1297537-41-7

Usage

Uses

Used in Medicinal Chemistry and Drug Discovery:
(S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile is used as a lead compound in medicinal chemistry for its potential to interact with biological targets due to its unique structural features. Its presence of various functional groups allows for further chemical modifications to optimize its pharmacological properties, such as potency, selectivity, and bioavailability.
Used in Organic Synthesis:
In the field of organic synthesis, (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile is utilized as a key intermediate or building block for the synthesis of novel compounds. Its versatile structure can be employed to create a range of chemical entities with potential applications in various industries, including pharmaceuticals, agrochemicals, and materials science.
Used in Research and Development:
(S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile is also used in research and development settings to explore its potential biological activities and understand its mechanism of action. Further studies are necessary to fully elucidate its therapeutic potential and to develop it into a viable drug candidate or a useful synthetic intermediate.
While the specific applications in different industries are not explicitly mentioned in the provided materials, the potential uses of (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile can be inferred from its structural features and the general applications of similar compounds in the fields of medicinal chemistry, organic synthesis, and research.

Upstream product

• 1297537-37-1 2-chloro-4-(1H-pyrazol-5-yl)benzonitrile 
• 79069-13-9 (S)-2-t-butoxycarbonylaminopropan-1-ol 
• 154607-01-9 4-bromo-2-chlorobenzonitrile 
• 548797-51-9 2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile 
• 1297537-37-1 2-chloro-4- (1H-pyrazol-3-yl)benzonitrile 
• 96042-30-7 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 
• 1297537-39-3 2-Chloro-4-(1H-pyrazol-5-yl)benzonitrile hydrochloride 
• 1297537-35-9 2-Chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile 

Downstream Products

• 1297538-32-9 N-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-3-(1-hydroxyethyl)-1H-pyrazole-5-carboxamide 
• 1297540-05-6 1-(5-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-ylcarbamoyl)-1H-pyrazol-3-yl)ethyl 2-(dimethylamino)acetate 
• 1297542-18-7 (S)-2-((1H-imidazol-1-yl)methyl)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)oxazole-4-carboxamide 
• 1297542-94-9 (S)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-((2,5-dioxopyrrolidin-1-yl)methyl)oxazole-4-carboxamide 
• 1297537-33-7 (S)-3-acetyl-N-(1-(3-(3-chloro-4-cyano-phenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-pyrazole-5-carboxamide 
• 1297537-95-1 (S)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)isoxazole-3-carboxamide 
• 1297539-13-9 (S)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(2-hydroxypropan-2-yl)isoxazole-3-carboxamide 
• 1297542-22-3 (S)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(chloromethyl)oxazole-4-carboxamide 
• 1297544-49-0 (S)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-methyl-1H-imidazole-4-carboxamide 
• 1403334-21-3 (S)-1-Butyl-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-methyl-1H-imidazole-4-carboxamide 
• 1403334-27-9 (S)-N-(1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-(2-cyanoethyl)-2-methyl-1H-imidazole-4-carboxamide 
• 1403334-28-0 N-((S)-1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-(1-cyanoethyl)-2-methyl-1H-imidazole-4-carboxamide 
• 1297537-33-7 5-acetyl-N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1H-pyrazole-3-carboxamide 
• 1403334-37-1 (S)-2-((tert-Butyldimethylsilyloxy)methyl)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-4-carboxamide 

Relevant academic research and scientific papers

SUBSTITUTED PYRAZOLE COMPOUNDS, COMPOSITIONS CONTAINING SAME, AND USE THEREOF

The present invention provides substituted pyrazole compounds, compositions containing same, and use thereof. The substituted pyrazole compounds comprise a compound represented by formula (I) or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate, or solvate thereof. The compound represented by formula (I) can serve as a tissue selective androgen receptor modulator (SARM), particularly serving as a drug for treating prostate cancer and other AR-dependent conditions and diseases in which AR antagonism is desired.

Metabolism and mass balance of the novel nonsteroidal androgen receptor inhibitor darolutamide in humans

The biotransformation and excretion of darolutamide were investigated in a phase I study. Six healthy male volunteers received a single dose of 300 mg 14C-darolutamide as an oral solution in the fasted state. Plasma, urine, and feces samples were analyzed for mass balance evaluation by liquid scintillation counting (LSC). Metabolite profiling and identification were determined using liquid chromatography mass-spectrometry with off-line radioactivity detection using LSC. Complete mass balance was achieved, with mean radioactivity recovery of 95.9% within 168 hours (63.4% in urine, 32.4% in feces). The administered 1:1 ratio of (S,R)- and (S,S)darolutamide changed to approximately 1:5, respectively, in plasma. Darolutamide and the oxidation product, keto-darolutamide, were the only components quantifiable by LSC in plasma, accounting for 87.4% of total radioactivity, with a 2.1-fold higher plasma exposure for keto-darolutamide. Aside from darolutamide, the most prominent metabolites in urine were O-glucoronide (M-7a/b) and N-glucuronide (M-15a/b), as well as pyrazole sulfates (M-29, M-24) and glucuronides (M-21, M-22) resulting from oxidative cleavage of the parent. The darolutamide diastereomers were mainly detected in feces. In vitro assays showed that darolutamide metabolism involves a complex interplay between oxidation and reduction, as well as glucuronidation. Interconversion of the diastereomers involves oxidation to keto-darolutamide, primarily mediated by CYP3A4, followed by reduction predominantly catalyzed by cytosolic reductase(s), with aldo-keto reductase 1C3 playing the major role. The latter reaction showed stereoselectivity with preferential formation of (S,S)-darolutamide.

Pyrazoleamide derivative and synthesis method and application

The present invention discloses a pyrazoleamide derivative and a synthetic method and application as an androgen receptor antagonist and the preparation of anti-prostate cancer drugs. The present invention provides a method of synthesizing a pentabasole r

Synthesis process of darolutamide

The invention relates to a synthesis process of darolutamide. Compared with an existing synthetic process route in which the reaction steps are 10 steps or more, the process of the invention has the advantages of less reaction steps in the route, high reaction yield of each step, simplicity and convenience in operation, and effective improvement of the total yield and industrial operability of thereaction.

Method for preparing antitumor drug darolutamide

The invention relates to a method for preparing an antitumor drug darolutamide. A one-step Suzuki reaction is carried out, and then deprotection, hydroxylamine condensation and amide condensation reactions are carried out to obtain the darolutamide. The method has the advantages of few reaction steps, high reaction yield of each step, and simplicity in operation, so the total yield of the whole route is high, and the method has good experiment operationality.

Novel androgen receptor inhibitor, synthesis method and applications thereof

The invention discloses a compound represented by a formula I or a stereoisomer, a pharmaceutically acceptable salt, a hydrate or a solvate thereof. The invention also discloses a preparation method and applications of the compound. According to the invention, the compound represented by the formula I is an excellent AR inhibitor, provides new choice for clinical screening and/or preparing of medicines for treating prostatic cancer, and has a good application prospect.

Preparation method of N-[(1S)-2-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]-1-methylethyl]-5-(1-hydroxyethyl)-1H-pyrazol-3-carboxamide

The invention relates to a preparation method of N-[(1S)-2-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]-1-methylethyl]-5-(1-hydroxyethyl)-1H-pyrazol-3-carboxamide, and in particular relates to two novel methods for preparing an intermediate (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile and a method for preparing N-[(1S)-2-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]-1-methylethyl]-5-(1-hydroxyethyl)-1H-pyrazol-3-carboxamide from the intermediate.

Discovery and biological evaluation of darolutamide derivatives as inhibitors and down-regulators of wild-type AR and the mutants

Androgen receptor (AR) has been a target of prostate cancer (PC) for nearly six decades. Recently, downregulating or degrading AR and the mutants especially the splice variant 7 (AR-V7) lacking ligand binding domain (LBD) emerged as an advantageous therapeutic approach to overcome drug resistance. Here, the structural modification of darolutamide resulted in the discovery of dual-action AR inhibitors and down-regulators. Unlike other traditional AR antagonists targeting the AR-LBD, compounds 4k and 4b not only inhibit the activities of wt-AR and AR-F876L mutant but also downregulate the protein expression of full-length (AR-full) and AR variant 7 (AR-V7) at mRNA level. In cell proliferation assays, compounds 4k and 4b exhibited better antiproliferative activities than darolutamide and enzalutamide against AR-V7-positive 22Rv1 cells and VCaP cells. In addition, 4k demonstrated better antitumor activity than clinically used enzalutamide in castration-resistant VCaP xenograft model. Collectively, combining the activities of AR inhibition and downregulation, compound 4k is proposed as an advantageous lead compound to disrupt AR signaling and overcome resistance.

PROCESS FOR THE PREPARATION OF ANDROGEN RECEPTOR ANTAGONISTS AND INTERMEDIATES THEREOF

The present invention relates to an improved process for the preparation of carboxamide structured androgen receptor (AR) antagonists such as N-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H- pyrazol-1-yl)-propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3- carboxamide (1A) and key intermediates thereof such as 2-chloro-4- (IH-pyrazol-3-yl)benzonitrile (V). AR antagonists are useful in the treatment of cancer, particularly prostate cancer and other diseases where AR antagonism is desired.

ANDROGEN RECEPTOR MODULATING CARBOXAMIDES

Compounds of formula (I) or (II) wherein Rx, Rz, R9, R10, R14, R14′, R15, R15′, A and B are as defined in the claims and pharmaceutically acceptable salts and esters thereof, are disclosed. The compounds possess utility as tissue-selective androgen receptor modulators (SARM) and are useful as medicaments in the treatment of prostate cancer and other AR dependent conditions and diseases where AR antagonism is desired.