3D Mol Similar

Silodosin

: Iupac Name：1-(3-hydroxypropyl)-5-[2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethylamino]propyl]-2,3-dihydroindole-7-carboxamide; CAS No.: 160970-54-7; Molecular Weight：495.53; Modify Date.: 2022-11-22 15:43; Introduction: Silodosin, an a1A adrenoceptor (a1A-AR) antagonist selective for prostaticreceptors, was launched as an oral treatment for dysuria associated withbenign prostatic hypertrophy (BPH). The regulation of smooth muscle tone in thebladder neck and prostate is thought to be primarily mediated by a1A-AR.Blockade of these receptors can cause smooth muscle relaxation in these areas,resulting in improved symptoms and urinary flow rates. Conversely, a1B-AR arelargely located on vascular smooth muscle, and antagonism of these receptorscan cause tissue relaxation and potentially decrease cardiac compensation mechanismsinvolved in regulating blood pressure. View more+

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1. Names and Identifiers

: 1.1 Name; Silodosin; 1.2 Synonyms; [14C]-Silodosin [3H]-Silodosin 1-(3-hydroxypropyl)-5-[(2R)-({2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}aMino)propyl]indoline-7-carboxaMide 1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7-carboxamide 1-(3-Hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl]-7-indolinecarboxamide 1H-Indole-7-carboxamide, 2,3-dihydro-1-(3-hydroxypropyl)-5-[(2R)-2-[[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl]amino]propyl]- 1H-Indole-7-carboxaMide,2,3-dihydro-1-(3-hydroxypropyl)-5-[(2R)-2-[[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl]aMino]propyl]- KAD 3213 KMD 3213 KMD-3213 Rapaflo Silodosin API Silodosin-d4 Silodoxin Silodyx UNII-CUZ39LUY82 Urief; View all

1.3 CAS No.: 160970-54-7

1.4 CID: 5312125

1.5 EINECS(EC#): 1308068-626-2

1.6 Molecular Formula: C25H32F3N3O4 (isomer)

1.7 Inchi: InChI=1S/C25H32F3N3O4/c1-17(30-8-12-34-21-5-2-3-6-22(21)35-16-25(26,27)28)13-18-14-19-7-10-31(9-4-11-32)23(19)20(15-18)24(29)33/h2-3,5-6,14-15,17,30,32H,4,7-13,16H2,1H3,(H2,29,33)/t17-/m1/s1

1.8 InChIkey: PNCPYILNMDWPEY-QGZVFWFLSA-N

1.9 Canonical Smiles: CC(CC1=CC2=C(C(=C1)C(=O)N)N(CC2)CCCO)NCCOC3=CC=CC=C3OCC(F)(F)F

1.10 Isomers Smiles: C[C@H](CC1=CC2=C(C(=C1)C(=O)N)N(CC2)CCCO)NCCOC3=CC=CC=C3OCC(F)(F)F

2. Properties

2.1 Density: 1.249

2.1 Melting point: Description

2.1 Boiling point: 601.4 °C at 760 mmHg

2.1 Refractive index: 1.552

2.1 Flash Point: 317.5 °C

2.1 Precise Quality: 495.234497

2.1 PSA: 97.05000

2.1 logP: 4.22730

2.1 Appearance: White to off-white solid

2.2 Chemical Properties: White Solid

2.3 Color/Form: Powder

2.4 pKa: 14.85±0.10(Predicted)

2.5 Water Solubility: H2O: Very slightly soluble

2.6 StorageTemp: Keep in dark place,Inert atmosphere,2-8°C

3. Use and Manufacturing

3.1 Usage: It can be used for treatment of benign prostatic hyperplasia.

4. Safety and Handling

4.1 Hazard Declaration: H300

4.1 Caution Statement: P201, P202, P264, P270, P273, P280, P281, P301+P310, P301+P312, P302+P352, P305+P351+P338, P308+P313, P310, P321, P330, P332+P313, P362, P405, P501

4.1 Specification: Silodosin (CAS NO.160970-64-9) is also named as Rapaflo ; Rapflo ; UNII-CUZ39LUY82 ; (-)-1-(3-Hydroxypropyl)-5-((2R)-2-((2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethyl)amino)propyl)-2,3-dihydro-1H-indole-7-carboxamide ; 160970-54-7 .

5. MSDS

2.Hazard identification

2.1 Classification of the substance or mixture

no data available

2.2 GHS label elements, including precautionary statements

Pictogram(s)	no data available
Signal word	no data available
Hazard statement(s)	no data available
Precautionary statement(s)
Prevention	no data available
Response	no data available
Storage	no data available
Disposal	no data available

2.3 Other hazards which do not result in classification

no data available

View all

6. NMR Spectrum

13C NMR : Predict

1H NMR : Predict

7. Synthesis Route

160970-54-7Total: 48 Synthesis Route

90-05-1 336 Suppliers

160970-54-7 227 Suppliers

Literatures:
WO2011/30356 A2, ;
Yield: null

120-80-9 163 Suppliers

160970-54-7 227 Suppliers

Literatures:
WO2011/30356 A2, ;
Yield: null

496-15-1 183 Suppliers

160970-54-7 227 Suppliers

Literatures:
WO2011/124704 A1, ;
Yield: null

View all

8. Precursor and Product

precursor:

160969-12-0

885340-13-6

239463-72-0

885340-11-4

175837-01-1

459868-73-6

120-80-9

175837-07-7

160969-20-0

350797-53-4

350797-52-3

90-05-1

160969-00-6

350797-55-6

350797-54-5

160969-02-8

160969-03-9

900518-67-4

900518-68-5

350797-51-2

161024-53-9

496-15-1

459868-63-4

350797-56-7

175870-34-5

View all

9. Other Information

9.0 Target: Value

9.1 Description: Silodosin, an a1A adrenoceptor (a1A-AR) antagonist selective for prostatic receptors, was launched as an oral treatment for dysuria associated with benign prostatic hypertrophy (BPH). The regulation of smooth muscle tone in the bladder neck and prostate is thought to be primarily mediated by a1A-AR. Blockade of these receptors can cause smooth muscle relaxation in these areas, resulting in improved symptoms and urinary flow rates. Conversely, a1B-AR are largely located on vascular smooth muscle, and antagonism of these receptors can cause tissue relaxation and potentially decrease cardiac compensation mechanisms involved in regulating blood pressure.

9.2 Originator: Kissei (Japan)

9.3 Uses: Silodosin is an α1a-adrenoceptor antagonist. It is used in treatment of benign prostatic hypertrophy.

9.4 Brand name: Urief

9.5 Chemical Synthesis: The synthesis of silodosin has been disclosed in several patents. The latest synthetic route disclosed in the 2006 patent is highlighted in the scheme. The synthesis started with Grignard generation from readily available bromoindoline 65 by treating it with Mg in the presence of a catalytic dibromoethane in THF. After initiation of the reaction with some heat and refluxing at a steady rate, CBZ protected oxazolidinone 66 [39b] was added over 1 h, refluxed for 4 h and then stirred at room temperature for 2 days. The reaction was quenched with 6 M aqueous HCl and stirred for 12 h after which time the reaction was worked up to provide product 67 in 53% yield. Ketone 67 was then treated with triethylsilane in TFA at 0oC and stirred at room temperature for 10 h to provide amine 68 in 61% yield. Bromination of the indoline 68 with bromine in warm acetic acid furnished bromide 69 in 53% yield which was reacted with copper cyanide in DMF at 130oC to give the cyano indoline 70 in 82% yield. Selective deprotection of the benzyloxycarbonyl over the benzyl group was accomplished by reacting indoline 70 with 1 atm hydrogen in the presence of 5% Pd/C in ethanol at room temperature. The resulting free amine 71 was then reacted with mesylate 72 in t-butanol with sodium carbonate as base at 80-90oC for 46 h to provide 73 in 67% yield. Removal of the benzyl ether was accomplished by reacting 73 with 1 atm hydrogen in the presence of 10%Pd/C to give alcohol 74, which upon hydrolysis provided the desired silodosin (X). No yield for the final reaction was given.; View all

9.6 Uses: It can be used for treatment of benign prostatic hyperplasia.

9.7 Chemical Properties: White Solid

9.8 Uses: An α1a-adrenoceptor antagonist. It is used in treatment of benign prostatic hypertophy.

9.9 Livertox Summary: Silodosin is a selective alpha-1a adrenergic antagonist used in the therapy of benign prostatic hypertrophy. Silodosin is associated with a low rate of serum aminotransferase elevations and to rare instances of clinically apparent acute liver injury.

9.10 Drug Classes: Benign Prostatic Hypertrophy Agents

9.11 Mesh: Drugs used in the treatment of urogenital conditions and diseases such as URINARY INCONTINENCE; PROSTATIC HYPERPLASIA; and ERECTILE DYSFUNCTION. (See all compounds classified as Urological Agents.)|Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS. (See all compounds classified as Adrenergic alpha-1 Receptor Antagonists.)

9.12 Absorption: Quickly absorbed and has a bioavailability of 32% at 8mg/day (therapeutic dose). When 8 mg of silodosin is taken once daily with food, the pharmacokinetic parameters are as follows: Cmax = 61.6 ± 27.54 ng/mL; Tmax = 2.6 ± 0.90 hours; AUC (0h-24h) = 373 ng?hr/ml. The AUC of its metabolite, KMD3213G, is four times greater than silodosin.|Fecal (54.9%); Renal (33.5%)|49.5 L|Plasma clearance = 10 L/h

9.13 Metabolism: Extensively metabolized in the liver. The main metabolite is generated via glucuronidation (KMD-3213G) by UDP-2B7. Oxidation by alcohol and aldehyde dehydrogenases produces the second major metabolite, KMD-3293. KMD-3213G accumulates in the plasma as it is very hydrophilic. KMD-3213G is also an active metabolite in which it has 50% of silodosin's inhibitory activity. KMD-3293 is inactive. Cytochrome P450 CYP 3A4 also generates some metabolites.

9.14 Biological Half Life: Silodosin = 13.3 ± 8.07 hours; KMD-3213G = 24 hours;

9.15 Mesh Entry Terms: 1-(3-hydroxypropyl)-5-(2-(2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethylamino)propyl)indoline-7-carboxamide

9.16 Use Classification: Human drugs -> Silodyx -> EMA Drug Category|Urologicals -> Human pharmacotherapeutic group|Human drugs -> Urorec -> EMA Drug Category|Human drugs -> Silodosin Recordati -> EMA Drug Category|Urologicals, Alpha-adrenoreceptor antagonists -> Human pharmacotherapeutic group|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients

10. Computational chemical data

Molecular Weight: 495.53g/mol
Molecular Formula: C₂₅H₃₂F₃N₃O₄
Compound Is Canonicalized: True
XLogP3-AA: 3.6
Exact Mass: 495.23449100
Monoisotopic Mass: 495.23449100
Complexity: 654
Rotatable Bond Count: 13
Hydrogen Bond Donor Count: 3
Hydrogen Bond Acceptor Count: 9
Topological Polar Surface Area: 97
Heavy Atom Count: 35
Defined Atom Stereocenter Count: 1
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Isotope Atom Count: 0
Covalently-Bonded Unit Count: 1
CACTVS Substructure Key Fingerprint: AAADcfB7OYAAAAAAAAAAAAAAAAAAAWAAAAAwYAAAAAAAAFgBQAAAHwAQCAAADCzhmBYyxoPABgCIAiVSUACCCAAlIAAIiIEOzMgPNjrE9ZuHearm0BHa6ceYyMCOCAACAAACQAAQAAQAAASAAAAAAAAAAA==

11. Question & Answer

Can Silodosin be the Solution for BPH Patients? Feb 05 2023
Background and Overview Watson Pharmaceuticals has officially launched its oral, effective treatment for benign prostatic hyperplasia (BPH) - the selective a1A-adrenergic receptor antagonist Silodosin..
What should be noted when taking Silodosin? Jun 06 2022
Silodosin is primarily used to treat benign prostatic hyperplasia in men. It is pale yellow-white in color and comes in powder form, which is easily soluble in acetic acid but insoluble in water. Silo..
What is Silodosin and how does it work? Sep 11 2021
Overview Silodosin is an α-1 adrenergic receptor antagonist used to treat symptoms associated with benign prostatic hyperplasia (BPH). It has the highest affinity for the α1A subtype. α1-adrenergic..