Compounds And Methods For Treating Candidiasis And Aspergillus Infections
AssigneePolymedix, Inc.
InventorsRichard W. Scott, Katie Freeman, Haizhong Tang, Gill Diamond
Life of this patent
Estimating the term…
Abstract
The present disclosure provides compounds, or pharmaceutically acceptable salts thereof, for killing or inhibiting the growth of a Candida or Aspergillus species or preventing or treating a mammal having candidiasis (oral and/or disseminated) or an Aspergillus infection.
Claims35
A method of killing or inhibiting the growth of a Candida or Aspergillus species or preventing or treating a mammal having oral or disseminated candidiasis or an aspergillus infection comprising contacting the Candida or Aspergillus species with or administering to the mammal in need thereof an effective amount of a compound of Formula I:
- wherein:
- each X is, independently, O, S, or S(═O)2;
- each R1 is, independently, —CH3, —(CH2)n—NH2, —(CH2)n—NH—C(═NH)NH2, or —(CH2)n—NH—C(═O)—R4, where each n is, independently, 1 to 4, and each R4 is, independently, H, C1-C3alkyl, or —(CH2)p—NH2, where each p is, independently, 1 or 2;
- each R2 is, independently, H, halo, CF3, or C(CH3)3;
- each V2 is H, and each V1 is, independently, —N—C(═O)—R3, where each R3 is, independently, —(CH2)n—NH2 or —(CH2)n—NH—C(═NH)NH2, where each n is, independently, 1 to 4;
- or each V1 is H and each V2 is, independently, —S—R5, where each R5 is, independently, —(CH2)n—NH2 or —(CH2)n—NH—C(═NH)NH2, where each n is, independently, 1 to 4;
- and
- each R6 is H, —S—(CH2)m—NH2, —S—(CH2)m—NH—C(═NH)NH2, —O—(CH2)m—NH2, or —O—(CH2)m—NH—C(═NH)NH2, where each m is, independently, 1 to 4;
- or a pharmaceutically acceptable salt thereof.
4-9. (canceled)
12-18. (canceled)
21-23. (canceled)
25-32. (canceled)
A method of killing or inhibiting the growth of a Candida or Aspergillus species or preventing or treating a mammal having oral or disseminated candidiasis or an aspergillus infection comprising contacting the Candida or Aspergillus species with or administering to the mammal in need thereof an effective amount of a compound of Formula II:
- wherein:
- R1 is H;
- R2 is NH2;
- each R11 is, independently, —(CH2)0-4—R4 where R4 is chosen from hydrogen, C1-C4 alkyl, C3-C12 branched alkyl, C3-C8cycloalkyl, phenyl optionally substituted with one or more C1-C4 alkyl groups, C1-C4 alkoxy groups, or halo groups, and heteroaryl optionally substituted with one or more C1-C4 alkyl groups, C1-C4 alkoxy groups, or halo groups;
- each R9 is, independently, hydroxyethoxymethyl, methoxyethoxymethyl, polyoxyethylene, or —(CH2)q—V where q is from 1 to 5, and each V is, independently, chosen from amino, hydroxyl, C1-C6 alkylamino, C1-C6 dialkylamino, C1-C6 alkylurea, —NH(CH2)1-4NH2, —N(CH2CH2NH2)2, amidine, guanidine, semicarbazone, imidazole, piperidine, piperazine, 4-alkylpiperazine, phenyl optionally substituted with an amino, C1-C6 alkylamino, or C1-C6 dialkylamino, and lower acylamino optionally substituted with one or more amino, lower alkylamino, or lower dialkylamino, where the alkylene chain is optionally substituted with an amino or hydroxyl group;
- and
- m is 2 to at least about 30;
- or a pharmaceutically acceptable salt thereof.
35-53. (canceled)
A method of killing or inhibiting the growth of a Candida or Aspergillus species or preventing or treating a mammal having oral or disseminated candidiasis or an aspergillus infection comprising contacting the Candida or Aspergillus species with or administering to the mammal in need thereof an effective amount of a compound of Formula III:
- wherein:
- X is C(R7)C(R), C(═O), N(R9), O, S, S(═O), or 8(═O)2;
- R7, R8, and R9 are, independently, H, C1-C8alkyl, C1-C8alkoxy, halo, OH, CF3, aromatic group, —(CH2)qNH2, or —(CH2)qNHC(═NH)NH2, where q is 0 to 4;
- R1 and R2 are, independently, H, C1-C8alkyl, C1-C8alkoxy, halo, OH, haloC1-C8alkyl, CN, or CF3;
- R3 and R4 are, independently, H or carbocycle(R5)(R6);
- each R5 and each R6 are, independently, H, C1-C8alkyl, C1-C8alkoxy, halo, amino, OH, CF3, —O—(CH2)p—NH2, —O—(CH2)pNHC(═NH)NH2, —S—(CH2)p—NH2, —N((CH2)pNH2)2, —S—(CH2)pNHC(═NH)NH2, —C(═O)NH(CH2)pNH2, —(CH2)pN((CH2)pNH2)2, where each p is, independently, 1 to 5, aromatic group, heterocycle, or the free base or salt form of —(CH2)n—NH2, —(CH2)n—NH—(CH2)n—NH2, or —(CH2)n—NH—C(═NH)NH2, where each n is, independently, 1 to 8;
- or a pharmaceutically acceptable salt thereof.
55-76. (canceled)
A method of killing or inhibiting the growth of a Candida or Aspergillus species or preventing or treating a mammal having oral or disseminated candidiasis or an aspergillus infection comprising contacting the Candida or Aspergillus species with or administering to the mammal in need thereof an effective amount of a compound of Formula IV:
- wherein:
- R1 and R2 are, independently, —C(═NH)NH2, —(CH2)nNH2, or —(CH2)nNC(═NH)NH2, where n is 2, 3, or 4;
- or a pharmaceutically acceptable salt thereof.
78-80. (canceled)
A method of killing or inhibiting the growth of a Candida or Aspergillus species or preventing or treating a mammal having oral or disseminated candidiasis or an aspergillus infection comprising contacting the Candida or Aspergillus species with or administering to the mammal in need thereof an effective amount of a compound of Formula V:
- wherein:
- R1 is —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)nNH2, —(CH2)nNC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, CH═CH—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NH2, —C≡C—(CH2)2NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R2 is —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)nNH2, —(CH2)NC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NH2, —C≡C—(CH2)2NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R3 is —NH(CH2)nNH2, —NH(CH2)NC(═N)NH2, —(CH2)nNH2, —(CH2)NC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NH2, —C≡C—(CH2)2NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R4 is H, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)nNH2, —O—(CH2)nNH2, —(CH2)nNC(═N)NH2, —O—(CH2)nNC(═N)NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NH2, —C≡C—(CH2)2NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R5 is H, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)nNH2, —O—(CH2)nNH2, —(CH2)NC(═N)NH2, —O—(CH2)nNC(═N)NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NH2, —C≡C—(CH2)2NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R6 is H, —NH(CH2)nNH2, —NH(CH2)NC(═N)NH2, —(CH2)nNH2, —O—(CH2)nNH2, —(CH2)NC(═N)NH2, —O—(CH2)nNC(═N)NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NH2, —C≡C—(CH2)2NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- and
- R7 is H, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)nNH2, —O—(CH2)nNH2, —(CH2)nNC(═N)NH2, —O—(CH2)nNC(═N)NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NH2, —C≡C—(CH2)2NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- or a pharmaceutically acceptable salt thereof.
82-122. (canceled)
A method of killing or inhibiting the growth of a Candida or Aspergillus species or preventing or treating a mammal having oral or disseminated candidiasis or an aspergillus infection comprising contacting the Candida or Aspergillus species with or administering to the mammal in need thereof an effective amount of a compound of Formula VI:
- wherein:
- R1 is H, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)nNH2, —O—(CH2)nNH2, —(CH2)NC(═N)NH2, —O—(CH2)nNC(═N)NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NH2, —C≡C—(CH2)2NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R2 is H, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)nNH2, —O—(CH2)nNH2, —(CH2)NC(═N)NH2, —O—(CH2)nNC(═N)NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NH2, —C≡C—(CH2)2NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R3 is H, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)nNH2, —O—(CH2)nNH2, —(CH2)nNC(═N)NH2, —O—(CH2)nNC(═N)NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NH2, —C≡C—(CH2)2NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R4 is H, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)nNH2, —O—(CH2)nNH2, —(CH2)NC(═N)NH2, —O—(CH2)nNC(═N)NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NH2, —C≡C—(CH2)2NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R5 is H, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)nNH2, —O—(CH2)nNH2, —(CH2)nNC(═N)NH2, —O—(CH2)nNC(═N)NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NH2, —C≡C—(CH2)2NH2, C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- and
- R6 is H, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)nNH2, —O—(CH2)nNH2, —(CH2)nNC(═N)NH2, —O—(CH2)nNC(═N)NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NH2, —C≡C—(CH2)2NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- or a pharmaceutically acceptable salt thereof.
124-159. (canceled)
A compound of Formula VIII:
- wherein:
- R1 is H, halo, haloalkyl, —NH2, —C1-3alkyl, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)nNH2, —(CH2)nNC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —C≡C—CH2NH2, —CH═CH—(CH2)2NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —C≡C—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R2 is H, halo, haloalkyl, —NH2, —C1-3alkyl, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)nNH2, —(CH2)nNC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —C≡C—CH2NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —C≡C—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R3 is H, halo, haloalkyl, —NH2, —C1-3alkyl, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, (CH2)nNH2, —(CH2)nNC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —C≡C—CH2NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —C≡C—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R4 is H, halo, haloalkyl, —NH2, —C1-3alkyl, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)nNH2, —(CH2)NC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —C≡C—CH2NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —C≡C—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R5 is H, halo, haloalkyl, —NH2, —C1-3alkyl, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)NH2, —(CH2)NC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —C≡C—CH2NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —C≡C—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R6 is H, halo, haloalkyl, —NH2, —C1-3alkyl, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)NH2, —(CH2)NC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —C≡C—CH2NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —C≡C—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R7 is H, halo, haloalkyl, —NH2, —C1-3alkyl, —NH(CH2)nNH2, —NH(CH2)NC(═N)NH2, —(CH2)NH2, —(CH2)NC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —C≡C—CH2NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —C≡C—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R8 is H, halo, haloalkyl, —NH2, —C1-3alkyl, —NH(CH2)nNH2, —NH(CH2)NC(═N)NH2, —(CH2)NH2, —(CH2)nNC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —C≡C—CH2NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —C≡C—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- and
- R9 is H, halo, haloalkyl, —NH2, —C1-3alkyl, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)nNH2, —(CH2)nNC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —C≡C—CH2NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —C≡C—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- or a pharmaceutically acceptable salt thereof.
161-179. (canceled)
A method of killing or inhibiting the growth of a Candida or Aspergillus species or preventing or treating a mammal having oral or disseminated candidiasis or an aspergillus infection comprising contacting the Candida or Aspergillus species with or administering to the mammal in need thereof an effective amount of a compound of Formula VIII:
- wherein:
- R1 is H, halo, haloalkyl, —NH2, —C1-3alkyl, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)nNH2, —(CH2)nNC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —C≡C—CH2NH2, —CH═CH—(CH2)2NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —C≡C—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R2 is H, halo, haloalkyl, —NH2, —C1-3alkyl, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)nNH2, —(CH2)NC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —C≡C—CH2NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —C≡C—(CH2)2NH2, CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R3 is H, halo, haloalkyl, —NH2, —C1-3alkyl, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)NH2, —(CH2)NC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —C≡C—CH2NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —C≡C—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R4 is H, halo, haloalkyl, —NH2, —C1-3alkyl, —NH(CH2)nNH2, —NH(CH2)NC(═N)NH2, —(CH2)NH2, —(CH2)NC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —C≡C—CH2NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —C≡C—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R5 is H, halo, haloalkyl, —NH2, —C1-3alkyl, —NH(CH2)nNH2, —NH(CH2)NC(═N)NH2, —(CH2)NH2, —(CH2)NC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —C≡C—CH2NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —C≡C—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R6 is H, halo, haloalkyl, —NH2, —C1-3alkyl, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)NH2, —(CH2)nNC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —C≡C—CH2NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —C≡C—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R7 is H, halo, haloalkyl, —NH2, —C1-3alkyl, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)nNH2, —(CH2)NC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —C≡C—CH2NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —C≡C—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- R8 is H, halo, haloalkyl, —NH2, —C1-3alkyl, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)NH2, —(CH2)NC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —C≡C—CH2NH2, CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —C≡C—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- and
- R9 is H, halo, haloalkyl, —NH2, —C1-3alkyl, —NH(CH2)nNH2, —NH(CH2)nNC(═N)NH2, —(CH2)NH2, —(CH2)NC(═N)NH2, —O—(CH2)nNH2, —O—(CH2)nNC(═N)NH2, —C≡C—CH2NH2, —CH═CH—CH2NH2, —CH═CH—CH2NC(═N)NH2, —CH═CH—(CH2)2NH2, —C≡C—(CH2)2NH2, —CH═CH—(CH2)2NC(═N)NH2, —C≡C—CH2NC(═N)NH2, or —C≡C—(CH2)2—NC(═N)NH2, where n is 2, 3, or 4;
- or a pharmaceutically acceptable salt thereof.
181-198. (canceled)
A compound of Formula IX:
- wherein:
- each X is, independently, O or S;
- each Y is, independently, O or S;
- each R2 is, independently, —C1-C9 straight or branched alkyl optionally substituted with one or more —NH2, —N(CH3)2 or —NH—C(═NH)NH2;
- each R3 is, independently, —C1-C9 straight or branched alkyl optionally substituted with one or more —NH2, —N(CH3)2 or —NH—C(═NH)NH2;
- and
- each R4 is, independently, —(CH2)n—NH2 or —(CH2)n—NH—C(═NH)NH2, where n is an integer from 1 to 4;
- or a pharmaceutically acceptable salt thereof.
200-218. (canceled)
A method of killing or inhibiting the growth of a Candida or Aspergillus species or preventing or treating a mammal having oral or disseminated candidiasis or an aspergillus infection comprising contacting the Candida or Aspergillus species with or administering to the mammal in need thereof an effective amount of a compound of Formula IX:
- wherein:
- each X is, independently, O or S;
- each Y is, independently, O or S;
- each R2 is, independently, —C1-C9 straight or branched alkyl optionally substituted with one or more —NH2, —N(CH3)2 or —NH—C(═NH)NH2;
- each R3 is, independently, —C1-C9 straight or branched alkyl optionally substituted with one or more —NH2, —N(CH3)2 or —NH—C(═NH)NH2;
- and
- each R4 is, independently, —(CH2)n—NH2 or —(CH2)n—NH—C(═NH)NH2, where n is an integer from 1 to 4;
- or a pharmaceutically acceptable salt thereof.
220-237. (canceled)
A compound of Formula X:
- wherein:
- X is
- and
- each R1 is, independently, —(CH2)n—NH2 or —(CH2)n—NH—C(═NH)NH2, where n is an integer from 1 to 4;
- or a pharmaceutically acceptable salt thereof.
239-243. (canceled)
A method of killing or inhibiting the growth of a Candida or Aspergillus species or preventing or treating a mammal having oral or disseminated candidiasis or an aspergillus infection comprising contacting the Candida or Aspergillus species with or administering to the mammal in need thereof an effective amount of a compound of Formula X:
- wherein:
- X is
- and
- each R1 is, independently, —(CH2)n—NH2 or —(CH2)n—NH—C(═NH)NH2, where n is an integer from 1 to 4;
- or a pharmaceutically acceptable salt thereof.
245-252. (canceled)
Dependencies are inferred from the claim text.