14-hydroxy-docosahexaenoic acid compounds

Patent metadata

Field	Value
Publication number	US-9611238-B2
Application number	US-201414557151-A
Country	US
Kind code	B2
Filing date	Dec 1, 2014
Priority date	Sep 16, 2008
Publication date	Apr 4, 2017
Grant date	Apr 4, 2017

Abstract

The invention describes novel 14-hydroxy docosahexaenoic acid (DHA) analogues, their preparation, isolation, identification, purification and uses thereof.

First claim

What is claimed is:

1. A pharmaceutical composition comprising a compound having the formula (II):

wherein each of P 1 and P 2 individually is a protecting group or a hydrogen atom;
wherein is a double bond;
wherein Z is —C(O)OR d , —C(O)NR c R c , —C(O)H, —C(NH)NR c R c , —C(S)H, —C(S)OR d , —C(S)NR c R c , or —CN;
each R a , is independently selected from hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, (C4-C11) cycloalkylalkyl, (C5-C10) aryl, phenyl, (C6-C16) arylalkyl, benzyl, 2-6 membered heteroalkyl, 3-8 membered cycloheteroalkyl, morpholinyl, piperazinyl, homopiperazinyl, piperidinyl, 4-11 membered cycloheteroalkylalkyl, 5-10 membered heteroaryl or 6-16 membered heteroarylalkyl;
each R c , is independently a protecting group or R a , or, alternatively, each R c is taken together with the nitrogen atom to which it is bonded to form a 5 to 8-membered cycloheteroalkyl or heteroaryl which may optionally include one or more of the same or different additional heteroatoms and which may optionally be substituted with one or more of the same or different R a or R b groups;
each R b is independently selected from ═O, —OR d , (C1-C3) haloalkyloxy, —OCF 3 , ═S, —SR d , ═NR d , ═NOR d , —NR c R c , halogen, —CF 3 , —CN, —NC, —OCN, —SCN, —NO, —NO 2 , ═N 2 , —N 3 , —S(O)R d , —S(O) 2 R d , —S(O) 2 OR d , —S(O)NR c R c , —S(O) 2 NR c R c , —OS(O)R d , —OS(O) 2 R d , —OS(O) 2 OR d , —OS(O) 2 NR c R c , —C(O)R d , —C(O)OR d , —C(O)NR c R c , —C(NH)NR c R c , —C(NR a )NR c R c , —C(NOH)R a , —C(NOH)NR c R c , —OC(O)R d , —OC(O)OR d , —OC(O)NR c R c , —OC(NH)NR c R c , —OC(NR a )NR c R c , —[NHC(O)] n R d , —[NR a C(O)] n R d , —[NHC(O)] n OR d , —[NR a C(O)] n OR d , —[NHC(O)] n NR c R c , —[NR a C(O)] n NR c R c , —[NHC(NH)] n NR c R c or —[NR a C(NR a )] n NR c R c ;
each n, independently is an integer from 0 to 3; and
each R d , independently is a protecting group or R a ;
or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable carrier.

2. The composition of claim 1 , wherein P 1 and P 2 are both hydrogen atoms.

3. A method of treating or preventing inflammation comprising administrating to a subject in need thereof an effective amount of a compound according to claim 1 .

4. A pharmaceutical composition comprising a compound having a formula (V):

wherein each of P 1 , P 2 and P 3 individually is a protecting group or a hydrogen atom;
wherein is a double bond;
wherein Z is —C(O)OR d , —C(O)NR c R c , —C(O)H, —C(NH)NR c R c , —C(S)H, —C(S)OR d , —C(S)NR c R c , or —CN;
each R a , is independently selected from hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, (C4-C11) cycloalkylalkyl, (C5-C10) aryl, phenyl, (C6-C16) arylalkyl, benzyl, 2-6 membered heteroalkyl, 3-8 membered cycloheteroalkyl, morpholinyl, piperazinyl, homopiperazinyl, piperidinyl, 4-11 membered cycloheteroalkylalkyl, 5-10 membered heteroaryl or 6-16 membered heteroarylalkyl;
each R c , is independently a protecting group or R a , or, alternatively, each R c is taken together with the nitrogen atom to which it is bonded to form a 5 to 8-membered cycloheteroalkyl or heteroaryl which may optionally include one or more of the same or different additional heteroatoms and which may optionally be substituted with one or more of the same or different R a or R b groups;
each R b is independently selected from ═O, —OR d , (C1-C3) haloalkyloxy, —OCF 3 , ═S, —SR d , ═NR d , ═NOR d , —NR c R c , halogen, —CF 3 , —CN, —NC, —OCN, —SCN, —NO, —NO 2 , ═N 2 , —N 3 , —S(O)R d , —S(O) 2 R d , —S(O) 2 OR d , —S(O)NR c R c , —S(O) 2 NR c R c , —OS(O)R d , —OS(O) 2 R d , —OS(O) 2 OR d , —OS(O) 2 NR c R c , —C(O)R d , —C(O)OR d , —C(O)NR c R c , —C(NH)NR c R c , —C(NR a )NR c R c , —C(NOH)R a , —C(NOH)NR c R c , —OC(O)R d , —OC(O)OR d , —OC(O)NR c R c , —OC(NH)NR c R c , —OC(NR a )NR c R c , —[NHC(O)] n R d , —[NR a C(O)] n R d , —[NHC(O)] n OR d , —[NR a C(O)] n OR d , —[NHC(O)] n NR c R c , —[NR a C(O)] n NR c R c , —[NHC(NH)] n NR c R c or —[NR a C(NR a )] n NR c R c ;
each n, independently is an integer from 0 to 3; and
each R d , independently is a protecting group or R a ;
or a pharmaceutically acceptable salt or ester thereof; and
a pharmaceutically acceptable carrier.

5. The composition of claim 4 , wherein P 1 , P 2 and P 3 are all hydrogen atoms.

6. A method of treating or preventing inflammation comprising administrating to a subject in need thereof an effective amount of a compound according to claim 4 .

7. A pharmaceutical composition comprising a compound of formula (IIa, IIb, or IIc):

wherein each of P 1 and P 2 individually is a protecting group or a hydrogen atom;
wherein is a double bond;
wherein Z is —C(O)OR d , —C(O)NR c R c , —C(O)H, —C(NH)NR c R c , —C(S)H, —C(S)OR d , —C(S)NR c R c , or —CN;
each R a , is independently selected from hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, (C4-C11) cycloalkylalkyl, (C5-C10) aryl, phenyl, (C6-C16) arylalkyl, benzyl, 2-6 membered heteroalkyl, 3-8 membered cycloheteroalkyl, morpholinyl, piperazinyl, homopiperazinyl, piperidinyl, 4-11 membered cycloheteroalkylalkyl, 5-10 membered heteroaryl or 6-16 membered heteroarylalkyl;
each R c , is independently a protecting group or R a , or, alternatively, each R c is taken together with the nitrogen atom to which it is bonded to form a 5 to 8-membered cycloheteroalkyl or heteroaryl which may optionally include one or more of the same or different additional heteroatoms and which may optionally be substituted with one or more of the same or different R a or R b groups;
each R b is independently selected from ═O, —OR d , (C1-C3) haloalkyloxy, —OCF 3 , ═S, —SR d , ═NR d , ═NOR d , —NR c R c , halogen, —CF 3 , —CN, —NC, —OCN, —SCN, —NO, —NO 2 , ═N 2 , —N 3 , —S(O)R d , —S(O) 2 R d , —S(O) 2 OR d , —S(O)NR c R c , —S(O) 2 NR c R c , —OS(O)R d , —OS(O) 2 R d , —OS(O) 2 OR d , —OS(O) 2 NR c R c , —C(O)R d , —C(O)OR d , —C(O)NR c R c , —C(NH)NR c R c , —C(NR a )NR c R c , —C(NOH)R a , —C(NOH)NR c R c , —OC(O)R d , —OC(O)OR d , —OC(O)NR c R c , —OC(NH)NR c R c , —OC(NR a )NR c R c , —[NHC(O)] n R d , —[NR a C(O)] n R d , —[NHC(O)] n OR d , —[NR a C(O)] n OR d , —[NHC(O)] n NR c R c , —[NR a C(O)] n NR c R c , —[NHC(NH)] n NR c R c or —[NR a C(NR a )] n NR c R c ;
R 1 and R 2 , if present, is/are each independently selected from (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, (C4-C11) cycloalkylalkyl, (C5-C10) aryl, phenyl, (C6-C16) arylalkyl, benzyl, 2-6 membered heteroalkyl, 3-8 membered cycloheteroalkyl, morpholinyl, piperazinyl, homopiperazinyl, piperidinyl, 4-11 membered cycloheteroalkylalkyl, 5-10 membered heteroaryl or 6-16 membered heteroarylalkyl;
each n, independently is an integer from 0 to 3; and
each R d , independently is a protecting group or R a ;
or a pharmaceutically acceptable salt or ester thereof; and
a pharmaceutically acceptable carrier.

8. The composition of claim 7 , wherein P 1 and P 2 are both hydrogen atoms.

9. A method of treating or preventing inflammation comprising administrating to a subject in need thereof an effective amount of a compound according to claim 7 .

10. A pharmaceutical composition comprising a

Assignees

• Brigham & Womens Hospital Inc

Inventors

• Serhan Charles N
• Yang Rong

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P5/00

  Drugs for disorders of the endocrine system · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title