Methods for preventing and treating pneumocystis infections
AssigneeCidara Therapeutics, Inc.
InventorsKenneth Bartizal, Paul Daruwala, Voon Ong, Maureen Roden, Taylor Sandison, Dirk Thye
Life of this patent
Estimating the term…
Abstract
The disclosure relates to methods of prophylactic and therapeutic treatments of a Pneumocystis infection (i.e., an infection caused by Pneumocystis jirovecii) in a subject by administering to the subject a compound of any of formulas (1)-(111) (e.g., a salt of Compound 1, or a neutral form thereof). The disclosure also relates to methods of inhibiting the replication of a Pneumocystis spp. The methods of the disclosure can be useful in immunocompromized subjects.
Claims26
A method of treating or reducing the risk of a Pneumocystis infection in a subject comprising administering to the subject in an amount and for a duration sufficient to treat or reduce the risk of the Pneumocystis infection a compound of any of formulas (I)-(III):
- wherein,
- R1 is O(CH2CH2O)nCH2CH2X1, O(CH2CH2NH)nCH2CH2X1, O(CH2CH2CH2O)nCH2CH2X1, NHCH2CH2X2, NH(CH2CH2O)mCH2CH2X2, NH(CH2CH2CH2O)mCH2CH2X2, NH(CH2CH2O)pCH2CH2X3, NH(CH2CH2CH2O)pCH2CH2X3, NHCH2CH2X4, NH[CH2(CH2)aO]bCH{CH2[OCH2(CH2)c]dX5}2, O[CH2(CH2)aO]bCH{CH2[OCH2(CH2)c]dX5}2, NH(CH2CH2NH)rCH2CH2X5, NHCH2(CH2)qX6, or OCH2(CH2)qX6;
- RT is n-pentyl, sec-pentyl, or iso-pentyl;
- X1 is NH2, NHRA1, NRA1RA2, NRA1RA2RA3, or NHCH2(CH2)vZ1;
- X2 is OH, ORB1, or OCH2(CH2)vZ1;
- X3 is NH2, NHRC1, NRC1RC2, or NRC1RC2RC3, or NHCH2(CH2)vZ1;
- X4 is NRD1RD2RD3 or NHCH2(CH2)vZ1;
- each X5 is, independently, selected from OH, ORE1, NH2, NHRE1, NRE1RE2, NRE1RE2RE3, OCH2(CH2)vZ1, and NHCH2(CH2)vZ1;
- X6 is selected from NRF1RF2RF3 and Z1;
- a is an integer from 1 to 2;
- b is an integer from 0 to 3;
- c is an integer from 1 to 2;
- d is an integer from 0 to 3;
- n is an integer from 1 to 5;
- m is an integer from 1 to 5;
- p is an integer from 1 to 5;
- r is an integer from 1 to 5;
- q is an integer from 1 to 3;
- v is an integer from 1 to 3;
- each of RA1, RA2, RA3, RB1, RC1, RC2, RC3, RD1, RD2, RD3, RE1, RE2, RE3, RF1, RF2, and RF3 is, independently, selected from CH3, CH2CH3, CH2CH2CH3, and CH(CH3)2;
- Z1 is selected from:
- and each of R1A, R2A, R3A, R4A, R5A, R6A, R7A, R8A, R9A, R10A, R11A, R12A, R13A, R14A, R15A, R16A, R17A, R18A, R19A, R20A, R21A, and R22A is, independently, selected from H, CH3, CH2CH3, CH2CH2CH3, and CH(CH3)2,
- or a pharmaceutically acceptable salt thereof.
A method of inhibiting the replication of a Pneumocystis spp. comprising contacting the Pneumocystis spp., in an amount and for a duration sufficient to inhibit replication of the Pneumocystis spp., with a compound of any of formulas (I)-(III):
- wherein,
- R1 is O(CH2CH2O)nCH2CH2X1, O(CH2CH2NH)nCH2CH2X1, O(CH2CH2CH2O)nCH2CH2X1, NHCH2CH2X2, NH(CH2CH2O)mCH2CH2X2, NH(CH2CH2CH2O)mCH2CH2X2, NH(CH2CH2O)pCH2CH2X3, NH(CH2CH2CH2O)pCH2CH2X3, NHCH2CH2X4, NH[CH2(CH2)aO]bCH{CH2[OCH2(CH2)c]dX5}2, O[CH2(CH2)aO]bCH{CH2[OCH2(CH2)c]dX5}2, NH(CH2CH2NH)rCH2CH2X5, NHCH2(CH2)qX6, or OCH2(CH2)qX6;
- RT is n-pentyl, sec-pentyl, or iso-pentyl;
- X1 is NH2, NHRA1, NRA1RA2, NRA1RA2RA3, or NHCH2(CH2)vZ1;
- X2 is OH, ORB1, or OCH2(CH2)vZ1;
- X3 is NH2, NHRC1, NRC1RC2, or NRC1RC2RC3, or NHCH2(CH2)vZ1;
- X4 is NRD1RD2RD3 or NHCH2(CH2)vZ1;
- each X5 is, independently, selected from OH, ORE1, NH2, NHRE1, NRE1RE2, NRE1RE2RE3, OCH2(CH2)vZ1, and NHCH2(CH2)vZ1;
- X6 is selected from NRF1RF2RF3 and Z1;
- a is an integer from 1 to 2;
- b is an integer from 0 to 3;
- c is an integer from 1 to 2;
- d is an integer from 0 to 3;
- n is an integer from 1 to 5;
- m is an integer from 1 to 5;
- p is an integer from 1 to 5;
- r is an integer from 1 to 5;
- q is an integer from 1 to 3;
- v is an integer from 1 to 3;
- each of RA1, RA2, RA3, RB1, RC1, RC2, RC3, RD1, RD2, RD3, RE1, RE2, RE3, RF1, RF2, and RF3 is, independently, selected from CH3, CH2CH3, CH2CH2CH3, and CH(CH3)2;
- Z1 is selected from:
- and each of R1A, R2A, R3A, R4A, R5A, R6A, R7A, R8A, R9A, R10A, R11A, R12A, R13A, R14A, R15A, R16A, R17A, R18A, R19A, R20A, R21A, and R22A is, independently, selected from H, CH3, CH2CH3, CH2CH2CH3, and CH(CH3)2,
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.