilic substitution reaction with a compound (13) or a compound (3) by a compound (18), hydrolyzing to prepare a compound (21) or a compound (22), reacting the compound (21) or the compound (22) with sulfonic acid chloride or pivaloyl chloride to obtain mixed anhydride, reacting the mixed anhydride with a compound (23) to prepare a compound (24) or a compound (25), then oxidizing the compound (24), subsequently reacting the compound (24) with a compound (9) to prepare avanafil, or directly reacting the compound (25) with the compound (9) to prepare avanafil. The synthesis method is high in controllability, simple in step, high in yield and low in cost, and is suitable for industrial production. The reaction route is shown in the description.
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Paragraph 0025; 0050; 0051; 0052; 0053; 0054; 0055; 0056
(2017/08/25)
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- A process for the preparation of atorvastatin that non-intermediate and its preparation method
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The invention provides a novel intermediate IV which is used for preparation of avanafil. The intermediate has a general formula IV as described in the specification; and in the general formula IV, R represents a C1-20 alkylsulfinyl group or a C1-20 alkylsulfonyl group. The intermediate has high purity, is suitable for industrial production and can be subjected to a one-step chemical reaction to prepare avanafil. The invention also provides a preparation method for the intermediate and a method for preparing avanafil from the intermediate.
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Paragraph 0035; 0036-0038; 0053-0055; 0069-0071; 0085-0087
(2017/08/25)
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- Prodrugs Of Bicyclic Substituted Pyrimidine Type PDE-5 Inhibitors
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Provided are prodrugs of a bicyclic substituted pyrimidine type PDE-5 inhibitors, pharmaceutically acceptable salts or stereoisomers thereof. Also provided are methods for preparing these prodrug compounds, pharmaceutical preparations, and pharmaceutical compositions, as well as a use of these compounds, pharmaceutical preparations and pharmaceutical compositions in the manufacture of medicaments for treatment and/or prophylaxis of sexual dysfunction and lower urinary tract symptoms.
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Paragraph 0204; 0205
(2016/03/13)
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- PROCESS FOR THE PREPARATION OF (S)-4-[(3-CHLORO-4-METHOXYBENZYL)AMINO]-2-[2- (HYDROXYMETHYL)-1-PYRROLIDINYL]-N-(2-PYRIMIDINYL METHYL-5-PYRIMIDINE CARBOXAMIDE
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The present invention relates to an improved process for the preparation of (S)-4-[(3- chloro-4-methoxybenzyl)amino]-2-[2-(hydroxymethyl)-1-pyrrolidinyl]-N-(2-pyrimidinyl ethyl)- 5-pyrimidine carboxamide compound of formula-1 represented by the following structural formula.
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- BICYCLIC SUBSTITUTED PYRIMIDINE COMPOUNDS
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The present invention relates to the technical field of medicine and pharmacy, and particularly relates to bicyclic group substituted pyrimidine compounds represented by general formula (I), pharmaceutical acceptable salts thereof or stereoisomers thereof, wherein R1, R2, R3, R4, R5 and R6 are as defined in the specification. The present invention also relates to preparation methods, pharmaceutical formulations, and pharmaceutical compositions of the compounds, and use of the compounds, pharmaceutical formulations, and pharmaceutical compositions for preparing a medicament for treating and/or preventing sexual dysfuntion diseases and diseases with lower urinay tract symptoms.
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Paragraph 0467; 0468
(2015/07/02)
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- 8-(3-Chloro-4-methoxybenzyl)-8H-pyrido[2,3-d]pyrimidin-7-one derivatives as potent and selective phosphodiesterase 5 inhibitors
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A novel series of highly selective phosphodiesterase 5 (PDE5) inhibitors was found. 8H-Pyrido[2,3-d]pyrimidin-7-one derivatives bearing an (S)-2-(hydroxymethyl)pyrrolidin-1-yl group at the 2-position and a 3-chloro-4-methoxybenzyl group at the 8-position
- Sakamoto, Toshiaki,Koga, Yuichi,Hikota, Masataka,Matsuki, Kenji,Mochida, Hideki,Kikkawa, Kohei,Fujishige, Kotomi,Kotera, Jun,Omori, Kenji,Morimoto, Hiroshi,Yamada, Koichiro
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p. 1431 - 1435
(2015/03/30)
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- A PROCESS FOR THE PREPARATION OF AVANAFIL AND ITS NOVEL INTERMEDIATES
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The present invention relates to a novel compound of Formula (II), and its use in preparation of Avanafil, [Formula should be inserted here] wherein R is -OH, -CI or -OR1 and R1 is C1 to C3 alkyl group.
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Page/Page column 14; 15
(2015/12/11)
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- The discovery of avanafil for the treatment of erectile dysfunction: A novel pyrimidine-5-carboxamide derivative as a potent and highly selective phosphodiesterase 5 inhibitor
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Novel pyrimidine-5-carboxamide derivatives bearing a 3-chloro-4-methoxybenzylamino group at the 4-position were identified as potent and highly selective phosphodiesterase 5 inhibitors. Among them, we successfully found 10j (avanafil) which exhibited a potent relaxant effect on isolated rabbit cavernosum (EC30 = 2.1 nM) and a high isozyme selectivity.
- Sakamoto, Toshiaki,Koga, Yuichi,Hikota, Masataka,Matsuki, Kenji,Murakami, Michino,Kikkawa, Kohei,Fujishige, Kotomi,Kotera, Jun,Omori, Kenji,Morimoto, Hiroshi,Yamada, Koichiro
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p. 5460 - 5465
(2015/01/08)
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- Cyclic compounds
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1. A cyclic compound of the formula (I) or a pharmacologically acceptable salt thereof, wherein X is ═CH— or ═N—, Y is —NH—, —NR4—, —S—, —O—, —CH═N—, —N═CH—, —N═N—, —CH═CH—, etc., R1 is a lower alkoxy group, an amino group, a heterocyclic ring containing N atom(s), or a hydroxy group substituted by a heterocyclic ring containing N atom(s) (each of which is optionally substituted), R2 is a lower alkylamino group which is optionally substituted by an aryl group, a lower alkoxy group which is optionally substituted by an aryl group, a lower alkoxy group substituted by an aromatic heterocyclic ring containing N atom(s), R3 is an aryl group, a heterocyclic ring containing N atom(s), a lower alkyl group, a lower alkoxy group, a cyclo lower alkoxy group, a hydroxy group substituted by a heterocyclic ring containing N atom(s), or an amino group (each of which is optionally substituted), and R3 and a substituent in Y may be combined to form a lactone ring. The compound of the present invention has excellent selective PDE V inhibitory activity and therefore, is useful as a therapeutic or prophylactic drug for treating various diseases due to functional disorders on cGMP-signaling.
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- TABLETS QUICKLY DISINTEGRATED IN ORAL CAVITY
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Intraorally rapidly disintegrating tablets which, when ingested, disintegrates in the oral cavity rapidly without presenting unpleasant taste, can be quickly absorbed in the digestive tract and express efficacy are provided. The intraorally rapidly disintegrating tablets contain a drug being hardly water-soluble under neutral or alkaline conditions and being highly water-soluble under acidic conditions yet presenting unpleasant taste, which tablets can be prepared by combining the medicinal substance with a water-soluble acidic substance, coating either or both of the substances with a water-soluble coating agent being insoluble in alcoholic solvent, further adding a water-soluble binding agent being soluble in alcoholic solvent and a water-soluble saccharide, subjecting the resultant mixture to compression, and treating the products with an alcoholic solvent.
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- Preparations for oral administration
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The present invention provides a preparation for oral administration containing a medicinal substance having cGMP-specific phosphodiesterase inhibitory activity and showing decrease of solubility in the neutral and alkaline regions, wherein an acidic substance is compounded promote the dissolution of the medicinal substance in digestive tract and thus the efficacy can be expressed at the early stage after administration, and which preparation is useful in treatment of erectile dysfunction.
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- Aromatic nitrogen-containing 6-membered cyclic compounds
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An aromatic nitrogen-containing 6-membered cyclic compound of the formula (I): wherein Ring A is a substituted or unsubstituted nitrogen-containing heterocyclic group; R1 is a substituted or unsubstituted lower alkyl group, —NH—Q—R3 (R3 is a substituted or unsubstituted nitrogen containing heterocyclic group, and Q is a lower alkylene group or a single bond), or —NH—R4 (R4 is a substituted or unsubstituted cycloalkyl group); R2 is a substituted or unsubstituted aryl group; one of Y and Z is ═CH—, and the other is ═N—, or a pharmaceutically acceptable salt thereof, these compounds exhibiting excellent selective PDE V inhibitory activities, and hence, being useful in the prophylaxis or treatment of penile erectile dysfunction, etc.
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- PYRIDOPYRIMIDINE OR NAPHTHYRIDINE DERIVATIVE
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A pyridopyrimidine or a naphthyridine derivative of the formula (I): wherein R1 is an optionally substituted nitrogen-containing heterocyclic group, etc.; R2 is H or a lower alkyl group; R3 is H or an optionally substitute
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Page/Page column 19
(2010/02/07)
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