Win 18446

Names

[ Name ]:
Win 18446

[Synonym ]:
2,2-dichloro-N-[8-[(2,2-dichloroacetyl)amino]octyl]acetamide
N,N'-Octane-1,8-diylbis(2,2-dichloroacetamide)
Fertilysin
N,N'-1,8-Octanediylbis(2,2-dichloroacetamide)
N,N'-1,8-Octanediylbis[2,2-dichloroacetamide]
N,N'-Octamethylenebis(2,2-dichloroacetamide)
Acetamide, N,N'-1,8-octanediylbis[2,2-dichloro-
N,N'-Octamethylenebis(dichloroacetamide)
EINECS 216-033-0
N,N'-Octamethylenebis(2,2-dichloro-N-ethylacetamide)
N,N'-Bis(dichloroacetyl)-1,8-octamethylenediamine

Biological Activity

[Description]:

Win 18446 is an orally active testes-specific enzyme ALDH1a2 inhibitor, with an IC50 of 0.3 μM. Win 18446 reversibly inhibits spermatogenesis in many species and inhibits Retinoic acid (HY-14649) biosynthesis from Retinol (HY-B1342) within the testes[1][2].

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> Aldehyde Dehydrogenase (ALDH)

Research Areas >> Endocrinology

[In Vitro]

WIN 18446 (1 μM, 24 h) is able to suppress Stra8 expression in whole-testes cultures that contained both germ and somatic cells[2]. RT-PCR[2] Cell Line: Testes were collected from 2-dpp mice. Concentration: 1 μM. Incubation Time: 24 h. Result: Results in a VAD-like phenotype in the testis. Alone or in combination with ROL significantly reduced Stra8 expression.

[In Vivo]

Win 18446 (200 mg/kg, Orally for 4, 8, and 16 weeks) significantly reduces intratesticular concentrations of retinoic acid, severely impaired spermatogenesis, and caused infertility[1]. Animal Model: Six-month-old male New Zealand white rabbits[1]. Dosage: 200 mg/kg. Administration: Orally for 4, 8, and 16 weeks. Result: Resulted in marked suppression of testicular weight over time. Dramatically suppressed spermatogenesis. Significantly reduces intratesticular concentrations of retinoic acid and Stra8 expression and very severely suppresses spermatogenesis and fertility.

[References]

[1]. John K Amory, et al. Suppression of spermatogenesis by bisdichloroacetyldiamines is mediated by inhibition of testicular retinoic acid biosynthesis. J Androl. Jan-Feb 2011;32(1):111-9.

[2]. Cathryn A Hogarth, et al. Suppression of Stra8 expression in the mouse gonad by WIN 18,446. Biol Reprod. 2011 May;84(5):957-65.

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
530.2±50.0 °C at 760 mmHg

[ Melting Point ]:
118-120ºC

[ Molecular Formula ]:
C₁₂H₂₀Cl₄N₂O₂

[ Molecular Weight ]:
366.111

[ Flash Point ]:
274.5±30.1 °C

[ Exact Mass ]:
364.027893

[ PSA ]:
58.20000

[ LogP ]:
1.96

[ Vapour Pressure ]:
0.0±1.4 mmHg at 25°C

[ Index of Refraction ]:
1.503

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: AC6800000

CHEMICAL NAME :: Acetamide, N,N'-octamethylenebis(2,2-dichloro-

CAS REGISTRY NUMBER :: 1477-57-2

LAST UPDATED :: 199612

DATA ITEMS CITED :: 23

MOLECULAR FORMULA :: C12-H20-Cl4-N2-O2

MOLECULAR WEIGHT :: 366.14

WISWESSER LINE NOTATION :: GYG&VM8MVYG&G

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 943 mg/kg/50D

TOXIC EFFECTS :: Gastrointestinal - nausea or vomiting

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >16 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 150 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 150 mg/kg

SEX/DURATION :: male 42 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2 gm/kg

SEX/DURATION :: male 70 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 943 mg/kg

SEX/DURATION :: male 50 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2250 mg/kg

SEX/DURATION :: male 3 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1313 mg/kg

SEX/DURATION :: male 21 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 100 mg/kg

SEX/DURATION :: female 10-11 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - respiratory system Reproductive - Specific Developmental Abnormalities - immune and reticuloendothelial system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1 gm/kg

SEX/DURATION :: female 10 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1 gm/kg

SEX/DURATION :: female 11-12 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - body wall Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 50 mg/kg

SEX/DURATION :: female 10-11 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Newborn - stillbirth Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 2 gm/kg

SEX/DURATION :: female 9-10 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - body wall Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 2 gm/kg

SEX/DURATION :: female 9-10 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - blood and lymphatic systems (including spleen and marrow) Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 2 gm/kg

SEX/DURATION :: female 12-13 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - body wall Reproductive - Specific Developmental Abnormalities - blood and lymphatic systems (including spleen and marrow) Reproductive - Specific Developmental Abnormalities - respiratory system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 6400 mg/kg

SEX/DURATION :: female 8-9 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2500 mg/kg

SEX/DURATION :: female 10 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 20 gm/kg

SEX/DURATION :: female 14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - hepatobiliary system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 4 gm/kg

SEX/DURATION :: female 10 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1875 mg/kg

SEX/DURATION :: male 30 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :: Sperm Morphology

MUTATION DATA

TYPE OF TEST :: Micronucleus test

TEST SYSTEM :: Rodent - mouse Cells - not otherwise specified

DOSE/DURATION :: 500 mg/kg

REFERENCE :: NKEZA4 Nippon Koshu Eisei Zasshi. Japanese Journal of Public Health. (Nippon Koshu Eisei Gakkai, 1-29-8 Shinjuku, Shinjuku-ku, Tokyo 160, Japan) V.1- 1954- Volume(issue)/page/year: 33,165,1986

Safety Information

[ Hazard Codes ]:
Xn

[ Risk Phrases ]:
20/21/22-40

[ Safety Phrases ]:
S24/25

[ HS Code ]:
2924199090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2924199090

[ Summary ]:
2924199090. other acyclic amides (including acyclic carbamates) and their derivatives; salts thereof. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%

Related Compounds

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