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Prous Science Drugs of the Future^TM, produced by Prous Science Publishers, contains comprehensive drug monographs providing product information on new compounds, including the synthesis and corresponding schemes, pharmacological action, pharmacokinetics and metabolism, toxicity, clinical studies, manufacturer, and references. Information on compounds is continuously updated as advances in development status are disclosed worldwide.

Prous Science Drugs of the Future allows users to easily track the evolution of bioactive compounds through the pipeline, from preclinical studies through clinical trials up to marketing. As many compounds selected in the database reach the marketplace at some time, Prous Science Drugs of the Future is a unique source for describing the state-of-the-art of pharmaceutical R&D worldwide.

This database is derived from the print publication Prous Science Drugs of the Future, a leading publication in the field of medicinal chemistry since its launch in 1976. Additional information is derived from current literature (1,500 journals are regularly screened); abstracts and proceedings from congresses and symposia (more than 300 meetings covered annually); and manufacturers' communications. Some information from patent sources is also entered in the database, and typically includes new routes of synthesis, new formulations, new combinations, etc.

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Fields in the Prous Science Drugs of the Future database include:

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• CAS registry number
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• related compounds
• chemical structure

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For Dialog's Redistribution and Archive Policy, enter HELP ERA online. The following terms and conditions also apply. (c)2000 J.R. Prous, S.A. All rights reserved. No part of this electronic database may be reproduced, abstracted, or transmitted in any form or by any means--electronic, mechanical, photocopying, recording, or otherwise--without the express written permission of the publisher, J.R. Prous, S.A. While great care has been taken in the preparation of this database, and the publisher has made a reasonable effort to supply complete and accurate information, it does not assume any liability for errors or omissions. J.R. Prous, S.A. makes no warranties, expressed or implied, with respect to the accuracy, quality, validity, or completeness of this database or the information therein or its merchantability or fitness for a particular purpose.

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	DIALOG(R)File 453:Prous Science Drugs of the Future
	(c) 2005 Prous Science. All rts. reserv.
	00170014
AA=	ENTRY NUMBER:  170014
/NA,NA=	DRUG NAME:     CDDD-5604
	HGP-1
	IDR-90102 (topical)
	IDR-90103 (oral formulation)
	P-5604
/SY,SY=/NA,NA=	GENERIC NAME:  Loteprednol etabonate (recommended INNM; USAN)
/TN,TN=	BRAND NAME:    Alrex (Bausch & Lomb, US)
	Lenoxin
	Locort (Ivax, US)
	Lotemax (Bausch & Lomb, US)
	Loterox
CN=	CHEM NAME:  11beta,17-Dihydroxy-3-oxoandrosta-1,4-diene-17beta-carbox
	ylic acid chloromethyl ester 17-(ethylcarbonate)
	17alpha-(Ethoxycarbonyloxy)-11beta-hydroxy-3-oxoandrosta-1,4
	-diene- 17-carboxylic acid chloromethyl ester
MF=	FORMULA:    C24H31CLO7
RN=	CAS REG. NO.:  82034-46-6
	129260-79-3 (loteprednol)
image
ST=	DEVEL. PHASE:  Launched (1998)
/LO,LO=	ORIGINATOR:    Bausch & Lomb
	Ivax
	Soft Drugs
/LI,LI=	LICENSEE:      Asta Medica
/TC,TC=	CLASS:         2400  (Corticosteroids)
	18200  (Antiinflammatory Ophthalmic Agents)
	18320  (Antiallergic Ophthalmic Agents)
	26105  (Drugs for Allergic Rhinitis)
	27000  (Asthma Therapy)
	59000  (Dermatologic Drugs)
SS=	SYNTHESIS:     65911
CX=	CONTEXT TABLE: 18200C (Ocular Antiinflammatory Agents)
	26105C (Miscellaneous Agents for Allergic Rhinitis)
/TX	Synthesis
	The oxidation of
	11beta,17,21-trihydroxypregnan-1,4-diene-3,20-dione (I) with sodium
	metaperiodate in THF/methanol gives 11beta,17alpha-
	dihydroxy-3-oxoandrosta-1,4-diene-17beta-carboxylic acid (II), which is
	treated with ethyl chloroformate and triethylamine in dichloromethane
	yielding 17alpha-(ethoxycarbonyloxy)-11beta-hydroxy-
	3-oxoandrosta-1,4-diene -17beta-carboxylic acid (III). Finally, this
	compound is esterified with chloromethyl iodide and NaOH
	in methanol/water(1,2). Scheme 1.
	Description
	Crystals, m.p. 220.5-3.5 C.
	Introduction
	Corticosteroid drugs have demonstrated excellent
	antiinflammatory activity in clinical practice. Their therapeutic
	effects, however, are unfortunately also often accompanied by
	unpleasant toxicities, including, in the case of ocular agents,
	posterior subcapsular cataract formation, elevation of intraocular
	pressure and resultant steroid-resistant glaucoma, secondary ocular
	infection, slowing of wound healing, uveitis, mydriasis, ptosis and
	transient ocular discomfort. Thus, the search for improved topical
	corticosteroids with less toxicity has been a major goal in
	pharmaceutical research and development in recent years.
	Loteprednol etabonate is a so-called "soft drug" that
	was designed using a concept developed by Bodor (3). According to this
	concept, the synthesis of a soft drug is achieved by starting with a
	known inactive metabolite of a known active drug. The inactive
	metabolite is then modified to an active form that, after having
	achieved its therapeutic role, will undergo a predictable and
	controllable one- or two-step transformation in vivo back to the
	inactive metabolite via known processes of enzymatic deactivation
	(4,5). In this case, unlike prednisolone, a metabolically
	labile ester function occupies the 17beta-position, while a stable
	carbonate group occupies the 17alpha- position. The ester is
	hydrolyzed to an inactive carboxylic acid, DELTA1-cortienic acid
	etabonate (91), and then into the lead compound DELTA1-cortienic
	acid (90), in biological systems (5,6). As a result of the
	predictable conversion of loteprednol etabonate into an inactive
	metabolite in the eye following topical administration,
	this corticosteroid compound has a low propensity for undesirable
	systemic toxicity while possessing increased antiinflammatory activity
	relative to loteprednol (7). Loteprednol etabonate is being developed
	as an ocular antiinflammatory agent as its initial indication;
	however, its use in the treatment of gastrointestinal inflammatory
	disorders has also been explored (5,8).
	(...)
	PREV. PUB. IN: Drugs of the Future, Vol. 22, No. 10, p. 1086, 1997
	Drug Data Report, Vol. 13, No. 6, p. 503, 1991
	Drug Data Report, Vol. 20, No. 7, p. 636, 1998
/RF,RF=	REFERENCES:
	1. Bodor, N.S., "Steroids with antiinflammatory activity", BE 0889563,
	US 4996335
	2. Druzgala, P.; Hochhaus, G.; Bodor, N., "Soft drugs - 10", Blanching
	activity and receptor binding affinity of a new type of glucocorticoid:
	Loteprednol etabonate. J Steroid Biochem Mol Biol 1991, 38: 149-54
	3. Bodor, N., "The application of soft drug approaches to the design of
	safer corticosteroids", In: Topical Corticosteroids Therapy: A Novel
	Approach to Safer Drugs, E. Christophers et al. (Eds.), Raven Press, Ltd.,
	New York, 1988, 13-25
	(...)
	104. "LOTEPREDNOL ETABONATE < Prop INNM; USAN >", Drug Data Report,
	Vol. 13, No. 6, p. 503, 1991
	105. "LOTEPREDNOL ETABONATE", Drug Data Report, Vol. 20, No. 7, p. 636,
	1998

SYNTHESIS SCHEME RECORD [top]

	(c) 2005 Prous Science. All rts. reserv.
	01018200
SS=	SYNTHESIS SCHEME:   65911
AA=	ENTRY NUMBER:       170014
/RF,RF=	REFERENCE:          Graul, A.; Martin, L.; Castaner, J., "Loteprednol
	Etabonate < Rec INNM; USAN >", Drugs of the Future, Vol. 22, No. 10, p.
	1086, 1997
image

CONTEXT TABLE RECORD

	(c) 2005 Prous Science. All rts. reserv.
	01018200
CX=	CONTEXT TABLE:    18200C  (Ocular Antiinflammatory Agents)
image

BASIC INDEX [top]

¹ Searchable in the Basic Index and in the Additional Indexes.

² Includes Licensee (/LI, LI=) and Originator (/LO, LO=).

³ Includes Chemical Name, Laboratory Code, Brand Name, and Generic Drug Name.

⁴ Includes Laboratory Code, Brand Name, and Generic Drug Name.

⁵ Also searchable using /DE.

ADDITIONAL INDEXES [top]

⁶ Available only in Context Table records and Synthesis Scheme records. May also use MAP CX and/or MAP SS.

⁷ The graphic structure can be displayed and edited using DialogLink 5.

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Rates [top]

Rates For File: Prous Science Drugs of the Future™[453]
Cost per DialUnit:                 $9.18
Cost per minute:                   $3.70
Rank Elements                      $0.00

Format    Types   Prints
     1    $0.00    $0.00
     2   $30.00   $30.00
     3   $10.00   $10.00
     4   $40.00   $40.00
     5   $30.00   $30.00
     6    $0.00    $0.00
     7   $30.00   $30.00
     8    $0.00    $0.00
     9   $40.00   $40.00
    12   $34.00    $0.00
    13   $23.00    $0.00
    14   $42.00    $0.00
    15   $34.00    $0.00
    16    $3.50    $0.00
    17   $34.00    $0.00
    18    $3.50    $0.00
    19   $40.00    $0.00
    33   $42.00   $42.00
KWIC95    $4.00       NA
KWIC96    $4.00       NA

REDIST/COPY Multiplier Table:

      Range      Multiplier
        1-2       1.00
       3-25       1.50
     26-100       3.00
    101-200       4.00
    201-500       6.00
   501-1000       8.00
 1001 or more    10.00

ARCHIVE Multiplier Table:

      Range      Multiplier
       1-25       1.50
     26-200       3.00
    201-500       6.00
   501-1000       8.00
 1001 or more    10.00
---------------------------------

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