US2021283113A1PendingUtilityA1
Inhibitors of short-chain dehydrogenase activity for treating fibrosis
Est. expiryMar 8, 2035(~8.7 yrs left)· nominal 20-yr term from priority
A61P 11/06A61P 9/12A61P 7/00A61P 17/02A61P 9/00A61P 27/02A61P 25/00A61P 43/00A61P 17/00A61P 21/00A61P 1/16A61P 1/04A61P 1/02A61P 39/02A61P 11/00A61P 35/00A61P 13/12A61P 13/02A61P 37/06C07D 277/02C07D 277/00A61K 31/4365A61K 31/426A61K 31/41Y02A50/30
64
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
A method of treating or preventing a fibrotic disease, disorder or condition includes administering to a subject in need of treatment a 15-PGDH inhibitor.
Claims
exact text as granted — not AI-modified1 - 22 . (canceled)
23 : A method of decreasing or reducing collagen secretion and/or collagen deposition and/or collagen accumulation and/or collagen fiber accumulation in a lung of a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of formula (VI):
wherein: n=1;
X 6 is N or CR c ;
R 1 is selected from the group consisting of branched or linear alkyl and
wherein n 2 =0-6 and X is any of the following: CF y H z (y+z=3), CCl y H z (y+z=3) OH, OAc, OMe, R 71 , OR 72 , CN, N(R 73 ) 2 ,
(n 3 =0-5, m=1-5), and
(n 4 =0-5);
R 5 is selected from the group consisting of H, Cl, F, NH 2 , and N(R 76 ) 2 ;
R 6 and R 7 are the same or different and are each independently one of the following:
and
each R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 37 , R 38 , R 39 , R 40 , R 41 , R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , R 49 , R 50 , R 51 , R 52 , R 53 , R 54 , R 55 , R 56 , R 57 , R 58 , R 59 , R 60 , R 61 , R 62 , R 63 , R 64 , R 65 , R 66 , R 67 , R 68 , R 69 , R 70 , R 71 , R 72 , R 73 , R 74 , R 76 , and R c are the same or different and are independently selected from the group consisting of hydrogen, substituted or unsubstituted C 1 -C 24 alkyl, C 2 -C 24 alkenyl, C 2 -C 24 alkynyl, C 3 -C 20 aryl, heterocycloalkenyl containing from 5-6 ring atoms, (wherein from 1-3 of the ring atoms is independently selected from N, NH, N(C 1 -C 6 alkyl), NC(O)(C 1 -C 6 alkyl), O, and S), heteroaryl or heterocyclyl containing from 5-14 ring atoms, (wherein from 1-6 of the ring atoms is independently selected from N, NH, N(C 1 -C 3 alkyl), O, and S), C 6 -C 24 alkaryl, C 6 -C 24 aralkyl, halo, silyl, hydroxyl, sulfhydryl, C 1 -C 24 alkoxy, C 2 -C 24 alkenyloxy, C 2 -C 24 alkynyloxy, C 5 -C 20 aryloxy, acyl, acyloxy (—O-acyl), C 2 -C 24 alkoxycarbonyl (—(CO)—O— alkyl), C 6 -C 20 aryloxycarbonyl (—(CO)—O-aryl), C 2 -C 24 alkylcarbonato (—O—(CO)—O-alkyl), C 6 -C 20 arylcarbonato (—O—(CO)—O-aryl), carboxy (—COOH), carboxylato (—COO − ), carbamoyl (—(CO)—NH 2 ), C 1 -C 24 alkyl-carbamoyl (—(CO)—NH(C 1 -C 24 alkyl)), arylcarbamoyl (—(CO)—NH-aryl), thiocarbamoyl (—(CS)—NH 2 ), carbamido (—NH—(CO)—NH 2 ), cyano (—CN), isocyano (—N + C − ), cyanato (—O—CN), isocyanato (—O—N + ═C − ), isothiocyanato (—S—CN), azido (—N═N + ═N − ), formyl (—(CO)—H), thioformyl (—(CS)—H), amino (—NH 2 ), mono- or di-(C 1 -C 24 alkyl)-amino that is optionally substituted with at least one hydroxyl, amino or mono- or di-(C 1 -C 24 alkyl)-amino, C 6 -C 20 aryl amino, C 2 -C 24 alkylamido (—NH—(CO)-alkyl), C 6 -C 20 arylamido (—NH—(CO)-aryl), sulfanamido (—SO2N(R) 2 where R is independently H, alkyl, aryl or heteroaryl), imino, alkylimino, arylimino, nitro (—NO 2 ), nitroso (—NO), sulfo (—SO 2 —OH), sulfonato (—SO 2 —O − ), C 1 -C 24 alkylsulfanyl, arylsulfanyl, C 1 -C 24 alkylsulfinyl (—(SO)-alkyl), C 5 -C 20 arylsulfinyl (—(SO)-aryl), C 1 -C 24 alkylsulfonyl (—SO 2 -alkyl), C 5 -C 20 arylsulfonyl (—SO 2 -aryl), sulfonamide (—SO 2 —NH 2 , —SO 2 NY 2 (wherein Y is independently H, aryl or alkyl), phosphono (—P(O)(OH) 2 ), phosphonato (—P(O)(O − ) 2 ), phosphinato (—P(O)(O − )), phospho (—PO 2 ), phosphino (—PH 2 ), polyalkyl ethers (—[(CH 2 ) n O] m ), phosphates, phosphate esters [—OP(O)(OR) 2 where R═H, methyl or other alkyl], and combinations thereof, or a pharmaceutically acceptable salt thereof.
24 - 29 . (canceled)
30 : The method of claim 23 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
31 : The method of claim 23 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
32 : The method of claim 32 , wherein:
R 1 is C 1 -C 24 alkyl; C 1 -C 24 alkyl substituted with a halo, C 1 -C 24 alkoxy, C 3 -C 7 cycloalkyl, or hydroxy; or C 3 -C 7 cycloalkyl; R 6 and R 7 are each independently
wherein R 33 , R 34 , R 48 , R 56 are the same or different and are independently selected from the group consisting of hydrogen, C 1 -C 24 alkyl, C 2 -C 24 alkenyl, C 2 -C 24 alkynyl, C 6 -C 20 aryl, heterocycloalkenyl containing from 5-6 ring atoms, heteroaryl or heterocyclyl containing from 5-14 ring atoms, C 6 -C 24 alkaryl, C 6 -C 24 aralkyl, halo, silyl, hydroxyl, sulfhydryl, C 1 -C 24 alkoxy that is optionally substituted with at least one hydroxyl, C 2 -C 24 alkenyloxy, C 2 -C 24 alkynyloxy, C 5 -C 20 aryloxy, acyl, acyloxy (—O-acyl), C 2 -C 24 alkoxycarbonyl (—(CO)—O-alkyl), C 6 -C 20 aryloxycarbonyl (—(CO)—O-aryl), C 2 -C 24 alkylcarbonato (—O—(CO)—O-alkyl), C 6 -C 20 arylcarbonato (—O—(CO)—O-aryl), carboxy (—COOH), carboxylato (—COO − ), carbamoyl (—(CO)—NH 2 ), C 1 -C 24 alkyl-carbamoyl (—(CO)—NH(C 1 -C 24 alkyl)), arylcarbamoyl (—(CO)—NH-aryl), thiocarbamoyl (—(CS)—NH 2 ), carbamido (—NH—(CO)—NH 2 ), cyano (—CN), isocyano (—N + C − ), cyanato (—O—CN), isocyanato (—O—N + ═C − ), isothiocyanato (—S—CN), azido (—N═N + ═N − ), formyl (—(CO)—H), thioformyl (—(CS)—H), amino (—NH 2 ), mono- or di-(C 1 -C 24 alkyl)-amino, mono- or di-(C 1 -C 24 alkyl)-amino that is substituted with at least one hydroxyl, C 5 -C 20 aryl amino, C 2 -C 24 alkylamido (—NH—(CO)-alkyl), C 6 -C 20 arylamido (—NH—(CO)-aryl), sulfanamido (—SO 2 N(R) 2 where R is independently H, alkyl, aryl or heteroaryl), imino, alkylimino, arylimino, nitro (—NO 2 ), nitroso (—NO), sulfo (—SO 2 —OH), sulfonato (—SO 2 —O − ), C 1 -C 24 alkylsulfanyl, arylsulfanyl, C 1 -C 24 alkylsulfinyl (—(SO)-alkyl), C 5 -C 20 arylsulfinyl (—(SO)-aryl), C 1 -C 24 alkylsulfonyl (—SO 2 -alkyl), C 5 -C 20 arylsulfonyl (—SO 2 -aryl), sulfonamide (—SO 2 —NH2, —SO 2 NY 2 (wherein Y is independently H, arlyl or alkyl), phosphono (—P(O)(OH) 2 ), phosphonato (—P(O)(O − ) 2 ), phosphinato (—P(O)(O − )), phospho (—PO 2 ), phosphino (—PH 2 ), polyalkyl ethers (—[(CH 2 ) n O] m ), phosphate, and phosphate ester [—OP(O)(OR) 2 where R═H, methyl or other alkyl]; and
X 6 is N or CH.
33 : The method of claim 23 , wherein the compound has an IC50 for 15-PGDH of less than 1 μM.
34 : The method of claim 23 , wherein the compound has an IC50 for 15-PGDH of less than 250 nM.
35 : The method of claim 23 , wherein the compound has an IC50 for 15-PGDH of less than 50 nM.
36 : The method of claim 23 , wherein the compound has an IC50 for 15-PGDH of less than 10 nM.
37 : The method of claim 23 , wherein the compound has an IC50 of less than 5 nM.
38 : The method of claim 23 , wherein:
R 1 is C 3 -C 7 cycloalkyl or C 1 -C 24 alkoxy; R 6 is
and R 58 is halo, C(O)NH 2 , C 1 -C 24 alkyl, amino, or mono- or di-(C 1 -C 24 alkyl)-amino that is optionally substituted with at least one hydroxyl;
R 7 is
and R 33 , R 34 , and R 48 are the same or different and are independently C 1 -C 24 alkyl, —COOH, mono- or di-(C 1 -C 24 alkyl)-amino, —C(O)NH 2 , or —C(O)NH(C 1 -C 24 alkyl); and
X 6 is N or CH.Cited by (0)
No later patents cite this yet.
References (0)
No backward citations on record.