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LANOCONAZOLE

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Lanoconazole

  • Latoconazole, Lanoconazole, TJN-318, NND-318, Astat,

Nihon Nohyaku (Originator), Tsumura (Licensee)

Synonym: 2-[4-(2-Chlorophenyl)-1,3-dithiolan-2-ylidene]-2-imidazol-1-yl-acetonitrile
Application: An antifungal compound
CAS Number: 101530-10-3
Molecular Weight: 319.83
Molecular Formula: C14H10ClN3S2

Brief background information

Technical Information
Appearance: Crystalline
Physical State: Solid
Solubility: Soluble in chloroform, and methanol. Insoluble in water.
Storage: Store at -20° C
Melting Point: 129-132 °C
Boiling Point: ~477.6 °C at 760 mmHg (Predicted)
Density: ~1.4 g/cm3 (Predicted)
Refractive Index: n20D 1.73 (Predicted)
pK Values: pKb: 3.76 (Predicted)
Safety and Reference Information
WGK Germany: 3
RTECS: NI3393500
PubChem CID: 3002820
Merck Index: 14: 5357
MDL Number: MFCD00865590
Beilstein Registry: 4819111
Salt ATC Formula MM CAS
D01 14 H 10 ClN 3 S 2 319.84 g / mol 101530-10-3

Lanoconazole

Application

  • antifungal

Synthesis pathway

Synthesis a)

Synthetic route
The reaction of 2- (1-imidazolyl) acetonitrile (I) with CS2 and KOH in DMF gives the dithiolate (II), which is then cyclized with 1- (2-chlorophenyl) -1,2-di (methanesulfonyloxy) ethane . (III) A column chromatography over silicagel allows the separation of the (E) -.? and (Z) -isomers (1-5)
Description Crystals, mp 141-5 Manufacturer Nihon Nohyaku Co., Ltd. (Japan) and Tsumura Juntendo (Japan).
References 1. Seo, A., Kanno, H., Hasegawa, N. et al. (Nihon Nohyaku Co., Ltd.). Antimycotic agent and fungicidal agent. US 4738976. 2. Seo, A ., Sugano, H., Hasegawa, C., Ikeda, K., Munechica, Y., Konoe, T., Konaka, M. (Nihon Nohyaku Co., Ltd.). Antifungal agent. JP 87093227. 3. Seo , A., Sugano, H., Hasegawa, C., Ikeda, K., Nishimura, A., Miyashiro, Y. (Nihon Nohyaku Co., Ltd.). Non-medicinal bactericidal agents and method for their preparation. JP 87093204. 4. Seo, A., Sugano, H., Hasegawa, C., Miyashiro, Y., Nishimura, A., Ikeda, K. (Nihon Nohyaku Co., Ltd.). Ketene S, S-acetals. JP 85218387. 5. Seo, A., Kanno, H., Hasegawa, N. et al. (Nihon Nohyaku Co., Ltd.). A novel ketene S, S-acetal deriv., a process for manufacturing thereof and a method for curing mycosis by administering it. EP 218736.

Trade Names

Country Trade name Manufacturer
Japan Astatine Tsumura
Ukraine No No

Formulations

  • 1% cream;
  • 1% ointment;
  • 1% solution

Links

  • EP 218 736 (Nihon Nohyaku; EP-prior. 9.10.1985).
References

1. Oka, H., et al., 1992. Therapeutic efficacy of latoconazole in formulations of clinical use on experimental dermatophytosis in guinea pigs. Arzneimittel-Forschung. 42(3): 345-9. PMID: 1497697
2. Niwano, Y., et al., 1994. Therapeutic efficacy of lanoconazole, a new imidazole antimycotic agent, for experimental cutaneous candidiasis in guinea pigs. Antimicrobial agents and chemotherapy. 38(9): 2204-6. PMID: 7811048

http://aac.asm.org/content/38/9/2204.full.pdf

References 1. Seo, A., Kanno, H., Hasegawa, N. et al. (Nihon Nohyaku Co., Ltd.). Antimycotic agent and fungicidal agent. US 4738976. 2. Seo, A ., Sugano, H., Hasegawa, C., Ikeda, K., Munechica, Y., Konoe, T., Konaka, M. (Nihon Nohyaku Co., Ltd.). Antifungal agent. JP 87093227. 3. Seo , A., Sugano, H., Hasegawa, C., Ikeda, K., Nishimura, A., Miyashiro, Y. (Nihon Nohyaku Co., Ltd.). Non-medicinal bactericidal agents and method for their preparation. JP 87093204. 4. Seo, A., Sugano, H., Hasegawa, C., Miyashiro, Y., Nishimura, A., Ikeda, K. (Nihon Nohyaku Co., Ltd.). Ketene S, S-acetals. JP 85218387. 5. Seo, A., Kanno, H., Hasegawa, N. et al. (Nihon Nohyaku Co., Ltd.). A novel ketene S, S-acetal deriv., a process for manufacturing thereof and a method for curing mycosis by administering it. EP 218736.

Title: Lanoconazole
CAS Registry Number: 101530-10-3
CAS Name: (E)-(±)-a-[4-(2-Chlorophenyl)-1,3-dithiolan-2-ylidene]-1H-imidazole-1-acetonitrile
Additional Names: latoconazole
Manufacturers’ Codes: TJN-318; NND-318
Trademarks: Astat (Nihon Nohyaku)
Molecular Formula: C14H10ClN3S2
Molecular Weight: 319.83
Percent Composition: C 52.57%, H 3.15%, Cl 11.08%, N 13.14%, S 20.05%
Literature References: Prepn: A. Soe et al., JP Kokai 85 218387idem et al., US 4636519 (1985, 1987 both to Nihon Nohyaku).In vivo antifungal activity: H. Oka et al., Arzneim.-Forsch. 42, 345 (1992); Y. Niwano et al., Antimicrob. Agents Chemother. 38,2204 (1994). Toxicity study: P. L. Munt et al., Oyo Yakuri 43, 195 (1992).
Properties: Light yellow crystals, mp 141.5°. LD50 in male, female mice, rats (mg/kg): 3224, 2715, 993, 652 orally; 2158, 1743, 1655, 2596 i.p.; >5000 both species s.c. LD50 dermally in rats: >5000 mg/kg (Munt).
Melting point: mp 141.5°
Toxicity data: LD50 in male, female mice, rats (mg/kg): 3224, 2715, 993, 652 orally; 2158, 1743, 1655, 2596 i.p.; >5000 both species s.c.; LD50 dermally in rats: >5000 mg/kg (Munt)
Therap-Cat: Antifungal.
Keywords: Antifungal (Synthetic); Imidazoles.

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DR ANTHONY CRASTO

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DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with AFRICURE PHARMA, ROW2TECH, NIPER-G, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Govt. of India as ADVISOR, earlier assignment was with GLENMARK LIFE SCIENCES LTD, as CONSUlTANT, Retired from GLENMARK in Jan2022 Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 32 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 32 PLUS year tenure till date Feb 2023, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 100 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 100 Lakh plus views on dozen plus blogs, 227 countries, 7 continents, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 38 lakh plus views on New Drug Approvals Blog in 227 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc He has total of 32 International and Indian awards

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