1. A starting apparatus for starting an engine comprising:
a drive motor; and
a reduction gear including:
a sun gear disposed to rotate by receiving an input from the drive motor;
an internal gear arranged concentrically with the sun gear and surrounding an outer periphery of the sun gear;
a planetary gear meshing with the sun gear and the internal gear;
a carrier rotatably supporting the planetary gear and outputting the input of the sun gear by reducing a speed thereof;
a rotation restricting member to restrict free rotation of the internal gear; and
a shock absorbing member interposed between the internal gear and the rotation restricting member to alleviate a shock applied to the internal gear;
wherein the internal gear includes a locking projection projecting from a side face of the internal gear in an axial direction of the reduction gear, and the rotation restricting member is formed with a guide groove for receiving the locking projection therein and guiding the locking projection in a circumferential direction, and
wherein the locking projection has a first circumferential surface and a second circumferential surface facing oppositely in the circumferential direction, and the shock absorbing member is held in the guide groove so as to elastically contact the first and second circumferential surfaces of the locking projection in the circumferential direction so that the locking projection is fitted in the shock absorbing member and held in a condition of being pressed by the shock absorbing member on both the first and second circumferential surfaces.
2. The starting apparatus according to claim 1,
wherein the shock absorbing member includes an elastic block having a first end portion, a second end portion and a middle portion between the first end portion and the second end portion in the circumferential direction, and the middle portion is narrower than the first and second end portions.
3. The starting apparatus according to claim 1,
wherein the shock absorbing member includes an elastic block; and
wherein the guide groove of the rotation restricting member has a bottom portion that is movable in the axial direction in accordance with contraction of the elastic block.
4. The starting apparatus according to claim 1,
wherein the shock absorbing member includes an elastic projection projecting in the axial direction, and the elastic projection is elastically in contact with the internal gear in the axial direction.
5. The starting apparatus according to claim 4,
wherein the elastic projection is elastically in contact with an axial end face of the locking projection of the internal gear.
6. The starting apparatus according to claim 1, wherein
the shock absorbing member includes a first elastic block portion and a second elastic block portion that are disposed in the guide groove, and
the locking projection is held between the first elastic block portion and the second elastic block portion in a pressed manner.
7. The starting apparatus according to claim 1, wherein
the reduction gear further includes a gear housing, and the rotation restricting member is fixed relative to the gear housing.
8. The starting apparatus according to claim 1, wherein
a load applied to the internal gear is absorbed by the shock absorbing member so that the internal gear is not rotated.
9. The starting apparatus according to claim 1,
wherein the rotation restricting member includes a plurality of guide grooves arranged uniformly in the circumferential direction, and
wherein the shock absorbing member includes a plurality of elastic blocks, each having a first elastic block portion, a second elastic block portion and a bridge portion connecting the first elastic block portion and the second elastic block portion, wherein the elastic block is arranged such that some of the first elastic block portions are held in one of the guide grooves and some of the second elastic block portions are held in an adjacent guide groove.
10. The starting apparatus according to claim 6,
wherein the bridging portion includes an elastic projection projecting in the axial direction,
wherein the elastic projection is elastically in contact with the internal gear in the axial direction.
11. The starting apparatus according to claim 9, wherein
the first elastic block portion has a first end, a second end and a middle portion between the first end and the second end in the circumferential direction, and
the middle portion is narrower than the first end and the second end.
12. The starting apparatus according to claim 9, wherein
the first and second circumferential surfaces of the locking projection are elastically in contact with circumferential surfaces of the first and second elastic block portions that are held in the same guide groove.
13. The starting apparatus according to claim 9, wherein
the rotation restricting member has a rib between adjacent guide grooves, and
the bridge portion of the elastic block is disposed along an axial end of the rib to connect the first elastic block portion and the second elastic block portion received in the adjacent guide grooves.
14. A starting apparatus for starting an engine, the starting apparatus comprising:
a drive motor; and
a speed reduction gear movable in accordance with operation of the drive motor, the speed reduction gear including a fixed gear housing, an internal gear disposed in the gear housing and movable in a circumferential direction with respect to the gear housing, a rotation restricting member integrated with the gear housing, and a shock absorbing member for absorbing a reaction force applied to the internal gear, wherein
the internal gear has a projection projecting from its axial face in an axial direction, the projection has a first circumferential surface and a second circumferential surface facing oppositely in the circumferential direction,
the rotation restricting member is formed with a guide groove for guiding the projection of the internal gear in the circumferential direction,
the shock absorbing member has a first elastic block portion and a second elastic block portion disposed in the guide groove, and
the projection of the internal gear is fitted between the first elastic block portion and the second elastic block portion such that the first elastic block portion and the second elastic block portion elastically contact the first circumferential surface and the second circumferential surface.
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. A compound represented by Formula I, its enantiomers, diastereoisomers, hydrates, solvates, crystal forms and individual isomers, tautomers or a pharmaceutically acceptable salt thereof,
wherein:
A is optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloalkyl or optionally substituted C3-8 cycloalkenyl;
B is optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloalkyl or optionally substituted C3-8 cycloalkenyl;
R1 is H, halogen, \u2014OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl;
R2 is H, halogen, \u2014OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl;
R3 is H, halogen, \u2014OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl;
R4 is H, halogen, \u2014OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl;
R5 is H, halogen, \u2014OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl;
R6 is H, halogen, \u2014OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl;
R7 is H, halogen, \u2014OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloakyl, optionally substituted C cycloalkenyl, NR12R13 or hydroxyl;
R8 is H, halogen, \u2014OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloakyl, optionally substituted C3-8 cycloalkenyl, NR12R13 or hydroxyl;
R9 is H, halogen, \u2014OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloakyl, optionally substituted C3-8 cycloalkenyl, NR12R13 or hydroxyl;
R10 is H, halogen, \u2014OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, C6-10 aryl, optionally substituted heterocycle, optionally substituted C cycloakyl, optionally substituted C3-8 cycloalkenyl, NR12R13 or hydroxyl;
L1 is O, S, NH or CHR12;
L2 is O, S or CHR12;
R11 is H, OH or C1-8 alkyl;
a is 1, 2, 3, 4, 5 or 6;
R12 is H or C1-8 alkyl; and
R13 is H or C1-8 alkyl.
2. A compound according to claim 1 wherein L1 is CH2.
3. A compound according to claim 1 wherein L2 is CH2.
4. A compound according to claim 1 wherein a is 1, 2 or 3.
5. A compound according to claim 1 wherein
6. A compound according to claim 5, wherein
7. A compound according to claim 5, wherein:
8. A compound according to claim 5, wherein
9. A compound according to claim 1, wherein:
R1 is H or halogen;
R2 is H or halogen;
R3 is H or halogen;
R4 is H or halogen;
R5 is H or C1-8 alkyl; and
R6 is H or C1-8 alkyl.
10. A compound according to claim 1, selected from:
1-(4-{5-(3-chlorophenyl)-6-(3,4-dimethylphenyl)hexyloxy}benzyl)azetidine-3-carboxylic acid;
1-{4-3-(3-chlorophenyl)-4-(3,4-dimethylphenyl)butoxybenzyl}azetidine-3-carboxylic acid;
1-(4-{4-(3,5-difluorophenyl)-5-(3,4-dimethylphenyl)pentyloxy}benzyl)azetidine-3-carboxylic acid;
1-(4-{4-(3-chlorophenyl)-5-(3,4-dimethylphenyl)pentyloxy}benzyl)azetidine-3-carboxylic acid;
1-(4-{4-(3,4-difluorophenyl)-5-(3,4-dimethylphenyl)pentyloxy}benzyl)azetidine-3-carboxylic acid;
1-(4-{5-(3,4-dimethylphenyl)-4-(3-thienyl)pentyloxy}benzyl)azetidine-3-carboxylic acid; and
1-(4-{4-(2,3-difluorophenyl)-5-(3,4-dimethylphenyl)pentyloxy}benzyl)azetidine-3-carboxylic acid.
11. A pharmaceutical composition comprising as active ingredient a therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable adjuvant, diluent or carrier.
12. A pharmaceutical composition according to claim 11 wherein the compound is selected from:
1-(4-{5-(3-chlorophenyl)-6-(3,4-dimethylphenyl)hexyloxy}benzyl)azetidine-3-carboxylic acid;
1-{4-3-(3-chlorophenyl)-4-(3,4-dimethylphenyl)butoxybenzyl}azetidine-3-carboxylic acid;
1-(4-{4-(3,5-difluorophenyl)-5-(3,4-dimethylphenyl)pentyloxy}benzyl)azetidine-3-carboxylic acid;
1-(4-{4-(3-chlorophenyl)-5-(3,4-dimethylphenyl)pentyloxy}benzyl)azetidine-3-carboxylic acid;
1-(4-{4-(3,4-difluorophenyl)-5-(3,4-dimethylphenyl)pentyloxy}benzyl)azetidine-3-carboxylic acid;
1-(4-{5-(3,4-dimethylphenyl)-4-(3-thienyl)pentyloxy}benzyl)azetidine-3-carboxylic acid; and
1-(4-{4-(2,3-difluorophenyl)-5-(3,4-dimethylphenyl)pentyloxy}benzyl)azetidine-3-carboxylic acid.
13. A method of treating a disorder associated with sphingosine-1-phosphate receptor modulation, which comprises administering to a mammal in need thereof, a pharmaceutical composition comprising a therapeutically effective amount of at least one compound of Formula I
wherein:
A is optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloalkyl or optionally substituted C3-8 cycloalkenyl;
B is optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloalkyl or optionally substituted C3-8 cycloalkenyl;
R1 is H, halogen, \u2014OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl;
R2 is H, halogen, \u2014OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl;
R3 is H, halogen, \u2014OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl;
R4 is H, halogen, \u2014OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl;
R5 is H, halogen, \u2014OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl;
R6 is H, halogen, \u2014OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl;
R7 is H, halogen, \u2014OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloakyl, optionally substituted C3-8 cycloalkenyl, NR12R13 or hydroxyl;
R8 is H, halogen, \u2014OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloakyl, optionally substituted C3-8 cycloalkenyl, NR12R13 or hydroxyl;
R9 is H, halogen, \u2014OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloakyl, optionally substituted C3-8 cycloalkenyl, NR12R13 or hydroxyl;
R10 is H, halogen, \u2014OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloakyl, optionally substituted C3-8 cycloalkenyl, NR12R13 or hydroxyl;
L1 is O, S, NH or CHR12;
L2 is O, S or CHR12;
R11 is H, OH or C1-8 alkyl;
a is 1, 2, 3, 4, 5 or 6;
R12 is H or C1-8 alkyl; and
R13 is H or C1-8 alkyl.
14. A method of claim 13, wherein the pharmaceutical composition is administered to the mammal to treat ocular disease, wet and dry age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, retinal edema, geographic atrophy, glaucomatous optic neuropathy, chorioretinopathy, hypertensive retinopathy, dry eye, ocular ischemic syndrome, prevention of inflammation-induced fibrosis in the back of the eye, various ocular inflammatory diseases including uveitis, scleritis, keratitis, and retinal vasculitis; or systemic vascular barrier related diseases , various inflammatory diseases, including acute lung injury, its prevention, sepsis, tumor metastasis, atherosclerosis, pulmonary edemas, and ventilation-induced lung injury; or autoimmune diseases and immunosuppression , rheumatoid arthritis, Crohn’s disease, Graves’ disease, inflammatory bowel disease, multiple sclerosis, Myasthenia gravis, Psoriasis, ulcerative colitis, antoimmune uveitis, renal ischemiaperfusion injury, contact hypersensitivity, atopic dermatitis, and organ transplantation; or allergies and other inflammatory diseases , urticaria, bronchial asthma, and other airway inflammations including pulmonary emphysema and chronic obstructive pulmonary diseases; or cardiac protection , ischemia reperfusion injury and atherosclerosis; or wound healing, scar-free healing of wounds from cosmetic skin surgery, ocular surgery, GI surgery, general surgery, oral injuries, various mechanical, heat and burn injuries, prevention and treatment of photoaging and skin ageing, and prevention of radiation-induced injuries; or bone formation, treatment of osteoporosis and various bone fractures including hip and ankles; or anti-nociceptive activity , visceral pain, pain associated with diabetic neuropathy, rheumatoid arthritis, chronic knee and joint pain, tendonitis, osteoarthritis, neuropathic pains.
15. The method of claim 13 wherein the mammal is a human.