139755-85-4

Usage

Uses

Used in Pharmaceutical Industry:
Hydroxyhomosildenafil is used as an enhancer for male sexual function. As an analog of Sildenafil, it shares similar properties that contribute to improving erectile dysfunction and overall sexual performance in men.
Used in Research and Development:
Due to its chemical structure and properties, Hydroxyhomosildenafil may also be utilized in research and development for the creation of new drugs and therapies, particularly in the field of sexual health and related conditions.

InChI:InChI=1/C23H32N6O5S/c1-4-6-18-20-21(27(3)26-18)23(31)25-22(24-20)17-15-16(7-8-19(17)34-5-2)35(32,33)29-11-9-28(10-12-29)13-14-30/h7-8,15,30H,4-6,9-14H2,1-3H3,(H,24,25,31)

Upstream product

• 103-76-4 1-(2-hydroxyethyl)piperazine 
• 139756-21-1 5-(2-ethoxy)-phenyl-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidine-7-one 
• 42926-52-3 2-ethoxybenzoyl chloride 
• 613-69-4 2-ethoxylbenzaldehyde 
• 1357931-55-5 4-ethoxy-3-(1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonic acid 
• 139756-22-2 5-(5-Chlorosulphonyl-2-ethoxyphenyl)-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one 
• 139756-03-9 4-[(2-ethoxybenzoyl)amino]-1-methyl-3-propyl-1H-pyrazole-5-carboxamide 
• 139756-02-8 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide 

Downstream Products

• 1007310-72-6 C₃₃H₅₀N₆O₆S 
• 1023327-69-6 5-{2-ethoxy-5-[(4-chlorobutyric acid ethyl ester)piperazin-1-ylsulfonyl]phenyl}-1-methyl-3-N-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one 

Relevant academic research and scientific papers

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.

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.

Phosphodiesterase type 5 (PDE5) inhibitors for the treatment of selective serotonin reuptake inhibitor (SSR) induced sexual dysfunction

This invention is directed to the use phosphodiesterase type 5 (PDE5) inhibitors in the treatment of selective serotonin reuptake inhibitor (SSRI) induced sexual dysfunction. Specifically, this invention is directed to a method for treating an animal to cure; prevent or ameliorate SSRI induced sexual dysfunction which comprises administering to the animal an effective amount of the inhibitor. The animal may be a male or a female human. The invention also includes the use of such inhibitors in the manufacture of a medicament to prevent; cure or ameliorate SSRI induced sexual dysfunction. Moreover, the invention includes a kit comprising a SSRI, such as sertraline, fluoxetine, paroxetine, and a PDE5 inhibitor, such as sildenafil citrate, for the treatment or prevention of serotonergic associated disorders such as depression, obsessive compulsive disorder or panic disorder, while reducing or preventing sexual dysfunction.

Methods and compositions for treating diseases and conditions of the eye

Methods for the prevention and treatment of diseases and conditions of the eye including, but are not limited to: central retinal artery occlusion; central retinal vein occlusion; optic neuropathy including, but not limited to, anterior ischemic optic neuropathy and glaucomatous optic neuropathy; and macular (dry) degeneration are disclosed. These methods comprise administering to a patient a prophylactically or therapeutically effective amount of a cyclic guanosine 3′,5′-monophosphate phosphodiesterase type 5 inhibitor. Pharmaceutical compositions and dosage forms comprising cyclic guanosine 3′,5′-monophosphate phosphodiesterase type 5 inhibitors are also disclosed.

Pyrazolopyrimidinones for the treatment of impotence

The use of a compound of formula (I) wherein R1is H; C1-C3alkyl; C1-C3perfluoroalkyl; or C3-C5cycloalkyl; R2is H; optionally substituted C1-C6alkyl; C1-C3perfluoroalkyl; or C3-C6cycloalkyl; R3is optionally substituted C1-C6alkyl; C1-C6perfluoroalkyl; C3-C5cycloalkyl; C3-C6alkenyl; or C3-C6alkynyl; R4is optionally substituted C1-C4alkyl, C2-C4alkenyl, C2-C4alkanoyl, (hydroxy)C2-C4alkyl or (C2-C3alkoxy)C1-C2alkyl; CONR5R6; CO2R7; halo; NR5R6; NHSO2NR5R6; NHSO2R8; SO2NR9R10; or phenyl, pyridyl, pyrimidinyl, imidazolyl, oxazolyl, thiazolyl, thienyl or triazolyl any of which is optionally substituted with methyl; R5and R6are each independently H or C1-C4alkyl, or together with the nitrogen atom to which they are attached form an optionally substituted pyrrolidinyl, piperidino, morpholino, 4-N(R11)-piperazinyl or imidazolyl group; R7is H or C1-C4 alkyl; R8is optionally substituted C1-C3alkyl; R9and R10together with the nitrogen atom to which they are attached form an optionally substituted pyrrolidinyl, piperidino, morpholino or 4-N(R12)-piperazinyl group; R11is H; optionally substituted C1-C3alkyl; (hydroxy)C2-C3alkyl; or C1-C4alkanoyl; R12is H; optionally substituted C1-C6alkyl; CONR13R14; CSNR13R14; or C(NH)NR13R14; and R?13? and R14are each independently H; C1-C4alkyl; or substituted C2-C4alkyl; or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing either entity, for the manufacture of a medicament for the curative or prophylactic treatment of erectile dysfunction in a male animal, including man; a pharmaceutical composition for said treatment; and a method of said treatment of said male animal with said pharmaceutical composition or with said either entity.

Methods and compositions for treating diseases and conditions of the eye

Methods for the prevention and treatment of diseases and conditions of the eye including, but are not limited to: central retinal artery occlusion; central retinal vein occlusion; optic neuropathy including, but not limited to, anterior ischemic optic neuropathy and glaucomatous optic neuropathy; and macular (dry) degeneration are disclosed. These methods comprise administering to a patient a prophylactically or therapeutically effective amount of a cyclic guanosine 3',5'-monophosphate phosphodiesterase type 5 inhibitor. Pharmaceutical compositions and dosage forms comprising cyclic guanosine 3',5'-monophosphate phosphodiesterase type 5 inhibitors are also disclosed.

Method of treating nitrate-induced tolerance

The present invention relates to methods for treating nitrate-induced tolerance in a mammal by administering a nitrate-induced tolerance treating amount of a compound of formulae (I), (II), (III) (IV), (V), (VI), (VII), (VIII), (IX), (XA) or (XB) as defined herein, or the pharmaceutically acceptable salts, prodrugs, polymorphs, hydrates, solvates, active metabolites or stereoisomers thereof. The invention also relates to pharmaceutical compositions for the treatment of nitrate-induced tolerance in a mammal comprising a nitrate-induced tolerance treating amount of a compound of formulae (I), (II), (III) (IV), (V), (VI), (VII), (VIII), (IX), (XA) or (XB) as defined herein, or the pharmaceutically acceptable salts, prodrugs, polymorphs, hydrates, solvates, active metabolites or stereoisomers thereof, and a pharmaceutically acceptable vehicle, diluent or carrier. The invention further relates to methods of preventing nitrate-induced tolerance in a mammal comprising administering a nitrate-induced tolerance preventing amount of a cGMP PDE inhibitor.

Method of treating impotence due to spinal cord injury

A class of cGMP PDE inhibitors, including sidenafil and pharmaceutically acceptable salts thereof, which can be used to treat sexual dysfunction in male and female animals, especially humans, with a spinal cord injury. The invention can be used to treat sexual dysfunction in male animals that exhibit essentially no residual penile function.

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.

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