Escolar Documentos
Profissional Documentos
Cultura Documentos
Wizel et al.
(54)
6,211,244 B1
6,313,146 B1
PREPARATION
2005/0147669 A1*
2005/0234261 A1
(75)
US 7,563,930 B2
WO 2006/125026
Notice:
(21)
(22)
Med
.
-
N-[l-(R)-(-)(1-naphthyl)]-3-[3-[3
Nov 22 2006
furt-Main, DE; XP002451055 (& Pharmazie, vol. 59, N0. 10, 2004,
(65)
11/2006
OTHER PUBLICATIONS
pp. 744-752).
(60)
(51)
Int Cl
2nd Ed., (1979), pp. 549-572, John Wiley & Sons, Inc.
I
C07C 211/00
(52)
587-592, (2003).
(200601)
1,
?l f
ee app lcanon
(56)
L h,
References Cited
lstory'
* Cited by examiner
(57)
ABSTRACT
A
A
A
A
10/1990
7/1997
1/2000
2/2000
Schinski et a1.
Van Wagenen et a1.
Nemeth et a1.
Nemeth et a1.
US. Patent
Ex53s_E25189235%
Sheet 1 of6
US 7,563,930 B2
US. Patent
5ExB5:3__E2285855
Sheet 2 of6
US 7,563,930 B2
US. Patent
EE25:$3EXE2U8SQ6E Q
Sheet 3 of6
US 7,563,930 B2
US. Patent
Sheet 4 of6
US 7,563,930 B2
'
Ir
Integral
29.68 mi
Integral
478.33 nlJ
narmaiized -57.16 Jg 1
Peak
Left Limit
172.89 C
157.41C
Peak
Left Limit
183.73 T
170.49 0C
Right Limit
176.07C
Right Limit
189.35 "C
% integral
normalized
mw
Peak
Integral
-14B.20 mJ
Left Limit
109.44 "0
Right Limit
139-.180
integral
40.74 m]
narmatized 12.89JgA1
Integral
114.18 mJ
narmatized 46.13.1974
Peak
Left Limit
71.63 0
37.611?
Peak
Lett Limit
165.47 "0
140660
Peak
Left Limit
176.82 "0
168.57%)
Right Limit
82.760
Right Limit
168.670
Right Limit
182.800
4a.6.0_s0I100120.100.10010010020240?
0"2'i
6'8
ia'i'21'41s'1072b'iinn
US. Patent
Sheet 5 of6
US 7,563,930 B2
Z Integral
41.i2 mJ
/ Peok
Left Limit
156.54 0C
148.35C
mW
_; Right Limit
16959 0C
W Integrol
-179.16 mJ
normalized 49.36 Jg'1
Peak
Letl Limit
1 78,70 C
169.59 cC
183.61 0
H 4p.60180I100_1Z0|tlt0_10010010012014011
0'2'i'ts'8'1o'1'2'1'4
i's'i'a'io'?n
FIG.6
ki
01
m9
Step
-76.2O6e03 %
-9.351e~03 mg
Left Limit 25.00C
40
l
I
60
l
I
80
|
|
100
|
|
4
I
120
l
140
l
160
1
180
a'10'1'2'1'4"1's'Tnin
US. Patent
Sheet 6 of6
US 7,563,930 B2
m'
Step
17.994 7;
.
Left Limit
1.645 mg
0
25.00 C
40
60
80
I 100
I 120 I 140
100 I 180
\_
0.1
Step
-0.322 2,
Left Limit
44.514e03 mg
25.00 "0
40
60
80
FIG.9
180
cI
US 7,563,930 B2
1
CROSS-REFERENCE TO RELATED
APPLICATIONS
the milled solid. FloWability affects the ease With Which the
FIELD OF INVENTION
phosphate.
20
25
2m
-HC1
30
CH3
35
45
55
60
65
US 7,563,930 B2
4
3
In another embodiment of the invention the present inven
GMP requirements.
25
30
40
45
55
60
65
US 7,563,930 B2
6
20
25
GMP requirements.
Pharmaceutical formulations/compositions of the present
the present invention may contain one or more excipients.
Excipients are added to the formulation for a variety of pur
poses. Selection of excipients and the amounts to use may be
vacuum.
55
US 7,563,930 B2
7
tableting
A capsule ?lling of the present invention may comprise any
EXAMPLES
Instrumentation
PXRD
20
25
and
intravenous),
inhalant
and
ophthalmic
30
samples Was about 3-5 mg; the samples Were scanned at a rate
of 10 C./min from 30 C. to 250 C. The oven Was constantly
purged With nitrogen gas at a How rate of 40 mL/min. Stan
Thermal Analysis
Differential Scanning Calorimetry (DSC) analysis Was
done using a Mettler Toledo 821 Starz. The crucible Was
40
Example 1
ethyl amine (14.5 ml) and anhydrous KZCO3 (24.9 gr) Were
50
and/ or a lubricant.
55
Example 2
room temperature. Then HCl gas Was bubbled into the solu
tion. The solution Was stirred at room temperature for 0.5
65
hydrochloride.
US 7,563,930 B2
9
10
Example 3
invention but are not intended to, and should not be construed
to limit its scope in any Way. The examples do not include
are Well knoWn to those of ordinary skill in the art and are
described in numerous publications. All references men
Example 4
Example 5
FIG. 2.
25
Example 6
Preparation of Cinacalcet HCl Form III
35
40
crystal form III Was then dried at 50 C. for 24 hours and the
crystalline structure Was maintained as form III.
Example 7
45
Example 8
Preparation of Cinacalcet HCl Form I
60
55
65
US 7,563,930 B2
11
12
30. The process of claim 28, Wherein maintaining is by
185 C.
in FIG. 6.
20
25
three days.
28. A process for preparing the crystalline form of Cina
calcet HCl of claim 16, comprising: dissolving Cinacalcet