1. A compound having the structural formula I
or a pharmaceutically acceptable salt thereof; wherein:
R is selected from the group consisting of R4-heteroaryl, R5-phenyl, (C4-C6)cycloalkenyl, \u2014C(\u2550CH2)CH3, \u2014C\u2261C\u2014CH3,
\u2014CH\u2550C(CH3)2,
and \u2014CH\u2550CH\u2014CH3;
R2 is selected from the group consisting of \u2014W\u2014X, \u2014NR19(CH2)m\u2014W\u2014X, and \u2014NR19CH(CH3)\u2014W\u2014X;
R3 is hydrogen;
R4 is 1 to 3 substituents, which can be the same or different, and are independently selected from the group consisting of hydrogen, (C1-C6)-alkyl, \u2014CF3, halogen, \u2014NO2, \u2014NR15R16, (C1-C6)alkoxy, (C1-C6)alkylthio, (C1-C6)alkylsulfinyl, (C1-C6)alkylsulfonyl, \u2014COOR17 and \u2014C(O)NR6R7;
R5 is 1 to 5 substituents, which can be the same or different, and are independently selected from the group consisting of hydrogen, halogen, (C1-C6)alkyl, hydroxy, (C1-C6)alkoxy, \u2014CN, \u2014NH2, (C1-C6)alkylamino, di-((C1-C6)alkyl)amino, \u2014CF3, \u2014OCF3, \u2014S(O)0-2(C1-C6)alkyl and \u2014CH2\u2014SO2-phenyl;
R6 and R7, which can be the same or different, are each independently selected from the group consisting of hydrogen and (C1-C6)alkyl;
R8 is 1 to 5 substituents, which can be the same or different, and are independently selected from the group consisting of hydrogen, halogen, (C1-C6)alkyl, hydroxy, C1-C6 alkoxy, \u2014CN, amino, di-((C1-C6)alkyl)amino, \u2014CF3, \u2014OCF3, acetyl, \u2014NO2, hydroxy(C1-C6)alkoxy, (C1-C6)-alkoxy(C1-C6)alkoxy, di-((C1-C6)-alkoxy)(C1-C6)alkoxy, (C1-C6)-alkoxy(C1-C6)alkoxy-(C1-C6)-alkoxy, carboxy(C1-C6)-alkoxy, (C1-C6)-alkoxycarbonyl(C1-C6)alkoxy, (C3-C6)cycloalkyl(C1-C6)alkoxy, di-((C1-C6)alkyl)amino(C1-C6)alkoxy, morpholinyl, (C1-C6)alkyl-SO2\u2014, (C1-C6)alkyl-SO2\u2014(C1-C6)alkoxy, tetrahydropyranyloxy, (C1-C6)alkylcarbonyl(C1-C6)-alkoxy, (C1-C6)-alkoxycarbonyl, (C1-C6)alkylcarbonyloxy(C1-C6)-alkoxy, \u2014SO2NH2, phenoxy,
\u2014O\u2014CH2\u2014P(O)(OR6)2,\u2014 and \u2014P(O)(OR6)2; or adjacent R8 substituents together are \u2014O\u2014CH2\u2014O\u2014, \u2014O\u2014CH2CH2\u2014O\u2014, \u2014O\u2014CF2\u2014O\u2014 or \u2014O\u2014CF2CF2\u2014O\u2014 and form a ring with the carbon atoms to which they are attached;
R9 is selected from the group consisting of (C1-C6)alkyl, R8-aryl-, R8-aryl(C1-C6)alkyl-, thienyl, pyridyl, (C3-C6)-cycloalkyl, (C1-C6)alkyl-OC(O)\u2014NH\u2014(C1-C6)alkyl-, di-((C1-C6)alkyl)aminomethyl, cycloheteroalkyl(C1-C6)alkyl, aryloxy(C1-C6)alkyl, alkoxy(C1-C6)alkyl and
R10 is 1-2 substituents, which can be the same or different, and are independently selected from the group consisting of hydrogen, (C1-C6)alkyl, R5-aryl and R4-heteroaryl, or two R10 substituents on the same carbon can form \u2550O;
R11 is hydrogen or (C1-C6)alkyl; \u2014C(O)alkyl, or R17 and R11 taken together are \u2014(CH2)p-A-(CH2)q, wherein p and q are each independently 2 or 3 and A is selected from the group consisting of a bond, \u2014CH2\u2014, \u2014S\u2014 and \u2014O\u2014, and form a ring with the nitrogen to which they are attached;
R12 is 1-2 substituents, which can be the same or different, and are independently selected from the group consisting of hydrogen, (C1-C6)alkyl, hydroxy, (C1-C6)alkoxy, halogen, and \u2014CF3;
R13 is selected from the group consisting of H, (C1-C6)alkyl, phenyl, benzyl, (C2-C6)alkenyl, (C1-C6)alkoxy(C1-C6)alkyl, di-((C1-C6)alkyl)amino(C1-C6)alkyl, pyrrolidinyl(C1-C6)alkyl and piperidino(C1-C6)alkyl;
R14 is selected from the group consisting of H, halogen, (C1-C6)alkyl or (C1-C6)alkoxy;
R15 is selected from the group consisting of H and (C1-C6)alkyl;
R16 is selected from the group consisting of H, (C1-C6)alkyl-C(O)\u2014 and (C1-C6)alkyl-SO2\u2014;
R17 is selected from the group consisting of (C1-C6)alkyl, (C1-C6)hydroxyalkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy(C1-C6)alkoxy, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl, allyl, propargyl, R8-heteroaryl-, R8-aryl- and R8-aryl(C1-C6)alkyl-;
R18 is selected from the group consisting of a bond, \u2014CH2\u2014, \u2014CH(OH)\u2014, \u2014CH(CH3)\u2014, \u2014C(CH3)n\u2014, \u2014(CH2)n\u2014, and \u2014O(CH2)n\u2014,
R19 is selected from the group consisting of H, (C1-C6)alkyl, (C1-C6)alkyl(C1-C6)cycloalkyl, (C1-C6)cycloalkyl(C1-C6)alkyl and (C1-C6)alkoxy(C1-C6)alkyl;
Q and Q1 can be the same or different and are each independently selected from the group consisting of
m and n are each independently 1-3;
p and q are each independently 0-2;
s is 0-4;
W is aryl pyridyl or thienyl, and wherein said aryl, pyridyl or thienyl is optionally substituted with 1-3 substituents, which can be the same or different, and are independently selected from the group consisting of alkyl,aryl, alkylcycloalkyl, halo, hydroxy, hydroxyalkyl, alkoxy, alkylalkoxy, alkoxyalkoxy, \u2014NR6R7, (C2-C6)alkenyl, and \u2014CN;
X is selected from the group consisting of H, NH2, \u2014N(R6)(CH2)s-aryl, \u2014N(R6)(CH2)s-heteroaryl, \u2014N(R6)(CH2)m+1\u2014OH, and \u2014N(CH3)2, or
X is \u2014R18\u2014Y-Z;
Y is selected from the group consisting of \u2014N(R5)CH2CH2N(R7)\u2014, \u2014N(R6)(CH2)naryl, \u2014OCH2CH2N(R6)\u2014, \u2014O\u2014, \u2014S\u2014, \u2014CH2S\u2014, \u2014(CH2)2-3\u2014N(R6)\u2014, R8-divalent heteroaryl,
Z is selected from the group consisting of H, alkyl, alkoxyalkyl, R8-aryl-, R8-aryl(C1-C6)alkyl-, R8-heteroaryl-, R8-bicyclicalkyl-, aminoalkyl, alkylamino, NH2, \u2014N\u2014(R6)(CH2)s-aryl, \u2014N(R6)(CH2)s-heteroaryl, \u2014N(R6)C(O)OR17, alkylcycloheteroalkyl, cycloheteroalkyl, cycloheteroalkylalkyl, alkoxycycloheteroalkyl, heteroaryl; R8-benzofused heteroaryl-, diphenylmethyl and R9\u2014C(O)\u2014; or
when Y is
Z can also be \u2014OH, R9\u2014SO2\u2014, R17\u2014N(R11)(CH2)s\u2014C(O)\u2014, R17\u2014OC(O)\u2014, R17\u2014O(CH2)nC(O)\u2014, benzofused heteroaryl(CH2)nC(O)\u2014, benzofused heteroaryl(CH2)n\u2014 or R17\u2014N(R11)\u2014C(S)\u2014; or
when Q is
Z can also be R17R11N\u2014, phenylamino or pyridylamino; or Z and Y taken together are selected from the group consisting of
2. The compound according to claim 1 wherein R is
3. The compound according to claim 1 wherein R3 is H.
4. The compound according to claim 1 wherein R is
and R3 is H.
5. A compound selected from the group consisting of
6. The compound according to claim 5 selected from the group consisting of:
7. A pharmaceutical composition comprising one or more compounds of claim 1 and one or more pharmaceutically acceptable carriers.
8. A method of treating psychoses, comprising administering one or more compounds of claim 1 to a patient in need of such treatment.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. Process for producing high purity heterophasic polypropylene copolymers comprising
(A) 73 to 98 wt. % of a propylene homo- or copolymer matrix with an MFR2 in accordance with ISO 1133 (230\xb0 C., 2.16 kg load) of 45 to 500 g10 min; wherein for the propylene copolymer matrix, the comonomer is ethylene andor one other C4 to C10 alpha-olefin and the comonomer content is 7.0 to 10.0 wt. % of component (A); and
(B) 2 to 27 wt. % of elastomeric copolymers, comprising propylene in an amount of at least 50 wt. % of component (B) and ethylene andor one other C4 to C10 alpha olefin in an amount of 20 to less than 50 wt. % of component (B),
wherein said high purity heterophasic polypropylene copolymers have the following properties: the amount of volatile organic compounds (VOC) is 336 to 408 \u03bcgTEg; the tensile modulus is 1475 to 1835 MPa; and, the flexural modulus is 1384 to 1743 MPa;
said process comprises the steps of:
providing a catalyst system
producing a polypropylene polymer matrix (A) using said catalyst system, wherein said catalyst system comprises a Ziegler-Natta procatalyst (I) which contains a trans-esterification product of lower alcohol having at least C5 alkyl and phthalic ester, an external donor (III) represented by formula (I) Si(OCH2CH3)3(NR1R2) wherein R1 and R2 can be the same or different and represent a hydrocarbon group having 1 to 12 carbon atoms, and an organometallic cocatalyst (ii) in a first slurry reactor and in a second slurry reactor, both slurry reactors using the same polymerization conditions,
transferring the slurry reactor product into a 1st GPR
producing an elastomeric copolymer (B) of propylene and ethylene andor one other C4 to C10 alpha olefin in the polymer matrix in the presence of the catalyst system in said 1st GPR
transferring the 1st GPR product into a 2nd GPR and producing a second elastomeric copolymer (B) of propylene and ethylene andor one other C4 to C10 alpha olefin in the polymer matrix in the presence of the catalyst system in said 2nd GPR, said 1st and 2nd copolymers of propylene and ethylene andor one other C4 to C10 alpha olefin may have the same or different composition ratios and
recovering the polymer product for further processing.
2. Process according to claim 1, wherein the propylene matrix (A) of the heterophasic polypropylene copolymers is a propylene homopolymer.
3. Process according to claim 1, wherein the elastomeric copolymer (B) is unimodal.
4. Process according to claim 1, wherein the elastomeric copolymer (B) comprises propylene and ethylene as the only polymerizable units.
5. High purity hetorophasic polypropylene copolymers having an MFR2 in accordance with ISO 1133 (230\xb0 C., 2.16 kg load) of above 35 g10 min, said copolymers comprise
(A) 73 to 98 wt. % of a propylene homo- or copolymer matrix with an MFR2 in accordance with ISO 1133 (230\xb0 C., 2.16 kg load)of 45 to 500 g10 min; wherein for the propylene copolymer matrix, the comonomer is ethylene andor one other C4 to C10 alpha-olefin and the comonomer content is 7.0 to 10.0 wt. % of component (A); and
(B) 2 to 27 wt. % of an elastomeric copolymer, comprising propylene in an amount of at least 50 wt. % of component (B) and ethylene andor one other C4 to C10 alpha olefin in an amount of 20 to less than 50 wt. % of component (B),
wherein said high purity heterophasic polypropylene copolymers have the following properties: the amount of volatile organic compounds (VOC) is 336 to 408 \u03bcgTEg; the tensile modulus is 1475 to 1835 MPa: and, the flexural modulus is 1384 to 1743 MPa;
the heterophasic polypropylene copolymers being obtained by a multistage polymerzation procees in the presence of a catalyst system comprising
(i)a Ziegler-Natta procatalyst which contains a trans-esterification product of a lower alcohol having at least C5 alkyl and a phthalic ester and
(ii) an organometallic cocatalyst and
(iii)an external donor represented by formula (I)
Si(OCH2CH3)3(NR1R2)
wherein R1 and R2 can be the same or different and represent a hydrocarbon group having 1 to 12 carbon atoms.
6. High purity heterophasic polypropylene copolymers according to claim 5, wherein the propylene matrix (A) of said heterophasic polypropylene copolymers is a propylene homopolymer.
7. The high purity heterophasic polypropylene copolymers according to claim 5 used in the manufacture of moulded articles and injection molded articles.
8. A process for producing high purity heterophasic polypropylene copolymers comprising
(A) 73 to 98 wt. % of a propylene homopolymer matrix with an MFR2 in accordance with ISO 1133 (230\xb0 C., 2.16 kg load) of 45 to 500 g10 min and
(B) 2 to 27 wt. % of elastomeric copolymers, comprising propylene in an amount of at least 50 wt. % of component (B) and at least ethylene andor one other C4 to C10 alpha olefin in an amount of 20 to less than 50 wt. % of component (B) in a multistage polymerization process, wherein said high purity heterophasic polypropylene copolymers have the following properties: the amount of volatile organic compounds (VOC) is 336 to 408 \u03bcgTEg; the tensile modulus is 1475 to 1835 MPa; and, the flexural modulus is 1384 to 1743 MPa;
said process for producing comprising process steps of:
providing a catalyst system
producing a polypropylene polymer matrix (A) using said catalyst system, said catalyst system comprising a Ziegler-Natta procatalyst (i) which contains a trans-esterification product of lower alcohol having at least C5 alkyl and a phthalic ester, (ii)an organometallic cocatalyst and an external donor (iii) represented by formula (I) Si(OCH2CH3)3(NR1R2) wherein R1 and R2 can be the same or different and represent a hydrocarbon group having 1 to 12 carbon atoms, and an organometallic cocatalyst (ii) in a first slurry reactor and in a second slurry reactor, both slurry reactors using the same polymerization conditions,
transferring the slurry reactor product into a 1st GPR
producing an elastomeric copolymer (B) of propylene and a ethylene andor one other C4 to C10 alpha olefin in the polymer matrix in the presence of the catalyst system in said 1st GPR
transferring the 1st GPR product into a 2nd GPR and producing a second elastomeric copolymer (B) of propylene and one comonomer which is ethylene or one other C4 to C10 alpha olefin in the polymer matrix in the presence of the catalyst system in said 2nd GPR, said 1st and 2nd copolymers of propylene and ethylene andor one other C4 to C10 alpha olefin may have the same or different composition ratios and
recovering the polymer product for further processing.
9. An article produced from heterophasic polypropylene copolymers, said heterophasic polypropylene copolymers having MFR2 in accordance with ISO 1133 (230\xb0 C., 216 kg load) of above 35 g10 min, said copolymer comprising
(A) 73 to 98 wt % of a propylene homo- or copolymer matrix with an MFR2 in accordance with ISO 1133 (230\xb0 C., 2.16 kg load) of 45 to 500 g10 min; wherein for the propylene copolymer matrix, the comonomer is ethylene andor one other C4 to C10 alpha-olefin and the comonomer content is 7.0 to 10.0 wt % of component (A); and
(B) 2 to 27 wt % of an elastormeric copolymer, comprising propylene in an amount of at least 50 wt % of component (B) and ethylene andor one other C4 to C10 alpha olefin in an amount of 20 to less than 50 wt % of component (B),
wherein said high purity heterophasic polypropylene copolymers have the following properties: the amount of volatile organic compounds (VOC) is 336 to 408 \u03bcgTEg; the tensile modulus is 1475 to 1835 MPa; and, the flexural modulus is 1384 to 1743 MPa;
the heterophasic polypropylene copolymers being obtained by a multistage polymerization process in the presence of a catalyst system comprising
(i) Ziegler-Natta procatalyst which contains a trans-esterification product of a lower alcohol having at least C5alkyl and a phthalic ester and
(ii)an organometallic cocatalyst and
(iii) an external donor represented by formula (I)
Si(OCH2CH3)3(NR1R2)
wherein R1 and R2 can be the same or different and represent a hydrocarbon group having 1 to 12 carbon atoms.