3D Mol Similar

Strontium ranelate

: Iupac Name：5-[bis(carboxymethyl)amino]-3-(carboxymethyl)-4-cyanothiophene-2-carboxylic acid;strontium; CAS No.: 135459-87-9; Molecular Weight：517.518; Modify Date.: 2022-11-25 02:18; Introduction: Strontium ranelate, a divalent strontium salt of ranelic acid, has been developedand launched for the treatment of osteoporosis. As early as 1910, investigationssuggested that strontium stimulates the formation of osteoid tissues while simultaneouslyrepressing the resorptive process in bones. Specifically, strontium enhancespre-osteoblastic cell replication, inhibits pre-osteoclast differentiation, andsuppresses the bone-resorbng activity of osteoclasts. From the evaluation of 26strontium salts, ranelic acid was selected as the ideal strontium carrier due to itsphysicochemical and pharmacokinetic properties. The thiophene core of ranelicacid is constructed by the condensation of dialkyl 3-oxoglutarate, malononitrile,and sulfur in a suitable alcohol in the presence of morpholine or diethylamine. Theresultant diester of 5-amino-3-carboxymethyl-4-cyano-2-thiophenecarboxylic acidis subsequently dialkylated with an alkyl bromoacetate to provide the tetraesterprecursor to strontium ranelate. Strontium ranelate is supplied in a 2 g sachet, andthe drug is evenly suspended in water prior to consumption. Since the simultaneousingestion of either calcium or food has a negative influence on the bioavailability ofstrontium ranelate, it is recommended that strontium ranelate be administered oncea day at bedtime. Following this regimen, the absolute bioavailability of strontiumis 27% while that of ranelic acid is 2.5%. Because strontium ranelate dissociatesafter intake, and ranelic acid has negligible absorption, the effects of the drug on bone metabolism are dependent on the pharmacokinetics of strontium. In postmenopausalwomen, the half-life of strontium is 6.3±2.3 days, and renal clearanceaccounts for 57%of the total clearance of 12mL/min. After a 25-day treatment, themaximum plasma concentration of strontium is 20±2.3 mg/L. In addition, not onlyis perfect stability of strontium plasma concentration achieved within 3 to 24months of chronic administration so is stabilization of strontium incorporation intobones. Strontium is incorporated into bone by two mechanisms. The predominantmode involves the rapid, saturable surface exchange with calcium. A slower mechanismembodies the incorporation of strontium into the crystal lattice of the bonemineral; however, only a small amount of calcium in the apatite is substituted bystrontium at pharmacological doses. A phase II clinical trial assessed the effect ofvarious strontium ranelate doses in postmenopausal women with established osteoporosis.The primary efficacy endpoint for this double-blind, randomized, placebo-controlled trial was the measure of mean lumbar bone mineral density (BMD)by dual-energy X-ray absorptiometry. A statistically significant dose-dependentincrease in lumbar BMD was observed; increases of 1.3, 5.9, 8.3, and 13.6%were recorded for placebo, 500-, 1000-, and 2000-mg doses of strontium ranelate,respectively. In a phase III trial encompassing 1,649 osteoporotic postmenopausalwomen from 12 countries, the efficacy of a 2 g/day dose in preventing new vertebralfractures was evaluated. The mean lumbar BMD was 0.73 g/cm2 while the meanage at baseline was 70 years. All of the enrolled patients had at least one priorvertebral fracture. The primary end point for this study was a reduction inthe incidence of patients experiencing fractures. While 222 women in the placebogroup experienced a new vertebral fracture, only 139 patients treated with strontiumranelate presented with new fractures. Furthermore, the risk of fracture wasreduced by 51% in the third year alone, implicating the sustained efficacy ofthe drug. For both the phase II and phase III studies, strontium ranelate was welltolerated with most of the adverse events being mild-to-moderate in severity. Themost commonly reported events in all treatment groups were musculoskeletal disorders(back pain, arthralgia, and lumbar pain). As for laboratory measurements,only creatine phosphokinase, the musculoskeletal isoenzyme, was significantly elevatedin the 1000-mg and 2000-mg strontium ranelate groups; however, this didnot translate into any particular clinical or biological abnormality. Withoutrelevant data regarding bone safety in patients with renal impairment, strontiumranelate is currently contraindicated in patients with creatine clearance below30mL/min. View more+

Request For Quotation

1. Names and Identifiers

: 1.1 Name; Strontium ranelate; 1.2 Synonyms; 2,2'-((5-Carboxy-4-(carboxyMethyl)-3-cyanothiophen-2-yl)azanediyl)diacetic acid, distrontiuM salt 2-[N,N-Di(carboxymethyl)amino]-3-cyano-4-carboxymethylthiophene-5-carboxylic acid strontium salt 3-Thiopheneacetic acid, 5-[bis(carboxymethyl)amino]-2-carboxy-4-cyano- 5-[Bis(carboxymethyl)amino]-3-(carboxymethyl)-4-cyano-2-thiophenecarboxylic acid 5-[Bis(carboxymethyl)amino]-3-(carboxymethyl)-4-cyanothiophene-2-carboxylic acid Ranelate StrontiuM Ranelic acid strontium salt StrontiuM 2,2'-((5-carboxylato-4-(carboxylatoMethyl)-3-cyanothiophen-2-yl)azanediyl)diacetate StrontiuM ranelate SynonyMs DistrontiuM renelate StrontiuM ranelate (Protelos) StrontiuM Ranelic; View all

1.3 CAS No.: 135459-87-9

1.4 CID: 6918182

1.5 EINECS(EC#): 1806241-263-5

1.6 Molecular Formula: C12H6N2O8SSr2 (isomer)

1.7 Inchi: InChI=1S/C12H10N2O8S.2Sr/c13-2-6-5(1-7(15)16)10(12(21)22)23-11(6)14(3-8(17)18)4-9(19)20;;/h1,3-4H2,(H,15,16)(H,17,18)(H,19,20)(H,21,22);;/q;2*+2/p-4

1.8 InChIkey: XXUZFRDUEGQHOV-UHFFFAOYSA-J

1.9 Canonical Smiles: C(C1=C(SC(=C1C#N)N(CC(=O)[O-])CC(=O)[O-])C(=O)[O-])C(=O)[O-].[Sr+2].[Sr+2]

1.10 Isomers Smiles: C(C1=C(SC(=C1C#N)N(CC(=O)[O-])CC(=O)[O-])C(=O)[O-])C(=O)[O-].[Sr+2].[Sr+2]

2. Properties

2.1 Density: 1.8±0.1 g/cm3

2.1 Melting point: >310°C (dec.)

2.1 Boiling point: 778.8 °C at 760 mmHg

2.1 Refractive index: 1.695

2.1 Flash Point: 424.8 °C

2.1 Precise Quality: 513.79600

2.1 PSA: 160.47000

2.1 logP: -0.32272

2.1 Solubility: H2O: soluble1mg/mL, clear (warmed)

2.2 Appearance: crystalline solid

2.3 Storage: -20°C Freezer

2.4 Chemical Properties: Crystalline Solid

2.5 Color/Form: Powder

2.6 Water Solubility: H2O: soluble 1mg/mL, clear (warmed)

2.7 StorageTemp: Inert atmosphere,Store in freezer, under -20°C

3. Use and Manufacturing

3.1 GHS Classification: Signal: Warning
GHS Hazard Statements
Aggregated GHS information provided by 26 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

H302+H312+H332 (92.31%): Harmful if swallowed, in contact with skin or if inhaled [Warning Acute toxicity, oral; acute toxicity, dermal; acute toxicity, inhalation]
H302 (92.31%): Harmful if swallowed [Warning Acute toxicity, oral]
H312 (92.31%): Harmful in contact with skin [Warning Acute toxicity, dermal]
H319 (11.54%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]
H332 (92.31%): Harmful if inhaled [Warning Acute toxicity, inhalation]

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

Precautionary Statement Codes
P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P312, P304+P340, P305+P351+P338, P312, P322, P330, P337+P313, P363, and P501; View all

3.2 Usage: It is mainly used for the treatment and prevention of osteoporosis in postmenopausal women and significantly reduces the risk of occurrence of vertebral fractures and hip fractures.

4. Safety and Handling

4.1 Symbol: GHS07

4.1 Hazard Codes: Xn

4.1 Signal Word: Warning

4.1 Risk Statements: 20/21/22

4.1 Safety Statements: 36/37

4.1 Hazard Declaration: H302 + H312 + H332

4.1 RIDADR: 3077

4.1 Caution Statement: P280

4.1 WGK Germany: 3

4.1 RTECS: XM7581000

4.1 Specification: ?Strontium ranelate , its cas register number is 135459-87-9. It also can be called?Distrontium renelate ;?Osseor ; Protelos ; Protos ; Ranelic acid distrontium salt ; 3-(3-cyano-4-carboxymethyl-5-carboxy-2-thienyl)-3-azapentanedioic distrontium salt ; 3-Thiopheneacetic acid, 5-(bis(carboxymethyl .It is a?crystalline solid.

5. MSDS

2.Hazard identification

2.1 Classification of the substance or mixture

Acute toxicity - Oral, Category 4

Acute toxicity - Dermal, Category 4

Acute toxicity - Inhalation, Category 4

2.2 GHS label elements, including precautionary statements

Pictogram(s)
Signal word	Warning
Hazard statement(s)	H302+H312+H332 Harmful if swallowed, in contact with skin or if inhaled
Precautionary statement(s)
Prevention	P264 Wash ... thoroughly after handling. P270 Do not eat, drink or smoke when using this product. P280 Wear protective gloves/protective clothing/eye protection/face protection. P261 Avoid breathing dust/fume/gas/mist/vapours/spray. P271 Use only outdoors or in a well-ventilated area.
Response	P301+P312 IF SWALLOWED: Call a POISON CENTER/doctor/\u2026if you feel unwell. P330 Rinse mouth. P302+P352 IF ON SKIN: Wash with plenty of water/... P312 Call a POISON CENTER/doctor/\u2026if you feel unwell. P321 Specific treatment (see ... on this label). P362+P364 Take off contaminated clothing and wash it before reuse. P304+P340 IF INHALED: Remove person to fresh air and keep comfortable for breathing.
Storage	none
Disposal	P501 Dispose of contents/container to ...

2.3 Other hazards which do not result in classification

none

View all

6. Other Information

6.0 Drug for the treatment of osteoporosis: Strontium ranelate is a drug for the treatment of osteoporosis with its appearance being white to light yellow powder or crystalline powder. It is odorless and slightly soluble in water but almost insoluble in ethanol and easily soluble in dilute hydrochloric acid. It was first studied and developed by the French Servier Company and had first entered into market in November 2004 in Ireland and entered into market in UK in December of same year. Japan's Fujisawa Pharmaceutical Company has owned the authorization of development, production and marketing right of this product in Japan. It is clinically mainly used for the treatment and prevention of osteoporosis in postmenopausal women with significantly reducing the risk of occurrence of vertebral fractures and hip fractures.
Strontium ranelate has dual pharmacological inhibitory effects of both inhibiting bone absorption and promoting bone formation. On the one hand, in the osteoblast-enriched cells, it can increase the synthesis of collagen and non-collagen proteins and promote the osteoblast-mediated bone formation mediated by osteoblasts through enhancing the proliferation of pre-osteoblast. On the other hand, through decreasing the osteoclast differentiation and reabsorbing activity and further reduction of bone absorption, it achieves the rebalance of bone turnover, further boosting the bone formation.
Strontium ranelate mainly exerts its pharmacological effects through its strontium atoms. Strontium is an alkaline earth metal element which is cognate with calcium and located under the calcium in the element periodic table. Its absorption, distribution, excretion is similar with calcium. After oral administration of 2g, the absolute bioavailability of strontium is 27%. Large doses of strontium cause abnormalities of bone mineral metabolism with low doses of strontium being able to the enhance the pre-osteoblast replication, increasing the number of osteoblasts to stimulate bone formation while reducing the activity of osteoclasts, reducing osteoclast quantity as well as reducing the rate of bone absorption. The results are consistent with the results found in animal and human in vivo studies.
s (OP) is a progressive skeletal disease, characterized by reduced bone mineral density (BMD) and degenerative changes in bone tissue microstructure. It is exhibited as bone fragility and fracture-prone with the latter most commonly happening in the spine, hip and wrist. For women, when after surgical removal of the ovaries or menopause, the body stops producing bone to maintain strong estrogen, thus, primary OP is particularly common in post-menopausal or menopausal women.
There are currently two major kinds of drugs used in the treatment of osteoporosis: one kind includes those drugs that inhibits osteoclast activity and therefore inhibiting bone absorption such as bisphosphonates, estrogen and calcitonin; the second category includes those drugs which promote the osteoblast activity, and thereby stimulating bone formation and there are currently only a product, human recombinant parathyroid hormone 1-34, that has entered into market. It however requires injection with high drug prices.; View all

6.1 Uses: It is mainly used for the treatment and prevention of osteoporosis in postmenopausal women and significantly reduces the risk of occurrence of vertebral fractures and hip fractures.

6.2 Chemical Properties: Crystalline Solid

6.3 Uses: Bone metabolism modulator; inhibits bone resorption while maintaining bone formation. Antiosteoporotic

6.4 Uses: Strontium ranelate (Protelos) is a strontium(II) salt of ranelic acid for (-)-desmethoxyverapamil binding to calcium channel with IC50 of 0.5 mM.

6.5 Mesh: Agents that inhibit BONE RESORPTION and/or favor BONE MINERALIZATION and BONE REGENERATION. They are used to heal BONE FRACTURES and to treat METABOLIC BONE DISEASES such as OSTEOPOROSIS. (See all compounds classified as Bone Density Conservation Agents.)

6.6 Mesh Entry Terms: 3-(3-cyano-4-carboxymethyl-5-carboxy-2-thienyl)-3-azapentanedioic distrontium salt

6.7 Use Classification: Human drugs -> Osseor -> EMA Drug Category|Drugs for treatment of bone diseases -> Human pharmacotherapeutic group|Human drugs -> Protelos -> EMA Drug Category|Human Drugs -> EU pediatric investigation plans

6.8 Target: Value

6.9 Cell Line:: Mouse calvaria (MC) cells

6.10 Concentration:: 0.1 mM, 0.3 mM or 1 mM

6.11 Incubation Time:: 22 days

6.12 Result:: The expression of mRNA for early osteoblast markers (ALP) was visualized by day 5, while late markers (OCN) were detectable only by day 15 and beyond.

6.13 Result:: Significantly increased the mRNA expression of the osteoblastic markers ALP, BSP and OCN at day 22 of MC cell culture.

6.14 体内研究: Strontium Ranelate increases bone formation and decreased bone resorption, which results in increased bone mass in the vertebrae of intact adult mice.
In intact adult rats, Strontium Ranelate also increases bone mass, as measured by dual-energy X-ray absorptiometry, in lumbar vertebra and femur, and this is confirmed by histological assessment of trabecular bone volume in the tibial metaphysis.
Strontium Ranelate is found to decrease bone resorption and to increase bone formation in alveolar bone in normal adult monkeys (Macaca fascicularis), which exhibits extensive bone remodeling.
In ovariectomized rats, short-term (3 months) treatment with Strontium Ranelate prevents trabecular bone loss induced by oestrogen deficiency, as demonstrated by bone ash, bone mineral content and histomorphometric analysis in the tibial metaphysis. This effect results from decreased bone resorption while bone formation was maintained. These beneficial effects of Strontium Ranelate on bone mass and microarchitecture in ovariectomized rats are confirmed in long-term experiments. In this long-term study (2 years), the increase in bone mass and microarchitecture induced by Strontium Ranelate results in a marked improvement in bone strength, supporting the beneficial effect of this drug on bone resistance.; View all

6.15 Description: Strontium ranelate, a divalent strontium salt of ranelic acid, has been developed and launched for the treatment of osteoporosis. As early as 1910, investigations suggested that strontium stimulates the formation of osteoid tissues while simultaneously repressing the resorptive process in bones. Specifically, strontium enhances pre-osteoblastic cell replication, inhibits pre-osteoclast differentiation, and suppresses the bone-resorbng activity of osteoclasts. From the evaluation of 26 strontium salts, ranelic acid was selected as the ideal strontium carrier due to its physicochemical and pharmacokinetic properties. The thiophene core of ranelic acid is constructed by the condensation of dialkyl 3-oxoglutarate, malononitrile, and sulfur in a suitable alcohol in the presence of morpholine or diethylamine. The resultant diester of 5-amino-3-carboxymethyl-4-cyano-2-thiophenecarboxylic acid is subsequently dialkylated with an alkyl bromoacetate to provide the tetraester precursor to strontium ranelate. Strontium ranelate is supplied in a 2 g sachet, and the drug is evenly suspended in water prior to consumption. Since the simultaneous ingestion of either calcium or food has a negative influence on the bioavailability of strontium ranelate, it is recommended that strontium ranelate be administered once a day at bedtime. Following this regimen, the absolute bioavailability of strontium is 27% while that of ranelic acid is 2.5%. Because strontium ranelate dissociates after intake, and ranelic acid has negligible absorption, the effects of the drug on bone metabolism are dependent on the pharmacokinetics of strontium. In postmenopausal women, the half-life of strontium is 6.3±2.3 days, and renal clearance accounts for 57%of the total clearance of 12mL/min. After a 25-day treatment, the maximum plasma concentration of strontium is 20±2.3 mg/L. In addition, not only is perfect stability of strontium plasma concentration achieved within 3 to 24 months of chronic administration so is stabilization of strontium incorporation into bones. Strontium is incorporated into bone by two mechanisms. The predominant mode involves the rapid, saturable surface exchange with calcium. A slower mechanism embodies the incorporation of strontium into the crystal lattice of the bone mineral; however, only a small amount of calcium in the apatite is substituted by strontium at pharmacological doses. A phase II clinical trial assessed the effect of various strontium ranelate doses in postmenopausal women with established osteoporosis. The primary efficacy endpoint for this double-blind, randomized, placebo- controlled trial was the measure of mean lumbar bone mineral density (BMD) by dual-energy X-ray absorptiometry. A statistically significant dose-dependent increase in lumbar BMD was observed; increases of 1.3, 5.9, 8.3, and 13.6% were recorded for placebo, 500-, 1000-, and 2000-mg doses of strontium ranelate, respectively. In a phase III trial encompassing 1,649 osteoporotic postmenopausal women from 12 countries, the efficacy of a 2 g/day dose in preventing new vertebral fractures was evaluated. The mean lumbar BMD was 0.73 g/cm2 while the mean age at baseline was 70 years. All of the enrolled patients had at least one prior vertebral fracture. The primary end point for this study was a reduction in the incidence of patients experiencing fractures. While 222 women in the placebo group experienced a new vertebral fracture, only 139 patients treated with strontium ranelate presented with new fractures. Furthermore, the risk of fracture was reduced by 51% in the third year alone, implicating the sustained efficacy of the drug. For both the phase II and phase III studies, strontium ranelate was well tolerated with most of the adverse events being mild-to-moderate in severity. The most commonly reported events in all treatment groups were musculoskeletal disorders (back pain, arthralgia, and lumbar pain). As for laboratory measurements, only creatine phosphokinase, the musculoskeletal isoenzyme, was significantly elevated in the 1000-mg and 2000-mg strontium ranelate groups; however, this did not translate into any particular clinical or biological abnormality. Without relevant data regarding bone safety in patients with renal impairment, strontium ranelate is currently contraindicated in patients with creatine clearance below 30mL/min.; View all

6.16 Originator: Fujisawa (Japan)

7. Computational chemical data

Molecular Weight: 517.518g/mol
Molecular Formula: C₁₂H₆N₂O₈SSr₂
Compound Is Canonicalized: True
XLogP3-AA: null
Exact Mass: 513.7957108
Monoisotopic Mass: 513.7957108
Complexity: 533
Rotatable Bond Count: 4
Hydrogen Bond Donor Count: 0
Hydrogen Bond Acceptor Count: 11
Topological Polar Surface Area: 216
Heavy Atom Count: 25
Defined Atom Stereocenter Count: 0
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Isotope Atom Count: 0
Covalently-Bonded Unit Count: 3
CACTVS Substructure Key Fingerprint: AAADcYBzPABAAAAABAAAAAAAAAAAASAAAAAAAAAAAAAAAAABgAAAHgQAAAAADADB2AQAiYMAAAicBgDQSACjAIBlCBgAiBGITMgKpjLglLGEEQhkwAH4yQ6YNwIOgAAAAAAAAAAAAAAAAAAAAAAAAAAAAA==

8. Question & Answer

What are the precautions for using and purchasing Strontium ranelate? Jun 16 2023
Strontium ranelate is a commonly used gastrointestinal medication that primarily works by inhibiting the secretion of gastric acid in the stomach, thereby relieving symptoms of gastrointestinal diseas..
What are the uses of Strontium ranelate? Jul 07 2022
As people age, they are more prone to developing osteoporosis. Some women experience osteoporosis after menopause, and Strontium ranelate can be used for treatment. This medication not only treats ost..
Can Strontium Ranelate be Used to Treat Osteoporosis? Jun 22 2022
Osteoporosis is a common disease among middle-aged and elderly people. It can also occur in young adults who lack exercise and spend long periods of time sitting. Strontium ranelate has been found to ..

9. Recommended Suppliers

Global235SuppliersView all >>

Wuhan Fortuna Chemical Co., Ltd. Diamond member

10YRS

Products:API,fine chemical&its intermediates,biological chemistry
Tel:0086-27-59207850
Email:info@fortunachem.com

Factory supply Strontium ranelate Cas 135459-87-9 with high quality and best price

Purity:99%Packing: 200kg/bag FOB
Price: 125 USD/kilogram
Time: 2023/09/21

Inquire

Xiamen wonderful Biotechnology Co., Ltd. Diamond member

1YR

Products:Top quality and high purity with safe transportation and low price
Tel:+86187-59294010-18759294010
Email:Beata@xmwonderfulbio.com

Strontium Ranelate

Purity:99%Packing: 200kg/bag FOB
Price: 50 USD/g
Time: 2023/09/21

Inquire

Hebei Chengcai Biotechnology Co., LTD Diamond member

1YR

Products:We are engaged in the development, marketing and sales of apis, intermediates, natural products (extracts), fine chemicals, food additives, agricultural chemicals and other products.
Tel:0086-0319-19131200228
Email:17610795226@chengcaibio.com

Strontium Ranelate CAS 135459-87-9