190791-29-8

Basic information

• Product Name: LASOFOXIFENE HCL
• Synonyms: 2-Naphthalenol, 5,6,7,8-tetrahydro-6-phenyl-5-(4-(2-(1-pyrrolidinyl)ethoxy)phenyl)-, (5R,6S)-, (2S,3S)-2,3-dihydroxybutanedioate (1:1) (salt);2-Naphthalenol, 5,6,7,8-tetrahydro-6-phenyl-5-(4-(2-(1-pyrrolidinyl)ethoxy)phenyl)-, (5R-cis)-, (S-(R*,R*))-2,3-dihydroxybutanedioate (1:1) (salt);Cb 336156eb;Unii-85X09V2gso;(-)-cis-6-Phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol tartrate;(5R,6S)-5,6,7,8-Tetrahydro-6-phenyl-5-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]-2-naphthalenol tartrate;CP-336,156 tartrate;LASOFOXIFENE HCL
• CAS NO: 190791-29-8
• Molecular Formula: C₄H₆O₆*C₂₈H₃₁NO₂
• Molecular Weight: 450.019
• Mol File: 190791-29-8.mol
• Article Data: 2

Chemical Properties

• Melting Point: 185 °C(dec.)
• Boiling Point: 572.4 ºC at 760 mmHg
• Flash Point: 300 ºC
• Appearance: white to beige/
• Vapor Pressure: 1.05E-13mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: DMSO: soluble10mg/mL, clear
• CAS DataBase Reference: LASOFOXIFENE HCL(CAS DataBase Reference)
• NIST Chemistry Reference: LASOFOXIFENE HCL(190791-29-8)
• EPA Substance Registry System: LASOFOXIFENE HCL(190791-29-8)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 190791-29-8(Hazardous Substances Data)

Usage

Uses

disintegrant, enteric coating, sustained release formulations

Biological Activity

lasofoxifene (tartrate) is a third-generation, nonsteroidal selective estrogen receptor modulator (serm).estrogen receptors are activated by the hormone estrogen (17β-estradiol). serms are characterized by having estrogen agonist action in some tissues while acting as estrogen antagonists in others [1][2].lasofoxifene, also known as cp 336,156, is a third-generation, nonsteroidal selective estrogen receptor modulator. lasofoxifene bound with high affinity to the human estrogen receptor-α with ic50 value of 1.5 nm [1]. lasofoxifene is also a cb2 inverse agonist [4].in aged female rats, lasofoxifene decreased total serum cholesterol and fat body mass, and no uterine hypertrophy was observed. in 5-month-old ovariectomized (ovx) sprague-dawley female rats, lasofoxifene completely prevented ovx-induced increases in body weight gain, total serum cholesterol, and serum osteocalcin. cp-336,156 completely prevented ovx-induced bone loss and inhibited the increased bone turnover associated with estrogen deficiency in lumbar vertebrae, proximal tibiae, and distal femora [1].in postmenopausal women with osteoporosis, lasofoxifene reduced risks of nonvertebral and vertebral fractures, er-positive breast cancer, coronary heart disease, and stroke but an increased risk of venous thromboembolic events [2][3].

Biochem/physiol Actions

Lasofoxifene is a third-generation selective estrogen receptor modulator (SERM).

references

[1]. ke hz, paralkar vm, grasser wa, et al. effects of cp-336,156, a new, nonsteroidal estrogen agonist/antagonist, on bone, serum cholesterol, uterus and body composition in rat models. endocrinology. 1998 apr;139(4):2068-76.[2]. cummings sr, ensrud k, delmas pd, et al. lasofoxifene in postmenopausal women with osteoporosis. n engl j med. 2010 feb 25;362(8):686-96.[3]. gennari l, merlotti d, nuti r. selective estrogen receptor modulator (serm) for the treatment of osteoporosis in postmenopausal women: focus on lasofoxifene. clin interv aging. 2010 feb 2;5:19-29.[4]. kumar p, song zh. cb2 cannabinoid receptor is a novel target for third-generation selective estrogen receptor modulators bazedoxifene and lasofoxifene. biochem biophys res commun. 2014 jan 3;443(1):144-9.

InChI:InChI=1/C28H31NO2.C4H6O6/c30-24-11-15-27-23(20-24)10-14-26(21-6-2-1-3-7-21)28(27)22-8-12-25(13-9-22)31-19-18-29-16-4-5-17-29;5-1(3(7)8)2(6)4(9)10/h1-3,6-9,11-13,15,20,26,28,30H,4-5,10,14,16-19H2;1-2,5-6H,(H,7,8)(H,9,10)/t26-,28+;1-,2-/m10/s1

Synthetic route

D-tartaric acid (147-71-7) + lasofoxifene → Lasofoxifene tartrate (190791-29-8)

Conditions	Yield
In ethanol for 0.0833333h; Reflux;	50.3%

D-tartaric acid (147-71-7) + lasofoxifene (180916-16-9) → Lasofoxifene tartrate (190791-29-8)

Conditions	Yield
In ethanol for 0.0833333h; Reflux;	50%

6-benzyloxy-1-[4-(2-(pyrrolidin-1-yl)ethoxy)phenyl]-3,4-dihydronaphthalen-2(1H) -one → Lasofoxifene tartrate (190791-29-8)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: cerium(III) chloride / tetrahydrofuran / 1.5 h / -10 - 0 °C / Inert atmosphere 1.2: 2 h / -10 - -5 °C 2.1: methanol 3.1: hydrogen; 5%-palladium/activated carbon / methanol; ethanol / 10 h / 50 °C / 7600.51 Torr / Autoclave 4.1: ethanol / 0.08 h / Reflux View Scheme

6-benzyloxy-2-phenyl-1-{4-[2-(pyrrolin-1-yl)ethoxy]phenyl}-3,4-dihydronaphthalene → Lasofoxifene tartrate (190791-29-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: methanol 2: hydrogen; 5%-palladium/activated carbon / methanol; ethanol / 10 h / 50 °C / 7600.51 Torr / Autoclave 3: ethanol / 0.08 h / Reflux View Scheme

1-[2-(4-bromophenoxy)ethyl]pyrrolidine (1081-73-8) → Lasofoxifene tartrate (190791-29-8)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: magnesium / tetrahydrofuran / 20 - 30 °C / Inert atmosphere 1.2: 1 h / Reflux 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 2 h / 0 - 5 °C 3.1: cerium(III) chloride / tetrahydrofuran / 1.5 h / -10 - 0 °C / Inert atmosphere 3.2: 2 h / -10 - -5 °C 4.1: methanol 5.1: hydrogen; 5%-palladium/activated carbon / methanol; ethanol / 10 h / 50 °C / 7600.51 Torr / Autoclave 6.1: ethanol / 0.08 h / Reflux View Scheme

6-benzyloxy-1-{4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}-3,4-dihydronaphthalene → Lasofoxifene tartrate (190791-29-8)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 2 h / 0 - 5 °C 2.1: cerium(III) chloride / tetrahydrofuran / 1.5 h / -10 - 0 °C / Inert atmosphere 2.2: 2 h / -10 - -5 °C 3.1: methanol 4.1: hydrogen; 5%-palladium/activated carbon / methanol; ethanol / 10 h / 50 °C / 7600.51 Torr / Autoclave 5.1: ethanol / 0.08 h / Reflux View Scheme

Upstream product

• 1081-73-8 1-[2-(4-bromophenoxy)ethyl]pyrrolidine 
• 147-71-7 D-tartaric acid 
• 180916-16-9 lasofoxifene 
• 180915-78-0 lasofoxifene 

Relevant articles and documents

LASOFOXIFENE MODULATION OF MEMBRANE-INITIATED ESTROGEN SIGNALS AND METHODS FOR TUMOR TREATMENT

The present invention found that lasofoxifene is an antagonist of ER-α36. It not only inhibits the growth of ER-α36 positive lung, colon and gastric cancers, and also it can inhibit the growth of acquired or de novo tamoxifen-resistant MCF-7 cells. Our finding also provides methods and compositions for treating cancer comprising lasofoxifene alone or in combination with at least one other agent selected from the group consisting of gefitinib and/or trastuzumab or functional equivalent thereof, and an inhibitor in hormonal or epidermal growth factor signal transduction pathways.