.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Details for Patent: 5,932,543

« Back to Dashboard

Details for Patent: 5,932,543

Title: Cyclic peptide antifungal agents and process for preparation thereof
Abstract:Provided are compounds of the formula (1): ##STR1## wherein R' is hydrogen, methyl or NH.sub.2 C(O)CH.sub.2 --; R" and R'" are independently methyl or hydrogen; R and R.sup.Y are independently hydroxy or hydrogen; R.sub.1 is hydroxy, hydrogen, or hydroxysulfonyloxy; R.sub.7 is hydroxy, hydrogen, hydroxysulfonyloxy or phosphonooxy; R.sub.2 is a novel acyl side chain. Also provided are novel formulations, methods of inhibiting fungal and parasitic activity, and a process for preparing dideoxy (R=H) forms of the compounds.
Inventor(s): Burkhardt; Frederick J. (Indianapolis, IN), Debono; Manuel (Indianapolis, IN), Nissen; Jeffrey S. (Indianapolis, IN), Turner, Jr.; William W. (Bloomington, IN)
Assignee: Eli Lilly and Company (Indianapolis, IN)
Filing Date:Jun 12, 1997
Application Number:08/873,480
Claims:1. A compound of the formula ( 1): ##STR251## wherein R' is hydrogen, methyl or NH.sub.2 C(O)CH.sub.2 --;

R" and R'" are independently methyl or hydrogen;

R and R.sup.y are independently hydroxy or hydrogen;

R.sub.1 is hydroxy, hydrogen, or hydroxysulfonyloxy;

R.sub.7 is hydroxy, hydrogen, or hydroxysulfonyloxy; and

I) R2 is a substituted benzoyl group represented by the formula ##STR252## wherein A) R3 is a polyoxa-alkyl group represented by the formula

wherein m and n are integers of from 2 to 4, and p is 0 or 1; or

B) R3 is an unsaturated hydrocarbon group represented by the formula

wherein Y is --C.tbd.C-- or --C.dbd.C--; or

C) R3 is a group of the formula --O(CH.sub.2).sub.m --G, wherein m is as defined and G is C.sub.7 -C.sub.10 bicycloalkyl or C.sub.7 -C.sub.14 tricycloalkyl; or

D) R3 is quinolyl; or

II) R2 is naphthoyl substituted with R.sub.4

wherein

A) R.sub.4 is hydrogen, C.sub.2 -C.sub.12 alkynyl, C.sub.2 -C.sub.12 substituted alkynyl, C.sub.3 -C.sub.12 cycloalkyl, C.sub.7 -C.sub.10 bicycloalkyl, C.sub.7 -C.sub.14 tricycloalkyl, C.sub.1 -C.sub.12 alkoxy, C.sub.3 -C.sub.12 cycloalkoxy, naphthyl, pyridyl, thienyl, benzothienyl, quinolyl or phenyl; or

B) R.sub.4 is phenyl substituted by amino, C.sub.1 -C.sub.12 alkylthio, halogen, C.sub.1 -C.sub.12 alkyl, C.sub.2 -C.sub.12 alkenyl, C.sub.2 -C.sub.12 alkynyl, C.sub.1 -C.sub.12 substituted alkyl, C.sub.2 -C.sub.12 substituted alkenyl, C.sub.2 -C.sub.12 substituted alkynyl, C.sub.1 -C.sub.12 alkoxy, trifluoromethyl, phenyl, substituted phenyl, phenyl substituted with a polyoxa-alkyl group represented by the formula

wherein m and n are integers of from 2 to 4, and p is 0 or 1; or

C) R.sub.4 is phenyl substituted with C.sub.1 -C.sub.6 alkoxy substituted by fluoro, bromo, chloro or iodo; or

D) R.sub.4 is C.sub.1 -C.sub.12 alkoxy substituted with C.sub.3 -C.sub.12 cycloalkyl, C.sub.7 -C.sub.10 bicycloalkyl, C.sub.7 -C.sub.14 tricycloalkyl, C.sub.2 -C.sub.12 alkynyl, amino, C.sub.1 -C.sub.4 alkylamino, di-(C.sub.1 -C.sub.4 alkyl) amino, C.sub.1 -C.sub.12 alkanoylamino, phenyl substituted with a polyoxa-alkyl group represented by the formula

wherein m, n and p are as defined above; or

E) R.sub.4 is C.sub.1 -C.sub.12 alkoxy substituted with a group of the formula ##STR253## wherein R.sub.8 is C.sub.1 -C.sub.6 alkoxy optionally substituted with phenyl; or

F) R.sub.4 is a group represented by the formula

wherein p' is an integer of from 2 to 4; W is pyrrolidino, piperidino or piperazino, and R.sub.5 is hydrogen, C.sub.1 -C.sub.12 alkyl, C.sub.3 -C.sub.12 cycloalkyl, benzyl or C.sub.3 -C.sub.12 cycloalkylmethyl; or

G) R.sub.4 is a group represented by the formula

wherein Y is --C.tbd.C-- or --CH.dbd.CH--; and

R.sub.6 is C.sub.1 -C.sub.12 alkyl, C.sub.1 -C.sub.12 substituted alkyl; C.sub.3 -C.sub.12 cycloalkyl, C.sub.7 -C.sub.10 bicycloalkyl, C.sub.7 -C.sub.14 tricycloalky, phenyl, C.sub.3 -C.sub.12 cycloalkenyl, naphthyl, benzothiazolyl, thienyl, indanyl, fluorenyl, phenyl substituted by amino, C.sub.1 -C.sub.12 alkylthio, halogen, C.sub.1 -C.sub.12 alkyl, C.sub.2 -C.sub.12 alkenyl, C.sub.2 -C.sub.12 alkynyl, C.sub.1 -C.sub.12 alkoxy, trifluoromethyl, --O--(CH.sub.2).sub.p' --W--R.sub.5, or C.sub.1 -C.sub.6 alkoxy substituted by fluoro, bromo, iodo or chloro; or

R.sub.6 is phenyl substituted by a polyoxa-alkyl group represented by the formula

wherein m, n and p are as defined above; or

III) R2 is a group having the formula ##STR254## wherein R.sup.x is C.sub.1 -C.sub.12 alkoxy or a polyoxa-alkyl group represented by the formula

wherein m, n and p are as defined above; or

IV) R2 is a group having the formula ##STR255## wherein R.sub.9 is phenyl, C.sub.1 -C.sub.12 alkyl, or C.sub.1 -C.sub.12 alkoxy; and the pharmaceutically acceptable non-toxic salts thereof;

with the proviso that when

R' is methyl or NH.sub.2 C(O)CH.sub.2 --;

R" is methyl;

R'" is methyl;

R.sup.y is hydroxy or hydrogen; and either a) or b) or c)

a) R.sub.1 is hydroxysulfonyloxy and R.sub.7 is hydroxy or hydroxysulfonyloxy;

b) R.sub.1 is hydrogen or hydroxysulfonyloxy and R.sub.7 is hydroxysulfonyloxy;

c) R.sub.1 is hydroxy and R.sub.7 is hydroxy:

R.sub.2 is not ##STR256## wherein R3 is

wherein p=0; nor

ii) naphthoyl substituted by R.sub.4 wherein R.sub.4 is hydrogen, phenyl, or C.sub.1 -C.sub.12 alkoxy.

2. The compound as recited in claim 1 wherein R', R" and R'" are methyl, R.sub.1 is hydrogen, and R.sub.7 and R.sup.y are OH.

3. The compound as recited in claim 1 wherein R is hydrogen.

4. A method for inhibiting parasitic activity comprising contacting a compound of claim 1 with a parasite.

5. A method for inhibiting fungal activity comprising contacting a compound of claim 1 with a fungus.

6. A method for inhibiting the growth of organisms responsible for opportunistic infections in immunosuppressed individuals comprising administering a compound of claim 1 to said immunosuppressed individuals.

7. A method for inhibiting the growth of pneumocystis carinii comprising contacting a compound of claim 1 with said pneumocystis carinii.

8. A pharmaceutical formulation comprising a compound of claim 1 and suitable pharmaceutical carrier.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc