IP Library Granted Patent US 9,085,555
Granted Patent B2
US 9,085,555 · App. 13/342,161 · Granted Jul 21, 2015

Complement pathway modulators and uses thereof

Inventors: Eva Altmann (Reinach, CH); Ulrich Hommel (Müllheim, DE); Edwige Liliane Jeanne Lorthiois (Niffer, FR); Juergen Klaus Maibaum (Weil-Haltingen, DE); Nils Ostermann (Binzen, DE); Jean Quancard (Huningue, FR); Stefan Andreas Randl (Frankfurt am Main, DE); Olivier Rogel (Hésingue, FR); Oliver Simic (Basel, CH); Anna Vulpetti (Basel, CH)
Assignee: NOVARTIS AG
C07D403/12A61K31/404A61K31/437C07D401/14C07D403/14C07D405/14C07D409/14C07D417/12C07D417/14C07D471/04C07D487/04
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Quick Facts
Patent No.
US 9,085,555
App. No.
13/342,161
Granted
Jul 21, 2015
Kind
B2
Abstract

The present invention provides a compound of formula I: a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

Claims (30)

1. A compound or salt thereof represented by one of the formulae (IIIb) or (IVb):

wherein

Z 2 is CH or N;

Z 5 is CR 5 or N;

Z 6 is CR 6 or N; or an N-oxide thereof

Z 7 is CH, C(CH 3 ) or N, wherein 0 or 1 or 2 of Z 5 , Z 6 and Z 7 is N;

R 3 is hydrogen, methyl, ethyl, iPr, amino, hydroxymethyl, CH2OMe, or mono-, di- and tri-fluoromethyl, NHMe;

R 5 is hydrogen, halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 2 -C 4 alkenyl, C 2 -C 4 alkenyloxy, hydroxy, CO 2 H, tetrazole, C 1 -C 4 alkoxycarbonyl, cyano, wherein each alkyl or alkoxy group is unsubstituted or substituted with up to 5 halogen atoms and with 0 or 1 additional substituents selected from the group consisting of hydroxy, cyano, tetrazole, C 1 -C 4 alkoxy, CO 2 H, C 1 -C 4 alkoxycarbonyl, tetrahydrofuranyl, optionally substituted phenyl, pyridyl and pyrimidinyl, and wherein the phenyl is unsubstituted or substituted with 1 or 2 substituents independently selected from halogen, hydroxy, methyl, methoxy and CO 2 H;

R 6 is hydrogen, halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 2 -C 4 alkenyl, C 2 -C 4 alkenyloxy, hydroxy, CO 2 H, C 1 -C 4 alkoxycarbonyl, cyano, wherein each alkyl or alkoxy group is unsubstituted or substituted with up to 5 halogen atoms and with 0 or 1 additional substituents selected from the group consisting of hydroxy, NR 10 R 11 , tetrazole, cyano, imidazolyl, C 1 -C 4 alkoxy, CO 2 H, C 1 -C 4 alkoxycarbonyl, optionally substituted phenyl, pyrrolyl, morpholino, piperidino, piperazino, and pyridyl, and wherein the phenyl is unsubstituted or substituted with 1 or 2 substituents independently selected from halogen, hydroxy, methyl, methoxy, mono- and dimethyl amino, and CO 2 H;

L is CH 2 or NH;

R 15 is hydrogen, fluoro, methyl, hydroxy, methoxy, ethoxy and OCH 2 CH 2 OMe, OCH 2 CH 2 N(CH 3 ) 2 , amino or OCH 2 CH 2 pyrrolyl;

R 16 is hydrogen, fluoro, methyl, amino, hydroxymethyl, methoxymethyl, or aminomethyl;

R 17 is hydrogen, fluoro or methyl;

R 19 is hydrogen or R 19 and R 17 , taken in combination, form a cyclopropyl ring; or

R 15 and R 16 , taken in combination, form a cyclopropyl ring;

G is —C(O)N(H)—; and

q is 0 or 1;

R 21 is hydrogen, methyl, or ethyl, which methyl and ethyl are unsubstituted or substituted with hydroxy, methoxy, cyano, amino, mono- or di-methyl amino, morpholinomethyl, optionally substituted azetidinomethyl, which azetidino ring is substituted with 0 or 1 fluoro or methoxy; or

R 22 is hydrogen;

CR 21 R 22 , taken in combination, from a cyclopropane ring;

Z is phenyl, pyridyl, pyrazinyl or thienyl, each of which is unsubstituted or substituted with 1, 2, or 3 residues independently selected at each occurrence from the group consisting of halogen, methyl, ethyl, isopropyl, cyclopropyl, methoxy, hydroxy, trifluoromethyl, di or trifluoromethoxy, SF 5 , CO 2 H, tetrazole, and NR 23 R 24 , unsubstituted or substituted phenyl and unsubstituted or substituted pyridinyl, which substituted phenyl and pyridinyl has 1 or 2 substituents independently selected from the group consisting of halogen and methyl.

2. The compound of claim 1 , wherein the compound is represented by formula:

or a pharmaceutically acceptable salt thereof.

3. A pharmaceutical composition comprising one or more pharmaceutically acceptable carriers and a therapeutically effective amount of a compound of claim 1 .

4. The compound of claim 1 , wherein the compound is represented by formula:

or a pharmaceutically acceptable salt thereof.

5. 1-(2-((1R,3S,5R)-3-((2-fluoro-3-(trifluoromethoxy)phenyl)carbamoyl)-2-azabicyclo[3.1.0]hexan-2-yl)-2-oxoethyl)-5-methyl-1H-pyrazolo[3,4-c]pyridine-3-carboxamide or a pharmaceutically acceptable salt thereof.

6. The pharmaceutical composition according to claim 3 , wherein the compound is a compound of claim 2 .

7. The pharmaceutical composition according to claim 3 , wherein the compound is a compound of claim 4 .

8. The pharmaceutical composition according to claim 3 , wherein the compound is a compound of claim 5 .

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 13, 2012
From: ALTMANN, EVA; HOMMEL, ULRICH; LORTHIOIS, EDWIGE LILIANE JEANNE; MAIBAUM, JUERGEN KLAUS; OSTERMANN, NILS; QUANCARD, JEAN; RANDL, STEFAN ANDREAS; ROGEL, OLIVIER; SIMIC, OLIVIER; VULPETTI, ANNA
To: NOVARTIS PHARMA AG
Reel/Frame 029284/0840 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 13, 2012
From: NOVARTIS PHARMA AG
To: NOVARTIS AG
Reel/Frame 029284/0921 →
Continuity (2)
Provisional Application 61429730 · Jan 4, 2011
Related Publication 20120295884A1 · Nov 22, 2012